title: Remodeling characteristics and collagen distribution in biological scaffold materials explanted from human subjects after abdominal soft tissue reconstruction: an analysis of scaffold remodeling characteristics by patient risk factors and surgical site classifications.

text: OBJECTIVE The study purpose was to evaluate the associations between patient characteristics or surgical site classifications and the histologic remodeling scores of biologic meshes biopsied from abdominal soft tissue repair sites in the first attempt to generate a multivariable risk-prediction model of nonconstructive remodeling. BACKGROUND Host characteristics and surgical site assessments may predict remodeling degree for biologic meshes used to reinforce abdominal tissue repair sites. METHODS Biologic meshes were biopsied from the abdominal tissue repair sites of n = 40 patients during an abdominal reexploration, stained with hematoxylin and eosin, and evaluated according to a semi-quantitative scoring system for remodeling characteristics (cell types, cell infiltration, extracellular matrix deposition, scaffold degradation, fibrous encapsulation, and neovascularization) and a mean composite score. Biopsies were stained with Sirius Red and Fast Green and analyzed to determine the collagen I:III ratio. On the basis of univariate analyses between subject clinical characteristics or surgical site classification and the histologic remodeling scores, cohort variables were selected for multivariable regression models using P ≤ 0.200. RESULTS The model selection process for cell infiltration score yielded 2 variables: age at mesh implantation and mesh classification (C statistic = 0.989). For the mean composite score, the model selection process yielded 2 variables: age at mesh implantation and mesh classification (r = 0.449). CONCLUSIONS These preliminary results constitute the first steps in generating a risk-prediction model that predicts the patients and clinical circumstances most likely to experience nonconstructive remodeling of abdominal tissue repair sites with biologic mesh reinforcement.


Assessment of QT Intervals in a Case Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With Hydroxychloroquine Alone or in Combination With Azithromycin in an Intensive Care Unit.


title: Cause-specific mortality associated with aging in patients with hepatocellular carcinoma undergoing percutaneous radiofrequency ablation.

text: OBJECTIVE The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) is expected to increase. The aim of this study is to evaluate the efficacy of radiofrequency ablation (RFA) in elderly patients with HCC and to investigate cause-specific excess deaths associated with increasing number of elderly patients. MATERIALS AND METHODS We enrolled 1401 naive patients with HCC who were treated initially by RFA from 1999 to 2011. Patients below 75 years of age were categorized as 'younger' and those at least 75 as 'elderly'. Differences in the demographic and laboratory data of these patients were assessed, along with Kaplan-Meier analysis of survival using the log-rank test. In addition, we assessed the causes of death, defined as liver related and liver unrelated, by competing risk analysis and risk factors for respective causes of death by a proportional subdistribution model. RESULTS Overall, 353 patients were categorized as elderly. Elderly patients were more likely to be women, infected with hepatitis C virus, and score better in the Child-Pugh classification. The mortality at 5 years was lower in the elderly than in the younger patients (47.3 vs. 37.1%; P<0.001). Competing risk analysis showed a significant difference in liver-unrelated death (P<0.001) between the two groups, whereas there were no significant differences in liver-related death (P=0.64). By the proportional subdistribution model, age was a significant risk factor only for liver-unrelated death. CONCLUSION RFA provided satisfactory 5-year survival rates in elderly patients with HCC. The elderly tended to die from liver-unrelated causes.


title: [What we learned from SARS may provide important insights into understanding and management of coronavirus disease 2019].

text: The rapid spread of the coronavirus disease 2019 (COVID-19) has become a global threat. But the pathogenesis and treatment of the disease are not clear yet. Virological researches revealed close relationship between 2019-nCoV and SARS-CoV. The experience and knowledge we gained from severe acute respiratory syndrome (SARS), especially with regard to the time course of viral replication, host immune response and clinical progression of the patient, may provide important insights into understanding and management of COVID-19. Clinical deterioration accompanied by decreasing viral load in the second week after symptom onset was noted both in SARS and COVID-19, suggesting that the lung damage at this phase is more related to excessive host immune response rather than uncontrolled viral replication.


Universal Masking in Hospitals in the Covid-19 Era.


title: Improving Outcomes in Colorectal Surgery by Sequential Implementation of Multiple Standardized Care Programs.

text: BACKGROUND The purpose of this study was to examine the impact of the sequential implementation of the enhanced recovery program (ERP) and surgical site infection bundle (SSIB) on short-term outcomes in colorectal surgery (CRS) to determine if the presence of multiple standardized care programs provides additive benefit. STUDY DESIGN Institutional ACS-NSQIP data were used to identify patients who underwent elective CRS from September 2006 to March 2013. The cohort was stratified into 3 groups relative to implementation of the ERP (February 1, 2010) and SSIB (July 1, 2011). Unadjusted characteristics and 30-day outcomes were assessed, and inverse proportional weighting was then used to determine the adjusted effect of these programs. RESULTS There were 787 patients included: 337, 165, and 285 in the pre-ERP/SSIB, post-ERP/pre-SSIB, and post-ERP/SSIB periods, respectively. After inverse probability weighting (IPW) adjustment, groups were balanced with respect to patient and procedural characteristics considered. Compared with the pre-ERP/SSIB group, the post-ERP/pre-SSIB group had significantly reduced length of hospitalization (8.3 vs 6.6 days, p = 0.01) but did not differ with respect to postoperative wound complications and sepsis. Subsequent introduction of the SSIB then resulted in a significant decrease in superficial SSI (16.1% vs 6.3%, p < 0.01) and postoperative sepsis (11.2% vs 1.8%, p < 0.01). Finally, inflation-adjusted mean hospital cost for a CRS admission fell from $31,926 in 2008 to $22,044 in 2013 (p < 0.01). CONCLUSIONS Sequential implementation of the ERP and SSIB provided incremental improvements in CRS outcomes while controlling hospital costs, supporting their combined use as an effective strategy toward improving the quality of patient care.


docid: ueskiyjy

title: Effects of β2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective β-blockers: a randomized trial.

text: Alveolar β2-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar β2-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) β-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8 ± 5.9 vs. 28.5 ± 5.6, p < 0.0001 and maximal PETCO2 36.7 ± 5.5 vs. 37.7 ± 5.8 mmHg, p < 0.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119 ± 34 vs. 113 ± 30 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise.


Accuracy or efficiency? Striking the balance for your chest pain pathway.


title: A systematic review of interventions aimed at improving the cardiovascular health of people diagnosed with personality disorders.

text: PURPOSE People with personality disorders have significantly reduced life expectancy and increased rates of cardiovascular disease compared to members of the general population. Given that more people die annually of cardiovascular disease across the globe than from any other cause, it is important to identify the evidence for interventions aimed at improving cardiovascular health among people with personality disorders. METHODS Systematic literature review. PsycINFO, MEDLINE and EMBASE were searched using NICE Healthcare Databases, as well as CENTRAL and trial registries. We sought to identify randomised controlled trials of interventions pertaining to adults with a primary diagnosis of personality disorder, where the primary outcome measure was cardiovascular health before and after the intervention. RESULTS A total of 1740 records were identified and screened by two independent reviewers. No papers meeting the inclusion criteria were identified. CONCLUSIONS This systematic review did not identify any randomised controlled trials testing interventions aimed at improving the cardiovascular health of people with personality disorders. Research in this area could have important public health implications, spanning the fields of psychiatry and general medicine.


title: The outcome and efficacy of recanalization in patients with acute internal carotid artery occlusion.

text: BACKGROUND AND PURPOSE Acute occlusion of the ICA is often associated with poor outcomes and severe neurologic deficits. This study was conducted to evaluate outcome of the occluded ICA and efficacy of recanalization under protective flow arrest. MATERIALS AND METHODS Fifty consecutive patients who underwent endovascular treatment for acute ICA occlusion were identified from the prospectively collected data base. We assessed NIHSSo, occlusion type (cardioembolism vs atherosclerosis), occlusion level (supraclinoid-terminal, petrocavernous, or bulb-cervical), recanalization degree (TICI), and efficacy of recanalization (protective flow arrest vs nonprotection) leading to better outcome. RESULTS Successful recanalization (TICI ≥ 2) was obtained in 90% of patients and good recovery (mRS ≤ 2) in 60% of patients. Good outcome was related to National Institutes of Health Stroke Scale score on admission (P < .001), TICI (P < .007), occlusion type (P = .022), and occlusion level (P = .038). Poor initial patient status, less recanalization, cardioembolism, and supraclinoid-terminal occlusion were associated with poor prognosis. Application of protective flow arrest led to better outcome in the distal ICA segment than in the bulb-cervical segment. CONCLUSIONS In addition to the initial patient status and successful recanalization, the occlusion level or type of the occluded ICA could affect clinical outcome. In this study, treatment benefits of protective flow arrest were accentuated in patients with ICA occlusion above the bulb-cervical segment.


title: Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors.

text: Two new classes of radiolabeled GRP receptor antagonists are studied and compared with the well-established statine-based receptor antagonist DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (RM2, 1; DOTA:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Sta:(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid). The bombesin-based pseudopeptide DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leuψ(CHOH-CH2)-(CH2)2-CH3 (RM7, 2), and the methyl ester DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-OCH3 (ARBA05, 3) analogues are labeled with (111)In and evaluated in vitro in PC-3 cell line and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was assessed by immunofluorescence-based receptor internalization and Ca(2+) mobilization assays. The conjugates showed good binding affinity, the IC50 value of 2 (3.2 ± 1.8 nM) being 2 and 10 times lower than 1 and 3. Compared to (111)In-1, (111)In-2 showed higher uptake in target tissues such as pancreas (1.5 ± 0.5%IA/g and 39.8 ± 9.3%IA/g at 4 h, respectively), whereas the compounds had similar tumor uptake (11.5 ± 2.4%IA/g and 11.8 ± 3.9%IA/g at 4h, respectively). The displacement of the radioligand in vivo was different in different receptor positive organs and depended on the displacing peptide.


