title: Viruses and autophagy.

text: Autophagy is an evolutionarily conserved intracellular process by which bulk cytoplasm is enveloped inside a double-membraned vesicle and shuttled to lysosomes for degradation. Within the last 15 years, the genes necessary for the execution of autophagy have been identified and the number of tools for studying this process has grown. Autophagy is essential for tissue homeostasis and development and defective autophagy is associated with a number of diseases. As intracellular parasites, during the course of an infection, viruses encounter autophagy and interact with the proteins that execute this process. Autophagy and/or autophagy genes likely play both anti-viral and pro-viral roles in the life cycles and pathogenesis of many different virus families. With respect to anti-viral roles, the autophagy proteins function in targeting viral components or virions for lysosomal degradation in a process termed xenophagy, and they also play a role in the initiation of innate and adaptive immune system responses to viral infections. Consistent with this anti-viral role of host autophagy, some viruses encode virulence factors that interact with the host autophagy machinery and block the execution of autophagy. In contrast, other viruses appear to utilise components of the autophagic machinery to foster their own intracellular growth or non-lytic cellular egress. As the details of the role (s) of autophagy in viral pathogenesis become clearer, new anti-viral therapies could be developed to inhibit the beneficial and enhance the destructive aspects of autophagy on the viral life cycle.


title: END-TIDAL-TO-ARTERIAL PCO2 RATIO AS SIGNIFIER FOR PHYSIOLOGIC DEAD-SPACE RATIO AND OXYGENATION DYSFUNCTION IN ACUTE RESPIRATORY DISTRESS SYNDROME.

text: BACKGROUND The ratio of end-tidal-to-arterial carbon dioxide tension (PETCO2/PaCO2) was recently suggested for monitoring pulmonary gas exchange in subjects with COVID-19 associated ARDS. Yet, no evidence was offered supporting that claim. Therefore, we evaluated whether PETCO2/PaCO2 might be relevant in assessing ARDS not associated with COVID-19. METHODS We evaluated the correspondence between PETCO2/PaCO2 and VD/VT measured in 561 subjects with ARDS from a previous study in whom PETCO2 data were also available. Subjects also were analyzed according to four categories representing increasing severity of PETCO2/PaCO2 (≥0.80, 0.61 to 0.79, 0.50-0.59 and < 0.50). Correlation was assessed by either Pearson Spearman tests, group comparisons were assessed using either ANOVA or Kruskal-Wallis tests, and dichotomous variables assessed by Fisher Exact test. Overall mortality risk was assessed by multivariate logistic regression. Alpha was set at 0.05. RESULTS PETCO2/PaCO2 correlated strongly with VD/VT (R = -0.87 [-0.89, -0.85] P < 0.001). Decreasing PETCO2/PaCO2 was associated with increased VD/VT and hospital mortality between all groups. In the univariate analysis for every 0.01 decrease in PETCO2/PaCO2 mortality risk increased by ∼1% (OR: 0.009 [0.003-0.029] P < 0.001), and maintained a strong independent association with mortality risk when adjusted for other variables: 0.19 (0.04-0.91) P = 0.039. PETCO2/PaCO2 < 0.50 was characterized both by very high VD/VT (0.82 ± 0.05, P < 0.001) and hospital mortality (70%). CONCLUSION PETCO2/PaCO2 as a surrogate for VD/VT may be a useful and practical measurement for both management and ongoing research into the nature of ARDS.


title: Respiratory viruses in HIV-infected patients with suspected respiratory opportunistic infection.

text: OBJECTIVE To assess the incidence and epidemiological pattern of respiratory viruses in HIV-infected patients and to evaluate their potential clinical impact. DESIGN AND METHODS A prospective population-based cohort study was conducted at three Swiss university hospitals. Study participants were HIV-infected patients who underwent a bronchoalveolar lavage to rule out an opportunistic event. All bronchoalveolar lavage specimens were screened using a set of real-time reverse transcriptase-polymerase chain reaction assays targeting 17 different respiratory viruses. RESULTS Between November 2003 and November 2006, 59 bronchoalveolar episodes from 55 HIV-infected patients were analysed. Eleven of 59 episodes (18.6%) were positive for at least one respiratory virus. Coronavirus OC43 was identified in three cases (27.3%) followed by influenza A in two (18.2%). Parainfluenza virus (PIV) 2, PIV 3, PIV 4, bocavirus, human rhinovirus A and human metapneumovirus were each identified in one case (9%). In the majority of these cases (63.6%) no other concomitant microorganism was isolated. CONCLUSIONS Clinical investigation of respiratory viral infections in HIV-infected patients should not be restricted to prototype viruses and also need to target all the different family of viruses as it seems likely that these viruses contribute to pulmonary complications and morbidity in this population.


