title: Assessment of Collateral Status by Dynamic CT Angiography in Acute MCA Stroke: Timing of Acquisition and Relationship with Final Infarct Volume.

text: BACKGROUND AND PURPOSE Dynamic CTA is a promising technique for visualization of collateral filling in patients with acute ischemic stroke. Our aim was to describe collateral filling with dynamic CTA and assess the relationship with infarct volume at follow-up. MATERIALS AND METHODS We selected patients with acute ischemic stroke due to proximal MCA occlusion. Patients underwent NCCT, single-phase CTA, and whole-brain CT perfusion/dynamic CTA within 9 hours after stroke onset. For each patient, a detailed assessment of the extent and velocity of arterial filling was obtained. Poor radiologic outcome was defined as an infarct volume of ≥70 mL. The association between collateral score and follow-up infarct volume was analyzed with Poisson regression. RESULTS Sixty-one patients with a mean age of 67 years were included. For all patients combined, the interval that contained the peak of arterial filling in both hemispheres was between 11 and 21 seconds after ICA contrast entry. Poor collateral status as assessed with dynamic CTA was more strongly associated with infarct volume of ≥70 mL (risk ratio, 1.9; 95% CI, 1.3-2.9) than with single-phase CTA (risk ratio, 1.4; 95% CI, 0.8-2.5). Four subgroups (good-versus-poor and fast-versus-slow collaterals) were analyzed separately; the results showed that compared with good and fast collaterals, a similar risk ratio was found for patients with good-but-slow collaterals (risk ratio, 1.3; 95% CI, 0.7-2.4). CONCLUSIONS Dynamic CTA provides a more detailed assessment of collaterals than single-phase CTA and has a stronger relationship with infarct volume at follow-up. The extent of collateral flow is more important in determining tissue fate than the velocity of collateral filling. The timing of dynamic CTA acquisition in relation to intravenous contrast administration is critical for the optimal assessment of the extent of collaterals.


title: Targeting RNA to treat neuromuscular disease.

text: The development of effective therapies for neuromuscular disorders such as Duchenne muscular dystrophy (DMD) is hampered by considerable challenges: skeletal muscle is the most abundant tissue in the body, and many neuromuscular disorders are multisystemic conditions. However, despite these barriers there has recently been substantial progress in the search for novel treatments. In particular, the use of antisense oligonucleotides, which are designed to target RNA and modulate pre-mRNA splicing to restore functional protein isoforms or directly inhibit the toxic effects of pathogenic RNAs, offers great promise and these approaches are now being tested in the clinic. Here, we review recent advances in the development of such antisense oligonucleotides and other promising novel approaches, including the induction of readthrough nonsense mutations.


EXPRESS: COVID-19 and Stroke - A Global World Stroke Organisation perspective.


title: Transanal endoscopic microsurgery for rectal neoplasms. How I do it.

text: INTRODUCTION Transanal endoscopic microsurgery (TEM) has revolutionized the technique and outcomes of transanal surgery, becoming the standard of treatment for large sessile rectal adenomas, and may represent a possible treatment modality for early rectal cancer. METHODS A full-thickness excision is made on the rectal wall down to the perirectal fatty tissue. The specimen is retrieved transanally. After the parietal defect is disinfected, the wound is closed with one or more running sutures secured with silver clips. RESULTS Peritoneal perforation during TEM is not associated with adverse short-term or oncologic outcomes. The postoperative morbidity rate ranges between 2 % and 15 %, and in most cases, complications can be conservatively managed. The local recurrence rate of large adenomas is about 6 %, and most recurrences can be safely re-resected by TEM. TEM represents an effective treatment for pT1 sm1 rectal malignancies, while pT1 sm2-3 and pT2 should be considered at high risk of recurrence if treated by TEM alone. Finally, TEM does not influence anorectal function or quality of life. CONCLUSION TEM is a safe procedure and provides excellent functional and oncologic outcomes in the treatment of large sessile benign rectal lesions and selected early rectal cancers.


Colchicine for the Treatment of Myocardial Injury in Patients With Coronavirus Disease 2019 (COVID-19)-An Old Drug With New Life?


title: Influence of intravenous regional limb perfusion with amikacin sulfate on Staphylococcus aureus bioburden in distal limb wounds in horses.

text: OBJECTIVE To quantify the influence of intravenous regional limb perfusion (IVRLP) with amikacin on bacterial bioburden in limb wounds. STUDY DESIGN In vivo, experimental. ANIMALS Four adult horses. METHODS Full thickness wounds created on each dorsal metacarpus were inoculated with Staphylococcus aureus. One forelimb was randomly assigned to cephalic vein IVRLP with amikacin on days 2, 3, and 4 post-wounding. Biopsies on day 2 prior to IVRLP, and on days 5 and 8 were cultured to quantify wound bioburden (CFU/g). Two horses repeated the study in a crossover design, receiving IVRLP on the opposite limb (n = 6 experiments). IVRLP was performed on both forelimbs simultaneously in 3 horses at the end of the study: limbs were perfused with a volume of new methylene blue equal to that of the amikacin, through the cephalic vein or palmar digital vein. After euthanasia, wounds were photographed to subjectively assess dye diffusion. RESULTS The bioburden did not differ between control and IVRLP limbs overall or at any individual time point. No difference was detected between groups in terms of frequency of positive bacterial growth at any time. Methylene blue was visible in all excised tissues after IVRLP through the palmar digital vein, but was not visible in limbs perfused through the cephalic vein. CONCLUSION IVRLP may not effectively concentrate amikacin within a wound bed and did not influence S. aureus bioburden in an experimentally created wound infection.


title: [Advances in reverse genetics to treat porcine epidemic diarrhea virus].

text: Porcine epidemic diarrhea virus (PEDV) is one of the major etiologies responsible for the acute, highly contagious disease in the digestive tract of pigs, especially neonatal piglets. Since PEDV was first identified in Europe in the late 1970s, it has resulted in significant economic losses in many Asian swine-raising countries, including China. Recently, reverse genetics techniques including targeted RNA recombination, bacteria artificial chromosome system and in vitro ligation have been successfully used to manipulate the genome of PEDV, which providing new strategies for the clear delineation of the functions of the viral proteins, the mechanisms behind PEDV pathogenesis and the design of novel vaccines against PEDV. Here, we review the progresses of different reverse genetics platforms developed for PEDV and their applications, covering the roles of trypsin in PEDV propagation, functions of S and ORF3 protein and the development of next generation PED vaccines, and the perspectives of reverse genetics for PEDV.


title: Anesthetic dreaming, anesthesia awareness and patient satisfaction after deep sedation with propofol target controlled infusion: A prospective cohort study of patients undergoing day case breast surgery.

text: BACKGROUND Anesthetic dreaming and anesthesia awareness are well distinct phenomena. Although the incidence of intraoperative awareness is more common among patients who reported a dream after surgery, the exact correlation between the two phenomena remains an unsolved rebus. The main purpose of this study was to investigate anesthetic dreaming, anesthesia awareness and psychological consequences eventually occurred under deep sedation. Intraoperative dreaming experiences were correlated with dream features in natural sleep. METHODS Fifty-one patients, undergoing surgical excision of fibroadenomas under a Bispectral index-guided deep sedation anesthesia with propofol target controlled infusion, were enrolled into this prospective study. Psychological assessment was performed through the State Trait Anxiety Inventory. A questionnaire was adopted to register dreaming and anesthesia awareness. Data were collected after emergence (t0), 24 hours (t1), 1 month (t2), 6 months (t3). RESULTS Six patients (12%) reported anesthetic dreaming at t0 confirming the response at each subsequent evaluation. One patient (2%) confirmed dreaming during anesthesia in all, but denied it at t0. There was a high correlation between the intraoperative dream contents and the features of dreams in natural sleep. No cases of anesthesia awareness were detected. A similar level of satisfaction was observed in dreaming and no-dreaming patients. CONCLUSIONS Anesthetic dreaming does not seem to influence satisfaction of patients undergoing deep sedation with propofol target controlled infusion. A psychological assessment would seem to improve the evaluation of possible psychological consequences in dreamer patient.


title: Measuring anxiety related to COVID-19: A Turkish validation study of the Coronavirus Anxiety Scale.

text: The aim of the current study is to validate the Turkish version of the Coronavirus Anxiety Scale (CAS). Participants were assessed across the CAS, Obsession with COVID-19 Scale (OCS) and Fear of COVID-19 Scale. We surveyed 1023 Turkish native speakers who participated online. Confirmatory factor analysis showed that the factor structure of the CAS was satisfactory. The scale was internally consistent with a Cronbach's alpha of 0.80. Positive correlations of the CAS with the OCS and the Fear of COVID-19 Scale demonstrated adequate convergent validity. These findings suggest that the CAS is a valid and reliable measure to assess the severity of dysfunctional coronavirus related anxiety.


A letter to the editor: the impact of COVID-19 on intercalating and non-clinical medical students in the UK.


title: Coronavirus disease 2019 (SARS-CoV-2) and colonization of ocular tissues and secretions: a systematic review

text: Coronavirus disease 19 (COVID-19) has been described to potentially be complicated by ocular involvement. However, scant information is available regarding severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and ocular structures tropism. We conducted a systematic review of articles referenced in PubMed, Cochrane Library, Web of Science and Chinese Clinical Trial Register (ChiCTR) from December 20, 2019 to April 6, 2020, providing information on the presence of SARS-CoV-2 in cornea, conjunctiva, lacrimal sac, and tears. We excluded ongoing clinical studies as for unobtainable conclusive results. Of 2422 articles, 11 met the inclusion criteria for analysis and were included in the study. None of the studies were multinational. Among the 11 selected papers there were three original articles, one review, four letters, two editorials, and one correspondence letter. Globally, 252 SARS-CoV-2 infected patients were included in our review. The prevalence of ocular conjunctivitis complicating the course of COVID-19 was demonstrated to be as high as 32% in one study only. Globally, three patients had conjunctivitis with a positive tear-PCR, 8 patients had positive tear-PCR in the absence of conjunctivitis, and 14 had conjunctivitis with negative tear-PCR. The majority of the available data regarding SARS-CoV-2 colonization of ocular and periocular tissues and secretions have to be considered controversial. However, it cannot be excluded that SARS-CoV-2 could both infect the eye and the surrounding structures. SARS-CoV-2 may use ocular structure as an additional transmission route, as demonstrated by the COVID-19 patients’ conjunctival secretion and tears positivity to reverse transcriptase-PCR SARS-CoV-2-RNA assay.