Covid-19: Intensive care consultant has suspension cut short to help fight pandemic.


title: [Analysis on epidemic situation and spatiotemporal changes of COVID-19 in Anhui].

text: We used the epidemic data of COVID-19 published on the official website of the municipal health commission in Anhui province. We mapped the spatiotemporal changes of confirmed cases, fitted the epidemic situation by the population growth curve at different stages and took statistical description and analysis of the epidemic situation in Anhui province. It was found that the cumulative incidence of COVID-19 was 156/100 000 by February 18, 2020 and the trend of COVID-19 epidemic declined after February 7, changing from J curve to S curve. The actual number of new cases began to decrease from February 2 to February 4 due to the time of case report and actual onset delayed by 3 to 5 days.


title: Advantages of Splenic Hilar Lymph Node Dissection in Proximal Gastric Cancer Surgery.

text: Gastrectomy with lymph node dissection remains the gold standard for curative treatment of gastric cancer. Dissection of splenic hilar lymph nodes has been included as a part of D2 lymph node dissection for proximal gastric cancer. Previously, pancreatico-splenectomy has been performed for dissecting splenic hilar lymph nodes, followed by pancreas-preserving splenectomy and spleen-preserving lymphadenectomy. However, the necessity of routine splenectomy or splenic hilar lymph node dissection has been under debate due to the increased morbidity caused by splenectomy and the poor prognostic feature of splenic hilar lymph node metastasis. In contrast, the relatively high incidence of splenic hilar lymph node metastasis, survival advantage, and therapeutic value of splenic hilar lymph node dissection in some patient subgroups, as well as the effective use of novel technologies, still supports the necessity and applicability of splenic hilar lymph node dissection. In this review, we aimed to evaluate the need for splenic hilar lymph node dissection and suggest the subgroup of patients with favorable outcomes.


title: Implications of COVID-19 for the busy gastroenterologist.

text: Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.


Proteomics search of influenza A viruses for adaptive mutations to human hosts.


SILC: significantly inferior laparoscopic cholecystectomy?


title: Impact of the COVID-19 pandemic on the sexual behavior of the population. The vision of the east and the west.

text: The COVID-19 pandemic has radically changed the way of life around the World. The state of alarm has forced the population to stay at home, radically changing both interpersonal and partner relationships; work at home, social distancing, the continued presence of children at home, fear of infection and not being able to physically meet with others have changed most people's sexual habits. We conducted a review by exploring the impact of the COVID-19 pandemic on sexual behavior in the population from three different countries: Iran, Italy and Spain from each country's perspective. The impact of the coronavirus will be very important in the sexual life of the people and we will attend in the next months or years, to some changes in the relationships at all the levels. The pandemic will negatively affect sexual behaviors due to multiple contact restrictions. In the future, we will be able to assess these effects in more detail.


title: Transanal Minimally Invasive Surgery: Review of Indications and Outcomes from 75 Consecutive Patients.

text: BACKGROUND Transanal minimally invasive surgery (TAMIS) is an advanced local excision platform that helps overcome technical limitations and morbidity associated with other resection methods. Our goal was to review the indications and outcomes of TAMIS in a large series. STUDY DESIGN A review of a prospective database identified patients who underwent TAMIS from 2010 to 2014. Demographic, perioperative, short-term outcomes, and recurrence data were analyzed. RESULTS There were 75 patients with 76 lesions analyzed. Mean age was 64.0 years (SD 11.6 years) and mean BMI was 27.4 kg/m(2) (SD 4.7 kg/m(2)). Median American Society of Anesthesiologists (ASA) score was 2 (range 1 to 4). There were 59 benign (77.3%) and 17 malignant (22.7%) lesions: 6 pT0, 6 pT1, 4 pT2, and 1 pT3. Median lesion distance from the anal verge was 10 cm (range 6 to 16 cm). Mean operative time was 76.0 minutes (SD 36.1 minutes). Three patients had intraperitoneal entry; all were closed transanally, but 2 had temporary diverting ileostomies fashioned to ensure healing. Median length of stay was 1 day (range 0 to 6). One patient had a fragmented lesion (1.3%). Five patients had positive margins: 2 in palliative pT2 resections, and 3 in pT1, pT2, and gastrointestinal stromal tumor (GIST) patients. They were managed with radical resection (pT1 and pT2 lesions) and surveillance/medical oncology (GIST). Postoperatively, 3 patients had complications (bleeding, rectal stricture, and recto-vaginal fistula), and all were managed nonoperatively. After median follow-up of 39.5 months (range 10.5 to 65.3 months), 1 pT1 patient with negative margins developed a local recurrence and underwent salvage APR. CONCLUSIONS Transanal minimally invasive surgery is a viable option for excision of benign or early stage rectal masses, with mid-term oncologic outcomes comparable to those of radical resection. Further, TAMIS minimizes the morbidity and can allow more patients to benefit from the minimally invasive approach.


title: Will There Be an Epidemic of Corollary Illnesses Linked to a COVID-19-Related Recession?

text: Currently, US unemployment claims have skyrocketed to 30 million in the past six weeks, continuing in a stark upward trend, and labor economists estimate the unemployment rate at minimally 18.3%. These unemployment figures are a feature of the COVID-19 recession that is characterized by sharp gross domestic product (GDP) growth decline. Despite the greatly damaging impact of the opioid crisis over 2015 to 2017 resulting in a decrease in life expectancy over these three years, the long-term increases in average GDP per capita from 1999 to 2018 managed to save lives on average (i.e., age-adjusted mortality rates declined in the United States). For example, during 1999 to 2018, the average GDP per capita annually increased 1.2%, whereas the related age-adjusted mortality rate has shown an annual decrease of approximately 1% on average (0.99%). However, recessions erase some of this beneficial effect of GDP growth on mortality reduction.1 (Am J Public Health. Published online ahead of print May 14, 2020: e1-e2. doi:10.2105/AJPH.2020.305724).


title: Cerebral Oximetry Monitoring to Maintain Normal Cerebral Oxygen Saturation during High-risk Cardiac Surgery: A Randomized Controlled Feasibility Trial.

text: BACKGROUND Cerebral oxygen desaturation during cardiac surgery has been associated with adverse perioperative outcomes. Before a large multicenter randomized controlled trial (RCT) on the impact of preventing desaturations on perioperative outcomes, the authors undertook a randomized prospective, parallel-arm, multicenter feasibility RCT to determine whether an intervention algorithm could prevent desaturations. METHODS Eight Canadian sites randomized 201 patients between April 2012 and October 2013. The primary outcome was the success rate of reversing cerebral desaturations below 10% relative to baseline in the intervention group. Anesthesiologists were blinded to the cerebral saturation values in the control group. Intensive care unit personnel were blinded to cerebral saturation values for both groups. Secondary outcomes included the area under the curve of cerebral desaturation load, enrolment rates, and a 30-day follow-up for adverse events. RESULTS Cerebral desaturations occurred in 71 (70%) of the 102 intervention group patients and 56 (57%) of the 99 control group patients (P = 0.04). Reversal was successful in 69 (97%) of the intervention group patients. The mean cerebral desaturation load (SD) in the operating room was smaller for intervention group patients compared with control group patients (104 [217] %.min vs. 398 [869] %.min, mean difference, -294; 95% CI, -562 to -26; P = 0.03). This was also true in the intensive care unit (P = 0.02). There were no differences in adverse events between the groups. CONCLUSIONS Study sites were successful in reversal of desaturation, patient recruitment, randomization, and follow-up in cardiac surgery, supporting the feasibility of conducting a large multicenter RCT.


THE GENETICS AND EVOLUTION OF INFECTIOUS DISEASESThe Genetics and Evolution of Infectious Diseases. Second Edition. By M. Tibayrenc (editor). Elsevier, Amsterdam, the Netherlands. 2017. 667 pp. ISBN: 978-0-12-799942-5. US $190 hardback.


The blunt truth behind coiling vs clipping: consumers as decision-drivers.


title: Robotic transanal endoscopic microsurgery: technical details for the lateral approach.

text: BACKGROUND Transanal endoscopic microsurgery is a minimally invasive approach reserved for the resection of selected rectal tumors. However, this approach is technically demanding. Although robotic technology may overcome the limitations of this approach, the system can be difficult to dock, especially in the lithotomy position. OBJECTIVE The study aim is thus to report the technical details of robotic transanal endoscopic microsurgery with the use of a lateral approach. DESIGN AND SETTINGS This study is a prospective evaluation of robotic transanal endoscopic microsurgery in a single tertiary institution, under a protocol approved by our local ethics committee. INTERVENTION Patients underwent a routine mechanical bowel preparation and were placed in the left or right lateral position according to the tumor location. A circular anal dilatator was used together with the glove port technique. The robotic system was then docked over the hip. A 30° optic and 2 articulated instruments were used with an additional assistant trocar. The tumor excision was realized with an atraumatic grasper and an articulated cautery hook, and the defect was closed with barbed continuous stiches in each case. MAIN OUTCOME MEASURE The primary outcome was the safety and feasibility of the procedure. RESULTS Three patients underwent a robotic transanal endoscopic microsurgery with the use of the lateral approach. Mean operative time was 110 minutes, including 20 minutes for the docking of the robot. There was 1 intraoperative complication (a pneumoperitoneum without intraabdominal lesion) and no postoperative complications. Mean hospital stay was 3 days. Margins were negative in all the cases. LIMITATIONS The study was limited by the small number of patients. CONCLUSION Robotic transanal endoscopic microsurgery with use of the lateral approach is feasible and may facilitate the local resection of small lesions of the mid and lower rectum. It might assume an important place in sphincter-preserving surgery, especially for selected and early rectal cancer (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A114).


title: The response of the composite variability index to a standardized noxious stimulus during propofol-remifentanil anesthesia.

