title: Discovery, synthesis, and structure-based optimization of a series of N-(tert-butyl)-2-(N-arylamido)-2-(pyridin-3-yl) acetamides (ML188) as potent noncovalent small molecule inhibitors of the severe acute respiratory syndrome coronavirus (SARS-CoV) 3CL protease.

text: A high-throughput screen of the NIH molecular libraries sample collection and subsequent optimization of a lead dipeptide-like series of severe acute respiratory syndrome (SARS) main protease (3CLpro) inhibitors led to the identification of probe compound ML188 (16-(R), (R)-N-(4-(tert-butyl)phenyl)-N-(2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl)furan-2-carboxamide, Pubchem CID: 46897844). Unlike the majority of reported coronavirus 3CLpro inhibitors that act via covalent modification of the enzyme, 16-(R) is a noncovalent SARS-CoV 3CLpro inhibitor with moderate MW and good enzyme and antiviral inhibitory activity. A multicomponent Ugi reaction was utilized to rapidly explore structure-activity relationships within S(1'), S(1), and S(2) enzyme binding pockets. The X-ray structure of SARS-CoV 3CLpro bound with 16-(R) was instrumental in guiding subsequent rounds of chemistry optimization. 16-(R) provides an excellent starting point for the further design and refinement of 3CLpro inhibitors that act by a noncovalent mechanism of action.


title: Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice.

text: Type 2 diabetes (T2D) has reached an epidemic level globally. Most current treatments ameliorate the hyperglycemic symptom of the disease but are not effective in correcting its underlying cause. One important causal factor of T2D is ectopic accumulation of lipids in metabolically sensitive organs such as liver and muscle. Mitochondrial uncoupling, which reduces cellular energy efficiency and increases lipid oxidation, is an appealing therapeutic strategy. The challenge, however, is to discover safe mitochondrial uncouplers for practical use. Niclosamide is an anthelmintic drug approved by the US Food and Drug Administration that uncouples the mitochondria of parasitic worms. Here we show that niclosamide ethanolamine salt (NEN) uncouples mammalian mitochondria at upper nanomolar concentrations. Oral NEN increases energy expenditure and lipid metabolism in mice. It is also efficacious in preventing and treating hepatic steatosis and insulin resistance induced by a high-fat diet. Moreover, it improves glycemic control and delays disease progression in db/db mice. Given the well-documented safety profile of NEN, our study provides a potentially new and practical pharmacological approach for treating T2D.


title: The Lurking Catastrophic Complication of an Equally Catastrophic Disease: The Lesson Learned.

text: BACKGROUND Medullary-bridging vein dural arteriovenous fistula (DAVF) is an uncommon type of DAVF with an aggressive clinical course due to direct fistulous shunting into medullary and brainstem veins. Important considerations need to be given to retrograde embolic migration or perforator involvement while treating these fistulas endovascularly with a liquid embolic agent. We report a lateral spinal artery feeding the DAVF, the recognition of which is important to avoid potential catastrophic complications during definitive therapy, and which has not been described before. OBJECTIVE To discuss the anatomy of the lateral spinal artery (LSA) and its communications with pial arteries such as the posterior inferior cerebellar artery (PICA) that may have important implications in the management of neurovascular diseases in and around the foramen magnum. METHODS A retrospective analysis of cerebral angiograms and 3-dimensional rotational angiograms of a patient with medullary-bridging vein DAVF treated by transarterial embolization under balloon protection was performed after the patient developed lateral medullary syndrome in the postoperative period. RESULTS Detailed analysis revealed a dural branch from the LSA feeding the DAVF which anastomosed with rudimentary PICA. CONCLUSION LSA has important anastomoses with perforating arteries of the medulla and cervical cord and, hence, it is important to recognize and identify LSA prospectively in the vascular pathologies of the foramen magnum to avoid fatal neurological complications during endovascular therapy. This is especially important while treating neurovascular pathologies using liquid embolic agents such as Onyx or SQUID, because they can percolate retrogradely through the anastomoses into PICA or other vertebrobasilar perforators.


title: Single-access transumbilical laparoscopic appendectomy and cholecystectomy using new curved reusable instruments: a pilot feasibility study.

text: BACKGROUND The umbilicus can be considered as the embryological opening for single-access laparoscopic procedures. We report on single-access transumbilical laparoscopic appendectomy (SATLA) and cholecystectomy (SATLC), performed using new curved reusable instruments. PATIENTS AND METHODS A retrospective review of a prospectively maintained database of 30 patients who underwent SATLA and 20 patients who underwent SATLC between May and November 2009 was undertaken. All procedures were performed with an 11-mm nondisposable trocar for the scope, and curved reusable instruments (Karl Storz-Endoskope, Tuttlingen, Germany) placed transumbilically without trocars. Outcome measures were conversion to standard laparoscopy, operative time, scar length, complications, hospital stay, and use of pain medication. RESULTS All SATLA patients had acute appendicitis, and SATLC patients had symptomatic gallstones (15), chronic cholecystitis (3), and acute cholecystitis (2). No extraumbilical trocars were necessary. Mean total operative times were 57.3 ± 15.9 min (SATLA) and 73.9 ± 20.1 min (SATLC). Mean laparoscopic times were 39 ± 13.1 min (SATLA) and 57.5 ± 18.9 min (SATLC). Mean scar lengths were 14.8 ± 2.2 mm (SATLA) and 15.8 ± 2.3 mm (SATLC). Five SATLA patients and one SATLC patient developed postoperative complications. Mean hospital stay was 2.9 ± 1.3 days for SATLA patients and 1.8 ± 0.8 days for SATLC patients. Pain medication used was minimal. At the minimum follow-up of 3 months no late complications were registered. CONCLUSIONS SATLA and SATLC can be performed safely using curved reusable instruments, which helps avoid the conflict between the surgeon's hands or between the instruments' tips and allows the surgeon to operate in an ergonomic position. The reusable instruments kept the cost similar to that of classic laparoscopy.


title: Efficacy of a new bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae (Fostera™ PCV MH) under experimental conditions.

text: The objective of this study was to evaluate the efficacy of a new bivalent vaccine (Fostera™ PCV MH, Zoetis) of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae in growing pigs under experimental conditions. A total of 80 pigs were randomly divided into 8 groups (10 pigs per group). The pigs were administered the bivalent vaccine intramuscularly as a 2.0 mL dose at 21 days of age based on the manufacturer's instructions. Three weeks after vaccination, the pigs were inoculated with either PCV2 (intranasal route) or M. hyopneumoniae (intratracheal route) or both. Regardless of the type of inoculation, vaccinated pigs after challenge exhibited effective reduction of clinical signs, PCV2 viremia levels and mycoplasma nasal shedding, and lung and lymphoid lesion when compared to unvaccinated challenged pigs. Vaccinated challenged pigs had significantly higher (P<0.05) levels of PCV2-specific neutralizing antibodies, and numbers of PCV2-and M. hyopneumoniae-specific interferon-γ secreting cells compared to unvaccinated challenged pigs. This study demonstrates that the bivalent vaccine is able to protect pigs against either PCV2 or M. hyopneumoniae infection or both based on clinical, microbiological, immunological, and pathological evaluation.


title: Reference ranges of thromboelastometry in healthy full-term and pre-term neonates.

text: BACKGROUND Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates. METHODS In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (<37 weeks' gestation) using peripheral arterial whole blood samples. RESULTS Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9-78); clot formation time (seconds), 70 (range, 40-165.2); maximum clot firmness (mm), 66 (range, 41-84.1); lysis index at 60 min (LI60, %), 97 (range, 85-100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates. CONCLUSIONS In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.


title: Attenuation correction of somatostatin receptor SPECT by integrated low-dose CT: is there an impact on sensitivity?

text: AIM Somatostatin receptor scintigraphy (SRS) is an established imaging modality for neuroendocrine tumors (NET). Additional single photon emission computed tomography (SPECT-CT) not only permits image fusion but also attenuation correction (AC) of SPECT data. This study evaluated whether attenuation corrected SPECT-images (SPECT[AC]) are more sensitive than nonattenuation corrected SPECT-reconstructions (SPECT[NAC]) for the detection of NET lesions. METHODS The imaging data (planar In-111-octreotide scintigraphy and SPECT-CT) of 50 consecutive patients (28 male; 22 female; age, 34-80; mean, 65 years) with NET were included in this retrospective analysis. SPECT data were reconstructed with and without integrated CT-based AC and then analyzed by 2 experienced readers for the presence of pathologic uptake in a blinded consensus reading. Fused SPECT-CT, contemporary CT/MRI, and clinical as well as imaging follow-up served as a reference standard. All foci were rated in both the SPECT(NAC)- and SPECT(AC)-reconstructions for intensity and contrast using a 6-point-score ("0 = no uptake/no delineation from surrounding tissue" to "5 = very high uptake/very strong delineation from surrounding tissue"). The scores were analyzed in a 6 x 6 contingency table using the McNemar Bowker test. RESULTS A total of 222 pathologic foci were detected by SPECT(NAC) and 227 foci by SPECT(AC), respectively. In 67 of 227 foci (29.5%), focus intensity/contrast increased after AC, whereas only 5 foci showed a decrease (P < 0.001). Sensitivity increased by 2.2% (P = 0.025; 95% CI: 0.02%-4.1%) as 5 foci were detected only by SPECT(AC). However, as these 3 patients were already diagnosed with systemic disease, there was no influence on the therapeutic strategy chosen. CONCLUSION Attenuation correction of somatostatin receptor scintigraphy-SPECT significantly improves focus visualization and, albeit slightly, also significantly increases sensitivity.


title: Single-incision sleeve gastrectomy for successful treatment of a gastrointestinal stromal tumor.

text: BACKGROUND Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that are located specifically in the gastrointestinal tract, with up to 60% of occurrences in the stomach, 30% in the small intestine, and 10% in the esophagus, colon, and rectum. The annual incidence of GISTs is about 15 cases per million, which in the United States equals 5000 cases per year. In most cases, these tumors are asymptomatic and are found incidentally on computed tomography scan or by endoscopy. Preoperative evaluation is based on location, size, and anatomic features and helps to confirm the diagnosis of the GIST and assess outcomes. Surgical intervention is the gold standard for treatment of nonmetastatic GISTs. CASE PRESENTATION We report the case of an 80-year-old man with a gastric mass on the posterior surface of the greater curvature of the stomach at the junction of the gastric antrum and the pylorus, found incidentally on a computed tomography scan. The patient underwent a diagnostic laparoscopy and a single-incision laparoscopic sleeve gastrectomy. After histologic evaluation, the resected lesion was determined to be a gastrointestinal stromal tumor. CONCLUSION A single-incision laparoscopic sleeve gastrectomy for the resection of GISTs is a feasible and appropriate method if the lesion is a safe distance from the pylorus and the gastroesophageal junction for gross negative margins to be obtained. Its advantages include decreased pain and a shorter hospital stay compared with other methods.


title: Minimally invasive surgery for diverticulitis.

text: The realm of minimally invasive surgery now encompasses the majority of abdominal operations in the field of colorectal surgery. Diverticulitis, a common pathology seen in most colorectal practices, poses unique challenges to surgeons implementing laparoscopic surgery in their practices due to the presence of an inflammatory phlegmon and distorted anatomical planes, which increase the difficulty of the operation. Although the majority of colon resections for diverticulitis are still performed through a standard laparotomy incision, laparoscopic techniques are becoming increasingly common. A large body of literature now supports laparoscopic surgery to be safe and effective as well as to provide significant advantages over open surgery for diverticular disease. Here, we review the most current literature supporting laparoscopic surgery for elective and emergent treatment of diverticulitis.