Severe acute respiratory symptoms and suspected SARS again 2020.


title: Simultaneous laparoscopic resection of distal pancreas and liver nodule for pancreatic neuroendocrine tumor.

text: Laparoscopic distal pancreatectomy (LDP) with or without splenic preservation is increasingly performed for benign or border-line neoplasms of the body and tail of the pancreas. Pancreatic neuroendocrine tumors appear as an excellent indication for laparoscopic resection and this procedure is becoming the gold standard for the surgical treatment of such neoplasms. The safety and advantage of laparoscopic resection over open distal pancreatectomy (ODP) have been proven. In this video, we present a LDP with splenectomy for a neuroendocrine tumor of distal pancreas, with associated wedge resection of a liver nodule. Technical considerations were also discussed.


title: Spectrum of renal findings in pediatric fibromuscular dysplasia and neurofibromatosis type 1.

text: BACKGROUND Fibromuscular dysplasia (FMD) and neurofibromatosis type 1 (NF1) are the most common causes of pediatric renal artery stenosis (RAS) in western countries, and characterization of their angiographic features could aid in an accurate diagnosis and in treatment. OBJECTIVE This study characterizes renal angiographic findings in pediatric fibromuscular dysplasia (FMD) and neurofibromatosis type 1(NF1). MATERIALS AND METHODS We reviewed 68 angiograms performed over 11 years on 43 children with renovascular hypertension (20 male, 23 females; ages 1 month to -19 years; median/average 9.8 years). Ten patients were diagnosed with NF1, and 33 had presumed FMD. The frequency, extent and distribution of lesions were determined and analyzed. RESULTS Stenosis was found in 91% of patients (n=39/43), with 86% showing stenosis of 1st or 2nd order arteries, and 12% distal to 2nd order. Stenoses in multiple 1st/2nd order arteries were found in 32% of patients, and 36/43 patients had 1-2 stenoses. The most common lesion was a ≤ 5 mm stenosis in a 1st/2nd order artery, in 42%. Mean percentage of stenosis in a 1st/2nd order vessel was 62%; ≥ 70% stenosis was found in 53%, and ≥ 90% stenosis in 29%. Bilateral disease was noted in 30% of patients. Intraparenchymal disease, distal to 2nd order branches, was seen in 30%. Aneurysms were seen in 28%, beading in 19% and collaterals in 51% (associated with ≥ 70% stenosis). Mid-aortic narrowing was seen in 16%, more often in patients with NF1. CONCLUSION We provide a descriptive characterization of renal angiographic findings in pediatric FMD and NF1.


title: Electrospun vascular scaffold for cellularized small diameter blood vessels: A preclinical large animal study.

text: The strategy of vascular tissue engineering is to create a vascular substitute by combining autologous vascular cells with a tubular-shaped biodegradable scaffold. We have previously developed a novel electrospun bilayered vascular scaffold that provides proper biological and biomechanical properties as well as structural configuration. In this study, we investigated the clinical feasibility of a cellularized vascular scaffold in a preclinical large animal model. We fabricated the cellularized vascular construct with autologous endothelial progenitor cell (EPC)-derived endothelial cells (ECs) and smooth muscle cells (SMCs) followed by a pulsatile bioreactor preconditioning. This fully cellularized vascular construct was tested in a sheep carotid arterial interposition model. After preconditioning, confluent and mature EC and SMC layers in the scaffold were achieved. The cellularized constructs sustained the structural integrity with a high degree of graft patency without eliciting an inflammatory response over the course of the 6-month period in sheep. Moreover, the matured EC coverage on the lumen and a thick smooth muscle layer were formed at 6months after transplantation. We demonstrated that electrospun bilayered vascular scaffolds in conjunction with autologous vascular cells may be a clinically applicable alternative to traditional prosthetic vascular graft substitutes. STATEMENT OF SIGNIFICANCE This study demonstrates the utility of tissue engineering to provide platform technologies for rehabilitation of patients recovering from severe, devastating cardiovascular diseases. The long-term goal is to provide alternatives to vascular grafting using bioengineered blood vessels derived from an autologous cell source with a functionalized vascular scaffold. This novel bilayered vascular construct for engineering blood vessels is designed to offer "off-the-shelf" availability for clinical translation.


title: Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial.

text: BACKGROUND There have been few randomized control trials comparing the incidence of stent fracture and primary patency among different self-expanding nitinol stents to date. The SMART™ CONTROL stent (Cordis Corp, Miami Lakes, Florida, United States) has a peak-to-valley bridge and inline interconnection, whereas the COMPLETE™-SE stent (Medtronic Vascular, Santa Rosa, California, United States) crowns have been configured to minimize crown-to-crown interaction, increasing the stent's flexibility without compromising radial strength. Further, the 2011 ESC (European society of cardiology) guidelines recommend that dual antiplatelet therapy with aspirin and a thienopyridine such as clopidogrel should be administered for at least one month after infrainguinal bare metal stent implantation. Cilostazol has been reported to reduce intimal hyperplasia and subsequent repeat revascularization. To date, there has been no randomized study comparing the safety and efficacy of two different antiplatelet regimens, clopidogrel and cilostazol, following successful femoropopliteal stenting. METHODS/DESIGN The primary purpose of our study is to examine the incidence of stent fracture and primary patency between two different major representative self-expanding nitinol stents (SMART™ CONTROL versus COMPLETE™-SE) in stenotic or occlusive femoropopliteal arterial lesion. The secondary purpose is to examine whether there is any difference in efficacy and safety between aspirin plus clopidogrel versus aspirin plus cilostazol for one month following stent implantation in femoropopliteal lesions. This is a prospective, randomized, multicenter trial to assess the efficacy of the COMPLETE™-SE versus SMART™ CONTROL stent for provisional stenting after balloon angioplasty in femoropopliteal arterial lesions. The study design is a 2x2 randomization design and a total of 346 patients will be enrolled. The primary endpoint of this study is the rate of binary restenosis in the treated segment at 12 months after intervention as determined by catheter angiography or duplex ultrasound. DISCUSSION This trial will provide powerful insight into whether the design of the COMPLETE™-SE stent is more fracture-resistant or effective in preventing restenosis compared with the SMART™ CONTROL stent. Also, it will determine the efficacy and safety of aspirin plus clopidogrel versus aspirin plus cilostazol in patients undergoing stent implantation in femoropopliteal lesions. TRIAL REGISTRATION Registered on 2 April 2012 with the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier# NCT01570803).


title: Can proportional ventilation modes facilitate exercise in critically ill patients? A physiological cross-over study : Pressure support versus proportional ventilation during lower limb exercise in ventilated critically ill patients.

text: BACKGROUND Early exercise of critically ill patients may have beneficial effects on muscle strength, mass and systemic inflammation. During pressure support ventilation (PSV), a mismatch between demand and assist could increase work of breathing and limit exercise. A better exercise tolerance is possible with a proportional mode of ventilation (Proportional Assist Ventilation, PAV+ and Neurally Adjusted Ventilatory Assist, NAVA). We examined whether, in critically ill patients, PSV and proportional ventilation have different effects on respiratory muscles unloading and work efficiency during exercise. METHODS Prospective pilot randomized cross-over study performed in a medico-surgical ICU. Patients requiring mechanical ventilation >48 h were enrolled. At initiation, the patients underwent an incremental workload test on a cycloergometer to determine the maximum level capacity. The next day, 2 15-min exercise, at 60% of the maximum capacity, were performed while patients were randomly ventilated with PSV and PAV+ or NAVA. The change in oxygen consumption (ΔVO2, indirect calorimetry) and the work efficiency (ratio of ΔVO2 per mean power) were computed. RESULTS Ten patients were examined, 6 ventilated with PSV/PAV+ and 4 with PSV/NAVA. Despite the same mean inspiratory pressure at baseline between the modes, baseline VO2 (median, IQR) was higher during proportional ventilation (301 ml/min, 270-342) compared to PSV (249 ml/min, 206-353). Exercise with PSV was associated with a significant increase in VO2 (ΔVO2, median, IQR) (77.6 ml/min, 59.9-96.5), while VO2 did not significantly change during exercise with proportional modes (46.3 ml/min, 5.7-63.7, p < 0.05). As a result, exercise with proportional modes was associated with a better work efficiency than with PSV. The ventilator modes did not affect patient's dyspnea, limb fatigue, distance, hemodynamics and breathing pattern. CONCLUSIONS Proportional ventilation during exercise results in higher work efficiency and less increase in VO2 compared to ventilation with PSV. These preliminary findings suggest that proportional ventilation could enhance the training effect and facilitate rehabilitation.


title: A simple and safe technique for performing single-port laparoscopic resection of appendiceal mucocele.

text: We report a new method of performing single-port laparoscopic surgery for appendiceal mucocele. The key points of our technique are placing a 3/4 circumferential skin incision with multiple radial splits on the confine of the umbilicus, use of a "home-made" multichannel port system, and trimming the skin incision straight through the confine of the umbilicus at the time of wound closure. A 65-year-old woman with appendiceal mucocele, 80 mm in diameter, successfully underwent ileocecal resection by this procedure. She remains in good health without any wound complications 8 months postoperatively.


title: Purple grape juices prevent pentylenetetrazol-induced oxidative damage in the liver and serum of Wistar rats.

text: Oxidative damages in hepatocytes may be caused by epilepsy and/or anticonvulsant drugs. Epilepsy is one of the most common neurological disorders, characterized by recurrent seizures, which may increase the content of reactive oxygen species. Organic and conventional grape juices are rich in polyphenols, compounds with important antioxidant activity. It is hypothesized that organic and conventional purple grape juices may have protective effect against oxidative damage induced by pentylenetetrazole (PTZ) (a standard convulsant drug) in the liver and serum of Wistar rats. Animals (n = 16 in each group) received, by gavage, saline, organic grape juice or conventional grape juice (10 μL/g of body weight) for 17 days. Subsequently, half of the rats in each group received PTZ (60 mg/kg). After 30 minutes, the animals were euthanized by decapitation. Liver and blood samples were isolated to evaluate oxidative parameters (lipid and protein oxidation, nitric oxide metabolite content, antioxidant defenses, and protein sulfhydryl content). The results of this study showed that although organic juice contains higher polyphenol content than conventional juice, both juices conferred protection against lipid and protein oxidative damage and limited the increase in PTZ-induced nitric oxide metabolite content in the liver and serum. In addition, both juices inhibited the PTZ-induced reduction in enzymatic antioxidant defenses (superoxide dismutase and catalase activities) and sulfhydryl protein content in the liver and serum. In summary, both organic and conventional grape juices were able to reduce oxidative damage induced by PTZ in the liver and serum of Wistar rats.