text: BACKGROUND Recently the Composite Variability Index (CVI) was developed to quantify nociception. This index is derived from the standard deviations (s) of the Bispectral Index (sBIS) and the electromyogram (sEMG). The primary aim of our study was to compare CVI before and after a noxious stimulus. As secondary end points, we investigated the influence of remifentanil on the CVI and tested the ability of the CVI to indicate patient movement after a noxious stimulus under changing remifentanil concentrations. Furthermore, we measured the increase in CVI after a noxious stimulus in comparison to other clinical variables (BIS, sBIS, sEMG, heart rate [HR], and systolic blood pressure [BP(sys)]). METHODS Twenty-four patients without a history of cardiac disease were investigated. Anesthesia was induced with propofol administered by target-controlled infusion. A standardized noxious electrical stimulus was applied (50 Hz, 70 mA, 30 seconds) to the ulnar nerve at increasing or decreasing remifentanil effect-compartment concentrations (Ce(remi)). Changes in baseline and poststimulus CVI, BIS, sBIS, sEMG, HR, and BP(sys) were investigated. Parameters' ability to indicate movement after a noxious stimulus was evaluated with the prediction probability (P(K)). RESULTS All investigated parameters (except BP(sys)) increased significantly after a noxious stimulus at 0, 1, 2, or 3 ng·mL(-1) Ce(remi). The association between poststimulus maximal parameters and movement were P(K) = 0.81 for HR, P(K) = 0.78 for sEMG, and P(K) = 0.72 for CVI (pairwise difference to CVI statistically nonsignificant). The association between ΔsEMG or ΔCVI (poststimulus value minus baseline value) and movement was significantly higher (P(K) = 0.76 and 0.75, respectively) compared with ΔHR (P(K) = 0.53) (P = 0.008 and P = 0.01, respectively). Receiver operating characteristic analysis revealed a threshold value for movement for ΔCVI of >0.39 (sensitivity of 0.71, specificity of 0.74) and for ΔsEMG of >0.31 (sensitivity of 0.68, specificity of 0.78). CONCLUSION In paralyzed patients, ΔsEMG and ΔCVI might help identify inadequately low levels of analgesia with an acceptable sensitivity and specificity. The impact of profound neuromuscular block on the CVI should be investigated in further studies.


COVID-19: Biomedical research in a world under social-distancing measures.


title: Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.

text: The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett's esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett's esophagus and EAC samples, together with one in-depth Barrett's esophagus case study sampled over time and space, we have provided the following new insights: (i) Barrett's esophagus is polyclonal and highly mutated even in the absence of dysplasia; (ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett's esophagus; and (iii) despite differences in specific coding mutations, the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett's epithelium, and a molecular Cytosponge technique overcomes sampling bias and has the capacity to reflect the entire clonal architecture.


Cannabis in the Time of Coronavirus Disease 2019: The Yin and Yang of the Endocannabinoid System in Immunocompetence.


title: Health system preparedness for emerging infectious diseases: A synthesis of the literature.

text: This review reflects on what the literature to date has taught us about how health systems of low- and middle-income countries (LMICs) respond to emerging infectious disease (EID) outbreaks. These findings are then applied to propose a conceptual framework characterising an EID prepared health system. A narrative synthesis approach was adopted to explore the key elements of LMIC health systems during an EID outbreak. Overarching themes ('core health system constructs') and sub-themes ('elements') relevant to EID preparedness were extracted from 49 peer-reviewed articles. The resulting conceptual framework recognised six core constructs: four focused on material resources and structures (i.e. system 'hardware'), including (i) Surveillance, (ii) Infrastructure and medical supplies, (iii) Workforce, and (iv) Communication mechanisms; and two focused on human and institutional relationships, values and norms (i.e. system 'software'), including (i) Governance, and (ii) Trust. The article reinforces the interconnectedness of the traditional health system building blocks to EID detection, prevention and response, and highlights the critical role of system 'software' (i.e. governance and trust) in enabling LMIC health systems to achieve and maintain EID preparedness. The review provides recommendations for refining a set of indicators for an 'optimised' health system EID preparedness tool to aid health system strengthening efforts.


title: Blocking of gastric acid induced histopathological alterations, multiplying DNA content and proliferation goblet cells in the acute lung injury mice models by Nano-fenugreek oral administration.

text: This current study aimed at detecting the potential protective role of Nano-fenugreek seed on acute lung injury induced by instillation gastric acid in male Swiss albino mice using histological, and histocemical studies. Forty animals grouped as follows: control group, HCl-treated group; low Nano-fenugreek + HCl treated group and high Nano-fenugreek + HCl treated group. Pretreatment with Nano-fenugreek in animal model of acute lung injury resulted in marked ameliorations of the lung histological lesions and injury induced by HCL instillation in a dose dependent manner. It also caused inhibition in the increase of the DNA content and prevented proliferation of goblet cells induced by HCl instillation alone. Pretreatment with Nano-fenugreek prior induction acute lung injury could suppress the aggregations of inflammatory cells, accumulation DNA content, and proliferation of goblet cells in a dose dependent manner. We suggest that Nano-fenugreek may be useful in combating lung injury induced.


docid: huvffbgv

title: Isolated Roux-en-Y anastomosis of the pancreatic stump in a duct-to-mucosa fashion in patients with distal pancreatectomy with en-bloc celiac axis resection.

text: BACKGROUND A pancreatic fistula is one of the most serious complications in distal pancreatectomy with en bloc celiac axis resection (DP-CAR), because the pancreatic transection is performed on the right side of the portal vein, which results in a large cross-section surface, and because post-pancreatectomy hemorrhage is hard to treat by interventional radiology. Therefore, a procedure to decrease the incidence of postoperative pancreatic fistula is urgently needed. METHODS Twenty-six consecutive patients who underwent DP-CAR between April 2008 and August 2012 were reviewed retrospectively. The first 13 consecutive patients underwent DP-CAR with no anastomosis, and the subsequent 13 consecutive patients were treated with Roux-en-Y pancreaticojejunostomy (PJ) in a duct-to-mucosa fashion. RESULTS Extremely high amylase levels (>4000 IU/l) of all drainage fluid specimens on postoperative day (POD) 1, 3 and 4 were detected more frequently in cases with no anastomosis (n = 7) compared to those with PJ (n = 1) (P = 0.056). CONCLUSION The incidence of grade B/C pancreatic fistulas was 15.4% in cases with isolated Roux-en-Y anastomosis of the pancreatic stump performed in a duct-to-mucosa fashion, and we are currently examining whether this anastomosis method reduces the pancreatic fistula rate in a multicenter, randomized controlled trial for distal pancreatectomy patients (ClinicalTrials.gov NCT01384617).


title: Absence of in-flight transmission of SARS-CoV-2 likely due to use of face masks on board.

text: Using flights was severely affected during the COVID19 pandemic. We describe a 14 hours flight of 11 passengers and 4 crew members in which 2 positive SARS-COV-2 were on board. No new viral acquisitions found in this flight, probably due to the use of masks.


title: Division of the mesoappendix with electrocautery in children is safe, effective, and cost-efficient.

text: INTRODUCTION Laparoscopic appendectomy is one of the most common procedures performed in children. There are several techniques available for dividing the mesoappendix including the using an endostapler, a LigaSure (Covidien, Boulder, CO), a harmonic scalpel (Ethicon Endosurgery, Cincinnati, OH), or electrocautery. Although it is the least expensive approach, many feel that electrocautery is an unsafe method of dividing the mesoappendix. Here we present our experience with the use of solely electrocautery to divide the mesoappendix. METHODS Over a period of 12 years, a total of 442 laparoscopic appendectomies were logged into our database. Each appendectomy was performed by coagulating and dividing the mesoappendix with a Maryland dissector or in some cases a hook electrocautery. Three 0-PDS Endoloops (Ethicon Endosurgery, Cincinnati, OH) were then used to ligate the base of the appendix, two proximal and one distal. Patient weight, age, operative time, perforated versus nonperforated, and intraoperative and postoperative complications were queried. RESULTS Of the 442 cases, 71 were perforated (16%). The mean time for nonperforated appendectomies was 26 minutes and 38 minutes for perforated. There was one case of postoperative bleeding managed nonoperatively in a patient with previously undiagnosed factor VIII deficiency. The cost of each endoloop was $22. CONCLUSION Although some have questioned the safety of using electrocautery alone to divide the mesoappendix for fear that it may not be adequate to seal the appendiceal artery, may take excessive time, or may cause collateral tissue injury, this has not been our experience. Therefore, the use of more costly instruments to divide the mesoappendix such as the endostapler, LigaSure, or harmonic scalpel seems unwarranted. This study demonstrates that electrocautery for the mesoappendix and endoloops for the appendix is safe, effective, and cost-efficient.


title: HIV-associated lung infections and complications in the era of combination antiretroviral therapy.

text: The spectrum of lung diseases associated with HIV is broad, and many infectious and noninfectious complications of HIV infection have been recognized. The nature and prevalence of lung complications have not been fully characterized since the Pulmonary Complications of HIV Infection Study more than 15 years ago, before antiretroviral therapy (ART) increased life expectancy. Our understanding of the global epidemiology of these diseases in the current ART era is limited, and the mechanisms for the increases in the noninfectious conditions, in particular, are not well understood. The Longitudinal Studies of HIV-Associated Lung Infections and Complications (Lung HIV) Study (ClinicalTrials.gov number NCT00933595) is a collaborative multi-R01 consortium of research projects established by the National Heart, Lung, and Blood Institute to examine a diverse range of infectious and noninfectious pulmonary diseases in HIV-infected persons. This article reviews our current state of knowledge of the impact of HIV on lung health and the development of pulmonary diseases, and highlights ongoing research within the Lung HIV Study.


title: Synthesis of a new series of phosphonylated 1,2,3-triazoles as acyclic analogs of ribavirin.