A frameless LNG-IUD may be preferred over framed LNG-IUD for the treatment of primary dysmenorrhea.


title: Instant reocclusion following mechanical thrombectomy of in situ thromboocclusion and the role of low-dose intra-arterial tirofiban.

text: BACKGROUND An in situ thromboocclusion (IST) is defined as an infarct extensively involving all or most of a stenosed arterial territory, which is one major stroke mechanism related to intracranial atherosclerosis (ICAS). We focused on ISTs occurring in major cerebral arteries and analyzed their rate of instant reocclusion during mechanical thrombectomy (MT) compared with non-ISTs. Also, we introduced a treatment strategy of low-dose intra-arterial tirofiban administration to prevent such reocclusion following repeat recanalization, and evaluated its safety and efficacy. METHODS We analyzed 168 consecutive patients treated with MT over a 2-year period from May 2011 to April 2013. During MT, if angiography following a successful recanalization showed stenosis at the occlusion site, we performed additional angiographic runs every 10 min for 30 min after the recanalization. Then, if angiography revealed reocclusion, we performed a repeat recanalization, using the same MT technique but additionally followed by low-dose intra-arterial tirofiban infusion. Time-of-flight MR angiography or CT angiography was performed to confirm any underlying ICAS at the occlusion site 5-7 days after the procedure. The patients who had confirmed underlying ICAS were included in the IST cohort. RESULTS Of 168 enrolled patients, we excluded 36 who could not be checked for underlying ICAS at the occlusion site for one of the following reasons: recanalization failure (n = 11), rescue stenting after tirofiban failure (n = 5) and lack of follow-up vascular imaging (n = 20). The incidence of IST was 30.3% (40/132). All IST patients were confirmed to have underlying ICAS by follow-up vascular imaging. Instant reocclusion after successful recanalization was significantly more frequent in the IST cohort [26/40 (65%) vs. 3/92 (3.3%); p < 0.001]. Regarding the efficacy of low-dose intra-arterial tirofiban infusion, 85.7% of the reocclusion patients finally achieved a thrombolysis in cerebral infarction score 2/3 recanalization, but in the remaining 14.3% of the cases, the condition was refractory to the procedure and required rescue stenting. There were no cases of symptomatic intracranial hemorrhage following the procedure. CONCLUSIONS In situ thromboocclusion was characterized by a significantly higher chance of instant reocclusion during MT. In such cases, low-dose intra-arterial tirofiban administration may be effective and safe. However, future confirmation by prospective multicenter trials seems necessary.


title: Initial Technical Experience with the SMART Coil for the Embolization of Intracranial Aneurysms.

text: BACKGROUND/OBJECTIVE Traditional platinum coils used for cerebral aneurysm embolization have a uniform degree of softness throughout an individual coil's length. Recently, SMART Coils (Penumbra Inc., Alameda, California, USA) have been developed, which transition in softness along the length of their coils. We report the initial clinical results with this technology. METHODS A retrospective study of all patients undergoing aneurysm coiling with SMART Coils at 2 centers was performed to evaluate the safety and efficacy of this new technology. Outcome and angiographic data were self-reported by individual treatment centers. RESULTS Fifty-nine patients underwent treatment for cerebral aneurysms with SMART Coils (44% in the setting of subarachnoid hemorrhage). Mean aneurysm size was 5.9 ± 2 mm × 4.5 ± 2 mm. Mean neck size was 3.4 ± 1 mm. More than half (54.2%) of the patients underwent coiling exclusively with SMART Coils. The remainder used either framing or finishing coils of another type. About one third (33.9%) underwent balloon-assisted coiling, and 47.5% underwent stent-assisted coiling. There were no device malfunctions in any of the patients. Six (10.1%) minor complications without clinical sequelae occurred. Raymond I or II occlusion was achieved in 71.2%. CONCLUSIONS Our results demonstrate adequate device safety in a variety of both ruptured and unruptured aneurysm locations. This design enables progressive changes in softness along the length of an individual coil, which offers several potential advantages in the clinical use. This initial investigation of SMART Coil technology demonstrates safety and efficacy in the treatment of a wide range of aneurysm sizes, locations, and morphologies in both ruptured and unruptured settings.


title: Real-time detection of influenza a, influenza B, and respiratory syncytial virus a and B in respiratory specimens by use of nanoparticle probes.

text: Seasonal epidemics of influenza and respiratory syncytial virus are responsible for significant morbidity and mortality worldwide. Infrequently, novel or reemergent strains of influenza A virus have caused rapid, severe global pandemics resulting in millions of fatalities. The ability to efficiently and accurately detect and differentiate respiratory viruses is paramount for effective treatment, infection control, and epidemiological surveillance. We evaluated the ability of two FDA-cleared nucleic acid-based tests, the semiautomated respiratory virus nucleic acid test (VRNAT) and the fully automated respiratory virus nucleic acid test SP (RVNAT(SP)) (Nanosphere Inc., Northbrook, IL) to detect influenza A virus, influenza B virus, and respiratory syncytial virus A and B (RSV A/B) from clinical nasopharyngeal swab specimens. Detection of viral RNA in both tests is based on nucleic acid amplification followed by hybridization to capture probes immobilized on a glass slide. A novel technology utilizing gold nanoparticle-conjugated probes is utilized to detect the presence of captured target DNA. This microarray-based approach to detection has proven to be more sensitive than the traditional culture/direct fluorescent-antibody assay (DFA) method for detecting RSV and influenza viruses in clinical specimens, including the novel 2009 H1N1 strain. Specifically, we report 98.0% sensitivity and 96.5% specificity for the VRNAT compared to culture/DFA. Further, the VRNAT detected virus in an additional 58% of specimens that were culture negative. These data were confirmed using bidirectional sequencing. Evaluation of the fully automated RVNAT(SP), which is built on the same detection technology as the VRNAT but contains an updated processor enabling complete automation, revealed the two tests to be functionally equivalent. Thus, the RVNAT(SP) is a fully automated sample-to-result test capable of reliable detection of select respiratory viruses directly from clinical specimens in 3.5 h.


Two specialty societies to run their own clinical trial of heart valve replacement.


IGICS: JGA Keynote Program. The 10th International Gastrointestinal Consensus Symposium (IGICS). Advanced Technology for Diagnosis and Treatment of Gastroenterological Diseases. February 18, 2017, Nagoya Congress Center, Aichi, Japan: Abstracts.


title: Cerebral micro-embolization during pulmonary vein isolation: Relation to post-ablation silent cerebral ischemia.

text: BACKGROUND High incidences of silent cerebral ischemia (SCI) have been revealed by diffusion-weighted magnetic resonance imaging (DW MRI) after pulmonary vein isolation (PVI) for atrial fibrillation. A high number of mostly gaseous micro-embolic signals (MESs) was detected by transcranial Doppler (TCD) during PVI. In this investigation the possible relationship between MESs detected intraoperatively by TCD and new SCI on DW MRI post-ablation is reported. METHODS 27 consecutive atrial fibrillation patients (6 female, age median: 64 interquartile range: 13.23) undergoing PVI with the pulmonary vein ablation catheter, pre- and post-ablation DW MRI and intra-operative MES detection by TCD were included in the study. Procedures were performed on a therapeutic international normalized ratio (2-3) and with a target activated clotting time ≥ 350 s in all patients. DW MRI scans performed pre- and post-ablation revealed new SCI in 6 out of 27 (22%) patients. RESULTS The median (interquartile range) MES count recorded during the whole procedure was 1642 (912) in patients with and 1019 (529) in those without SCI (p = 0.129). The number of MESs recorded during pulmonary vein angiography was significantly higher in patients as compared to those without a new lesion on the post-ablation DW MRI: 257 (249) vs. 110 (71), respectively (p = 0.0009). On mul-tivariate logistic regression, the total MES count was predictive of SCI in patients older than 68 years. CONCLUSIONS Micro-embolus generation detected by TCD during pulmonary vein angiography significantly correlates with new SCI on DW MRI post-ablation.


title: Non-exposure simple suturing endoscopic full-thickness resection (NESS-EFTR) versus laparoscopic wedge resection: a randomized controlled trial in a porcine model.