title: Metabolic vs. hedonic obesity: a conceptual distinction and its clinical implications.

text: Body weight is determined via both metabolic and hedonic mechanisms. Metabolic regulation of body weight centres around the 'body weight set point', which is programmed by energy balance circuitry in the hypothalamus and other specific brain regions. The metabolic body weight set point has a genetic basis, but exposure to an obesogenic environment may elicit allostatic responses and upward drift of the set point, leading to a higher maintained body weight. However, an elevated steady-state body weight may also be achieved without an alteration of the metabolic set point, via sustained hedonic over-eating, which is governed by the reward system of the brain and can override homeostatic metabolic signals. While hedonic signals are potent influences in determining food intake, metabolic regulation involves the active control of both food intake and energy expenditure. When overweight is due to elevation of the metabolic set point ('metabolic obesity'), energy expenditure theoretically falls onto the standard energy-mass regression line. In contrast, when a steady-state weight is above the metabolic set point due to hedonic over-eating ('hedonic obesity'), a persistent compensatory increase in energy expenditure per unit metabolic mass may be demonstrable. Recognition of the two types of obesity may lead to more effective treatment and prevention of obesity.


title: Oesophageal perforation in a neonate during transoesophageal echocardiography for cardiac surgery.

text: Oesophageal perforation is a rarely reported complication of transoesophageal echocardiography in infants. This case involves a 3.1-kg neonate with Trisomy 21, atrioventricular septal defect, and hypoplastic aortic arch undergoing aortic arch advancement and pulmonary artery banding. A paediatric transoesophageal echocardiography probe was placed intraoperatively causing a contained false passage from the oesophagus below the cricopharyngeus muscle with extension into the left posterior mediastinum. The perforation healed within 2 weeks without permanent sequelae after conservative medical management.


title: From "Infodemics" to Health Promotion: A Novel Framework for the Role of Social Media in Public Health.

text: Despite the ubiquity of health-related communications via social media, no consensus has emerged on whether this medium, on balance, jeopardizes or promotes public health. During the COVID-19 pandemic, social media has been described as the source of a toxic "infodemic" or a valuable tool for public health. No conceptual model exists for examining the roles that social media can play with respect to population health.We present a novel framework to guide the investigation and assessment of the effects of social media on public health: the SPHERE (Social media and Public Health Epidemic and REsponse) continuum. This model illustrates the functions of social media across the epidemic-response continuum, ranging across contagion, vector, surveillance, inoculant, disease control, and treatment.We also describe attributes of the communications, diseases and pathogens, and hosts that influence whether certain functions dominate over others. Finally, we describe a comprehensive set of outcomes relevant to the evaluation of the effects of social media on the public's health. (Am J Public Health. Published online ahead of print June 18, 2020: e1-e4. doi:10.2105/AJPH.2020.305746).


title: Pelvic circumferential compression devices for prehospital management of suspected pelvic fractures: a rapid review and evidence summary for quality indicator evaluation.

text: BACKGROUND Pelvic fractures, especially when unstable, may cause significant haemorrhage. The early application of a pelvic circumferential compression device (PCCD) in patients with suspected pelvic fracture has established itself as best practice. Ambulance services conduct corresponding performance measurement. Quality indicators (QIs) are ideally based on high-quality evidence clearly demonstrating that the desirable effects outweigh the undesirable effects. In the absence of high-quality evidence, best available evidence should be combined with expert consensus. OBJECTIVES The aim of the present study was to identify, appraise and summarize the best available evidence regarding PCCDs for the purpose of informing an expert panel tasked to evaluate the validity of the following QI: A patient with suspected pelvic fracture has a PCCD applied. METHODS A rapid review of four databases was conducted to identify relevant literature published up until 9 June 2020. Systematic reviews, experimental, quasi-experimental and observational analytic studies written in English were included. One author was responsible for study selection and quality appraisal. Data extraction using a priori extraction templates was verified by a second reviewer. Study details and key findings were summarized in tables. RESULTS A total of 13 studies were assessed to be eligible for inclusion in this rapid review. Of these, three were systematic reviews, one was a randomized clinical trial (crossover design), two were before-after studies, and seven were retrospective cohort studies. The systematic reviews included mostly observational studies and could therefore not be considered as high-level evidence. Overall, the identified evidence is of low quality and suggests that PCCD may provide temporary pelvic ring stabilization and haemorrhage control, although a potential for adverse effects exists. CONCLUSION Given the low quality of the best available evidence, this evidence would need to be combined with expert consensus to evaluate the validity of a related quality indicator before its implementation.