title: Targeting Transmission Pathways for Emerging Zoonotic Disease Surveillance and Control.

text: We used literature searches and a database of all reported emerging infectious diseases (EIDs) to analyze the most important transmission pathways (e.g., vector-borne, aerosol droplet transmitted) for emerging zoonoses. Our results suggest that at the broad scale, the likelihood of transmission occurring through any one pathway is approximately equal. However, the major transmission pathways for zoonoses differ widely according to the specific underlying drivers of EID events (e.g., land-use change, agricultural intensification). These results can be used to develop better targeting of surveillance for, and more effective control of newly emerged zoonoses in regions under different underlying pressures that drive disease emergence.


title: Rapid detection of superficial head and neck squamous cell carcinoma by topically spraying fluorescent probe targeting dipeptidyl peptidase-IV.

text: BACKGROUND A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG), which becomes fluorescent after cleavage by dipeptidyl peptidase-IV (DPP-IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can be detected by spraying EP-HMRG. METHODS Fluorescence imaging of 17 cases of HNSCCs resected using endoscopic or surgical resection was performed ex vivo after spraying EP-HMRG, and then the fluorescence intensity of the tumors and normal mucosa were measured. RESULTS Iodine-voiding lesions became fluorescent within a few minutes after the application of EP-HMRG in 12 resected tumors without a history of radiotherapy but this was not observed in the normal mucosa. Fluorescence intensity in tumor lesions was significantly higher than normal lesions. However, 5 other tumors that developed after radiotherapy did not have sufficient contrast against normal mucosa. CONCLUSION Fluorescence imaging with EP-HMRG would be useful for rapid detection of superficial HNSCC without a history of radiotherapy.


title: Identification of aerosol types over Indo-Gangetic Basin: implications to optical properties and associated radiative forcing.

text: The aerosols in the Indo-Gangetic Basin (IGB) are a mixture of sulfate, dust, black carbon, and other soluble and insoluble components. It is a challenge not only to identify these various aerosol types, but also to assess the optical and radiative implications of these components. In the present study, appropriate thresholds for fine-mode fraction and single-scattering albedo have been used to first identify the aerosol types over IGB. Four major aerosol types may be identified as polluted dust (PD), polluted continental (PC), black carbon-enriched (BCE), and organic carbon-enriched (OCE). Further, the implications of these different types of aerosols on optical properties and radiative forcing have been studied. The aerosol products derived from CIMEL sun/sky radiometer measurements, deployed under Aerosol Robotic Network program of NASA, USA were used from four different sites Karachi, Lahore, Jaipur, and Kanpur, spread over Pakistan and Northern India. PD is the most dominant aerosol type at Karachi and Jaipur, contributing more than 50% of all the aerosol types. OCE, on the other hand, contributes only about 12-15% at all the stations except at Kanpur where its contribution is ∼38%. The spectral dependence of AOD was relatively low for PD aerosol type, with the lowest AE values (<0.5); whereas, large spectral dependence in AOD was observed for the remaining aerosol types, with the highest AE values (>1.0). SSA was found to be the highest for OCE (>0.9) and the lowest for BCE (<0.9) type aerosols, with drastically different spectral variability. The direct aerosol radiative forcing at the surface and in the atmosphere was found to be the maximum at Lahore among all the four stations in the IGB.


Influenza A (H7N9) and the importance of digital epidemiology.


title: Outcome after conservative management or intervention for unruptured brain arteriovenous malformations.

text: IMPORTANCE Whether conservative management is superior to interventional treatment for unruptured brain arteriovenous malformations (bAVMs) is uncertain because of the shortage of long-term comparative data. OBJECTIVE To compare the long-term outcomes of conservative management vs intervention for unruptured bAVM. DESIGN, SETTING, AND POPULATION Population-based inception cohort study of 204 residents of Scotland aged 16 years or older who were first diagnosed as having an unruptured bAVM during 1999-2003 or 2006-2010 and followed up prospectively for 12 years. EXPOSURES Conservative management (no intervention) vs intervention (any endovascular embolization, neurosurgical excision, or stereotactic radiosurgery alone or in combination). MAIN OUTCOMES AND MEASURES Cox regression analyses, with multivariable adjustment for prognostic factors and baseline imbalances if hazards were proportional, to compare rates of the primary outcome (death or sustained morbidity of any cause by Oxford Handicap Scale [OHS] score ≥2 for ≥2 successive years [0 = no symptoms and 6 = death]) and the secondary outcome (nonfatal symptomatic stroke or death due to bAVM, associated arterial aneurysm, or intervention). RESULTS Of 204 patients, 103 underwent intervention. Those who underwent intervention were younger, more likely to have presented with seizure, and less likely to have large bAVMs than patients managed conservatively. During a median follow-up of 6.9 years (94% completeness), the rate of progression to the primary outcome was lower with conservative management during the first 4 years of follow-up (36 vs 39 events; 9.5 vs 9.8 per 100 person-years; adjusted hazard ratio, 0.59; 95% CI, 0.35-0.99), but rates were similar thereafter. The rate of the secondary outcome was lower with conservative management during 12 years of follow-up (14 vs 38 events; 1.6 vs 3.3 per 100 person-years; adjusted hazard ratio, 0.37; 95% CI, 0.19-0.72). CONCLUSIONS AND RELEVANCE Among patients aged 16 years or older diagnosed as having unruptured bAVM, use of conservative management compared with intervention was associated with better clinical outcomes for up to 12 years. Longer follow-up is required to understand whether this association persists.


title: Impact of reduced marker set estimation of genomic relationship matrices on genomic selection for feed efficiency in Angus cattle.

text: BACKGROUND Molecular estimates of breeding value are expected to increase selection response due to improvements in the accuracy of selection and a reduction in generation interval, particularly for traits that are difficult or expensive to record or are measured late in life. Several statistical methods for incorporating molecular data into breeding value estimation have been proposed, however, most studies have utilized simulated data in which the generated linkage disequilibrium may not represent the targeted livestock population. A genomic relationship matrix was developed for 698 Angus steers and 1,707 Angus sires using 41,028 single nucleotide polymorphisms and breeding values were estimated using feed efficiency phenotypes (average daily feed intake, residual feed intake, and average daily gain) recorded on the steers. The number of SNPs needed to accurately estimate a genomic relationship matrix was evaluated in this population. RESULTS Results were compared to estimates produced from pedigree-based mixed model analysis of 862 Angus steers with 34,864 identified paternal relatives but no female ancestors. Estimates of additive genetic variance and breeding value accuracies were similar for AFI and RFI using the numerator and genomic relationship matrices despite fewer animals in the genomic analysis. Bootstrap analyses indicated that 2,500-10,000 markers are required for robust estimation of genomic relationship matrices in cattle. CONCLUSIONS This research shows that breeding values and their accuracies may be estimated for commercially important sires for traits recorded in experimental populations without the need for pedigree data to establish identity by descent between members of the commercial and experimental populations when at least 2,500 SNPs are available for the generation of a genomic relationship matrix.


title: Evolution of SILS Cholecystectomy in the Caribbean: The Direct Transfascial Puncture Technique Using Conventional Instruments without Working Ports.

text: Introduction. Single incision laparoscopic cholecystectomy (SILC) has become accepted as an alternative to conventional multiport cholecystectomy. However, SILC is still limited in applicability in low resource centres due to the expense associated with specialized access platforms, curved instruments, and flexible scopes. Presentation of Case. We present three cases where a modified SILC technique was used with conventional instruments and no working ports. The evolution of this technique is described. Discussion. In order to contain cost, we used conventional instruments and three transfascial ports placed in an umbilical incision, but we noted significant instrument clashes that originated at the port platforms. Therefore, we modified our technique by omitting ports for the working instruments. The technique allowed us to exchange instruments as necessary, maximized ergonomics, and prevented collisions from the bulky port platforms. Finally, the puncture left by the instrument alone did not require fascial closure at the termination of the procedure. Conclusion. The direct transfascial puncture using conventional laparoscopic instruments without working ports is a feasible option that minimizes cost and increases ergonomics.


The current state of respiratory research in the UK.


title: Refinement of a chronic cranial window implant in the rat for longitudinal in vivo two-photon fluorescence microscopy of neurovascular function.

text: Longitudinal studies using two-photon fluorescence microscopy (TPFM) are critical for facilitating cellular scale imaging of brain morphology and function. Studies have been conducted in the mouse due to their relatively higher transparency and long term patency of a chronic cranial window. Increasing availability of transgenic rat models, and the range of established behavioural paradigms, necessitates development of a chronic preparation for the rat. However, surgical craniotomies in the rat present challenges due to craniotomy closure by wound healing and diminished image quality due to inflammation, restricting most rat TPFM experiments to acute preparations. Long-term patency is enabled by employing sterile surgical technique, minimization of trauma with precise tissue handling during surgery, judicious selection of the size and placement of the craniotomy, diligent monitoring of animal physiology and support throughout the surgery, and modification of the home cage for long-term preservation of cranial implants. Immunohistochemical analysis employing the glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (Iba-1) showed activation and recruitment of astrocytes and microglia/macrophages directly inferior to the cranial window at one week after surgery, with more diffuse response in deeper cortical layers at two weeks, and amelioration around four weeks post craniotomy. TPFM was conducted up to 14 weeks post craniotomy, reaching cortical depths of 400 µm to 600 µm at most time-points. The rate of signal decay with increasing depth and maximum cortical depth attained had greater variation between individual rats at a single time-point than within a rat across time.


title: High-dose intravenous metoprolol usage for reducing heart rate at CT coronary angiography: efficacy and safety.