text: BACKGROUND Current endoscopic full-thickness resection (EFTR) methods produce transmural communication and expose the tumor to the peritoneum. An EFTR method with a simple suturing technique that does not expose the gastric mucosa to the peritoneum (non-exposure simple suturing, NESS) was recently developed. To date, there have been no prospective studies that compare EFTR with laparoscopic wedge resection in human or animal. The aim of this study was to compare outcomes between NESS-EFTR and laparoscopic wedge resection (LWR) using the linear staplers in a randomized animal study. METHODS NESS-EFTR includes steps of laparoscopic seromuscular suturing, EFTR of the inverted stomach wall, and endoscopic mucosal suturing with endoloops and clips. Sixteen pigs underwent NESS-EFTR (n = 8) or LWR (n = 8). The resected locations were the cardia, fundus, upper body anterior and greater curvature, antrum lesser and greater curvature side. The pigs were killed 3 weeks after surgery. Rates of successful complete resection (en-bloc resection with clear margins), successful closure, and complications were evaluated. RESULTS The complete resection rates in the NESS-EFTR and LWR groups were 100 and 75%, respectively (P = 0.467). All wounds were successfully closed in both groups. Resected tissues were significantly larger in the LWR group (mean ± SD: 8.0 ± 0.8 cm vs. 4.4 ± 0.5 cm, P < 0.001). Procedure time was significantly shorter in the LWR group (31.7 ± 10.0 min vs. 118.1 ± 23.4 min, P < 0.001). Early deaths due to complications only occurred in the LWR group (a leakage at cardia and a stenosis at the antrum lesser curvature side). CONCLUSIONS Incomplete resection and complications were occurred in only LWR group. NESS-EFTR was feasible and safe in animal.


title: The contribution of diabetic micro-angiopathy to adverse outcomes in COVID-19

text: Increasing evidence points to endothelial cell dysfunction as a key pathophysiological factor in severe coronavirus disease-19 (COVID-19), manifested by platelet aggregation, microthrombi and altered vasomotor tone. This may be driven by direct endothelial cell entry by the virus, or indirectly by activated inflammatory cascade. Major risk groups identified for adverse outcomes in COVID-19 are diabetes, and those from the Black, Asian and ethnic minority (BAME) populations. Hyperglycaemia (expressed as glycated haemoglobin or mean hospital glucose) correlates with worse outcomes in COVID-19. It is not known whether hyperglycaemia is causative or is a surrogate marker - persistent hyperglycaemia is well known as an aetiological agent in microangiopathy. In this article, we propose that pre-existing endothelial dysfunction of microangiopathy, more commonly evident in diabetes and BAME groups, makes an individual vulnerable to the subsequent ‘endothelitis’ of COVID-19 infection.


Type 1 Diabetes and COVID-19: Preliminary Findings From a Multicenter Surveillance Study in the U.S.


title: Outcomes of an algorithmic approach to management of pneumothorax complicating thermal ablation of pulmonary neoplasms.

text: PURPOSE To investigate the outcomes of an algorithm for treatment of pneumothorax in association with radiofrequency (RF) and microwave (MW) ablation of pulmonary neoplasms. MATERIALS AND METHODS This retrospective study included data from 248 ablation sessions for lung tumors in 164 patients (92 men; mean age, 59.7 y ± 9.8): 200 RF ablations (80.6%) and 48 MW ablations (19.4%). Pneumothorax was classified as mild, moderate, or severe. Twelve patients developed mild pneumothorax and were observed for further complications, and 33 developed moderate or severe pneumothorax and were managed with percutaneous aspiration of the pneumothorax. The decision to abort or continue ablation was determined based on clinical response to percutaneous aspiration, clinical distress, and feasibility of applying the applicator within the lesion. RESULTS Incidence of pneumothorax was 18.1% (45 of 248 sessions), with four (8.9%) occurrences during MW ablation and 41 (91.1%) during RF ablation. Pneumothoraces were mild in 12 sessions (26.7%), moderate in 27 (60%), and severe in six (13.3%). Complete evacuation of the pneumothorax was achieved in 25 of 33 sessions (75.8%). Intercostal tube drainage was indicated in eight sessions (24.2%), including six severe and two moderate pneumothoraces. Pneumothorax evolved immediately after thoracic puncture in 10 patients. Ablation therapy was aborted in two sessions in which severe pneumothorax occurred, and an intercostal chest tube was inserted. CONCLUSIONS Mild pneumothorax can be managed by close observation without interruption of ablation therapy. Manual evacuation was an effective strategy for management of moderate pneumothorax and allowed for adequate positioning of the electrode, but did not suffice for severe and progressive pneumothorax, which required placement of an intercostal chest tube.


Case report: Third-degree skin and soft tissue burn after radiofrequency ablation of an osteoid osteoma guided through a triple-crown biopsy cannula.


title: Thoracoscopic lobectomy: is a training program feasible with low postoperative morbidity?

text: OBJECTIVE To evaluate the feasibility of training program in video assisted thoracic surgery (VATS) lobectomy comparing intraoperative and postoperative data of patients operated on by an established consultant and trainees. METHODS Retrospective analysis of 100 consecutive patients who underwent VATS lobectomies between May 2008 and May 2012. 66 patients were operated on by an established consultant (Group A) and 34 by trainees (Group B). RESULTS The groups were comparable for clinical characteristics and pathological staging. The mean operating time in Group A was 125 ± 30 min and in Group B was 133 ± 26 min (p = 0.18). The rate of conversion was similar in both groups: 9.1% in Group A and 8.8% in Group B (p = 0.6). The complication rate was comparable (p = 0.4): 36.3% in Group A and 32.3% in Group B. Median time to drain removal and median length of hospital stay was 3 and 5.5 days in Group A and 3 and 5 days in Group B, showing no statistical differences between the two groups (p = 0.3 and 0.5). There were no differences in term of long-term complications between the two groups. CONCLUSION Our study showed that a training program in VATS lobectomy is feasible, without increasing the operative time, conversion rate, postoperative complication, time to drain removal, and length of hospital stay.


title: Mutagen resistance and mutation restriction of St. Louis encephalitis virus.

text: The error rate of the RNA-dependent RNA polymerase (RdRp) of RNA viruses is important in maintaining genetic diversity for viral adaptation and fitness. Numerous studies have shown that mutagen-resistant RNA virus variants display amino acid mutations in the RdRp and other replicase subunits, which in turn exhibit an altered fidelity phenotype affecting viral fitness, adaptability, and pathogenicity. St. Louis encephalitis virus (SLEV), like its close relative West Nile virus (WNV), is a mosquito-borne flavivirus which has the ability to cause neuroinvasive disease in humans. Here, we describe the successful generation of multiple ribavirin-resistant populations containing a shared amino acid mutation in the SLEV RdRp (E416K). These E416K mutants also displayed resistance to the antiviral T-1106, an RNA mutagen similar to ribavirin. Structural modeling of the E416K polymerase mutation indicate its location in the pinky finger domain of the RdRp, distant from the active site. Deep-sequencing of the E416K mutant revealed lower genetic diversity than wildtype SLEV after growth in both vertebrate and invertebrate cells. Phenotypic characterization showed E416K mutants displayed similar or increased replication in mammalian cells, as well as modest attenuation in mosquito cells, consistent with previous work with WNV high-fidelity variants. In addition, attenuation was limited to mosquito cells with a functional RNA interference (RNAi) response, suggesting an impaired capacity to escape RNAi could contribute to attenuation of high-fidelity variants. Our results provide increased evidence that RNA mutagen resistance arises through modulation of the RdRp and gives further insight into the consequences of altered fidelity of flaviviruses.


title: Design of the Swiss Atrial Fibrillation Cohort Study (Swiss-AF): structural brain damage and cognitive decline among patients with atrial fibrillation.

text: BACKGROUND Several studies found that patients with atrial fibrillation (AF) have an increased risk of cognitive decline and dementia over time. However, the magnitude of the problem, associated risk factors and underlying mechanisms remain unclear. METHODS This article describes the design and methodology of the Swiss Atrial Fibrillation (Swiss-AF) Cohort Study, a prospective multicentre national cohort study of 2400 patients across 13 sites in Switzerland. Eligible patients must have documented AF. Main exclusion criteria are the inability to provide informed consent and the presence of exclusively short episodes of reversible forms of AF. All patients undergo extensive phenotyping and genotyping, including repeated assessment of cognitive functions, quality of life, disability, electrocardiography and cerebral magnetic resonance imaging. We also collect information on health related costs, and we assemble a large biobank. Key clinical outcomes in Swiss-AF are death, stroke, systemic embolism, bleeding, hospitalisation for heart failure and myocardial infarction. Information on outcomes and updates on other characteristics are being collected during yearly follow-up visits. RESULTS Up to 7 April 2017, we have enrolled 2133 patients into Swiss-AF. With the current recruitment rate of 15 to 20 patients per week, we expect that the target sample size of 2400 patients will be reached by summer 2017. CONCLUSION Swiss-AF is a large national prospective cohort of patients with AF in Switzerland. This study will provide important new information on structural and functional brain damage in patients with AF and on other AF related complications, using a large variety of genetic, phenotypic and health economic parameters.


title: Guidance for the management of adult patients with coronavirus disease 2019.

text: In December 2019, a novel coronavirus was identified in Wuhan City, Hubei Province, China and later the disease was named coronavirus disease 2019 (COVID-19). On March 11, 2020, the World Health Organization (WHO) officially announced that COVID-19 had reached global pandemic status. This article summarized the understanding of the etiology, pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and prevention and control measures of COVID-19 based on the available data and anti-epidemic experience in China.


title: Effects of stress on the immune response to Theiler's virus--implications for virus-induced autoimmunity.

text: Psychological stress is an important factor in susceptibility to many diseases. Our laboratory has been investigating the impact of stress on the susceptibility to Theiler's virus-induced demyelination (TVID), a mouse model of multiple sclerosis. Using immunodominant viral peptides specific for identification of either CD4(+) or CD8(+) T cells, stress reduced IFN-gamma-producing virus-specific CD4(+) and CD8(+) T cells in the spleen and CD8(+) T cells in the CNS. Expression of mRNA for the Th1 transcription factor T-bet and the Th2 transcription factor GATA-3 were decreased in spleen cells isolated from stressed mice. Cytokine production by cells isolated from the CNS or spleens following stimulation with virus indicated that stress decreased both type 1 and type 2 responses. The adverse effects of stress were partially reversed by concurrent RU486 administration but mimicked by dexamethasone, indicating a major role for glucocorticoids. Global stress-induced immunosuppression resulted in higher levels of virus replication and dissemination. The higher viral load subsequently led to an earlier disease onset and more severe clinical and histological signs of demyelinating disease. Our results have important implications for understanding the pathogenesis of MS, and suggest that stressful events during early infection with an agent capable of inducing demyelination may result in immunosuppression and failure to eliminate the pathogen, which in turn may lead to the development of MS.