title: 2019-novel coronavirus survey: knowledge and attitudes of hospital staff of a large Italian teaching hospital.

text: One week after the World Health Organization (WHO) declared the 2019 novel coronavirus (2019-nCoV) outbreak a global health emergency we conducted a survey to explore knowledge and attitudes on 2019-nCoV, recently renamed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in a large cohort of hospital staff. A representative sample of 2,046 hospital staff of a large university hospital in northern Italy (54% healthcare workers and 46% administrative staff, overall response rate: 25%) was administered an online questionnaire: overall there is good knowledge on 2019-nCoV control measures. The mean of correct answers for questions on general aspects of 2019-nCoV epidemic was 71.6% for HCWs and 61.2% for non-HCWs. The mean of correct answers for questions on 2019-nCoV patient management was 57.8% among HCWs. Nevertheless, on recommended precautions, also among healthcare workers there is still much to do in order to promote effective control measures and correct preventive behaviours at the individual level.


title: Spider surgical system versus multiport laparoscopic surgery: performance comparison on a surgical simulator.

text: BACKGROUND The rising interest towards minimally invasive surgery has led to the introduction of laparo-endoscopic single site (LESS) surgery as the natural evolution of conventional multiport laparoscopy. However, this new surgical approach is hampered with peculiar technical difficulties. The SPIDER surgical system has been developed in the attempt to overcome some of these challenges. Our study aimed to compare standard laparoscopy and SPIDER technical performance on a surgical simulator, using standardized tasks from the Fundamentals of Laparoscopic Surgery (FLS). METHODS Twenty participants were divided into two groups based on their surgical laparoscopic experience: 10 PGY1 residents were included in the inexperienced group and 10 laparoscopists in the experienced group. Participants performed the FLS pegboard transfers task and pattern cutting task on a laparoscopic box trainer. Objective task scores and subjective questionnaire rating scales were used to compare conventional laparoscopy and SPIDER surgical system. RESULTS Both groups performed significantly better in the FLS scores on the standard laparoscopic simulator compared to the SPIDER. Inexperienced group: Task 1 scores (median 252.5 vs. 228.5; p = 0.007); Task 2 scores (median 270.5 vs. 219.0; p = 0.005). Experienced group: Task 1 scores (median 411.5 vs. 309.5; p = 0.005); Task 2 scores (median 418.0 vs. 331.5; p = 0.007). Same aspects were highlighted for the subjective evaluations, except for the inexperienced surgeons who found both devices equivalent in terms of ease of use only in the peg transfer task. CONCLUSIONS Even though the SPIDER is an innovative and promising device, our study proved that it is more challenging than conventional laparoscopy in a population with different degrees of surgical experience. We presume that a possible way to overcome such challenges could be the development of tailored training programs through simulation methods. This may represent an effective way to deliver training, achieve mastery and skills and prepare surgeons for their future clinical experience.


title: Specificities of broadly neutralizing anti-HIV-1 sera.

text: PURPOSE OF REVIEW Effective vaccine-elicited immunity against HIV-1 infection will likely require broadly neutralizing antibodies to interrupt the fusion-promoting functions of the viral envelope glycoprotein spikes. Efforts in this area have, however, been fraught with challenges. The handful of existing broadly neutralizing monoclonal antibodies has provided information on some of the virus' sites of vulnerability, fueling a decade of structure-informed vaccine design. The fact that very few bnmAbs have been recovered to date illustrates the poor immunogenicity of these epitopes. Recognizing that progress may require more basic information, there has been a notable shift in the field toward identifying new chinks in HIV-1's armor. These efforts are based on the observation that some infected patients develop exceptionally broad serum neutralizing antibodies responses, a better understanding of which would be valuable for vaccine efforts aimed at eliciting similar specificities. RECENT FINDINGS New mapping methodologies are now providing an appreciation of the incidence of specificities similar to the existing known bnmAbs as well as some intriguing insights into novel specificities. SUMMARY The new information emerging from mapping efforts should help to sharpen efforts to isolate new bnmAbs and moreover, may provide crucial information for the rational design of novel vaccine candidates.