text: A novel series of phosphonylated 1,2,3-triazoles as structural acyclic analogs of ribavirin, in which the 1,2,3-triazole ring was substituted at C4' with COOMe, CONH2, CONHOH, and CH2 NHBoc groups, were synthesized from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl-, 2-azidoethoxymethyl- and 2-azidoethoxyethylphosphonate. The efficient synthesis of diethyl azidomethylphosphonate from diethyl 4-nitrobenzenesulfonylmethylphosphonate employing the in situ formed azides is described. All synthesized compounds were evaluated in vitro for their inhibitory activity against a broad variety of RNA and DNA viruses. No antiviral activity was observed at 100 µM. Only compound 13g exhibited inhibitory effects on the proliferation of HeLa cells (IC50=169±45 µM).


title: The First Case of Total Laparoscopic Living Donor Right Hemihepatectomy in Mainland China and Literature Review.

text: BACKGROUND Total laparoscopic living donor right hemihepatectomy (LDRH) has been successfully performed in several transplant centers. Here we report the first LDRH performed in mainland China and review current literature, focusing on perioperative donor evaluation and surgical procedure to secure donor safety. METHODS A 47-year-old man volunteered for living donation to his wife who suffered from sclerosing cholangitis-related liver cirrhosis and hepatocellular carcinoma. Donor height is 165 cm and weight is 65 kg, whereas the body mass index is 23.9. The CT volume evaluation showed that the graft-to-body weight ratio was 1.42%, and the remnant liver volume was 36.3% for right graft without middle hepatic vein (MHV). The anatomy of hepatic vein, artery, portal vein, and bile duct was normal. Preoperative liver function tests were normal. RESULTS Intraoperative biopsy result showed minimal steatosis. A transection was performed along the right side of the MHV. Two branches of MHV (V5 and V8) were <5 mm in diameter, and there was no need for reconstruction in the back table. Hilar dissection was meticulously performed. Right portal vein, hepatic artery, and bile duct were transected above the bifurcation. The right hepatic vein was transected by a laparoscopic linear stapler. The real graft volume was 660 mL, with a revised graft-to-body weight ratio of 1.14%. Warm ischemia time was about 4 minutes. The donor's postoperative course was uneventful. CONCLUSIONS Total LDRH has been proven to be technically feasible in selected adult donors. Following increased experience, it might be a safe and minimally invasive option for adult donors.


title: Single incision laparoscopic resection for diverticulitis.

text: BACKGROUND Laparoscopic sigmoidectomy is the standard procedure in elective surgery for recurrent diverticular disease. Recently, Single Incision Laparoscopic Surgery (SILS) have been developed as the next generation technique of minimally invasive surgery. SILS advantages include reduced surgical trauma due to reduction in the number of surgical incisions, faster recovery times, and reduced hospitalization. However, the use of SILS in colorectal surgery is technically demanding and requires expert surgeons, which has hampered the reproducibility and the diffusion of this technique. METHODS Between October 2009 and August 2013, 488 consecutive patients were referred to Evangelisches Hochstift Hospital (Worms, Germany) and/or Stadt Klinikum Frankental Hospital (Frankenthal, Germany) for sigmoidectomy for diverticular disease. SILS sigmoidectomy via the umbilicus was performed in 484/488 cases. Clinical outcomes such as the rate of conversion to standard laparoscopy and/or to open surgery, operation time, post-operative complications and hospitalization time were recorded. RESULTS SILS sigmoidectomy was successfully completed for 484 out of 488 patients. SILS was converted to standard laparoscopy in 3 patients (0.6%) and to an open procedure in 1 patient (0.2%). Median time for the procedures was 103.26 min (range, 52-156 min). No mortalities or major complications were noted. The average hospitalization period was of 5 days. CONCLUSION Our work demonstrates that SILS sigmoidectomy via the umbilicus is effective in the treatment of patients affected by diverticular disease on a routine basis and, moreover, is technically feasible also in patients who have been subjected to previous abdominal surgery, with high Body Mass Index and/or patients with perforation at presentation. Thus this procedure represents a valid alternative to standard laparoscopy.


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title: 18F-FDG PET, genotype-corrected ACE and sIL-2R in newly diagnosed sarcoidosis.

text: PURPOSE Angiotensin-converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R) are serological markers, widely used for determining sarcoidosis activity. (18)F-FDG PET has proven to be a sensitive technique in the imaging of sarcoidosis. The aim of this study was to determine sensitivity of (18)F-FDG PET, genotype-corrected ACE and sIL-2R in active sarcoidosis as well as their correlation. METHODS This retrospective study included 36 newly diagnosed, symptomatic sarcoidosis patients. ACE and sIL-2R levels were simultaneously obtained within 4 weeks of (18)F-FDG PET. ACE was corrected for genotype and expressed as Z-score. (18)F-FDG PET was visually evaluated and scored as positive or negative. Maximum and average standardized uptake values (SUV(max) and SUV(avg)) were compared with ACE and sIL-2R. RESULTS (18)F-FDG PET was found positive in 34 of 36 patients (94%). Thirteen patients (36%) showed an increased ACE with the highest sensitivity found in patients with the I/I genotype (67%). Seventeen patients (47%) showed an increased sIL-2R. No correlation was found between SUV and ACE or sIL-2R. Increased ACE and sIL-2R correlated with a positive (18)F-FDG PET in 12 patients (92%) and 16 patients (94%), respectively. CONCLUSION (18)F-FDG PET is a very sensitive technique to assess active sarcoidosis, in contrast with ACE and sIL-2R, suggesting a pivotal role for (18)F-FDG PET in future sarcoidosis assessment.


title: Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition.

text: Residues within processed protein fragments bound to major histocompatibility complex class I (MHC-I) glycoproteins have been considered to function as a series of "independent pegs" that either anchor the peptide (p) to the MHC-I and/or interact with the spectrum of alphabeta-T-cell receptors (TCRs) specific for the pMHC-I epitope in question. Mining of the extensive pMHC-I structural database established that many self- and viral peptides show extensive and direct interresidue interactions, an unexpected finding that has led us to the idea of "constrained" peptides. Mutational analysis of two constrained peptides (the HLA B44 restricted self-peptide (B44DPalpha-EEFGRAFSF) and an H2-D(b) restricted influenza peptide (D(b)PA, SSLENFRAYV) demonstrated that the conformation of the prominently exposed arginine in both peptides was governed by interactions with MHC-I-orientated flanking residues from the peptide itself. Using reverse genetics in a murine influenza model, we revealed that mutation of an MHC-I-orientated residue (SSLENFRAYV --> SSLENARAYV) within the constrained PA peptide resulted in a diminished cytotoxic T lymphocyte (CTL) response and the recruitment of a limited pMHC-I specific TCR repertoire. Interactions between individual peptide positions can thus impose fine control on the conformation of pMHC-I epitopes, whereas the perturbation of such constraints can lead to a previously unappreciated mechanism of viral escape.


title: Optimizing endovascular stroke treatment: removing the microcatheter before clot retrieval with stent-retrievers increases aspiration flow.

text: BACKGROUND Flow control during endovascular stroke treatment with stent-retrievers is crucial for successful revascularization. The standard technique recommended by stent-retriever manufacturers implies obstruction of the respective access catheter by the microcatheter, through which the stent-retriever is delivered. This, in turn, results in reduced aspiration during thrombectomy. In order to maximize aspiration, we fully retract the microcatheter out of the access catheter before thrombectomy-an approach we term the 'bare wire thrombectomy' (BWT) technique. We verified the improved throughput with systematic in vitro studies and assessed the clinical effectiveness and safety of this method. METHODS We compared aspiration flow of water through various access catheters (5-8 F) with a Rebar microcatheter (0.18 inch and 0.27 inch) and a Trevo stent-retriever using the standard technique and the BWT technique in vitro. We also retrospectively analyzed 302 retrieval maneuvers in 117 patients who received endovascular treatment with a stent-retriever between February 2010 and April 2015. RESULTS In the in vitro experiment, removal of the microcatheter in all tested settings resulted in significantly increased aspiration flow through the access catheter (p<0.001). This effect was particularly pronounced in access catheters with a diameter of ≤7 F. In the clinical study, the revascularization rate (Thrombolysis In Cerebral Infarction ≥2b) was 91%. There were no complications associated with the BWT technique in 302 retrieval maneuvers. CONCLUSIONS The BWT technique results in improved aspiration flow rates compared with the standard deployment technique. Our clinical data show that the BWT technique is effective and safe.


title: Logic in the time of coronavirus.

text: Much has happened here since the local news media trumpeted the first Australian COVID-19 fatality, and stirred up a medieval fear of contagion. We now need to take a step back to examine the logic underlying the use of our limited COVID-19 countermeasures. Emerging infectious diseases by their nature, pose new challenges to the diagnostic-treatment-control nexus, and push our concepts of causality beyond the limits of the conventional Koch-Henle approach to aetiology. We need to use contemporary methods of assessing causality to ensure that clinical, laboratory and public health measures draw on a rational, evidence-based approach to argumentation. The purpose of any aetiological hypothesis is to derive actionable insights into this latest emerging infectious disease. This review is an introduction to a conversation with medical microbiologists, which will be supported by a moderated blog.


title: Fatty Liver Caused by Glycogen Storage Disease Type IX: A Small Series of Cases in Children.