title: Three-year results after directional atherectomy of calcified stenotic lesions of the superficial femoral artery.

text: OBJECTIVE To investigate the 3-year outcome of patients with peripheral arterial disease (PAD) and heavily calcified stenotic lesions of the superficial femoral artery after directional atherectomy. MATERIALS AND METHODS Fifty-three patients (mean age 67 ± 10 years; 18 females, 35 males, TASC B and C, mean lesion length 7.9 ± 3.5 cm) with PAD (Rutherford 2-6) were enrolled into this prospective monocentric study. In total, 59 calcified lesions of the superficial femoral artery were treated with the Silverhawk atherectomy device (Covidien, Plymouth, MN, USA). Patients were followed-up for 36 months with a 6-month interval to perform clinical re-evaluation, including measurement of maximum walking distance and ankle-brachial index (ABI) as well as duplex-sonography. RESULTS The primary success rate of the procedure was 92 %. In five cases (8 %), additional balloon-PTA and/or stent-PTA was necessary. Procedure-related embolization occurred in seven cases (12 %), which were all successfully treated by aspiration. The primary patency rate after 3 years was 55 %. Median Rutherford score decreased significantly from 5 to 0 after 36 months (p < 0.001). At the same time, the ABI increased from 0.65 to 1.12 (not significant). The limb-salvage rate after 3 years was 87 %. CONCLUSION In this subgroup of patients with POD and calcified stenotic lesions, atherectomy was successfully applied to decrease the plaque burden. Results after 3 years showed a significant decrease of Rutherford score with persistent improvement of ABI and reasonable patency rate.


title: Choice of Surgical Procedure for Patients With Non-Small-Cell Lung Cancer ≤ 1 cm or > 1 to 2 cm Among Lobectomy, Segmentectomy, and Wedge Resection: A Population-Based Study.

text: PURPOSE According to the lung cancer staging project, T1a (≤ 2 cm) non-small-cell lung cancer (NSCLC) should be additionally classified into ≤ 1 cm and > 1 to 2 cm groups. This study aimed to investigate the surgical procedure for NSCLC ≤ 1 cm and > 1 to 2 cm. METHODS We identified 15,760 patients with T1aN0M0 NSCLC after surgery from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared among patients after lobectomy, segmentectomy, or wedge resection. The proportional hazards model was applied to evaluate multiple prognostic factors. RESULTS OS and LCSS favored lobectomy compared with segmentectomy or wedge resection in patients with NSCLC ≤ 1 cm and > 1 to 2 cm. Multivariable analysis showed that segmentectomy and wedge resection were independently associated with poorer OS and LCSS than lobectomy for NSCLC ≤ 1 cm and > 1 to 2 cm. With sublobar resection, lower OS and LCSS emerged for NSCLC > 1 to 2 cm after wedge resection, whereas similar survivals were observed for NSCLC ≤ 1 cm. Multivariable analyses showed that wedge resection is an independent risk factor of survival for NSCLC > 1 to 2 cm but not for NSCLC ≤ 1 cm. CONCLUSION Lobectomy showed better survival than sublobar resection for patients with NSCLC ≤ 1 cm and > 1 to 2 cm. For patients in whom lobectomy is unsuitable, segmentectomy should be recommended for NSCLC > 1 to 2 cm, whereas surgeons could rely on surgical skills and the patient profile to decide between segmentectomy and wedge resection for NSCLC ≤ 1 cm.


title: Strategies to reduce the tampering and subsequent abuse of long-acting opioids: potential risks and benefits of formulations with physical or pharmacologic deterrents to tampering.

text: Increased prescribing of opioid analgesics for chronic noncancer pain may reflect acceptance that opioid benefits outweigh risks of adverse events for a broadening array of indications and patient populations; however, a parallel increase in the abuse, misuse, and diversion of prescription opioids has resulted. There is an urgent need to reduce opioid tampering and subsequent abuse without creating barriers to safe, effective analgesia. Similar to the "magic bullet" concept of antibiotic development (kill the bacteria without harming the patient), the idea behind reformulating opioid analgesics is to make them more difficult to tamper with and abuse by drug abusers but innocuous to the compliant patient. As antibiotics exploit differences in bacterial and human physiology, tamper-resistant formulations depend on differences in the way drug abusers and compliant patients consume opioids. Most opioid abusers tamper with tablets to facilitate oral, intranasal, or intravenous administration, whereas compliant patients usually take intact tablets. Pharmaceutical strategies to deter opioid abuse predominantly focus on tablet tampering, incorporating physical barriers (eg, crush resistance) or embedded chemicals that render tampered tablets inert, unusable, or noxious. Deterring tampering and abuse of intact tablets is more challenging. At present, only a few formulations with characteristics designed to oppose tampering for abuse have received approval by the US Food and Drug Administration, and none has been permitted to include claims of abuse deterrence or tamper resistance in their labeling. This review discusses the potential benefits, risks, and limitations associated with available tamper-resistant opioids and those in development.


title: Detection of circulating tumor cells in pulmonary venous blood for resectable non-small cell lung cancer.

text: Intraoperative manipulation causes circulating tumor cell (CTC) shedding into the blood and accelerates metastasis in non-small cell lung cancer (NSCLC). The present study was conducted to assess the degree of dissemination resulting from surgery and to explore the biological features of CTCs. In patients with NSCLC who underwent complete resection, the pulmonary vein (PV) was isolated and stapled following thoracotomy. The number of CTCs retained per 7.5 ml PV blood (CTC-PV) and peripheral blood were detected. Following hematopoietic cell depletion, a xenograft assay was performed using the CTC-PV. A total of 32 consecutive patients were enrolled in the study, the majority of whom had CTCs in their PV blood (n=29, 90.6%). Circulating tumor microemboli (CTM) were identified in 12 patients (37.5%). The CTC-PV and CTM-PV counts were positively correlated with tumor size (P=0.012 and P=0.028, respectively). Patients with small tumors (<3.0 cm) also had considerable CTC-PV and CTM-PV. A total of 8 patients received platinum-based chemotherapy prior to surgery. The CTC-PV and CTM-PV counts in patients with partial response were significantly lower than those in patients with stable disease or who did not receive induction therapy (P=0.025 and P=0.044, respectively). The enriched CTC-PV from 3 patients were injected into 3 immunodeficient mice, and 1 mouse developed a xenograft tumor. To conclude, the present study indicates that intraoperative manipulation contributes to the hematogenous dissemination of tumorigenic CTCs and CTM. Lobectomy is recommended for lung cancer of any tumor size and stage according to oncological principles, in addition to ligating the PV, if possible, prior to any other treatment.


title: Circular stapler size and risk of anastomotic complications in gastroduodenostomy for gastric cancer.

text: BACKGROUND A Billroth I reconstruction with a mechanically sutured anastomosis is commonly performed in gastric cancer patients. Some surgeons prefer to use large circular staplers during suturing to minimize risks for anastomotic stricture and gastric stasis after surgery. The effect of stapler size on anastomotic complications has not been validated. METHODS This study was conducted with 1,031 patients who underwent gastrectomy and Billroth I reconstruction at Samsung Medical Center in Seoul, Korea, between January 2007 and October 2008. Patients were assigned to group A (384 patients) or group B (647 patients) depending on the size of the circular stapler that the surgeon selected for mechanical anastomosis. A 25 mm circular stapler was used for patients in group A, and a 28 or 29 mm circular stapler was used for patients in group B. Postoperative complications were analyzed retrospectively. RESULTS The incidence of complications (e.g., gastric stasis, anastomotic stricture, and bleeding) did not differ significantly between groups. Age greater than 60 years was the only significant risk factor for anastomotic complications identified in univariate and multivariate analyses. CONCLUSIONS Stapler size was unrelated to complications, such as stricture and gastric stasis. Age was the only significant risk factor for anastomotic complications after gastroduodenostomy.


title: Reduced port laparoscopic gastrectomy: a review, techniques, and perspective.

text: Reduced port laparoscopic surgery has been used increasingly. It is a concept that has grown out of the various efforts aimed at minimally invasive surgery, with SILS being the ultimate reduced port technique. Reduced port laparoscopic surgery has been used to perform sleeve gastrectomy in bariatric surgery and excision of benign gastric submucosal tumor, applications that generally do not require lymph node dissection or complicated reconstruction. It can be done safely, result in a permanent cure, and offer good cosmetic outcomes. Reduced port laparoscopic surgery for gastric cancer has a short history, and its usefulness has not yet been fully established. This review describes the present situation and challenges faced as well as standardized procedures and the future prospects of reduced port laparoscopic gastrectomy for gastric cancer, which my team performs almost daily. These aspects of reduced port laparoscopic surgery are presented in light of the literature.


title: Severe acute respiratory syndrome: 11 years later--a radiology perspective.

text: OBJECTIVE Severe acute respiratory syndrome (SARS) was a highly virulent atypical pneumonia caused by a novel coronavirus that resulted in a pandemic in 2003. Singapore was one of the most severely affected countries, and SARS took a heavy toll on our health care system. The lessons learned during the pandemic have shaped our national contagion response plan and have proved valuable in subsequent epidemics. We describe the lessons learned for the radiology department. CONCLUSION Our experience with SARS has shaped and changed our daily practice of radiology.


title: An implantable wireless biosensor for the immediate detection of upper GI bleeding: a new fluorescein-based tool for diagnosis and surveillance (with video).

text: BACKGROUND Early recurrent hemorrhage after endoscopic intervention for acute upper GI bleeding (UGIB) can approach 20% and leads to increased morbidity and mortality. Little has changed over the past several decades regarding immediate posthemorrhage surveillance, and there has likewise been no significant improvement in outcomes. OBJECTIVE To develop and test an endoscopically implantable wireless biosensor for real-time detection of fluorescein-labeled blood in ex vivo and in vivo porcine models of UGIB. SETTING Animal laboratory. DESIGN Benchtop and acute animal studies. SUBJECTS Five pigs. INTERVENTIONS UGIB models were surgically created in living pigs. Biosensors were endoscopically deployed in the stomach using standard endoscopic clips. The ability to detect acute UGIB and estimated blood loss leading to biosensor activation were recorded. Feasibility of wireless data transmission out of the body to an external computer and cell phone was assessed. MAIN OUTCOME MEASUREMENTS Technical feasibility and immediate complications. RESULTS A porcine UGIB model was successfully created. Biosensors were able to detect all acute bleeding events and wirelessly transmit out of the body, and successfully sent an emergency text message to the intended cell phone in all cases. Average estimated blood loss leading to biosensor activation was 30 mL (10-75 mL). LIMITATIONS Animal study; small numbers. CONCLUSIONS An endoscopically implantable wireless biosensor successfully detected acute hemorrhage in a porcine UGIB model and sent an emergency cell-phone alert in real time.