title: Spray Diathermy Versus Harmonic Scalpel Technique for Hepatic Parenchymal Transection of Living Donor.

text: BACKGROUND Liver parenchymal transection is the most invasive and challenging part in the living donor operation. The study was planned to compare the safety, efficacy, and outcome of harmonic scalpel versus spray diathermy as a method of parenchymal liver transection in donor hepatectomy. PATIENT AND METHOD Eighty consecutive patients, who were treated by living donor liver transplantation (LDLT), were included in the study. The study population was divided into two groups according to the method of liver transection: group A by harmonic scalpel (HS) and group B by spray diathermy (SD). The primary outcome was the volume of blood loss during transection. Secondary outcomes were time of transection, number of ligatures needed during transection, pathological changes at cut surface, postoperative morbidities, cost, and hospital stay RESULTS: Blood loss during overall liver transection and in each zone was significantly less in the SD than in the HS group (P = 0.015). The number of ligatures was significantly less in the SD than in the HS group (P = 0.0001). The SD group had significantly higher level of serum bilirubin, serum glutamic pyruvic transaminase (SGPT), and international normalized ratio (INR) levels on postoperative day 3 than the HS group. Lateral tissue coagulation and hepatic necrosis are significantly less in HS group. The overall incidence of postoperative morbidities was the same in both groups. The cost was higher in HS group than SD group (US$760 vs. US$40 P = 0.0001). CONCLUSION Spray diathermy is an effective method of parenchymal transection with significantly lower blood loss and lower cost compared to HS with no increase in morbidity. HS is associated with earlier recovery of liver functions.


title: Molecular characterization and phylogenetic analysis of porcine epidemic diarrhea virus samples obtained from farms in Gansu, China.

text: Porcine epidemic diarrhea poses significant sanitation problems in the porcine industry, and has negatively affected the economy in recent years. In this study, 48 fecal specimens were collected from piglets from four intensive swine farms located in the Gansu Province of China. The molecular diversity and phylogenetic relationships between porcine epidemic diarrhea viruses (PEDV) prevalent in Gansu were probed, and the resultant proteins were characterized. Sequence analysis of the spike protein (S) genes showed that each specimen had unique characteristics, and that the PEDV1/S/4 strain could be differentiated from the others via a unique mutation of the S gene. The phylogeny of S glycoprotein showed that all strains were clustered into two major groups. The four Gansu PEDV field strains were characterized into different groups; this finding was consistent with the results of the protein characterization prediction. This analysis additionally revealed the unique characteristics of each specimen. The results of this study could be used to elucidate the prevalence of PEDV and contribute to the prevention of PEDV in Gansu.


title: Kind of blue: A systematic review and meta-analysis of music interventions in cancer treatment.

text: OBJECTIVES Music may be a valuable and low-cost coping strategy for cancer patients. We conducted a systematic review and meta-analysis to identify the psychological and physical effects of music interventions in cancer treatment. METHODS We included randomized, controlled trials with adult patients in active cancer treatment exposed to different music interventions versus control conditions. Qualitative studies and systematic reviews were excluded. We identified a total of 2624 records through 2 systematic searches (June 2015 and September 2016) in PubMed, Scopus, EMBASE, Cinahl, Web of Science, Cochrane, and PsycINFO and used Risk of Bias Assessment, GRADE and Checklist for Reporting Music-Based Interventions to evaluate the music applied and quality of the studies. We conducted meta-analyses using Review Manager (version 5.3). PROSPERO reg. no. CRD42015026024. RESULTS We included 25 RCT's (N = 1784) of which 20 were eligible for the meta-analysis (N = 1565). Music reduced anxiety (SMD -0·80 [95% CI, -1.35 to -0.25]), pain (SMD -0.88 [95% CI -1.45 to -0.32]), and improved mood (SMD -0.55 [95% CI, -0.98 to -0.13]). However, studies were hampered by heterogeneity with I2 varying between 54% and 96%. Quality of the studies ranged from very low to low. The most effective mode of music intervention appeared to be passive listening to self-selected, recorded music in a single session design. CONCLUSIONS Music may be a tool in reducing anxiety, pain, and improving mood among patients with cancer in active treatment. However, methodological limitations in the studies conducted so far prevent firm conclusions.