text: AIM To evaluate the usage, safety, and efficacy of high-dose intravenous metoprolol for heart rate reduction in computer tomographic (CT) coronary angiography. MATERIALS AND METHODS As this was retrospective analysis of anonymous data, medical ethics committee approval was waived by the regional health research authority. Patients, who had known iodinated contrast medium allergy, contraindications to β-blockers, atrial fibrillation, and indications other than suspected coronary artery disease, were excluded from analysis. The ultimate study population of 662 were analysed with details of intravenous metoprolol doses, complications, heart rate before administration of intravenous metoprolol (resting heart rate, RHR), heart rate at acquisition of scan (acquisition heart rate, AHR), and usage of low radiation dose protocols. RESULTS Of the ultimate study population of 662 patients, 183 had no intravenous metoprolol with mean acquisition heart rate (AHR) of 58 beats per minute (bpm), 257 had 1-15 mg intravenous metoprolol with mean AHR of 57 bpm, 114 had 16-29 mg intravenous metoprolol with mean AHR of 62 bpm and 108 had ≥30 mg intravenous metoprolol with mean AHR of 66 bpm. In the group receiving intravenous metoprolol, average usage was 19 mg (maximum 67 mg) with average reduction in HR of 15 bpm. There were no clinical incidents in relation to the use of high-dose intravenous metoprolol. CONCLUSION Higher doses of intravenous metoprolol are beneficial in achieving target heart rates to facilitate usage of low radiation dose protocols. With appropriate exclusion criteria, higher doses of intravenous metoprolol, well in excess of 15 mg, can be safely administered when carefully titrated.


title: Single-Incision Laparoscopic Surgery (SILS) in Biliary and Pancreatic Diseases.

text: Laparoscopic cholecystectomy is the gold standard for gallbladder removal and the most common laparoscopic procedure worldwide. With the advent of laparoscopic surgery and its continuous development, the focus has shifted to 'scarless' surgery. In recent times, the innovative technique of single-incision laparoscopic surgery (SILS) has been applied in gallbladder removal and even more complex biliopancreatic procedures to further minimize the invasiveness of the surgery. Newer developments in laparoscopic equipments and instrumentation have helped to further evolve this field of minimally invasive surgery. Literature search was performed using the following online search engines: Google, Medline, PubMed, Cochrane, and the online Springer link library. The terms used for the search were as follows: SILS, LESS, single-incision laparoscopic surgery, single-port laparoscopic surgery, SILS cholecystectomy, and SILS pancreatic surgery. Articles that matched the search criteria were selected and extensively reviewed. Moreover, pertinent information on instrumentation and technology for SILS and LESS was obtained by accessing websites of manufacturers. Although SILS represents the search for an essentially scarless surgery, there is still not a widespread use and uniformity of this procedure. SILS is performed either by single- or multiple-port technique. In the present article, we present a review of the potential benefits, limitations, and risks of SILS in biliary and pancreatic diseases. There are many studies showing benefits in cholecystectomy. A few case reports have also emerged about its feasibility in procedures such as cystogastrostomy and limited pancreatic resection. Further research and development of this technique is needed to arrive at a tangible conclusion about the perceived benefits of SILS. Randomized studies to compare SILS with traditional laparoscopy are essential.


title: Femur shaft fracture following osteoid osteoma radiofrequency ablation.

text: Introduction Radiofrequency ablation is an effective modality in treating osteoid osteoma while avoiding the complications of an open procedure. Its complications are usually self-limited consisting mostly of local skin burns. This report presents a major complication, a femur shaft fracture following an osteoid osteoma radiofrequency ablation. The fracture occurred approximately one year after the ablation at the site of the osteoid osteoma. Discussion Few case reports have been published regarding subtrochanteric femur fracture after ablation of an osteoid osteoma. To our knowledge this is the first report of a femoral shaft fracture following an ablation. Another unique characteristic of the presented case is the late presentation, approximately one year following ablation. Factors which may have contributed to the fracture include lateral entry point of the drill which may have weakened the femur when taking its biological and mechanical properties into account, and the fact that the patient was a soldier who was allowed to continue his military training only six weeks after the ablation. Conclusion Radiofrequency ablation is an effective and relatively safe technique in treating osteoid osteomas, however the physician should be aware of the fracture risk involved, consider mechanical and biologic factors of the bone prior to drilling, and be very conservative when recommending return to high level activity. In addition, a close follow-up should be carried on after the procedure in order to supervise bone remodeling.


title: Respiratory infections in the military.

text: Military training facilities and operational theatres, and the stressful activities undertaken in such settings, are unique. Military personnel living and working in these environments are at considerable risk of the acquisition and onward transmission of a variety of respiratory infections. While these generally cause mild illness, severe disease may occur with significant associated morbidity and, occasionally, mortality. Epidemic outbreaks among military personnel may have a significant detrimental impact on training schedules and operational effectiveness. The recognition of the burden of such illness among British military personnel, and the development of strategies required to prevent or limit negative impacts, can only be achieved through the use of comprehensive laboratory-based surveillance programmes.


title: Symptoms and Critical Illness Among Obstetric Patients With Coronavirus Disease 2019 (COVID-19) Infection.

text: OBJECTIVE To characterize symptoms and disease severity among pregnant women with coronavirus disease 2019 (COVID-19) infection, along with laboratory findings, imaging, and clinical outcomes. METHODS Pregnant women with COVID-19 infection were identified at two affiliated hospitals in New York City from March 13 to April 19, 2020, for this case series study. Women were diagnosed with COVID-19 infection based on either universal testing on admission or testing because of COVID-19-related symptoms. Disease was classified as either 1) asymptomatic or mild or 2) moderate or severe based on dyspnea, tachypnea, or hypoxia. Clinical and demographic risk factors for moderate or severe disease were analyzed and calculated as odds ratios (ORs) with 95% CIs. Laboratory findings and associated symptoms were compared between those with mild or asymptomatic and moderate or severe disease. The clinical courses and associated complications of women hospitalized with moderate and severe disease are described. RESULTS Of 158 pregnant women with COVID-19 infection, 124 (78%) had mild or asymptomatic disease and 34 (22%) had moderate or severe disease. Of 15 hospitalized women with moderate or severe disease, 10 received respiratory support with supplemental oxygen and one required intubation. Women with moderate or severe disease had a higher likelihood of having an underlying medical comorbidity (50% vs 27%, OR 2.76, 95% CI 1.26-6.02). Asthma was more common among those with moderate or severe disease (24% vs 8%, OR 3.51, 95% CI 1.26-9.75). Women with moderate or severe disease were significantly more likely to have leukopenia and elevated aspartate transaminase and ferritin. Women with moderate or severe disease were at significantly higher risk for cough and chest pain and pressure. Nine women received ICU or step-down-level care, including four for 9 days or longer. Two women underwent preterm delivery because their clinical status deteriorated. CONCLUSION One in five pregnant women who contracted COVID-19 infection developed moderate or severe disease, including a small proportion with prolonged critical illness who received ICU or step-down-level care.


Response by Hopkins and Holmes to Letter Regarding Article, "Public Health Urgency Created by the Success of Mechanical Thrombectomy Studies in Stroke".


title: Migration of eroded laparoscopic adjustable gastric band causing small bowel obstruction and perforation.

text: We present an unusual and rare complication caused by gastric band erosion into the stomach after band placement 15 years ago. The complication was only picked up after the band had subsequently migrated from the stomach at the site of erosion, to the distal ileum causing acute small bowel obstruction and focal perforation requiring emergency laparotomy.Abdominal pain in patients with gastric band should always be treated as serious until proven otherwise.


title: Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

text: BACKGROUND The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).


title: Production and nitrogen utilization in lactating dairy cows fed ground field peas with or without ruminally protected lysine and methionine.

text: Previous research has shown that cows fed ≥24% of the diet dry matter (DM) as field peas decreased milk yield as well as concentration and yield of milk protein, possibly due to reduced DM intake and limited supply of Lys and Met. Twelve multiparous and 4 primiparous lactating Holstein cows were randomly assigned to 1 of 4 diets in a replicated 4 × 4 Latin square design. The diets contained (DM basis) 34.8% corn silage, 15.2% grass-legume silage, 5.9% roasted soybean, 2.4% mineral-vitamin premix, 2.0% alfalfa pellets, and either (1) 36% ground corn, 2.4% soybean meal, and 1.3% urea (UR), (2) 29.7% ground corn, 9.8% soybean meal, 0.13% ruminally protected (RP) Lys, and 0.07% RP-Met (CSBAA), (3) 25% ground field peas, 12.3% ground corn, and 2.4% soybean meal (FP), or (4) FP supplemented with 0.15% RP-Lys and 0.05% RP-Met (FPAA). Our objective was to test the effects of FP versus UR, FPAA versus CSBAA, and FPAA versus FP on milk yield and composition, N utilization, nutrient digestibility, ruminal fermentation profile, and plasma concentration of AA. Milk yield did not differ across diets. Compared with cows fed UR, those fed FP had greater DM intake, concentration and yield of milk true protein, apparent total-tract digestibility of fiber, urinary excretion of purine derivatives, and concentrations of total volatile fatty acids in the rumen and Lys in plasma, and less milk urea N and ruminal NH3-N. The concentration of milk urea N, as well as the concentration and yield of milk fat increased in cows fed FPAA versus CSBAA. Moreover, cows fed FPAA had greater ruminal concentration of total volatile fatty acids, increased proportions of acetate and isobutyrate, and decreased proportions of propionate and valerate than those fed CSBAA. The plasma concentrations of His, Leu, and Phe decreased, whereas plasma Met increased and plasma Lys tended to increase in cows fed FPAA versus CSBAA. Concentration of milk true protein, but not yield, was increased in cows fed FPAA versus FP. However, cows fed FPAA showed decreased concentrations of His and Leu in plasma compared with those fed FP. Overall, compared with the CSBAA diet, feeding FPAA did not negatively affect milk yield and milk protein synthesis. Furthermore, RP-Lys and RP-Met supplementation of the FP diet did not improve milk yield or milk protein synthesis, but decreased urinary urea N excretion.