text: Background The prevalence of non-alcoholic fatty liver disease (NAFLD) affecting children and adolescents has increased dramatically in recent years. This increase is most probably related to the obesity pandemic and the high consumption of fructose. However, hepatic steatosis has some rare causes (e.g., some metabolic diseases) of which clinicians should be aware, particularly (but not only) when patients are non-obese or non-overweight. Differential diagnosis is notably important when pathologies have a specific treatment, such as for glycogenosis type IX (GSD-IX). Aims To contribute to the knowledge on the differential diagnosis of NAFLD in paediatric age and to the clinical, biochemical, molecular, and histological characterisations of GSD-IX, a rare metabolic disorder. Methods We performed a retrospective study of a small series of cases (n = 3) of GSD-IX diagnosed in the past 6 years, who were currently being followed up in the Units of Gastroenterology or Metabolic Diseases of the Paediatric Division of our hospital and whose clinical presentation was NAFLD in paediatric age. Results Three male patients were diagnosed with NAFLD before 2 years of age, 2 with confirmed diagnosis before the age of 3 years (alanine aminotransferase [ALT], liver ultrasound, and molecular analysis) and 1 whose diagnosis was confirmed at 11 years (ALT, liver ultrasound, liver histology, and molecular analysis). None of the patients were obese or overweight, and the daily fructose consumption was unknown. The outcome was favourable in all 3 patients, with follow-up periods ranging from 2 to 6 years. Conclusion The decision on how far the search for secondary causes of NAFLD should go can be difficult, and GSD-IX must be on the list of possible causes.


title: A systematic review and meta-analysis of hypothermia in experimental traumatic brain injury: why have promising animal studies not been replicated in pragmatic clinical trials?

text: Therapeutic hypothermia was a mainstay of severe traumatic brain injury (TBI) management for half a century. Recent trials have suggested that its effect on long term functional outcome is neutral or negative, despite apparently promising preclinical data. Systematic review and meta-analysis is a useful tool to collate experimental data and investigate the basis of its conclusions. We searched three online databases to identify studies testing systemic hypothermia as monotherapy for treatment of animals subjected to a TBI. Data pertaining to TBI paradigm, animal subjects and hypothermia management were extracted as well as those relating to risk of bias. We pooled outcome data where sufficient numbers allowed and investigated heterogeneity in neurobehavioral outcomes using multivariate meta-regression. We identified 90 publications reporting 272 experiments testing hypothermia in animals subject to TBI. The subjects were mostly small animals, with well-established models predominating. Target temperature was comparable to clinical trial data but treatment was initiated very early. Study quality was low and there was some evidence of publication bias. Delay to treatment, comorbidity and blinded outcome assessment appeared to predict neurobehavioral outcome on multivariate meta-regression. Therapeutic hypothermia appears to be an efficacious treatment in experimental TBI, which differs from the clinical evidence. The preclinical literature showed limitations in quality and design and these both appeared to affect neurobehavioral experiment outcome. These should be acknowledged when designing and interpreting preclinical TBI studies in the future.


title: Prevalence and genetic characterisation of respiratory syncytial viruses circulating in Bulgaria during the 2014/15 and 2015/16 winter seasons.

text: The respiratory syncytial virus (RSV) is a leading cause of acute respiratory illnesses (ARI) in infants and young children. The objectives of this study were to investigate the RSV circulation among children aged <5 years in Bulgaria, to identify the RSV-A and RSV-B genotypes and to perform an amino acid sequence analysis of second hypervariable region (HVR2) of the G gene. During the 2014/15 and 2015/16 winter seasons, nasopharyngeal specimens of 610 children aged <5 years with ARI were tested using Real Time RT-PCR for influenza viruses, RSV, metapneumovirus, parainfluenza viruses, rhinoviruses and adenoviruses. Viral respiratory pathogens were detected in 429 (70%) out of 610 patients examined and RSV was the most frequently identified virus (26%) followed by influenza A(H1N1)pdm09 virus (14%) (p < .05). RSV was the most prevalent pathogen in patients with bronchiolitis (48%) and pneumonia (38%). In the 2014/15 season, RSV-A dominated slightly (53%), while in the next season RSV-B viruses prevailed more strongly (66%). The phylogenetic analysis based on the G gene indicated that all 21 studied RSV-A strains belonged to the ON1 genotype; the vast majority (96%) of the RSV-B strains were classified into BA9 genotype and only one - into BA10 genotype. All Bulgarian RSV-A and RSV-B sequences contained a 72-nt and a 60-nt duplication in the HVR2, respectively. The study showed the leading role of this pathogen as a causative agent of serious respiratory illnesses in early childhood, year-on-year fluctuations in RSV incidence, a shift from RSV-A to RSV-B subgroup dominance and relatively low genetic divergence in the circulating strains.


title: An HIV testing conundrum: balancing the health and privacy considerations of multiple stakeholders.

text: Legal standards for HIV testing are evolving in an attempt to achieve an ethical equilibrium between the privacy rights of infected or potentially infected individuals and public health considerations that seek to limit the spread and severity of the disease through early recognition and treatment. Although guided by US Centers for Disease Control and Prevention recommendations, these standards are determined by state law. In this case, an ethical dilemma is presented and discussed in which the privacy interests of an HIV-infected individual come into conflict with the health considerations of an inadvertently exposed neurology resident and her unborn child, a conundrum amplified by the restricted HIV testing laws of the state in which the incident took place.


title: Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis: a systematic review and meta-analysis.

text: OBJECTIVE To compare the efficacy of embedded nurse-led versus conventional physician-led follow-up on disease activity in patients with rheumatoid arthritis (RA). METHODS In a systematic literature search, we identified randomised controlled trials (RCTs) reporting on the efficacy of nurse-led follow-up on disease control in patients with RA compared with physician-led follow-up. Primary outcome was disease activity indicated by Disease Activity Score (DAS)-28. Secondary outcomes were: patient satisfaction, physical disability, fatigue, self-efficacy and quality of life. Outcomes were assessed after 1-year and 2 year follow-ups. RESULTS Seven studies representing five RCTs, including a total of 723 participants, were included. All but one study included stable patients in low disease activity or remission at baseline. No difference in DAS-28 was found after 1 year (mean difference (MD) -0.07 (95% CI -0.23 to 0.09)). After 2 years, a statistically significant difference was seen in favour of nurse-led follow-up (MD -0.28 (95% CI -0.53 to -0.04)). However, the difference did not reach a clinically relevant level. No difference was found in patient satisfaction after 1 year (standard mean difference (SMD) -0.17 (95 % CI -1.0 to 0.67), whereas a statistical significant difference in favour of nurse-led follow-up was seen after 2 years (SMD: 0.6 (95% CI -0.00 to 1.20)). CONCLUSION After 1 year no difference in disease activity, indicated by DAS-28, were found between embedded nurse-led follow-up compared with conventional physician-led follow-up, in RA patients with low disease activity or remission.


What we are talking about when we talk of steroid in COVID-19?


title: Elevations in D-dimer and C-reactive protein are associated with the development of osteonecrosis of the hip in HIV-infected adults.

text: BACKGROUND A high incidence of nontraumatic osteonecrosis has been reported in HIV-infected patients. We investigated the levels of D-dimer and C-reactive protein (CRP) in a cohort of HIV-infected adults with and without osteonecrosis of the femoral head. METHODS Forty-three HIV-infected patients with osteonecrosis of the femoral head and a comparison group of 50 HIV-infected patients with negative MRI of the hips and for whom serial plasma samples were available were included. D-dimer and CRP levels were measured prior to and at the time of diagnosis for osteonecrosis patients, at the time of negative MRI of the hips for controls, and at least 6 months later for both groups. RESULTS Biomarker levels were elevated at the time of diagnosis in the osteonecrosis cohort compared with controls. Median D-dimer value was 0.32 μg/ml in the osteonecrosis group compared with less than 0.22 μg/ml in the control group (P = 0.016). For CRP, the corresponding values were 2.52 mg/l and 1.23 mg/l (P = 0.003). Postdiagnosis, D-dimer and CRP levels were also elevated in the osteonecrosis patients compared with controls. Linear regression demonstrated a rise in D-dimer levels from prediagnosis to diagnosis in the osteonecrosis patients whereas CRP levels did not change significantly over time. CONCLUSION Compared to controls, patients who developed osteonecrosis had elevated levels of D-dimer and CRP at diagnosis. D-dimer levels increased whereas CRP levels did not change significantly from prediagnosis to diagnosis. These data suggest that patients with higher levels of inflammation are at an increased risk of osteonecrosis.


title: Avian influenza rapidly induces antiviral genes in duck lung and intestine.

text: Ducks are the natural reservoir of influenza A and survive infection by most strains. To characterize the duck immune response to influenza, we sought to identify innate immune genes expressed early in an infection. We used suppressive subtractive hybridization (SSH) to construct 3 libraries enriched in differentially expressed genes from lung RNA of a duck infected with highly pathogenic avian influenza virus A/Vietnam/1203/04 (H5N1), or lung and intestine RNA of a duck infected with low pathogenic avian influenza A/mallard/BC/500/05 (H5N2) compared to a mock-infected duck. Sequencing of 1687 clones identified a transcription profile enriched in genes involved in antiviral defense and other cellular processes. Major histocompatibility complex class I (MHC I), interferon induced protein with tricopeptide repeats 5 (IFIT5), and 2'-5' oligoadenylate synthetase-like gene (OASL) were increased more than 1000-fold in relative transcript abundance in duck lung at 1dpi with highly pathogenic VN1203. These genes were induced much less in lung or intestine following infection with low pathogenic BC500. The expression of these genes following infection suggests that ducks initiate an immediate and robust response to a potentially lethal influenza strain, and a minimal response to a low pathogenic strain.


title: Laparoscopic versus open sigmoid resection for diverticulitis: long-term results of a prospective, randomized trial.