title: Nasal epithelial repair and remodeling in physical injury, infection, and inflammatory diseases.

text: PURPOSE OF REVIEW To summarize the current knowledge of cellular and molecular mechanisms of nasal epithelial repair and remodeling during physical and pathophysiological conditions. RECENT FINDINGS Nasal epithelial repair and remodeling is a highly organized and well coordinated process, involving inflammation, proliferation, differentiation, matrix deposition, and remodeling, and is regulated by a wide variety of growth factors and cytokines. From the in-vivo and in-vitro studies conducted in both human and animal models, undifferentiated basal cells (progenitors) are able to migrate from adjacent epithelium, spread over the denuded basement membrane, and proliferate in injured regions (self-renewal) in necessary (homeostasis) or excessive (hyperplasia) degree. Progenitor cells reorient to an apical-basal polarity, and progressively differentiate into ciliated and nonciliated columnar cells and goblet cells, reconstituting a functional respiratory epithelium after several weeks. This recovery process can be observed during various types and severity of injury, and also in common nasal diseases, including acute viral, allergic, and nonallergic rhinitis, as well as chronic rhinosinusitis with and without nasal polyps. SUMMARY Although nearly 10 000 articles about nasal epithelium have been published in the last decade, the mechanisms underlying the nasal epithelial repair are still understood at only a superficial descriptive level. In order to advance rhinology to the next level of a comprehensive knowledge of the orchestrated genetic and molecular processes acting during epithelial repair, combined clinical and experimental studies using sophisticated investigational plans to elucidate the functions of both the protein-coding and regulatory portions of the human genome are required.


title: Pharmacologic labour analgesia and its relationship to postpartum psychiatric disorders: a scoping review.

text: PURPOSE This scoping review aimed to summarize the current literature on postpartum psychiatric disorders (e.g., postpartum depression, postpartum anxiety, postpartum post-traumatic stress disorder) and the possible relationship of these disorders to the use of pharmacologic labour analgesia (e.g., epidural analgesia, nitrous oxide, parenteral opioids) to identify knowledge gaps that may aid in the planning of future research. SOURCES PubMed, PsycINFO, CINAHL, and EMBASE were searched from inception to November 9, 2018 for studies that included both labour analgesia and the postpartum psychiatric disorders specified above. PRINCIPAL FINDINGS Two reviewers assessed the studies and extracted the data. Of the 990 identified citations, 17 studies were included for analysis. Existing studies have small sample sizes and are observational cohorts in design. Patient psychiatric risk factors, method of delivery, and type of labour analgesia received were inconsistent among studies. Most studies relied on screening tests for diagnosing postpartum psychiatric illness and did not assess the impact of labour analgesia on postpartum psychiatric illness as the primary study objective. CONCLUSIONS Future studies should correlate screen-positive findings with clinical diagnosis; consider adjusting the timing of screening to include the antepartum period, early postpartum, and late postpartum periods; and consider the degree of labour pain relief and the specific pharmacologic labour analgesia used when evaluating postpartum psychiatric disorders.


title: Predictive Value of Computed Tomography Angiography-Determined Occlusion Type in Stent Retriever Thrombectomy.