Scientific Editing in the COVID-19 Era - Personal Vignettes from the JBMR Editors.


title: Influenza vaccine effectiveness among Hajj pilgrims: a test-negative case-control analysis of data from different Hajj years.

text: Background: Influenza is a common respiratory infection at Hajj. Thus, influenza vaccine is recommended for Hajj pilgrims but data on its effectiveness from a large sample is unavailable. This analysis aims to assess the effectiveness of trivalent seasonal influenza vaccine (TIV) among Hajj pilgrims. Patients and methods: A 'test-negative' case-control analysis using data from individual studies was conducted. Included studies involved participants from Saudi Arabia, India, Australia and the United Kingdom who attended Hajj in Makkah, Saudi Arabia in different years between 2005 and 2015. Pilgrims who developed symptoms of respiratory infection during Hajj were included in these studies. Participants' vaccination histories were recorded and respiratory samples were collected to test for influenza by PCR. Vaccine effectiveness (VE) was calculated after adjusting for potential confounders. Results: A total of 1,569 pilgrims were included in this analysis. Influenza vaccine uptake was 52.2% and the prevalence of influenza was 8.2%. The estimated overall VE was 43.4% (95% CI 11.4% to 63.9%, P= 0.01). VE against a specific subtype of influenza was not significant. Conclusion: The current analysis has shown that TIV is moderately effective among Hajj pilgrims, but the vaccine uptake has been suboptimal. Power was much reduced when testing for influenza subtypes.


title: Personal Experience With COVID-19 and Diabetes in the South of France: Technology Facilitates the Management of Diabetes in Disruptive Times.

text: We report our experience with COVID-19 epidemic in patients with type 1 diabetes using diabetes technology in the South of France. Use of insulin pumps and continuous glucose monitoring appeared as an effective way to prevent the risk of acute metabolic complications related to the changes of daily life associated with requested confinement . Care by telemedicine was facilitated in these patients who used diabetes technology while structured education delivered during training and support from home care services were helpful to master the disruptive conditions.


title: Simplified models for exhaled airflow from a cough with the mouth covered.

text: UNLABELLED Covering a cough can be useful in reducing the transmission of airborne infectious diseases. However, no simple method is available in the literature for predicting the exhaled airflow from a cough with the mouth covered. This investigation used smoke to visualize the airflow exhaled by 16 human subjects. Their mouths were covered by a tissue, a cupped hand, a fist, and an elbow with and without a sleeve. This study then developed simplified models for predicting the airflow on the basis of the smoke visualization data. In addition, this investigation performed numerical simulations to assess the influence of mouth coverings on the receptor's exposure to exhaled particles. It was found that covering a cough with a tissue, a cupped hand, or an elbow can significantly reduce the horizontal velocity and cause the particles to move upward with the thermal plumes generated by a human body. In contrast with an uncovered cough, a covered cough or a cough with the head turned away may prevent direct exposure. PRACTICAL IMPLICATIONS This study developed simplified models for predicting the exhaled airflow from a cough with the mouth covered. The proposed models can easily be used to investigate the risk of transmission of airborne infectious diseases in enclosed environments.


title: Validation of criteria for the definition of transient lower esophageal sphincter relaxations using high-resolution manometry.

text: BACKGROUND Criteria for transient lower esophageal sphincter relaxations (TLESRs) are well-defined for Dentsleeve manometry. As high-resolution manometry (HRM) is now the gold standard to assess esophageal motility, our aim was to propose a consensus definition of TLESRs using HRM. METHODS Postprandial esophageal HRM combined with impedance was performed in 10 patients with gastroesophageal reflux disease. Transient lower esophageal sphincter relaxations identification was performed by 17 experts using a Delphi process. Four investigators then characterized TLESR candidates that achieved 100% agreement (TLESR events) and those that achieved less than 25% agreement (non-events) after the third round. Logistic regression and decision tree analysis were used to define optimal diagnostic criteria. KEY RESULTS All diagnostic criteria were more frequently encountered in the 57 TLESR events than in the 52 non-events. Crural diaphragm (CD) inhibition and LES relaxation duration >10 seconds had the highest predictive value to identify TLESR. Based on decision tree analysis, reflux on impedance, esophageal shortening, common cavity, upper esophageal sphincter relaxation without swallow and secondary peristalsis were alternate diagnostic criteria. CONCLUSION & INFERENCES Using HRM, TLESR might be defined as LES relaxation occurring in absence of swallowing, lasting more than 10 seconds and associated with CD inhibition.


title: Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2'-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases.

text: Norovirus (NoV) is a positive-sense single-stranded RNA virus that causes acute gastroenteritis and is responsible for 200,000 deaths per year worldwide. No effective vaccine or treatment is available. Recent studies have shown that the nucleoside analogs favipiravir (T-705) and 2'-C-methyl-cytidine (2CM-C) inhibit NoV replication in vitro and in animal models, but their precise mechanism of action is unknown. We evaluated the molecular interactions between nucleoside triphosphates and NoV RNA-dependent RNA polymerase (NoVpol), the enzyme responsible for replication and transcription of NoV genomic RNA. We found that T-705 ribonucleoside triphosphate (RTP) and 2CM-C triphosphate (2CM-CTP) equally inhibited human and mouse NoVpol activities at concentrations resulting in 50% of maximum inhibition (IC50s) in the low micromolar range. 2CM-CTP inhibited the viral polymerases by competing directly with natural CTP during primer elongation, whereas T-705 RTP competed mostly with ATP and GTP at the initiation and elongation steps. Incorporation of 2CM-CTP into viral RNA blocked subsequent RNA synthesis, whereas T-705 RTP did not cause immediate chain termination of NoVpol. 2CM-CTP and T-705 RTP displayed low levels of enzyme selectivity, as they were both recognized as substrates by human mitochondrial RNA polymerase. The level of discrimination by the human enzyme was increased with a novel analog of T-705 RTP containing a 2'-C-methyl substitution. Collectively, our data suggest that 2CM-C inhibits replication of NoV by acting as a classic chain terminator, while T-705 may inhibit the virus by multiple mechanisms of action. Understanding the precise mechanism of action of anti-NoV compounds could provide a rational basis for optimizing their inhibition potencies and selectivities.


title: Cerebral tissue O2 saturation during prolonged robotic surgery in the steep Trendelenburg position: an observational case series in a diverse surgical population.

text: Demands associated with the Trendelenburg position (TP) are well known yet there is little attention given to regional cerebral tissue O2 saturation (SctO2) in those undergoing robotic surgery in the TP with CO2 insufflation (C-INSF). This is the first study to report on SctO2 in a wide range of patients undergoing lengthy TP and robotic surgery. We measured SctO2 during robotic surgery in patients in the TP with C-INSF, as well as a control robotic thyroid surgery group who were supine with no C-INSF. We recorded relevant variables and periods of cerebral desaturation (CD). We studied 42 patients in 25°-45° of TP for ≥125 min. Management was at the providers' discretion. The INVOS(®) 5100C Cerebral Oximeter (Covidien, Boulder, CO) recorded SctO2. CD was defined as a >20 % decrease from baseline SctO2 or a value ≤55 % for ≥10 min. Patients were assessed for adverse outcome. The sample consisted of 13 males and 29 females aged 22-73, BMI 22-36 had general (N = 3), urological (N = 14) and gynecological (N = 25) surgery; two patients had CD lasting 150 and 190 min and two had episodic CD lasting 10-35 min. The four were female aged 22-60 in 38°-45° of TP. Eleven cases had multiple episodic CD for ≤15 min, 27 TP cases had no CD. Other observations included a consistent fall in SctO2 with phenylephrine; an increased SctO2 with ephedrine; and FiO2 and EtCO2 being generally strong, direct modifiers of SctO2. High MAP was inconsistently associated with high SctO2. BMI had no observed effect on SctO2. Pulse oximetry was ≥97 % in all cases. We observed no adverse cerebral events on follow-up. Additional clinical studies are warranted.


title: Impact of Access Site on Bleeding and Ischemic Events in Patients With Non-ST-Segment Elevation Myocardial Infarction Treated With Prasugrel: The ACCOAST Access Substudy.

text: OBJECTIVES This study assessed whether the choice of vascular access site influenced outcomes among non-ST-segment elevation myocardial infarction (NSTEMI) patients enrolled in the ACCOAST (A Comparison of prasugrel at the time of percutaneous Coronary intervention Or as pre-treatment At the time of diagnosis in patients with non-ST-segment elevation myocardial infarction NCT01015287). BACKGROUND Transfemoral access (TFA) has been associated with the risk of bleeding and increased mortality that is elevated compared to transradial access (TRA) in acute coronary syndromes, although less consistently in NSTE acute coronary syndrome (NSTE-ACS) than in STE-ACS. METHODS The ACCOAST study evaluated a prasugrel loading dose of 60 mg given at the start of percutaneous coronary intervention (PCI) versus a split loading dose of 30 mg given at the time of diagnosis of NSTE-ACS (prior to coronary angiography), followed by 30 mg given at the start of PCI. In the study, choice of access site was at the investigator's discretion. We compared ischemic and bleeding outcomes with TFA versus those with TRA, using propensity score correction. RESULTS Of 4,033 patients, 1,711 (42%) underwent TRA. Use of TRA varied widely by country. TFA was not associated with significant increases in noncoronary bypass graft (CABG)-related thrombolysis in myocardial infarction (TIMI) (hazard ratio [HR] for TFA = 1.46; 95% confidence interval [CI]: 0.59 to 3.62; p = 0.42), nor in GUSTO (Global Utilization Of Streptokinase and Tpa for Occluded arteries) or STEEPLE (Safety and Efficacy of Enoxaparin in PCI) major bleeding after propensity score correction. TFA, however, increased combined non-CABG TIMI major or minor bleeding (HR for TFA = 2.34; 95% CI: 1.17 to 4.69; p = 0.017). Primary ischemic outcomes did not differ by access site, albeit individual endpoint analysis suggested an association between TFA with an increase in urgent revascularizations and reduced risk of procedure-related stroke. CONCLUSIONS In the ACCOAST trial, TFA did not significantly increase TIMI major bleeding, although TRA was associated with a reduction in TIMI major or minor bleeding. Further study is needed to determine whether wider application of radial approach to NSTE-ACS patients at high risk for bleeding improves overall outcomes. (A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction [ACCOAST]; NCT01015287).


title: Transcystic approach to laparoscopic common bile duct exploration.

text: BACKGROUND AND OBJECTIVES One-stage laparoscopic management for common bile duct stones in patients with gallbladder stones has gained wide acceptance. We developed a novel technique using a transcystic approach for common bile duct exploration as an alternative to the existing procedures. METHODS From April 2010 to June 2012, 9 consecutive patients diagnosed with cholelithiasis and common bile duct stones were enrolled in this study. The main inclusion criteria included no upper abdominal surgical history and the presence of a stone measuring <5 mm. After the gallbladder was dissected free from the liver connections in a retrograde fashion, the fundus of the gallbladder was extracted via the port incision in the right epigastrium. The choledochoscope was inserted into the gallbladder through the small opening in the fundus of the gallbladder extracorporeally and was advanced toward the common bile duct via the cystic duct under the guidance of both laparoscopic imaging and endoscopic imaging. After stones were retrieved under direct choledochoscopic vision, a drainage tube was placed in the subhepatic space. RESULTS Of 9 patients, 7 had successful transcystic common bile duct stone clearance. A narrow cystic duct and the unfavorable anatomy of the junction of the cystic duct and common bile duct resulted in losing access to the common bile duct. No bile leakage, hemobilia, or pancreatitis occurred. Wound infection occurred in 2 patients. Transient epigastric colic pain occurred in 2 patients and was relieved by use of anisodamine. A transient increase in the amylase level was observed in 3 patients. Short-term follow-up did not show any recurrence of common bile duct stones. CONCLUSION Our novel transcystic approach to laparoscopic common bile duct exploration is feasible and efficient.