text: BACKGROUND Elective laparoscopic sigmoid resection for diverticulitis has proven short-term benefits, but little data are available from prospective randomized trials regarding long-term outcome, quality of life, and functional results. METHODS Of 113 patients randomized to undergo laparoscopic (LAP) versus open (OP) sigmoid resection for diverticulitis, 105 (93%, LAP = 54, OP = 51) patients were examined and answered the Gastrointestinal Quality of Life Index (GIQLI) questionnaire, with a median follow-up of 30 (range, 9-63) months after surgery. RESULTS Incisional hernias were detected in five (9.8%) patients in the OP group versus seven (12.9%) in the LAP group, P = 0.84). Overall satisfaction with the operation on a scale of 0 (very poor) to 10 (excellent) was 9 (range, 2-10) in the OP group versus 9 (range, 2-10) in the LAP group (P = 0.78). Median GIQLI score was 115 (range, 57-144) in the OP group versus 110 (range, 61-134) in the LAP group (P = 0.17). Overall satisfaction with the cosmetic aspect of the scar on a scale of 0 (very poor) to 10 (excellent) was 8 (range, 1-10) in the OP group versus 9 (range, 0-10) in the LAP group (P = 0.01). Finally, median hospital cost (including reoperations for hernias) was 11,606 (5,230-147,982) CHF in the LAP group versus 12,138 (6,098-39,786) CHF in the OP group (P = 0.47). CONCLUSIONS Both open and laparoscopic approaches for sigmoid resection achieve good long-term results in terms of gastrointestinal function, quality of life, and patients' satisfaction. Significant long-term benefits of laparoscopic surgery are restricted to cosmetic (ClinicalTrials.gov protocol #NCT00453830).


title: KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

text: In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.


title: Single-Port Inflatable Mediastinoscopy Combined With Laparoscopic-Assisted Small Incision Surgery for Radical Esophagectomy Is an Effective and Safe Treatment for Esophageal Cancer.

text: BACKGROUND We previously developed a novel non-trans thoracic esophagectomy, the single-port inflatable mediastinoscopy combined with laparoscopy for the radical esophagectomy of esophageal cancer. The purpose of this study was to report its therapeutic efficacy and safety. METHODS From May 2016 to August 2017, we have completed 80 cases of radical resection of esophageal carcinoma using this novel surgical technique. The intraoperative findings and postoperative complications were reported. RESULTS The operation was successfully performed in all patients except for one patient switched from laparoscopic-assisted operation to open surgery. The mean operation duration was 191.4 ± 27 min, and the mean intraoperative blood loss was 147.3 ± 28.9 mL. The mean number of removed lymph node was 21.9 ± 4.1. Five patients (6.4%) who had preoperative type I respiratory failure needed to stay in the intensive care unit for 24 h postoperatively. Postoperative complications included anastomotic leakage (8.9%), anastomotic stricture (21.25%), pleural effusion (9%), and hoarseness postoperative hoarseness (18.8%). The incidence of hoarseness at 3 months postoperation was reduced to 3.8%. All the complications were Clavien-Dindo grades I-III. There were no perioperative death and postoperative cardiopulmonary complications. CONCLUSION These results showed that the single-port inflatable mediastinoscopy combined with laparoscopy is feasible for radical esophagectomy and possesses good therapeutic efficacy and safety.


title: Feasibility of a new approach for creating a preperitoneal space in transabdominal preperitoneal repair inguinal hernia repair: using a sandwich approach.

text: PURPOSE In Japan, transabdominal preperitoneal (TAPP) inguinal hernia repair is performed by firmly pulling the peritoneum inwards to lift it from the underlying deep layer of subperitoneal fascia. It decreases the postoperative pain and discomfort in the inguinal area. The aim of this study was to evaluate the feasibility of the sandwich approach, which is a new technique for creating a preperitoneal space. METHODS The operation was performed via the sandwich approach. We made sure to protect the preperitoneal fascia areolar layer when making the preperitoneal space. RESULTS We performed TAPP in 745 patients (876 hernias) treated between October 2006 and April 2015 at Himeji Medical Center and Kurashiki Central Hospital. Before October 2010, we did not use the sandwich approach, and recurrence was observed in three patients. From October 2010, we always used the sandwich approach and never experienced any cases of recurrence. Clavien-Dindo classification Grade 3 or higher postoperative complications occurred in 6 patients (0.8%) between October 2006 and April 2015. Mesh-related ileus was the most frequently observed morbidity. There were no cases of vas differentia or spermatic vessel injury, postoperative chronic pain, or urinary retention. CONCLUSION The sandwich approach is feasible as another standard dissective procedure for TAPP.


title: Blockade of viral interleukin-6 expression of Kaposi's sarcoma-associated herpesvirus.

text: Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8, is associated with several malignant disorders, including Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. An early lytic gene of KSHV encodes viral interleukin-6 (vIL-6), a viral homologue of the proinflammatory cytokine and an autocrine/paracrine growth factor human IL-6. In this study, we examined the effects of suppressing vIL-6 expression in PEL cells with antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO). PPMO are ssDNA-analogues that have a modified backbone and enter cells readily. Treatment of PEL cells with a PPMO designed against vIL-6 mRNA led to a marked reduction in the proportion of vIL-6-positive cells detected by immunofluorescence assay. Analysis by Western blot confirmed a specific reduction in the vIL-6 protein level and showed that the reduction was dependent on the dose of vIL-6 PPMO. PEL cells treated with the vIL-6 PPMO exhibited reduced levels of cellular growth, IL-6 expression and KSHV DNA, and an elevated level of p21 protein. Treatment of PEL cells with a combination of two vIL-6 PPMO compounds targeting different sequences in the vIL-6 mRNA led to an inhibitory effect that was greater than that achieved with either PPMO alone. These results show that PPMO targeting vIL-6 mRNA can potently reduce vIL-6 protein translation and indicate that further exploration of these compounds in an animal model for potential clinical application is warranted.


title: A scenario to safely ease the covid-19 lockdown while allowing economic recovery.

text: If they work as expected, the strict containment measures enforced to stop the French Covid-19 epidemic will leave a large proportion of the population "naive" about the SARS-CoV-2 virus. In these conditions, how can we prevent the epidemic from rebounding, at a time when this restrictive policy will soon become untenable economically and socially? Based on the figures, now well known, of the lethality of covid-19 according to age classes, I suggest that a gradual release of the containment be instituted, which will keep retirees in isolation (the 65+ age class), whose risk is maximal and the impact on economic production the lowest. This scenario might be applicable to most European countries that enforce mandatory retirement ages for most of workers.


The race is on for antibodies that stop the new coronavirus.


title: Restarting gastrointestinal endoscopy in the deceleration and early recovery phases of COVID-19 pandemic: Guidance from the British Society of Gastroenterology.

text: Many non-emergency clinical services were suspended during COVID-19 pandemic peak. It is essential to develop a plan for restarting services following the peak. It is equally important to protect patients and staff and to use resources and personal protective equipment (PPE) efficiently. The British Society of Gastroenterology Endoscopy Committee and Quality Improvement Programme has produced guidance on how a restart can be safely delivered. Key recommendations include the following: all patients should have need for endoscopy assessed by senior clinicians and prioritised according to criteria we have outlined; once the need for endoscopy is confirmed, patients should undergo telephone screening for symptoms using systematic questionnaires; all outpatients should undergo RT-PCR testing for COVID-19 virus 1-3 days prior to endoscopy; and PPE should be determined by patient risk stratification, the nature of the procedure and the results of testing. While this guidance is tailored to endoscopy services, it could be adapted for any interventional medical discipline.


title: Exhaled breath temperature increases during mild exacerbations in children with virus-induced asthma.

text: BACKGROUND Exhaled breath temperature (EBT) has been suggested as a non-invasive surrogate marker of airway inflammation in asthma. The aim of the study was to evaluate differences in EBT between periods of controlled disease and during exacerbations in children with virus-induced asthma. METHODS Twenty-nine children (aged 6-14 years) with a history of intermittent, virus-induced asthma were included in this case-control study. Cases presented with a common cold and/or mild exacerbation of asthma, while controls were free of asthmatic or common cold symptoms during the previous 6 weeks. A baseline questionnaire was obtained. Atopy assessment, central temperature and a spirometric measurement were recorded. EBT was measured with a new device (Delmedica, Singapore). A nasal wash (for identification of common respiratory viruses) was obtained. RESULTS Twenty-four children (12 from each group) completed the study. Groups were homogeneous with respect to baseline characteristics. PCR revealed the presence of a virus in 3 out of 17 controls and 10 out of 12 cases (17.6 and 83.3%, respectively, p = 0.002). The most commonly identified virus was rhinovirus (3/3 controls and 7/10 cases, p = 0.02). EBT values were significantly higher for cases (34.91 +/- 0.62 degrees C) compared to controls (34.18 +/- 1.1 degrees C, p = 0.032). No important differences were observed in the increase rate of EBT (Deltae degrees T) between groups. CONCLUSIONS Changes in airway inflammation during virus-induced asthma exacerbations are reflected in EBT changes. These preliminary data suggest a possible role of EBT measurements in the assessment of airway inflammation in children with virus-induced asthma.


title: Comparison of the Effect of Instrument Type on Transanal Endoscopic Surgery Learning Curves.

text: BACKGROUND Transanal endoscopic surgery (TES) can be technically difficult due to the constraints of operating through a narrow proctoscope channel. In this study, we compared the performance of surgical novices using instruments with and without articulating shafts to perform a simulated TES task. METHODS Medical students each performed 10 repetitions of the Fundamentals of Laparoscopic Surgery circle-cut task. Participants were randomized into 3 groups: 2 performed the task through a TES proctoscope using scissors with either a rigid (TES-R) or articulating (TES-A) shaft. The third group performed the task laparoscopically (LAP). RESULTS A total of 31 medical students participated. The LAP group had a faster mean task time than both the TES-R and TES-A groups (LAP 201±120 s vs. TES-R 362±212 s and TES-A 405±212 s, both P <0.001). The TES-R group made more errors (ie, deviation from a perfect circle) than both the other groups. The TES-R group adjusted the proctoscope position during more repetitions than the TES-A group. CONCLUSIONS Students had faster task times when operating laparoscopically than through a TES protoscope. Task times were similar between the TES groups using scissors with articulating and rigid shafts; however, use of the articulating instruments resulted in fewer errors and less need to adjust proctoscope position.


title: COVID-19: ACE2centric infective disease?

text: Diffuse pulmonary inflammation, endothelial inflammation and enhanced thrombosis are cardinal features of COVID-19, the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These features are reminiscent of several adverse reactions triggered by angiotensin II, and opposed by angiotensin1-7, in many experimental models. SARS-CoV-2 binds to ACE2 receptors and entries into the cell through the fusion of its membrane with that of the cell. Hence, it down-regulates these receptors. The loss of ACE2 receptor activity from the external site of the membrane will lead to less angiotensin II inactivation and less generation of antiotensin1-7. In various experimental models of lung injury, the imbalance between angiotensin II over-activity and of antiotensin1-7 deficiency triggered inflammation, thrombosis and other adverse reactions. In COVID-19, such imbalance could play an important role in influencing the clinical picture and outcome of the disease. According to this line of thinking, some therapeutic approaches including recombinant ACE2, exogenous angiotensin1-7 and angiotensin receptor blockers appear particularly promising and are being actively tested.