title: Spot urine samples to estimate 24-hour urinary calcium excretion in school-age children.

text: Urinary calcium/creatinine ratio (UCa/Cr) on a single spot urine sample is frequently used in children to evaluate calciuria, but its accuracy to estimate 24-h urinary calcium excretion (24hUCa) has not been properly assessed. We analyzed the correlation between UCa/Cr in various spot samples and 24hUCa among healthy children. A 24-h urine specimen and three spot urine samples (evening, first, and second morning) were collected in a convenience sample of children aged 6 to 16 years (n = 101). Measured 24hUCa was compared with UCa/Cr in each of the three spot samples. The ability of UCa/Cr to discriminate between children with and without hypercalciuria (calciuria > 4 mg/kg/24 h, 1 mmol/kg/24 h) and optimal timing of the spot sample were determined. Eighty-five children completed an adequate 24-h urine collection. Pearson correlation coefficients between the UCa/Cr on the spot sample and 24hUCa were 0.64, 0.71, and 0.52 for the evening, first, and second morning spot samples, respectively. Areas under the ROC curve were 0.90, 0.82, and 0.75, respectively, for the corresponding spot samples.Conclusion: The relatively strong correlation between 24hUCa and UCa/Cr in evening and first morning spot urine samples suggests that these spots could be preferred in clinical practice.Trial registration:ClinicalTrials.gov, NCT02900261, date of trial registration 14 September 2016.What is Known:•Urinary calcium/creatinine ratio on a single spot urine sample is frequently used as a proxy for 24-h urinary calcium excretion.•Correlation of these indicators, including the best timing for spot urine sampling, has not been properly assessed.What is New:•Relatively strong correlations were found between the calcium/creatinine ratio on a single spot urine sample and 24-h urinary calcium excretion in healthy children.•Evening and first morning spot samples had the highest correlation.


title: Novel "glove" access port for single port surgery in right hemicolectomy: a pilot study.

text: The trend of single port surgery is increasing recently, and it is technically feasible for right hemicolectomy. However, the operation requires special and expensive access port for the insertion of the instruments. Day et al reported the use of a novel "glove" access port for right hemicolectomy in this pilot study. Four single port right hemicolectomies were performed by using this access port. The access port was found to be user-friendly and durable. No adverse outcome was associated with this access port. This "glove" access port is a suitable device for single port right hemicolectomy.


title: Validation of SARS-CoV-2 detection across multiple specimen types.

text: Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused considerable disruption across the world, resulting in more than 235,000 deaths since December 2019. SARS-CoV-2 has a wide tropism and detection of the virus has been described in multiple specimen types, including various respiratory secretions, cerebrospinal fluid, and stool. Objective To evaluate the accuracy and sensitivity of a laboratory modified CDCbased SARS-CoV-2 N1 and N2 assay across a range of sample types. Study Design We compared the matrix effect on the analytical sensitivity of SARS-CoV-2 detection by qRT-PCR in nasal swabs collected in viral transport medium (VTM), bronchoalveolar lavage (BAL), sputum, plasma, cerebral spinal fluid (CSF), stool, VTM, phosphate buffered saline (PBS), and Hanks' Balanced Salt Solution (HBSS). Initial limits of detection (LoD) were subsequently narrowed to confirm an LoD for each specimen type and target gene. Results LoDs were established using a modified CDC-based laboratory developed test and ranged from a mean CT cut-off of 33.8-35.7 (10-20 copies/reaction) for the N1 gene target, and 34.0-36.2 (1-10 copies/reaction) for N2. Alternatives to VTM such as PBS and HBSS had comparable LoDs. The N2 gene target was found to be most sensitive in CSF. Conclusion A modified CDC-based laboratory developed test is able to detect SARSCoV- 2 accurately with similar sensitivity across all sample types tested.


Belgium - concerns about coronavirus contact-tracing apps.


title: Anastomosis during robot-assisted radical prostatectomy: randomized controlled trial comparing barbed and standard monofilament suture.

text: OBJECTIVE To compare perioperative and functional outcomes after urethrovesical anastomosis (UVA) with barbed polyglyconate and monofilament poliglecaprone in robot-assisted radical prostatectomy (RARP). Barbed polyglyconate suture was first used for the UVA during RARP beginning in January 2010; safety and feasibility were previously demonstrated in 51 patients. METHODS From May to September 2010, 64 patients meeting all the inclusion criteria participated in the present multisurgeon prospective, randomized, controlled trial and underwent posterior repair and UVA during RARP with either barbed polyglyconate (n=33) or monofilament poliglecaprone (n=31) suture. The primary outcomes were the anastomotic (UVA) and posterior reconstruction times. Secondary outcomes included cystogram leak, bladder neck reconstruction rate, and 6-week functional outcomes assessed by a self-administered validated patient questionnaire. RESULTS Posterior reconstruction was performed within 3.3 minutes with the barbed suture versus 4.3 minutes with the monofilament poliglecaprone suture (23.3% reduction) and UVA within 10.1 versus 13.8 minutes, respectively (26.8% reduction). The absolute time difference for the 2-layer anastomosis was 4.7 minutes (a 26.0% reduction in the total anastomosis time). All other perioperative outcomes were equivalent between the 2 groups. Urinary functional outcomes, including the pad use and leakage rates, were equivalent at 6 weeks. CONCLUSION Anastomosis during RARP with the V-Loc barbed suture can be performed safely and more efficiently than with standard monofilament suture. We demonstrated a 26% decrease in the anastomotic time with no increase in the adverse events, no instances of urinary retention and equivalent functional outcomes were measured with the self-administered patient questionnaire.


title: Using information theory to optimise epidemic models for real-time prediction and estimation.

text: The effective reproduction number, Rt, is a key time-varying prognostic for the growth rate of any infectious disease epidemic. Significant changes in Rt can forewarn about new transmissions within a population or predict the efficacy of interventions. Inferring Rt reliably and in real-time from observed time-series of infected (demographic) data is an important problem in population dynamics. The renewal or branching process model is a popular solution that has been applied to Ebola and Zika virus disease outbreaks, among others, and is currently being used to investigate the ongoing COVID-19 pandemic. This model estimates Rt using a heuristically chosen piecewise function. While this facilitates real-time detection of statistically significant Rt changes, inference is highly sensitive to the function choice. Improperly chosen piecewise models might ignore meaningful changes or over-interpret noise-induced ones, yet produce visually reasonable estimates. No principled piecewise selection scheme exists. We develop a practical yet rigorous scheme using the accumulated prediction error (APE) metric from information theory, which deems the model capable of describing the observed data using the fewest bits as most justified. We derive exact posterior prediction distributions for infected population size and integrate these within an APE framework to obtain an exact and reliable method for identifying the piecewise function best supported by available epidemic data. We find that this choice optimises short-term prediction accuracy and can rapidly detect salient fluctuations in Rt, and hence the infected population growth rate, in real-time over the course of an unfolding epidemic. Moreover, we emphasise the need for formal selection by exposing how common heuristic choices, which seem sensible, can be misleading. Our APE-based method is easily computed and broadly applicable to statistically similar models found in phylogenetics and macroevolution, for example. Our results explore the relationships among estimate precision, forecast reliability and model complexity.


title: Protein refolding using chemical refolding additives.

text: In laboratories and manufacturing settings, a rapid and inexpensive method for the preparation of a target protein is crucial for promoting resesrach in protein science and engineering. Inclusion-body-based protein production is a promising method because high yields are achieved in the upstream process, although the refolding of solubilized, unfolded proteins in downstream processes often leads to significantly lower yields. The most challenging problem is that the effective condition for refolding is protein dependent and is therefore difficult to select in a rational manner. Accordingly, considerable time and expense using trial-and-error approaches are often needed to increase the final protein yield. Furthermore, for certain target proteins, finding suitable conditions to achieve an adequate yield cannot be obtained by existing methods. Therefore, to convert such a troublesome refolding process into a routine one, a wide array of methods based on novel technologies and materials have been developed. These methods select refolding conditions where productive refolding dominates over unproductive aggregation in competitive refolding reactions. This review focuses on synthetic refolding additives and describes the concepts underlying the development of reported chemical additives or chemical-additive-based methods that contribute to the emergence of a universal refolding method.


Potential mechanisms by which the oxygen-ozone (O2-O3) therapy could contribute to the treatment against the coronavirus COVID-19.


title: Comparison of Abbott ID Now, Diasorin Simplexa, and CDC FDA EUA methods for the detection of SARS-CoV-2 from nasopharyngeal and nasal swabs from individuals diagnosed with COVID-19.

text: Dozens of in vitro diagnostics (IVDs) have received emergency use authorization (EUA) from the U.S. Food & Drug Administration (FDA) for the detection of SARS-CoV-2, but little has been studied to determine how well these assays perform using clinical specimens.….