Practical Aspects of Otolaryngologic Clinical Services During the 2019 Novel Coronavirus Epidemic: An Experience in Hong Kong.


title: Kissing Aneurysms at Fenestrated Proximal Basilar Artery: Double-barrel Stent-assisted Coiling Using Dual Closed-cell Stents.

text: Kissing aneurysms associated with a proximal basilar artery fenestration are an exceedingly rare and unique therapeutic challenge due to anatomical complexity. This report describes double-barrel stent-assisted technique with dual closed-cell stents for the successful endovascular coiling of kissing aneurysms from a proximal basilar artery fenestration.


title: Application of the single access technique in laparoscopic surgery.

text: UNLABELLED Laparoscopic single access technique is a next step in development of minimally invasive surgery. The aim of the study was to present results of different laparoscopic single incision procedures and evaluate application of this technique. MATERIAL AND METHODS 102 patients (15 males and 87 females) who underwent laparoscopic single incision procedure from 15th October 2009 to 31st December 2012 were included in the study. RESULTS In the analyzed period we performed 72 cholecystectomies (70.6%), 8 left adrenalectomies (7.8%), 3 right adrenalectomies (2.9%), 7 splenectomies (6.9%), 5 spleen cysts unroofings (4.9%), 2 appendectomies (2%), 1 Nissen fundoplication procedure (1%), 1 removal of the adrenal cyst (1%) and 3 concomitant splenectomies and cholecystectomies (2.9%). There were 3 technical conversions to multiport laparoscopy, but no conversion to open technique. Complications were observed in 5 patients (4.9%). Average operation time was 79 min (SD=40), average hospitalization time 2.4 day (SD=1.4). CONCLUSIONS Laparoscopic single incision technique is a safe method and can be used as a reasonable alternative to multiport laparoscopy in different minimally invasive procedures especially in young patients to whom an excellent cosmetic effect is particularly important.


title: Indoor air quality and thermal comfort-results of a pilot study in elderly care centers in Portugal.

text: The age of the European population is rising and percentage of adults aged 65 years and older is projected to increase from 16% in 2000 to 20% in 2020. It has been estimated that older subjects spend approximately 19 to 20 h/d indoors. Older individuals may be particularly at risk for detrimental effects from pollutants, even at low concentrations, due to reduced immunological defenses and multiple underlying chronic diseases. Six Porto, Portugal, urban area elderly care centers (ECC), housing a total of 425 older persons, were studied to assess indoor air quality (IAQ) and thermal comfort (TC) in two seasons. This study presents the IAQ and TC results in 36 rooms and constitutes part of a wider and ongoing study. The study areas were all naturally ventilated, and indoor concentrations in winter were within Portuguese reference values. However, 42% of the participants were dissatisfied with indoor thermal conditions, rating it "slightly cool." In summer, the index rate of dissatisfied individuals was lower (8%). Significant differences were found between seasons in predicted percent of dissatisfied people (PPD) and predicted mean vote (PMV) indices. Fungal concentrations frequently exceeded reference levels (>500 colony-forming units [CFU]/m(3)). In addition, other pollutants occasionally exceeded reference levels. To our knowledge, this is the first study in Portugal to assess effects of indoor air contaminants on the health status and quality of life in older subjects living in ECC. Although IAQ and TC parameters were mostly within reference values, the results suggest a need to improve the balance between IAQ and TC in ECC, a critical environment housing a susceptible population.


title: Surgical Technique for Osteocutaneous Pedicle Flap Transfer for Salvage of Transtibial Amputation After Severe Lower-Extremity Injury.

text: Introduction Osteocutaneous pedicle flap transfer from the foot can be used to "salvage" a transtibial amputation level when the severity of an injury precludes a transtibial amputation. Step 1 Preoperative Assessment If the posterior tibial artery is not palpable, obtain an angiogram to determine the vascular supply distal to the traumatic zone and to prepare for conversion to a composite free microvascular transfer. Step 2 Remove Provisional Implants Remove provisional stabilization implants and minimize surgery about the knee. Step 3 Develop the Flap The dissection about the tarsal tunnel is the critical portion of the operative technique. Step 4 Contour the Calcaneus Any deviation from perpendicular will translate to an axial deformity in the reconstructed limb. Step 5 Prepare the Proximal Part of the Tibia and Surrounding Tissues Retain viable soft tissues and bone, but resect the fibula obliquely. Step 6 Secure the Calcaneus to the Tibia Avoid varus and recurvatum malalignment. Step 7 Repair and Reconstruct the Soft Tissues The injured limb is routinely very swollen, and in some cases complete coverage requires split-thickness skin-grafting. Step 8 Postoperative Care and Rehabilitation As the initial reconstruction is sometimes extremely bulbous, continually advise the patient that the shape will improve dramatically over time with shrinkage of the limb. Results In our original study, ten men and four women with a mean age of 43.2 years (range, twenty-four to sixty-four years) underwent an osteocutaneous pedicle flap transfer with use of the ipsilateral foot for salvage to achieve a transtibial amputation level. What to Watch For IndicationsContraindicationsPitfalls & Challenges.


title: Protective effects of laparoscopic sleeve gastrectomy on atherosclerotic and hemocytic parameters in obese patients.

text: OBJECTIVES The aim of this study was to evaluate the effects of the change in the body mass index following laparoscopic sleeve gastrectomy on the vascular morphology structure and biochemical and hemocytic parameters. MATERIAL AND METHODS A prospective evaluation of 60 patients who underwent sleeve gastrectomy was conducted. The relationship was evaluated between the vascular morphological parameters and biochemical and hemocytic inflammatory variables of the patients preoperatively and at 6, 12, and 18 months postoperatively. RESULTS Compared to the baseline values, a significant decrease was determined in the carotid intima media thickness at 6, 12, and 18 months (p<0.001, p<0.001, p<0.001, respectively). The compliance and distensibility values were observed to increase over time (p<0.05, p<0.001, p<0.001, respectively). A statistically significant difference was determined in the carotid intima media thickness values according to gender, with males (n:7) measuring 0.618±0.123 mm and females (n:53) measuring 0.506±0.113 mm (p<0.01). When patients were grouped as neutrophil-to-lymphocyte ratio ≤2.54 (n:41) and neutrophil-to-lymphocyte ratio>2.55 (n:19), the increasing neutrophil-to-lymphocyte ratio values were observed to be in proportion to the carotid intima media thickness, and the difference was statistically significant (p<0.001). When factors affecting the vascular morphology parameters measured at baseline and throughout the study were evaluated with the correlation analysis, there was observed to be a positive correlation between the baseline carotid intima media thickness thickness and neutrophil percentage (r=0.736, p<0.001) and neutrophil-to-lymphocyte ratio (r=0.676, p<0.001), and between the negative correlation and lymphocyte percentage (r=-0.628, p<0.001). CONCLUSION Laparoscopic sleeve gastrectomy is not only a cosmetic procedure reducing the body mass index values, but it also has a beneficiary effect on vascular morphology, biochemical, and hemocytic parameters.


title: The promises and pitfalls of RNA-interference-based therapeutics.

text: The discovery that gene expression can be controlled by the Watson-Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence - a process known as RNA interference - has markedly advanced our understanding of eukaryotic gene regulation and function. The ability of short RNA sequences to modulate gene expression has provided a powerful tool with which to study gene function and is set to revolutionize the treatment of disease. Remarkably, despite being just one decade from its discovery, the phenomenon is already being used therapeutically in human clinical trials, and biotechnology companies that focus on RNA-interference-based therapeutics are already publicly traded.


Treating asthma in the COVID-19 pandemic.