Povidone iodine.


Sudden and Complete Olfactory Loss Function as a Possible Symptom of COVID-19.


title: Clinical and surgical outcomes after lumbar laminectomy: An analysis of 500 patients.

text: BACKGROUND The objective of this study is to determine the clinical and surgical outcomes following lumbar laminectomy. METHODS We retrospectively reviewed medical records of neurosurgical patients who underwent first-time, bilateral, 1-3 level laminectomies for degenerative lumbar disease. Patients with discectomy, complete facetectomy, and fusion were excluded. RESULTS Five hundred patients were followed for an average of 46.79 months. Following lumbar laminectomy, patients experienced statistically significant improvement in back pain, neurogenic claudication, radiculopathy, weakness, and sensory deficits. The rate of intraoperative durotomy was 10.00%; however, 1.60% experienced a postoperative cerebrospinal fluid leak. The risk of experiencing at least one postoperative complication with a lumbar laminectomy was 5.60%. Seventy-two patients (14.40%) required reoperations for progression of degenerative disease over a mean of 3.40 years. The most common symptoms prior to reoperation included back pain (54.17%), radiculopathy (47.22%), weakness (18.06%), sensory deficit (15.28%), and neurogenic claudication (19.44%). The relative risk of reoperation for patients with postoperative back pain was 6.14 times higher than those without postoperative back pain (P < 0.001). Of the 72 patients undergoing reoperations, 55.56% underwent decompression alone, while 44.44% underwent decompression and posterolateral fusions. When considering all-time reoperations, the lifetime risk of requiring a fusion after a lumbar laminectomy based on this study (average follow-up of 46.79 months) was 8.0%. CONCLUSION Patients experienced statistically significant improvements in back pain, neurogenic claudication, radiculopathy, motor weakness, and sensory deficit following lumbar laminectomy. Incidental durotomy rate was 10.00%. Following a first-time laminectomy, the reoperation rate was 14.4% over a mean of 3.40 years.


docid: fgdoybew

title: Dual loop (Roux en Y) reconstruction with isolated gastric limb reduces delayed gastric emptying after pancreatico-duodenectomy.

text: BACKGROUND Single loop reconstruction (SLR) was routine in our institution for patients undergoing pancreatico-duodenectomy (PD). Roux-en Y reconstruction with an isolated gastric limb (RIGL) recently became the reconstruction of choice. AIM To evaluate the impact of RIGL on incidence and severity of delayed gastric emptying (DGE). METHODS This is a single institution, retrospective analysis of patients undergoing PD. All patients undergoing PD from July 2010 through December 2016 were included in the study. Outcome of RIGL were compared to SLR. Primary measure of outcome included incidence and severity of DGE. Secondary measures of outcome were overall complications and postoperative mortality. RESULTS One hundred and seventy-nine patients were included in the study. Fifty-two had RIGL, 127 had SLR. Overall complication rate was 40.2%, patients in the RIGL group experienced lower rates of DGE (15.4% vs 59.1%, P = 0.001). Other patient related outcomes were also significantly reduced: day of nasogastric tube removal (3 vs 5, P < 0.001), regain of normal diet (8 vs 9, P < 0.001). On multivariate analysis RIGL was associated independently with reduced rates of DGE (P < 0.001, OR 0.14). CONCLUSION The current study shows that RIGL reduces the rate of DGE after PD. Further prospective randomized controlled trials are required to affirm the current data.


title: Survey of Hospital Employees' Personal Preparedness and Willingness to Work Following a Disaster.

text: OBJECTIVES Little is known about the personal readiness of hospital staff for disasters. As many as 30% of hospital staff say that they plan not to report for work during a large-scale disaster. We sought to understand the personal disaster preparedness for hospital staff. METHODS Surveys were distributed to the staff of a large academic tertiary-care hospital by either a paper-based version distributed through the departmental safety coordinators or a Web-based version distributed through employee e-mail services, depending on employee familiarity with and access to computer services. Surveys assessed the demographic variables and characteristics of personal readiness for disaster. RESULTS Of the individuals who accessed the survey, 1334 (95.9%) enrolled in it. Women made up 75% of the respondents, with a mean age of 43 years. Respondents had worked at the hospital an average of 9 years, with the majority (90%) being full-time employees. Most households (93%) reported ≤4 members, 6% supported a person with special medical needs, and 17% were headed by a single parent. A small number (24%) of respondents reported an established meeting place for reuniting households during a disaster. Many reported stockpiling a 3-day supply of food (86%) and a 3-day supply of water (51%). Eighteen percent of respondents were not aware of workplace evacuation plans. Most respondents were willing to report to work for natural disasters (eg, tornado, snowstorm; all categories >65%), but fewer respondents were willing to report during events such as an influenza epidemic (54%), a biological outbreak (41%), a chemical exposure, (40%), or a radiation exposure (39%). Multivariate analysis revealed being female, having a child in the household younger than 6 years old, and having a child in school lowered the likelihood of being willing to report to work in two or more event types, whereas pet ownership, being a clinical healthcare worker, and being familiar with the work emergency plan increased the likelihood. CONCLUSIONS Despite being employed at the same facility for a prolonged period, employees reported being willing to report for work at a low rate in a variety of disasters. Subjects reported suboptimal personal preparedness for disaster, which may further limit the number of staff who will report for work. Hospitals should promote personal disaster preparedness for staff and explore staffing models with an understanding of reduced staff availability during disasters.


title: Safeguarding the Future of Urological Research and Delivery of Clinical Excellence by Harnessing the Power of Youth to Spearhead Urological Research.

text: Trainee-led collaboratives offer exciting new perspectives and approaches to urological research. They provide a central network of expertise in methodology, mentoring, and knowledge of research processes that allows the conduct of large multicentre studies that can recruit quickly. This provides the consultant workforce of tomorrow with the skills required to deliver practice-changing clinical studies in urology.


title: Oral Surgical Procedures Performed Safely in Patients With Head and Neck Arteriovenous Malformations: A Retrospective Case Series of 12 Patients.

text: PURPOSE This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss. MATERIALS AND METHODS Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites. RESULTS Direct puncture sclerotherapy with Surgiflo or n-butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively. CONCLUSION Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon.


COVID-19 and Rapid Research Translation: universal masking as a case study.


title: From 'screen time' to the digital level of analysis: protocol for a scoping review of digital media use in children and adolescents.

text: INTRODUCTION Research on the relationship between digital media exposure and child development is complex, inconsistent and fraught with debate. A highlighted area of inadequacy surrounds the methodological limitations of measuring digital media use for both researchers and clinicians, alike. This protocol aims to (1) identify core concepts in the area of screen time and digital media use in children and adolescents (2) map existing research paradigms and screening/measurement tools that serve to underpin and operationalise core concepts and (3) provide an initial step in integrating these findings into a consolidated screening toolkit. It is expected this enterprise will help advance research and clinical evaluation in fields concerned with digital media use, namely medicine, child development and the social sciences. METHODS AND ANALYSIS The planned scoping review will search relevant electronic databases, including Ovid MEDLINE, PsycINFO and Scopus, in addition to grey literature. All empirical investigations and presentation of original research will be considered, and measurement/screening tools for digital media usage in children and adolescents will be identified and reported on. Two reviewers will pilot test the screening criteria, and data extraction forms prior to independently screening all relevant literature and extracting the data. A three-stage synthesis process will be used to map the existent measurement and screening tools for digital media usage in children and adolescents. ETHICS AND DISSEMINATION There are no ethical considerations for this scoping review. Plans for dissemination include publication in a top-tier, open-access journal, public presentations and conference proceedings. Presentation of the full scoping review has been accepted to the American Academy of Child & Adolescent Psychiatry 66th Annual Meeting.


title: The minimum alveolar concentration of sevoflurane in ring-tailed lemurs (Lemur catta) and aye-ayes (Daubentonia madagascariensis).

text: OBJECTIVE To determine the minimum alveolar concentration (MAC) of sevoflurane for ring-tailed lemurs (Lemur catta) and aye-ayes (Daubentonia madagascariensis). STUDY DESIGN Prospective experimental trial. ANIMALS Six adult ring-tailed lemurs, aged 1.3-11.2 years (median age: 8.26) and weighing a mean ± standard deviation (SD) of 2283 ± 254 g. Five adult aye-ayes, aged 4.4-19.3 years (median age: 8.0) and weighing 2712 ± 191 g. METHODS Minimum alveolar concentration of sevoflurane was determined using a tail-clamp stimulus. The end-tidal sevoflurane (Fe'Sevo) concentration was increased or decreased by approximately 10% after a positive or negative response to tail clamping, respectively. This procedure was repeated until a positive and negative result were seen on two consecutive trials (i.e. a negative result was achieved and a single 10% decrease in Fe'Sevo concentration resulted in a positive test). The MAC for that animal was determined to be the mean of the concentrations at the two consecutive trials. RESULTS The mean ± SD MAC of sevoflurane for ring-tailed lemurs was 3.48 ± 0.55% and 1.84 ± 0.17 for aye-ayes. This represents a 47.1% higher MAC in ring-tailed lemurs compared to aye-ayes. CONCLUSIONS AND CLINICAL RELEVANCE The sevoflurane MAC was significantly higher in ring-tailed lemurs, compared to aye-ayes. The MAC of sevoflurane in aye-ayes is consistent with reported MAC values in other species. Extrapolation of sevoflurane anesthetic dose between different species of lemurs could lead to significant errors in anesthetic dosing.