Silver Linings: An Opportunity to Improve Clinical Paradigms After the COVID-19 Pandemic.


title: Could interferon-gamma be a therapeutic target for treating heart failure?

text: The cytokine interferon-gamma (IFN-γ) is the only known member of the type II family of interferons, and as such, binds to its own distinct receptor. It is important in host defense against infection, as well as adaptive immune responses. While a wide array of cytokines are known to be involved in adverse remodeling of the heart and the progression to heart failure, the role of IFN-γ is unclear. Recent evidence from clinical studies, animal models of myocarditis and hypertension, as well as isolated cell studies, provide conflicting data as to whether IFN-γ is pathological or protective in the heart. Thus, it is important to highlight these discrepant findings so that areas of future investigation can be identified to more clearly determine the precise role of IFN-γ in the heart. Accordingly, this review will (1) discuss the source of IFN-γ in the diseased heart; (2) summarize the data from animal studies; (3) discuss the effects of IFN-γ on isolated cardiac fibroblasts and cardiomyocytes; (4) identify signaling mechanisms that may be invoked by IFN-γ in the heart; and (5) present the clinical evidence supporting a role for IFN-γ in heart failure.


title: Isolation of an infectious endogenous retrovirus in a proportion of live attenuated vaccines for pets.

text: The genomes of all animal species are colonized by endogenous retroviruses (ERVs). Although most ERVs have accumulated defects that render them incapable of replication, fully infectious ERVs have been identified in various mammals. In this study, we isolated a feline infectious ERV (RD-114) in a proportion of live attenuated vaccines for pets. Isolation of RD-114 was made in two independent laboratories using different detection strategies and using vaccines for both cats and dogs commercially available in Japan or the United Kingdom. This study shows that the methods currently employed to screen veterinary vaccines for retroviruses should be reevaluated.


title: Superior vena cava syndrome: role of the interventionalist.

text: Superior vena cava syndrome results from the obstruction of blood flow through the superior vena cava and is most often due to thoracic malignancy. However, benign etiologies are on the rise secondary to more frequent use of intravascular devices such as central venous catheters and pacemakers. Although rarely a medical emergency, the symptoms can be alarming, particularly to the patient. Traditionally, superior vena cava syndrome has been managed with radiotherapy and chemotherapy. But interventional endovascular techniques have made inroads that offer a safe, rapid, and durable response. In many cases, it may be the only reasonable treatment. Because of this, an approach to endovascular treatment of this condition must be in the armamentarium of the interventional radiologist. This review will provide the reader with an insight into the etiology, pathophysiology, and various management principles of superior vena cava syndrome. The focus will be on understanding the techniques used during various endovascular interventions, including angioplasty, stenting, and pharmacomechanical thrombolysis. Discussion will also be centred on possible complications and current evidence as well as controversies regarding these approaches.


title: Laparoscopic gastrectomy with D2 lymphadenectomy for gastric cancer: initial Egyptian experience at the National Cancer Institute.

text: BACKGROUND Laparoscopic gastrectomy has been used as a superior alternative to open gastrectomy for the treatment of early gastric cancer. However, the application of laparoscopic D2 lymphadenectomy remains controversial. This study aimed to evaluate the feasibility and outcomes of laparoscopic gastrectomy with D2 lymphadenectomy for gastric cancer. RESULTS Between May 2016 and May 2018, twenty-five consecutive patients with gastric cancer underwent laparoscopic D2 gastrectomy: eighteen patients (72%) underwent distal gastrectomy, four patients (16%) underwent total gastrectomy, and three patients (12%) underwent proximal gastrectomy. The median number of lymph nodes retrieved was 18 (5-35). A positive proximal margin was detected in 2 patients (8%). The median operative time and amount of blood loss were 240 min (200-330) and 250 ml (200-450), respectively. Conversion to an open procedure was performed in seven patients (28%). The median hospital stay period was 8 days (6-30), and the median time to start oral fluids was 4 days (3-30). Postoperative complications were detected in 4 patients (16%). There were two cases of mortality (8%) in the postoperative period, and two patients required reoperation (8%). CONCLUSIONS Laparoscopic gastrectomy with D2 lymphadenectomy can be carried out safely and in accordance with oncologic principles.


Guidelines for laparoscopic peritoneal dialysis access surgery.


title: Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallel-group, non-inferiority trial.

text: BACKGROUND The Solitaire Flow Restoration Device is a novel, self-expanding stent retriever designed to yield rapid flow restoration in acute cerebral ischaemia. We compared the efficacy and safety of Solitaire with the standard, predicate mechanical thrombectomy device, the Merci Retrieval System. METHODS In this randomised, parallel-group, non-inferiority trial, we enrolled patients from 18 sites (17 in the USA and one in France). Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset. We used a computer-generated randomisation sequence to randomly allocate patients to receive thrombectomy treatment with either Solitaire or Merci (1:1; block sizes of four and stratified by centre and stroke severity). The primary endpoint was Thrombolysis In Myocardial Ischemia (TIMI) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage, after up to three passes of the assigned device, as assessed by an independent core laboratory, which was masked to study assignment. Primary analysis was done by intention to treat. A prespecified efficacy stopping rule triggered an early halt to the trial. The study is registered with ClinicalTrials.gov, number NCT 01054560. RESULTS Between February, 2010, and February, 2011, we randomly allocated 58 patients to the Solitaire group and 55 patients to the Merci group. The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group (61%vs 24%; difference 37% [95% CI 19-53], odds ratio [OR] 4·87 [95% CI 2·14-11·10]; p(non-inferiority)<0·0001, p(superiority)=0·0001). More patients had good 3-month neurological outcome with Solitaire than with Merci (58%vs 33%; difference 25% [6-43], OR 2·78 [1·25-6·22]; p(non-inferiority)=0·0001, p(superiority)=0·02). 90-day mortality was lower in the Solitaire group than it was in the Merci group (17 vs 38; difference -21% [-39 to -3], OR 0·34 [0·14-0·81]; p(non-inferiority)=0·0001, p(superiority)=0·02). INTERPRETATION The Solitaire Flow Restoration Device achieved substantially better angiographic, safety, and clinical outcomes than did the Merci Retrieval System. The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke. FUNDING Covidien/ev3.


title: Efficacy and safety of a vessel sealing system in oral cancer resection and reconstructive surgery.

text: OBJECTIVE Currently, many studies are being performed that focus on the efficacy and safety of the vessel sealing system (VSS) in various fields of surgery. However, in the field of oral cancer surgery, the efficacy and safety of VSS use have not been clarified. METHODS One hundred and fifty-one patients underwent oral cancer resection and reconstructive surgery. They were divided into two groups: Ligasure vessel sealing system (LVSS) group and conventional surgery (CS) as control. Intra-operative blood loss, operating time, and incidence of post-operative complications and recurrence were analyzed. RESULTS LVSS use significantly reduced intra-operative blood loss. The operating time was shortened only in mandibular gingiva cancer surgery. There were no differences between the two groups with regard to the incidence of post-operative complications and recurrence. CONCLUSIONS LVSS use was found to be effective and proved to be efficient and safe, and may be useful in oral cancer surgery.


title: Evaluating the Commercial Airliner Cabin Environment with Different Air Distribution Systems.

text: Ventilation systems for commercial airliner cabins are important in reducing contaminant transport and maintaining thermal comfort. To evaluate the performance of a personalized displacement ventilation system, a conventional displacement ventilation system, and a mixing ventilation system, this study first used the Wells-Riley equation integrated with CFD to obtain the SARS quanta value based on a specific SARS outbreak on a flight. This investigation then compared the three ventilation systems in a seven-row section of a fully occupied, economy-class cabin in Boeing 737 and Boeing 767 airplanes. The SARS quanta generation rate obtained for the index patient could be used in future studies. For all the assumed source locations, the passengers' infection risk by air in the two planes was the highest with the mixing ventilation system, while the conventional displacement ventilation system produced the lowest risk. The personalized ventilation system performed the best in maintaining cabin thermal comfort and can also reduce the infection risk. This system is recommended for airplane cabins. This article is protected by copyright. All rights reserved.


title: Perioperative Considerations During Emergency General Surgery in the Era of COVID-19: A U.S. Experience.

text: The novel coronavirus SARS-CoV-2 (COVID-19) strain has caused a pandemic that affects everyday clinical practice. Care of patients with acute surgical problems is adjusted to minimize exposing health care providers to this highly contagious virus. Our goal is to describe a specific and reproducible perioperative protocol aiming to keep health care providers safe and, simultaneously, not compromise standard of care for surgical patients.


title: Cure or curse? Ambivalent attitudes towards neuroleptic medication in schizophrenia and non-schizophrenia patients.

text: Neuroleptic non-compliance remains a serious challenge for the treatment of psychosis. Non-compliance is predominantly attributed to side effects, lack of illness insight, reduced well-being or poor therapeutic alliance. However, other still neglected factors may also play a role. Further, little is known about whether psychiatric patients without psychosis who are increasingly prescribed neuroleptics differ in terms of medication compliance or about reasons for non-compliance by psychosis patients. As direct questioning is notoriously prone to social desirability biases, we conducted an anonymous survey. After a strict selection process blind to results, 95 psychiatric patients were retained for the final analyses (69 participants with a presumed diagnosis of schizophrenia psychosis, 26 without psychosis). Self-reported neuroleptic non-compliance was more prevalent in psychosis patients than non-psychosis patients. Apart from side effects and illness insight, main reasons for non-compliance in both groups were forgetfulness, distrust in therapist, and no subjective need for treatment. Other notable reasons were stigma and advice of relatives/acquaintances against neuroleptic medication. Gain from illness was a reason for non-compliance in 11-18% of the psychosis patients. Only 9% of all patients reported no side effects and full compliance and at the same time acknowledged that neuroleptics worked well for them. While pills were preferred over depot injections by the majority of patients, depot was judged as an alternative by a substantial subgroup. Although many patients acknowledge the need and benefits of neuroleptic medication, non-compliance was the norm rather than the exception in our samples.


title: The Effects of Social Media Use on Preventive Behaviors during Infectious Disease Outbreaks: The Mediating Role of Self-relevant Emotions and Public Risk Perception.

text: While there has been increasing attention to the role of social media during infectious disease outbreaks, relatively little is known about the underlying mechanisms by which social media use affects risk perception and preventive behaviors during such outbreaks. Using data collected during the 2015 Middle East Respiratory Syndrome coronavirus (MERS-CoV) outbreak in South Korea, this study explores the relationships among social media use, risk perception, and preventive behaviors by examining the mediating role of two self-relevant emotions: fear and anger. The findings demonstrate that social media use is positively related to both of these emotions, which are also positively related to the public's risk perception. The findings also indicate that social media use can significantly increase preventive behaviors via the two self-relevant emotions and the public's risk perception.