Covid-19 management: it's inappropriate to make judgments in hindsight that rely on information not available at the outset.


title: A review of 65 years of human adenovirus seroprevalence.

text: Introduction: Human adenovirus (HAdV)-derived vectors have been used in numerous pre-clinical and clinical trials during the last 40 years. Current research in HAdV-based vaccines focuses on improving transgene immunogenicity and safety. Because pre-existing humoral immunity against HAdV types correlate with reduced vaccine efficacy and safety, many groups are exploring the development of HAdV types vectors with lower seroprevalence. However, global seroepidemiological data are incomplete. Areas covered: The goal of this review is to centralize 65 years of research on (primarily) HAdV epidemiology. After briefly addressing adenovirus biology, we chronical HAdV seroprevalence studies and highlight major milestones. Finally, we analyze data from about 50 studies with respect to HAdVs types that are currently used in the clinic, or are in the developmental pipeline. Expert opinion: Vaccination is among the most efficient tools to prevent infectious disease. HAdV-based vaccines have undeniable potential, but optimization is needed and antivector immunity remains a challenge if the same vectors are to be administrated to different populations. Here, we identify gaps in our knowledge and the need for updated worldwide epidemiological data.


title: A report from the 26th International Conference on Antiviral Research (May 11-15, San Francisco, California, USA).

text: As described in the following report, numerous research programs reported during this year's International Conference on Antiviral Research (ICAR) in San Francisco resulted in novel agents with antiviral activity against a number of viral pathogens, including programs aimed at compounds active against specific pathogens as well as broad preclinical research that identified compounds with putative activity against many virus families. As an example of the latter, a research program was reported that identified compounds with activity against HIV-1 and -2, herpes virus, influenza virus and Coxsackie virus (Dejmek, M. et al., Abst 35), while studies with Griffithsin, a red algae-derived protein with potent, broad antiviral activity against hepatitis C virus, coronavirus and Japanese encephalitis virus, among others, showed it also inhibited HIV, although only when the tight dimer structure is respected (Xue, J. et al., Abst 104).


title: [An update on the epidemiological characteristics of novel coronavirus pneumonia（COVID-19）].

text: Through literature review and group discussion, Special Expert Group for Control of the Epidemic of Novel Coronavirus Pneumonia of the Chinese Preventive Medicine Association formulated an update on the epidemiological characteristics of novel coronavirus pneumonia (NCP). The initial source of the 2019 novel coronavirus (2019-nCoV) was the Huanan seafood market in Wuhan, Hubei province, China, with pangolins as a potential animal host. Currently the main source of infection is NCP patients, and asymptomatic carriers may also be infectious. The virus is believed transmitted mostly via droplets or contact. People are all generally susceptible to the virus. The average incubation period was 5.2 days, and the basic reproductive number R(0) was 2.2 at the onset of the outbreak. Most NCP patients were clinically mild cases. The case fatality rate was 2.38%, and elderly men with underlying diseases were at a higher risk of death. Strategies for prevention and control of NCP include improving epidemic surveillance, quarantining the source of infection, speeding up the diagnosis of suspected cases, optimizing the management of close contacts, tightening prevention and control of cluster outbreaks and hospital infection, preventing possible rebound of the epidemic after people return to work from the Chinese Spring Festival holiday, and strengthening community prevention and control.


title: The currency, completeness and quality of systematic reviews of acute management of moderate to severe traumatic brain injury: A comprehensive evidence map.

text: OBJECTIVE To appraise the currency, completeness and quality of evidence from systematic reviews (SRs) of acute management of moderate to severe traumatic brain injury (TBI). METHODS We conducted comprehensive searches to March 2016 for published, English-language SRs and RCTs of acute management of moderate to severe TBI. Systematic reviews and RCTs were grouped under 12 broad intervention categories. For each review, we mapped the included and non-included RCTs, noting the reasons why RCTs were omitted. An SR was judged as 'current' when it included the most recently published RCT we found on their topic, and 'complete' when it included every RCT we found that met its inclusion criteria, taking account of when the review was conducted. Quality was assessed using the AMSTAR checklist (trichotomised into low, moderate and high quality). FINDINGS We included 85 SRs and 213 RCTs examining the effectiveness of treatments for acute management of moderate to severe TBI. The most frequently reviewed interventions were hypothermia (n = 17, 14.2%), hypertonic saline and/or mannitol (n = 9, 7.5%) and surgery (n = 8, 6.7%). Of the 80 single-intervention SRs, approximately half (n = 44, 55%) were judged as current and two-thirds (n = 52, 65.0%) as complete. When considering only the most recently published review on each intervention (n = 25), currency increased to 72.0% (n = 18). Less than half of the 85 SRs were judged as high quality (n = 38, 44.7%), and nearly 20% were low quality (n = 16, 18.8%). Only 16 (20.0%) of the single-intervention reviews (and none of the five multi-intervention reviews) were judged as current, complete and high-quality. These included reviews of red blood cell transfusion, hypothermia, management guided by intracranial pressure, pharmacological agents (various) and prehospital intubation. Over three-quarters (n = 167, 78.4%) of the 213 RCTs were included in one or more SR. Of the remainder, 17 (8.0%) RCTs post-dated or were out of scope of existing SRs, and 29 (13.6%) were on interventions that have not been assessed in SRs. CONCLUSION A substantial number of SRs in acute management of moderate to severe TBI lack currency, completeness and quality. We have identified both potential evidence gaps and also substantial research waste. Novel review methods, such as Living Systematic Reviews, may ameliorate these shortcomings and enhance utility and reliability of the evidence underpinning clinical care.


Single incision total extraperitoneal (one SITE) laparoscopic inguinal hernia repair using a single access port device.


title: Isothermal amplified detection of DNA and RNA.

text: This review highlights various methods that can be used for a sensitive detection of nucleic acids without using thermal cycling procedures, as is done in PCR or LCR. Topics included are nucleic acid sequence-based amplification (NASBA), strand displacement amplification (SDA), loop-mediated amplification (LAMP), Invader assay, rolling circle amplification (RCA), signal mediated amplification of RNA technology (SMART), helicase-dependent amplification (HDA), recombinase polymerase amplification (RPA), nicking endonuclease signal amplification (NESA) and nicking endonuclease assisted nanoparticle activation (NENNA), exonuclease-aided target recycling, Junction or Y-probes, split DNAZyme and deoxyribozyme amplification strategies, template-directed chemical reactions that lead to amplified signals, non-covalent DNA catalytic reactions, hybridization chain reactions (HCR) and detection via the self-assembly of DNA probes to give supramolecular structures. The majority of these isothermal amplification methods can detect DNA or RNA in complex biological matrices and have great potential for use at point-of-care.


title: Epidemiology: Then and Now.

text: Twenty-five years ago, on the 75th anniversary of the Johns Hopkins Bloomberg School of Public Health, I noted that epidemiologic research was moving away from the traditional approaches used to investigate "epidemics" and their close relationship with preventive medicine. Twenty-five years later, the role of epidemiology as an important contribution to human population research, preventive medicine, and public health is under substantial pressure because of the emphasis on "big data," phenomenology, and personalized medical therapies. Epidemiology is the study of epidemics. The primary role of epidemiology is to identify the epidemics and parameters of interest of host, agent, and environment and to generate and test hypotheses in search of causal pathways. Almost all diseases have a specific distribution in relation to time, place, and person and specific "causes" with high effect sizes. Epidemiology then uses such information to develop interventions and test (through clinical trials and natural experiments) their efficacy and effectiveness. Epidemiology is dependent on new technologies to evaluate improved measurements of host (genomics), epigenetics, identification of agents (metabolomics, proteomics), new technology to evaluate both physical and social environment, and modern methods of data collection. Epidemiology does poorly in studying anything other than epidemics and collections of numerators and denominators without specific hypotheses even with improved statistical methodologies.


title: Active virological surveillance in backyard ducks in Bangladesh: Detection of avian influenza and gamma-coronaviruses.

text: Domestic waterfowl plays an important role in the perpetuation and transmission of avian pathogens including avian influenza viruses (AIV) of low and high pathogenicity, which pose severe economic and public health concerns in Bangladesh. This study focused on active surveillance of several avian viral pathogens with a special reference to AIV in selected backyard duck populations in Bangladesh. A total of 500 pooled oropharyngeal and cloacal samples from individual ducks of four districts were tested by real time PCRs for the presence of AIV, avian avulavirus-1, anatid herpesvirus-1, avian parvovirus, avian bornavirus and avian coronavirus. The investigation identified 27 (5.4%) ducks positive for AIV and 12 (2.4%) for avian coronavirus. In 13 samples, RNA specific for AIV H4N6 was detected. Phylogenetic analysis of the AIV hemagglutinin H4 and neuraminidase N6 genes suggested a clustering of Bangladeshi AIV H4N6 in Eurasian lineage group 2. Other AIV positive sample had very low virus loads (Cq >36) and were not subtyped. Coronaviral sequences of a fragment of the polymerase gene were related to Eurasian-Australian duck gamma-coronaviruses. Our current active surveillance in free-range domestic backyard ducks in Bangladesh failed to detect highly pathogenic (HP) AIV in contrast to our previous passive monitoring study. Nevertheless, active monitoring of domestic duck populations may be important to highlight presence and transmission dynamics of economically less important AIV that still may serve as reassortment partners for the generation of new HP and zoonotic AIV.Research highlights Active surveillance for viral pathogens in domestic free-range backyard ducks.Detection of avian influenza virus subtype H4N6.First identification of avian gamma-coronavirus in ducks in Bangladesh.


title: Management of staple line leaks after sleeve gastrectomy in a consecutive series of 378 patients.

text: INTRODUCTION Laparoscopic sleeve gastrectomy (LSG) is gaining acceptance as a stand-alone bariatric procedure with proven efficacy on weight loss and obesity-related comorbidities. A specific and potentially severe complication of LSG is the staple line leak (SLL). Our aim was to report the SLL rate and its management in a prospective cohort of 378 LSGs. PATIENTS AND METHODS A total of 378 patients underwent LSG from July 2005 to July 2011. The gastric transection was performed by an initial 60 mm firing of 4.5 mm staples at the antrum and successive 60 mm firings of 3.5 mm staples at the gastric body and fundus toward the left diaphragmatic crus. A 36 Fr bougie was used to calibrate the gastric tube. The staple line was systematically reinforced with a partial-thickness running suture. RESULTS The overall complications and SLL rate were 20/378 (5.29%) and 9/378 (2.38%), respectively. SLLs were managed by laparoscopic (n=2) or open (n=1) exploration, drainage and endoscopic self-expandable covered stent, computed tomography-guided percutaneous drainage (n=2), or a self-expandable covered stent alone (n=4). Medical support including total parenteral nutrition and adapted antibiotics was started in all patients. The combined treatment modalities were successful in all cases. CONCLUSIONS SLL was the most common complication of LSG accounting for half of the overall complications. Percutaneous drainage and self-covered stents combined with antibiotics and parenteral nutrition are effective for SLL and should be proposed as first-line treatment in stable patients.


Mystery deepens over animal source of coronavirus.