title: Constitutive immune function in European starlings, Sturnus vulgaris, is decreased immediately after an endurance flight in a wind tunnel.

text: Life-history theory predicts that animals face a trade-off in energy allocation between performing strenuous exercise, such as migratory flight, and mounting an immune response. We experimentally tested this prediction by studying immune function in European starlings, Sturnus vulgaris, flown in a wind tunnel. Specifically, we predicted that constitutive immune function decreases in response to training and, additionally, in response to immediate exercise. We compared constitutive immune function among three groups: (1) 'untrained' birds that were kept in cages and were not flown; (2) 'trained' birds that received flight training over a 15 day period and performed a 1-4 h continuous flight, after which they rested for 48 h before being sampled; and (3) 'post-flight' birds that differed from the 'trained' group only in being sampled immediately after the final flight. A bird in our trained group represents an individual during migration that has been resting between migratory flights for at least 2 days. A bird in our post-flight group represents an individual that has just completed a migratory flight and has not yet had time to recover. Three of our four indicators (haptoglobin, agglutination and lysis) showed the predicted decrease in immune function in the post-flight group, and two indicators (haptoglobin, agglutination) showed the predicted decreasing trend from the untrained to trained to post-flight group. Haptoglobin levels were negatively correlated with flight duration. No effect of training or flight was detected on leukocyte profiles. Our results suggest that in European starlings, constitutive immune function is decreased more as a result of immediate exercise than of exercise training. Because of the recent emergence of avian-borne diseases, understanding the trade-offs and challenges faced by long-distance migrants has gained a new level of relevance and urgency.


title: Financing Common Goods for Health: Core Government Functions in Health Emergency and Disaster Risk Management.

text: In the absence of good data on the costs and comparative benefits from investing in health emergency and disaster risk management (EDRM), governments have been reluctant to invest adequately in systems to reduce the risks and consequences of emergencies and disasters. Yet they spend heavily on their response. We describe a set of key functional areas for investment and action in health EDRM, and calculate the costs needed to establish and operate basic health EDRM services in low- and middle-income countries, focusing on management of epidemics and disasters from natural hazards.We find that health EDRM costs are affordable for most governments. They range from an additional US$4.33 capital and US$4.16 annual recurrent costs per capita in low-income countries to US$1.35 capital to US$1.41 recurrent costs in upper middle-income countries. These costs pale in comparison to the costs of not acting-the direct and indirect costs of epidemics and other emergencies from natural hazards are more than 20-fold higher.We also examine options for the institutional arrangements needed to design and implement health EDRM. We discuss the need for creating adaptive institutions, strengthening capacities of countries, communities and health systems for managing risks of emergencies, using "all-of-society" and "all-of-state institutions" approaches, and applying lessons about rules and regulations, behavioral norms, and organizational structures to better implement health EDRM. The economic and social value, and the feasibility of institutional options for implementing health EDRM systems should compel governments to invest in these common goods for health that strengthen national health security.


title: Structural and functional insights into alphavirus polyprotein processing and pathogenesis.

text: Alphaviruses, a group of positive-sense RNA viruses, are globally distributed arboviruses capable of causing rash, arthritis, encephalitis, and death in humans. The viral replication machinery consists of four nonstructural proteins (nsP1-4) produced as a single polyprotein. Processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. Here, we report the structure of P23 in a precleavage form. The proteins form an extensive interface and nsP3 creates a ring structure that encircles nsP2. The P2/3 cleavage site is located at the base of a narrow cleft and is not readily accessible, suggesting a highly regulated cleavage. The nsP2 protease active site is over 40 Å away from the P2/3 cleavage site, supporting a trans cleavage mechanism. nsP3 contains a previously uncharacterized protein fold with a zinc-coordination site. Known mutations in nsP2 that result in formation of noncytopathic viruses or a temperature sensitive phenotype cluster at the nsP2/nsP3 interface. Structure-based mutations in nsP3 opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P23, affect RNA infectivity, and alter viral RNA production levels, highlighting the importance of the nsP2/nsP3 interaction in pathogenesis. A potential RNA-binding surface, spanning both nsP2 and nsP3, is proposed based on the location of ion-binding sites and adaptive mutations. These results offer unexpected insights into viral protein processing and pathogenesis that may be applicable to other polyprotein-encoding viruses such as HIV, hepatitis C virus (HCV), and Dengue virus.


Technical considerations in performing posterior component separation with transverse abdominis muscle release.


title: Performance comparison of peripherally inserted central venous catheters in gastrointestinal surgery: a randomized controlled trial.

text: BACKGROUND & AIMS Peripherally inserted central venous catheters (PICC) are long-term vascular access devices inserted through a peripheral vein of the arm and serve as an alternative to traditional central venous catheters. Currently different types of PICCs are available. No data, however, are available in regard to materials and tip designs. We designed a prospective, randomized trial comparing two major PICCs with different material and tip design: a silicone catheter with distal side slits (Groshong Catheter) and a polyurethane catheter with open-end tip (PI Catheter). METHODS Twenty-six patients who underwent PICCs placement between August 2010 and December 2010 were enrolled in the study. The primary endpoint was the completion rate of PICC indication. Secondary endpoints were complications rate. RESULT The completion rate of PICC indication was not different significantly (81.8% and 92.9%, p = 0.5648) and the total complication rate were also not different significantly (9.1% and 14.3%, P = 1.0000) between two catheters. In detail, PI Catheter were associated with a significantly higher incidence of catheter occlusion, and Groshong Catheter were associated with a significantly hemorrhages after removal. CONCLUSION There was no difference in the durability and the complication between Groshong Catheter and PI Catheter. (UMIN Clinical Trial Registry UMIN000005451).


Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19?


title: Respiratory syncytial virus infection in adults.

text: Human respiratory syncytial virus (RSV) belongs to the recently defined Pneumoviridae family, Orthopneumovirus genus. It is a negative sense, single stranded RNA virus that results in epidemics of respiratory infections that typically peak in the winter in temperate climates and during the rainy season in tropical climates. Generally, one of the two genotypes (A and B) predominates in a single season, alternating annually, although regional variation occurs. RSV is a cause of disease and death in children, older people, and immunocompromised patients, and its clinical effect on adults admitted to hospital is clarified with expanded use of multiplex molecular assays. Among adults, RSV produces a wide range of clinical symptoms including upper respiratory tract infections, severe lower respiratory tract infections, and exacerbations of underlying disease. Here we discuss the latest evidence on the burden of RSV related disease in adults, especially in those with immunocompromise or other comorbidities. We review current therapeutic and prevention options, as well as those in development.


title: [Component separation for closing large abdominal wall defects: evolution of a method from 1990 to present day].

text: BACKGROUND The separation of autologous and functional active components of the lateral abdominal wall for closing large midline defects was introduced in 1990. The original components separation technique (CS) has undergone numerous modifications. The aim of this work is to summarise the essential steps of the development. METHODS Based on a literature review, the original technique, the modifications and advancements are presented and evaluated regarding indication, techniques and results. RESULTS The original technique still has a high status, because of the large extent of rectus complex medialisation. Numerous modifications of the anterior conventional component separation with different clinical results were described. The development of a minimally invasive technique with balloon dilatation trocars was an essential step and decreased wound morbidity. The modified posterior component separation by transverse abdominis release currently seems to be an encouraging alternative to be regarded as a widening of the sublay technique. All methods can be combined with implantation of prosthetic or biological implants in intraperitoneal, sublay or onlay technique, whereby the recurrence rate can be decreased. CONCLUSION From where we stand today no single technique can generally be recommended. The latest methods aim for decreasing complications and recurrences by means of minimally invasive procedures. The surgical strategy still depends on the complexity and extent of abdominal wall defect and has to be determined according to individual aspects and sometimes requires an interdisciplinary approach.


title: Interaction between TIM-1 and NPC1 Is Important for Cellular Entry of Ebola Virus.

text: UNLABELLED Multiple host molecules are known to be involved in the cellular entry of filoviruses, including Ebola virus (EBOV); T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) have been identified as attachment and fusion receptors, respectively. However, the molecular mechanisms underlying the entry process have not been fully understood. We found that TIM-1 and NPC1 colocalized and interacted in the intracellular vesicles where EBOV glycoprotein (GP)-mediated membrane fusion occurred. Interestingly, a TIM-1-specific monoclonal antibody (MAb), M224/1, prevented GP-mediated membrane fusion and also interfered with the binding of TIM-1 to NPC1, suggesting that the interaction between TIM-1 and NPC1 is important for filovirus membrane fusion. Moreover, MAb M224/1 efficiently inhibited the cellular entry of viruses from all known filovirus species. These data suggest a novel mechanism underlying filovirus membrane fusion and provide a potential cellular target for antiviral compounds that can be universally used against filovirus infections. IMPORTANCE Filoviruses, including Ebola and Marburg viruses, cause rapidly fatal diseases in humans and nonhuman primates. There are currently no approved vaccines or therapeutics for filovirus diseases. In general, the cellular entry step of viruses is one of the key mechanisms to develop antiviral strategies. However, the molecular mechanisms underlying the entry process of filoviruses have not been fully understood. In this study, we demonstrate that TIM-1 and NPC1, which serve as attachment and fusion receptors for filovirus entry, interact in the intracellular vesicles where Ebola virus GP-mediated membrane fusion occurs and that this interaction is important for filovirus infection. We found that filovirus infection and GP-mediated membrane fusion in cultured cells were remarkably suppressed by treatment with a TIM-1-specific monoclonal antibody that interfered with the interaction between TIM-1 and NPC1. Our data provide new insights for the development of antiviral compounds that can be universally used against filovirus infections.