Benefits, Open questions and Challenges of the use of Ultrasound in the COVID-19 pandemic era. The views of a panel of worldwide international experts.


title: Screening strategies for hypertension.

text: BACKGROUND Hypertension is a major public health challenge affecting more than one billion people worldwide; it disproportionately affects populations in low- and middle-income countries (LMICs), where health systems are generally weak. The increasing prevalence of hypertension is associated with population growth, ageing, genetic factors, and behavioural risk factors, such as excessive salt and fat consumption, physical inactivity, being overweight and obese, harmful alcohol consumption, and poor management of stress. Over the long term, hypertension leads to risk for cardiovascular events, such as heart disease, stroke, kidney failure, disability, and premature mortality. Cardiovascular events can be preventable when high-risk populations are targeted, for example, through population-wide screening strategies. When available resources are limited, taking a total risk approach whereby several risk factors of hypertension are taken into consideration (e.g. age, gender, lifestyle factors, diabetes, blood cholesterol) can enable more accurate targeting of high-risk groups. Targeting of high-risk groups can help reduce costs in that resources are not spent on the entire population. Early detection in the form of screening for hypertension (and associated risk factors) can help identify high-risk groups, which can result in timely treatment and management of risk factors. Ultimately, early detection can help reduce morbidity and mortality linked to it and can help contain health-related costs, for example, those associated with hospitalisation due to severe illness and poorly managed risk factors and comorbidities. OBJECTIVES To assess the effectiveness of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce morbidity and mortality associated with hypertension. SEARCH METHODS An Information Specialist searched the Cochrane Register of Studies (CRS-Web), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS) Bireme, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) without language, publication year, or publication status restrictions. The searches were conducted from inception until 9 April 2020. SELECTION CRITERIA Randomised controlled trials (RCTs) and non-RCTs (NRCTs), that is, controlled before and after (CBA), interrupted time series (ITS), and prospective analytic cohort studies of healthy adolescents, adults, and elderly people participating in mass, targeted, or opportunistic screening of hypertension. DATA COLLECTION AND ANALYSIS Screening of all retrieved studies was done in Covidence. A team of reviewers, in pairs, independently assessed titles and abstracts of identified studies and acquired full texts for studies that were potentially eligible. Studies were deemed to be eligible for full-text screening if two review authors agreed, or if consensus was reached through discussion with a third review author. It was planned that at least two review authors would independently extract data from included studies, assess risk of bias using pre-specified Cochrane criteria, and conduct a meta-analysis of sufficiently similar studies or present a narrative synthesis of the results. MAIN RESULTS We screened 9335 titles and abstracts. We identified 54 potentially eligible studies for full-text screening. However, no studies met the eligibility criteria. AUTHORS' CONCLUSIONS There is an implicit assumption that early detection of hypertension through screening can reduce the burden of morbidity and mortality, but this assumption has not been tested in rigorous research studies. High-quality evidence from RCTs or programmatic evidence from NRCTs on the effectiveness and costs or harms of different screening strategies for hypertension (mass, targeted, or opportunistic) to reduce hypertension-related morbidity and mortality is lacking.


title: Call for a bigger vision.

text: Science in Canada cannot realize its full potential without clear direction from government.


title: Identification and management of cardiometabolic risk in Canada: a position paper by the cardiometabolic risk working group (executive summary).

text: With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations.


title: Robotic-assisted laparoscopic myomectomy: the feasibility in single-site system.

text: Objective To evaluate the feasibility of robotic single-site myomectomy (RSSM). Methods Medical records of 355 consecutive women who underwent robotic-assisted laparoscopic myomectomy were retrospectively reviewed. Clinical characteristics were compared between multi-site and single-site systems. After 1:1 propensity score matching for the total myoma number, largest myoma size, and total tumor weight (105 women in each group), surgical outcomes were also compared between the 2 systems. Results A total of 105 (29.6%) and 250 (70.4%) women underwent RSSM and robotic multi-site myomectomy (RMSM), respectively. RSSM was more commonly performed in women with lower body mass index (21.6 vs. 22.5 kg/m2, P=0.014), without peritoneal adhesions (7.6% vs. 24.8%, P<0.001), and less (2.6 vs. 4.6, P<0.001) and smaller (6.3 vs. 7.7 cm, P<0.001) myomas compared to RMSM. After propensity score matching, the largest myoma size (P=0.143), total myoma number (P=0.671), and tumor weight (P=0.510) were not significantly different between the 2 groups. Although the docking time was significantly longer in the RSSM group (5.1 vs. 3.8 minutes, P=0.005), total operation time was similar between RSSM and RMSM groups (145.9 vs. 147.3 minutes, P=0.856). Additionally, hemoglobin decrement was lower in the RSSM group than in the RMSM group (1.4 vs. 1.8 g/dL, P=0.009). No surgical complication was observed after RSSM, while 1 ileus and 2 febrile complications occurred in women that underwent RMSM (0% vs. 2.9%, P=0.246). Conclusion Although RMSM is preferred for women with multiple large myomas in real clinical practice, RSSM seems to be a feasible surgical method for less complicated cases, and is associated with minimal surgical morbidity.


title: Improved arterial blood oxygenation following intravenous infusion of cold supersaturated dissolved oxygen solution.

text: BACKGROUND One of the primary goals of critical care medicine is to support adequate gas exchange without iatrogenic sequelae. An emerging method of delivering supplemental oxygen is intravenously rather than via the traditional inhalation route. The objective of this study was to evaluate the gas-exchange effects of infusing cold intravenous (IV) fluids containing very high partial pressures of dissolved oxygen (>760 mm Hg) in a porcine model. METHODS Juvenile swines were anesthetized and mechanically ventilated. Each animal received an infusion of cold (13 °C) Ringer's lactate solution (30 mL/kg/hour), which had been supersaturated with dissolved oxygen gas (39.7 mg/L dissolved oxygen, 992 mm Hg, 30.5 mL/L). Arterial blood gases and physiologic measurements were repeated at 15-minute intervals during a 60-minute IV infusion of the supersaturated dissolved oxygen solution. Each animal served as its own control. RESULTS Five swines (12.9 ± 0.9 kg) were studied. Following the 60-minute infusion, there were significant increases in PaO2 and SaO2 (P < 0.05) and a significant decrease in PaCO2 (P < 0.05), with a corresponding normalization in arterial blood pH. Additionally, there was a significant decrease in core body temperature (P < 0.05) when compared to the baseline preinfusion state. CONCLUSIONS A cold, supersaturated dissolved oxygen solution may be intravenously administered to improve arterial blood oxygenation and ventilation parameters and induce a mild therapeutic hypothermia in a porcine model.


title: Initial experience of single-port surgery assisted by percutaneous instruments for gastric bypass: a combination of safety and minimally invasive surgery.

text: BACKGROUND We present here the first reported cases of patients undergoing gastric bypass with a hybrid technique that involves a new concept of percutaneous instruments and provides the advantages of minimally invasive single-port surgery while maintaining the triangulation, safety, and timing of operative procedures. METHODS This was a prospective pilot study of eight patients selected for gastric bypass between December 2011 and January 2012 and treated by a technique that combined single SSL port and percutaneous surgical set PPS. We performed hand-sewn gastrojejunostomy in all cases. We analyzed preliminary results at 1 month and focused on the feasibility of the technique, duration of surgery, perioperative complications, and cosmetic results. The Ethics Committee of our institution approved this study and we obtained the informed consent of each patient. RESULTS We completed the procedure successfully in all patients. No conversions to laparotomy or classic laparoscopy were required. The average time of surgery was 112 min (85-155). Length of hospital stay was 4 days (3-5). One patient was re-admitted on the seventh postoperative day for gastrointestinal bleeding from the gastrojejunostomy suture and treated by endoscopic clipping. Residual scars were less than 2 cm for the single midline port and 2 mm for the percutaneous instruments. CONCLUSIONS This new technique combines the advantages of single-port surgery with the safety of conventional laparoscopy by using percutaneous instruments and leaves minimal scarring. It is likely that the use of percutaneous instrumentation will become widespread in all areas of laparoscopic surgery.


title: A novel technique to retrieve a maldeployed vascular closure device.

text: PURPOSE To report a novel technique for endovascular retrieval of a maldeployed vascular closure device, obviating the need for a femoral cutdown. TECHNIQUE To remove a 6-F Angio-Seal device that embolized to the superficial femoral artery, the contralateral common femoral artery was accessed, and an 8-F, 65-cm-long sheath was inserted just proximal to the embolus. A second semistiff 0.035-inch buddy wire was advanced past the lesion along the sheath. A 0.014-inch wire was advanced past the embolus, and a SpiderFX embolic protection device was deployed 1 cm past the embolized Angio-Seal device. The sheath was advanced so as to push the embolus into the filter. The sheath and the filter containing the Angio-Seal device were then removed. CONCLUSION Endovascular retrieval of an embolized Angio-Seal device can be done using an embolic filter device, restoring arterial flow to the limb.


Nepalese Medical Students in the COVID-19 Pandemic: Ways Forward.


title: Fate of Environmental Pollutants.

text: This annual review covers the literature published in 2017 on topics related to the occurrence and fate of emerging environmental pollutants in wastewater. Due to the vast amount of literature published on this topic, we have discussed only a portion of the quality research publications, due to the limitation of space. The abstract search was carried out using Web of Science, and the abstracts were selected based on their relevance. In few cases, full-text articles were referred to better understand new findings. This review is divided into the following sections: antibioticresistant bacteria (ARBs) and antibiotic-resistant genes (ARGs), disinfection by-products (DBPs), estrogens, pesticides, pharmaceuticals and personal care products (PPCPs), and microplastics, a new section added this year.


title: Guidance for management of cancer surgery during the COVID-19 pandemic.

text: Summary During the coronavirus disease 2019 (COVID-19) pandemic, delaying lifesaving cancer surgeries must be done with extreme caution and thoughtfulness. Modelling indicates that delays in high-risk cancer surgeries beyond 6 weeks could affect long-term outcomes for thousands of Canadians. Consequently, it is possible that postponing cancer surgery without consideration of its implications could cost more lives than can be saved by diverting all surgical resources to COVID-19. This article provides general guidance on supporting curative surgical treatment where appropriate and with available resources.