COVID-19 and Postinfection Immunity: Limited Evidence, Many Remaining Questions.


title: Epidemiology and Clinical Characteristics of COVID-19.

text: Since December 2019, there has been an outbreak of a novel coronavirus (COVID-19) infection in Wuhan, China. Meanwhile, the outbreak also drew attention and concern from the World Health Organization (WHO). COVID-19 is another human infectious disease caused by coronavirus. The transmission of COVID-19 is potent and the infection rate is fast. Since there is no specific drug for COVID-19, the treatment is mainly symptomatic supportive therapy. In addition, it should be pointed out that patients with severe illness need more aggressive treatment and meticulous care. Recently, accurate RNA detection has been decisive for the diagnosis of COVID-19. The development of highly sensitive RT-PCR has facilitated epidemiological studies that provide insight into the prevalence, seasonality, clinical manifestations and course of COVID-19 infection. In this review, we summarize the epidemiology and characteristics of COVID-19.


title: Simultaneous laparoscopic hand-assisted hepatectomy and splenectomy for liver cancer with hypersplenism: report of a case.

text: Hepatocellular carcinoma accompanied by portal hypertension and hypersplenism is difficult to treat medically and surgically due to pancytopenia and the development of collateral circulation. In this study, we were able to safely and simultaneously perform a laparoscopically-assisted splenectomy and partial hepatectomy. The characteristics of this procedure include: (1) the shared use of a medial wound made through laparoscopically-assisted surgery; (2) improved safety for manipulating areas that were difficult to observe with a camera in a case of splenomegaly; (3) a preventive ligation of the splenic artery; (4) improved hemostatic function using LigaSure Impact; and (5) hemorrhage control through manual manipulations and the Pringle maneuver during liver parenchymal transection. The surgery was safely performed using the above points.


title: Host phylogenetic distance drives trends in virus virulence and transmissibility across the animal-human interface.

text: Historically, efforts to assess 'zoonotic risk' have focused mainly on quantifying the potential for cross-species emergence of viruses from animal hosts. However, viruses clearly differ in relative burden, both in terms of morbidity and mortality (virulence) incurred and the capacity for sustained human-to-human transmission. Extending previously published databases, we delineated host and viral traits predictive of human mortality associated with viral spillover, viral capacity to transmit between humans following spillover and the probability of a given virus being zoonotic. We demonstrate that increasing host phylogenetic distance from humans positively correlates with human mortality but negatively correlates with human transmissibility, suggesting that the virulence induced by viruses emerging from hosts at high phylogenetic distance may limit capacity for human transmission. Our key result is that hosts most closely related to humans harbour zoonoses of lower impact in terms of morbidity and mortality, while the most distantly related hosts-in particular, order Chiroptera (bats)-harbour highly virulent zoonoses with a lower capacity for endemic establishment in human hosts. As a whole, our results emphasize the importance of understanding how zoonoses manifest in the human population and also highlight potential risks associated with multi-host transmission chains in spillover. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.


title: Perception of sound and gravity by TMC1 and TMC2.

text: Central to our ability to hear and sense gravity is a cellular process known as mechanotransduction, which is initiated by the opening of mechanosensitive cation channels located near the tips of the stereocilia of auditory and vestibular inner ear hair cells. The molecular identity of the mechanotransduction channels has eluded researchers despite intensive investigations over the years. In this issue of the JCI, Kawashima et al. report their results obtained using mice with targeted deletion of both transmembrane channel-like 1 (Tmc1) and Tmc2. The use of inner ear hair cells isolated from these mice provided a nearly perfect system for testing the mechanotransduction channels without disrupting functions of other accessory proteins needed in the complicated molecular apparatus, and it allowed the authors to show that the proteins encoded by these genes are integral components of the mechanotransduction complex.


title: Reference ranges for the fetal mitral, tricuspid, and interventricular septum annular plane systolic excursions (mitral annular plane systolic excursion, tricuspid annular plane systolic excursion, and septum annular plane systolic excursion) between 20 and 36 + 6 weeks of gestation.

text: Objectives This study aimed to establish reference ranges for fetal mitral, tricuspid, and interventricular septum annular plane systolic excursions (MAPSE, TAPSE, and SAPSE) in normal pregnant women between 20 and 36 + 6 weeks of gestation. Methods This prospective and cross-sectional study included 360 low-risk singleton pregnancies between 20 and 36 + 6 weeks of gestation. MAPSE, TAPSE, and SAPSE were measured by M-mode in real time in an apical or basal four-chamber view through placing the cursor at the atrioventricular junction, marked by the valve rings at the tricuspid, mitral, and basal septum, respectively. A regression analysis was done to determine the appropriate polynomial equation model for both measurements and standard deviation (SD) values in relation to gestational age (GA). The intra- and inter-observer reproducibility was evaluated using the concordance correlation coefficient (CCC) and limits of agreement (LoA). Results There was a significant positive correlation between MAPSE (r=0.705, p<0.0001), TAPSE (r=0.804, p<0.0001), and SAPSE (r=0.690, p<0.0001) and GA. The mean of each parameter ranged as follows: 2.87-5.56 mm, MAPSE; 3.98-8.07 mm, TAPSE; and 2.34-4.21 mm, SAPSE. Poor/moderate intra- and inter-observer reliability (CCC between 0.70 and 0.90) and poor/moderate agreement of all the tested parameters were evaluated (LoA between 10 and 50%). Conclusions Reference values were established for the fetal MAPSE, TAPSE, and SAPSE between 20 and 36 + 6 weeks of gestation in low-risk pregnant women. These parameters showed poor/moderate reproducibility.


title: Fermentation in the large intestine of single-stomached animals and its relationship to animal health.

text: The phasing out of antibiotic compounds as growth promoters from the animal industry means that alternative practices will need to be investigated and the promising ones implemented in the very near future. Fermentation in the gastrointestinal tract (GIT) is being recognized as having important implications for health of the gut and thus of the host animal. Fermentation in single-stomached animals occurs to the largest extent in the large intestine, mainly because of the longer transit time there. The present review examines the micro-ecology of the GIT, with most emphasis on the large intestine as the most important site of fermentative activity, and an attempt is made to clarify the importance of the microfloral activity (i.e. fermentation) in relation to the health of the host. The differences between carbohydrate and protein fermentation are described, particularly in relation to their endproducts. The roles of volatile fatty acids (VFA) and NH3 in terms of their relationship to gut health are then examined. The large intestine has an important function in relation to the development of diarrhoea, particularly in terms of VFA production by fermentation and its role in water absorption. Suggestions are made as to feeds and additives (particularly those which are carbohydrate-based) which could be, or are, added to diets and which could steer the natural microbial population of the GIT. Various methods are described which are used to investigate changes in microbial populations and reasons are given for the importance of measuring the kinetics of fermentation activity as an indicator of microbial activity.


title: Survey of Ebola Preparedness in Washington State Emergency Departments.

text: OBJECTIVE The 2014 Ebola virus disease (EVD) outbreak in West Africa remains the most deadly in history. Emergency departments (EDs) are more likely to come into contact with potential EVD patients. It is important for EDs to be prepared to care for suspected EVD patients. Our objective was to understand the perceived challenges experienced by Washington State ED medical directors in EVD preparedness. METHODS An anonymous, electronic survey was sent to a convenience sample of ED medical directors across Washington State between November and February of 2014-2015. The perceived challenges of and attitudes toward EVD preparations were assessed and reported as stratified proportions. RESULTS Of 85 medical directors contacted, 59 responses (69%) were received. This included EDs with annual patient volumes of 60,000 (12 hospitals, 20%). Among the perceived challenges in EVD preparations were spatial modifications (eg, building an anteroom for donning and doffing of personal protective equipment) and waste management planning. Ninety-five percent of respondents moderately or strongly agreed that it is important to have a predesignated hospital to care for EVD patients. CONCLUSIONS Washington State ED medical directors have faced significant challenges in ensuring their EDs are prepared to safely care for suspected EVD patients. Attitudes toward EVD preparations are mixed. Varying levels of perceived importance may represent an additional barrier to statewide EVD preparedness. (Disaster Med Public Health Preparedness. 2016;10:662-668).


title: Sedation in non-invasive ventilation: do we know what to do (and why)?

text: This review examines some of the issues encountered in the use of sedation in patients receiving respiratory support from non-invasive ventilation (NIV). This is an area of critical and intensive care medicine where there are limited (if any) robust data to guide the development of best practice and where local custom appears to exert a strong influence on patterns of care. We examine aspects of sedation for NIV where the current lack of structure may be contributing to missed opportunities to improve standards of care and examine the existing sedative armamentarium. No single sedative agent is currently available that fulfils the criteria for an ideal agent but we offer some observations on the relative merits of different agents as they relate to considerations such as effects on respiratory drive and timing, and airways patency. The significance of agitation and delirium and the affective aspect(s) of dyspnoea are also considered. We outline an agenda for placing the use of sedation in NIV on a more systematic footing, including clearly expressed criteria and conditions for terminating NIV and structural and organizational conditions for prospective multicentre trials.


title: Gastrointestinal delivery of propofol from fospropofol: its bioavailability and activity in rodents and human volunteers.

text: BACKGROUND Propofol is a safe and widely used intravenous anesthetic agent, for which additional clinical uses including treatment of migraine, nausea, pain and anxiety have been proposed (Vasileiou et al. Eur J Pharmacol 605:1-8, 2009). However, propofol suffers from several disadvantages as a therapeutic outside anesthesia including its limited aqueous solubility and negligible oral bioavailability. The purpose of the studies described here was to evaluate, in both animals and human volunteers, whether fospropofol (a water soluble phosphate ester prodrug of propofol) would provide higher propofol bioavailability through non-intravenous routes. METHODS Fospropofol was administered via intravenous, oral and intraduodenal routes to rats. Pharmacokinetic and pharmacodynamic parameters were then evaluated. Based on the promising animal data we subsequently conducted an oral and intraduodenal pharmacokinetic/pharmacodynamic study in human volunteers. RESULTS In rats, bioavailability of propofol from fospropofol delivered orally was found to be appreciable, in the order of around 20-70%, depending on dose. Availability was especially marked following fospropofol administration via the intraduodenal route, where bioavailability approximated 100%. Fospropofol itself was not appreciably bioavailable when administered by any route except for intravenous. Pharmacologic effect following oral fospropofol was confirmed by observation of sedation and alleviation of thermal hyperalgesia in the rat chronic constrictive injury model of neuropathic pain. The human data also showed systemic availability of propofol from fospropofol administration via oral routes, a hereto novel finding. Assessment of sedation in human volunteers was correlated with pharmacokinetic measurements. CONCLUSIONS These data suggest potential utility of oral administration of fospropofol for various therapeutic indications previously considered for propofol.