Industry shows increased appetite for macrophage biology.


title: Targeted benefits of prolonged-infusion piperacillin-tazobactam in an in vitro infection model of Pseudomonas aeruginosa.

text: Given the inconsistent clinical findings, our goal was to characterize the pharmacodynamics (PDs) of prolonged-infusion piperacillin-tazobactam (TZP) in an in vitro pharmacodynamic model of Pseudomonas aeruginosa. Specifically, the study was designed to investigate the influence of MIC on the activity of prolonged-infusion TZP using pharmacokinetics (PKs) consistent with a non-critically ill patient population. There was no benefit with prolonged- compared with standard-infusion TZP against isolates with susceptible MICs of 8 or 16 mg/L. However, prolonged-infusion TZP produced more than two times the final bacterial kill against less susceptible isolates with an intermediate MIC of 32 mg/L. The PDs of TZP were well described by a sigmoid Emax model (r(2) = 0.84) where %ƒT>MIC thresholds of 27 and 75% were associated with bacteriostatic and bactericidal effects, respectively. However, the well-established PD relationship with %ƒT>MIC was not observed with prolonged-infusion TZP. In conclusion, this study characterizes the targeted benefits of prolong-infusion TZP based on pathogen MIC, and supports the assertion that the benefits are selective and most likely observed in patients with less susceptible pathogens or altered PKs.


Guidelines for privileging, credentialing, and proctoring to perform GI endoscopy.


Proposed protocol to keep COVID-19 out of hospitals.


title: Antibiotic prophylaxis for prevention of urinary tract infections in the first year of life in children with vesicoureteral reflux diagnosed in the workup of antenatal hydronephrosis: a systematic review.

text: BACKGROUND Children with antenatal hydronephrosis (ANH) diagnosed with postnatal asymptomatic vesicoureteral reflux (VUR) are thought to be at higher risk of urinary tract infection (UTI). As such, continuous antibiotic prophylaxis (CAP) is empirically recommended until age of toilet training; however, there are limited data to support this. The objective of this systematic review was to summarize the existing data and compare UTI rates in infants with asymptomatic VUR on CAP during the first year of life, to those not on CAP. Secondary objectives were to determine associated risk factors with UTI development. METHODS A systematic search of all relevant studies and abstracts was conducted using 4 electronic databases by utilizing appropriate key words by an expert hospital librarian. Eligible studies included children with prenatal hydronephrosis, asymptomatic VUR with or without CAP, and reported on development of UTI in the first year. RESULTS Of 6903 citations screened, 18 were selected, giving a total population of 829 (69.4% male, median age 57 days) who met the inclusion criteria. Most studies were retrospective and of low-quality evidence. Overall, 15.4% of patients developed at least one breakthrough UTI and females had a higher risk of UTI (odds ratio (OR) 2.3, 95% CI 1.1-4.7). Comparison with children not taking CAP was not readily reported, and meta-analysis could not be completed. CONCLUSIONS Randomized controlled trials and standardized reporting of clinical variables are required to understand the protective effect of antibiotic prophylaxis in this cohort.


title: Simultaneous Prediction of New Morbidity, Mortality, and Survival Without New Morbidity From Pediatric Intensive Care: A New Paradigm for Outcomes Assessment.

text: OBJECTIVES Assessments of care including quality assessments adjusted for physiological status should include the development of new morbidities as well as mortalities. We hypothesized that morbidity, like mortality, is associated with physiological dysfunction and could be predicted simultaneously with mortality. DESIGN Prospective cohort study from December 4, 2011, to April 7, 2013. SETTING General and cardiac/cardiovascular PICUs at seven sites. PATIENTS Randomly selected PICU patients from their first PICU admission. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Among 10,078 admissions, the unadjusted morbidity rates (measured with the Functional Status Scale and defined as an increase of ≥ 3 from preillness to hospital discharge) were 4.6% (site range, 2.6-7.7%) and unadjusted mortality rates were 2.7% (site range, 1.3-5.0%). Morbidity and mortality were significantly (p < 0.001) associated with physiological instability (measured with the Pediatric Risk of Mortality III score) in dichotomous (survival and death) and trichotomous (survival without new morbidity, survival with new morbidity, and death) models without covariate adjustments. Morbidity risk increased with increasing Pediatric Risk of Mortality III scores and then decreased at the highest Pediatric Risk of Mortality III values as potential morbidities became mortalities. The trichotomous model with covariate adjustments included age, admission source, diagnostic factors, baseline Functional Status Scale, and the Pediatric Risk of Mortality III score. The three-level goodness-of-fit test indicated satisfactory performance for the derivation and validation sets (p > 0.20). Predictive ability assessed with the volume under the surface was 0.50 ± 0.019 (derivation) and 0.50 ± 0.034 (validation) (vs chance performance = 0.17). Site-level standardized morbidity ratios were more variable than standardized mortality ratios. CONCLUSIONS New morbidities were associated with physiological status and can be modeled simultaneously with mortality. Trichotomous outcome models including both morbidity and mortality based on physiological status are suitable for research studies and quality and other outcome assessments. This approach may be applicable to other assessments presently based only on mortality.


title: Increased diaphragmatic contribution to inspiratory effort during neurally adjusted ventilatory assistance versus pressure support: an electromyographic study.

text: BACKGROUND Neurally adjusted ventilatory assist (NAVA), regulated exclusively by the electromyographic activity (EA) of the diaphragm (EAdi), could affect the distribution of neural drive to the various inspiratory muscles. The objective of this study was to compare EAdi, EA of the scalene (EAscal), and EA of the alae nasi (EAan), according to the ventilatory mode and assist level in 12 mechanically ventilated patients. METHODS Seven assist levels of pressure support ventilation (PSV) and NAVA were sequentially applied. EAdi, EAscal, and EAan were quantified and expressed as a percentage of their maximum values. The relative contributions of extradiaphragmatic muscles to inspiratory efforts were assessed by calculating EAscal/EAdi and EAan/EAdi ratios. Three assist levels for each of the two ventilatory modes that resulted in EAdi values of 80 to 100%, 60 to 80%, and 40 to 60% were assigned to three groups (N1, N2, and N3). Results are expressed as median and interquartile range. RESULTS EA of inspiratory muscles decreased during PSV and NAVA (P < 0.0001). Although EAdi remained constant within groups (P = 0.9), EAscal was reduced during NAVA compared with PSV in N1 and N3 (65% [62 to 64] and 27% [18 to 34] in NAVA vs. 90% [81 to 100] and 49% [40 to 55] in PSV, P = 0.007). Altogether, EAscal/EAdi and EAan/EAdi ratios were lower in NAVA than PSV (0.7 [0.6 to 0.7] and 0.7 [0.6 to 0.8] in NAVA vs. 0.9 [0.8 to 1.1] and 0.9 [0.7 to 1.1] in PSV, P < 0.05). CONCLUSIONS NAVA and PSV both reduced extradiaphragmatic inspiratory muscle activity, in proportion to the level of assistance. Compared with PSV, NAVA resulted in a predominant contribution of the diaphragm to inspiratory effort.


Pectoralis block for breast surgery: A surgical concern?


Posterior Tracheal Laceration Treated with a Stent.


title: Post-consumer plastic packaging waste in England: Assessing the yield of multiple collection-recycling schemes.

text: The European Commission (EC) recently introduced a 'Circular Economy Package', setting ambitious recycling targets and identifying waste plastics as a priority sector where major improvements are necessary. Here, the authors explain how different collection modalities affect the quantity and quality of recycling, using recent empirical data on household (HH) post-consumer plastic packaging waste (PCPP) collected for recycling in the devolved administration of England over the quarterly period July-September 2014. Three main collection schemes, as currently implemented in England, were taken into account: (i) kerbside collection (KS), (ii) household waste recycling centres (HWRCs) (also known as 'civic amenity sites'), and (iii) bring sites/banks (BSs). The results indicated that: (a) the contribution of KS collection scheme in recovering packaging plastics is higher than HWRCs and BBs, with respective percentages by weight (wt%) 90%, 9% and 1%; (b) alternate weekly collection (AWC) of plastic recyclables in wheeled bins, when collected commingled, demonstrated higher yield in KS collection; (c) only a small percentage (16%) of the total amount of post-consumer plastics collected in the examined period (141 kt) was finally sent to reprocessors (22 kt); (c) nearly a third of Local Authorities (LAs) reported insufficient or poor data; and (d) the most abundant fractions of plastics that finally reached the reprocessors were mixed plastic bottles and mixed plastics.


Borrow crisis tactics to get COVID-19 supplies to where they are needed.


title: Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion imaging with CT fusion imaging in the assessment of treatment effect of radiofrequency ablation of hepatocellular carcinoma.

text: PURPOSE To assess the feasibility of fusion of pre- and post-ablation gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images PATIENTS AND METHODS This retrospective study included 67 patients with 92 HCCs treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The minimal ablative margin measured on fusion imaging was categorized into three groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin ≥5.0 mm beyond the tumor boundary. The categorization of minimal ablative margins was compared between CT and MR fusion images. RESULTS In 57 (62.0%) HCCs, treatment evaluation was possible both on CT and MR fusion images, and the overall agreement between them for the categorization of minimal ablative margin was good (κ coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92 [93.5%] vs. 62/92 [67.4%], P < 0.05). CONCLUSIONS Fusion of pre- and post-ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may enable accurate treatment evaluation in cases where CT fusion imaging is not helpful.


title: Immunopathology of SARS-CoV-2 Infection: Immune Cells and Mediators, Prognostic Factors, and Immune-Therapeutic Implications.

text: The present is a comprehensive review of the immunopathology of Covid-19. The immune reaction to SARS-CoV-2 infection is characterized by differentiation and proliferation of a variety of immune cells with immune mediator production and release, and activation of other pathogen resistance mechanisms. We fully address the humoral and cellular immune changes induced by the virus, with particular emphasis on the role of the "cytokine storm" in the evolution of the disease. Moreover, we also propose some immune alterations (i.e., inflammatory parameters, cytokines, leukocytes and lymphocyte subpopulations) as prognostic markers of the disease. Furthermore, we discuss how immune modifying drugs, such as tocilizumab, chloroquine, glucocorticoids and immunoglobulins, and blood purification therapy, can constitute a fundamental moment in the therapy of the infection. Finally, we made a critical analysis of a number of substances, not yet utilized, but potentially useful in SARS-CoV-2 patients, such as IFN lambda, TNF blockers, ulinastatin, siponimod, tacrolimus, mesenchymal stem cells, inhibitors of mononuclear macrophage recruitment, IL-1 family antagonists, JAK-2 or STAT-3 inhibitors.


Underpromise, overdeliver.