text: BACKGROUND AND PURPOSE We investigated whether occlusion type identified with computed tomography angiography (CTA-determined occlusion type) could predict endovascular treatment success using stent retriever (SR) thrombectomy. METHODS Consecutive patients with stroke who underwent CTA and then endovascular treatment for intracranial large artery occlusion were retrospectively reviewed. CTA-determined occlusion type was classified into truncal-type occlusion or branching-site occlusion and compared with digital subtraction angiography-determined occlusion type during endovascular treatment. Three rapidly- and readily-assessable pre-procedural findings (CTA-determined occlusion type, atrial fibrillation, and hyperdense artery sign), which may infer occlusion pathomechanism (embolic versus nonembolic) before endovascular treatment, were evaluated for association with SR success along with stroke risk factors and laboratory results. In addition, the predictive power of the 3 pre-procedural findings for SR success was compared with receiver operating characteristic curve analyses. RESULTS A total of 238 patients (mean age, 70.0 years; male patients, 52.9%) were included in this study. CTA-determined occlusion type corresponded adequately with digital subtraction angiography-determined occlusion type (P=0.453). Atrial fibrillation (odds ratio, 2.66; 95% confidence interval, 1.25-5.66) and CTA-determined branching-site occlusion (odds ratio, 8.20; confidence interval, 3.45-19.5) were independent predictors for SR success. For predicting SR success, the area under the receiver operating characteristic curve value for CTA-determined branching-site occlusion (0.695) was significantly greater than atrial fibrillation (0.594; P=0.038) and hyperdense artery sign (0.603; P=0.023). CONCLUSIONS CTA-determined branching-site occlusion was significantly associated with SR success. Furthermore, among the 3 rapidly- and readily-assessable pre-procedural findings, CTA-determined branching-site occlusion had the greatest predictive power for SR success.


title: Late-occurring pulmonary pathologies following inhalation of mixed oxide (uranium + plutonium oxide) aerosol in the rat.

text: Accidental exposure by inhalation to alpha-emitting particles from mixed oxide (MOX: uranium and plutonium oxide) fuels is a potential long-term health risk to workers in nuclear fuel fabrication plants. For MOX fuels, the risk of lung cancer development may be different from that assigned to individual components (plutonium, uranium) given different physico-chemical characteristics. The objective of this study was to investigate late effects in rat lungs following inhalation of MOX aerosols of similar particle size containing 2.5 or 7.1% plutonium. Conscious rats were exposed to MOX aerosols and kept for their entire lifespan. Different initial lung burdens (ILBs) were obtained using different amounts of MOX. Lung total alpha activity was determined by external counting and at autopsy for total lung dose calculation. Fixed lung tissue was used for anatomopathological, autoradiographical, and immunohistochemical analyses. Inhalation of MOX at ILBs ranging from 1-20 kBq resulted in lung pathologies (90% of rats) including fibrosis (70%) and malignant lung tumors (45%). High ILBs (4-20 kBq) resulted in reduced survival time (N = 102; p < 0.05) frequently associated with lung fibrosis. Malignant tumor incidence increased linearly with dose (up to 60 Gy) with a risk of 1-1.6% Gy for MOX, similar to results for industrial plutonium oxide alone (1.9% Gy). Staining with antibodies against Surfactant Protein-C, Thyroid Transcription Factor-1, or Oct-4 showed differential labeling of tumor types. In conclusion, late effects following MOX inhalation result in similar risk for development of lung tumors as compared with industrial plutonium oxide.


title: Beyond adenotonsillectomy: outcomes of sleep endoscopy-directed treatments in pediatric obstructive sleep apnea.

text: OBJECTIVES In this study we determine the subjective and objective outcomes of pediatric patients with refractory OSA undergoing drug-induced sleep endoscopy (DISE)-directed surgical treatment. METHODS 31 consecutive children with OSA following TA underwent DISE. 26 completed DISE-directed operative management of the level(s) of ongoing upper airway obstruction. Pre- and postoperative OSA were assessed through a detailed history (of nighttime symptoms (NS) and daytime symptoms (DS)), physical examination, and polysomnography. RESULTS Age ranged 5-18 years (mean 9.7 ± 3.4). Fourteen of 26 had trisomy 21 (51%). Operations were performed in the following frequencies: lingual tonsillectomy (LT) (22), midline posterior glossectomy (MPG) (16), revision adenoidectomy (11), inferior turbinate submucosal resection (7), uvulopalatoplasty (2), and supraglottoplasty (2). Overall, 92% reported subjective improvement. NS improved from 5.8 ± 2.9 preoperatively to 2.1 ± 2.5 postoperatively (p<0.05), while DS improved from 2.1 ± 1.3 preoperatively to 0.6 ± 1.1 postoperatively (p<0.05). Seventeen patients completed preoperative polysomnography, while only 11 of them also completed postoperative polysomnography. Mean OAHI fell from 7.0 (±5.8) events/hr to 3.6 (±1.8) events/hr (t-test, p=0.09). CONCLUSIONS Individualized, multilevel, DISE-directed operative therapy was associated with substantial improvement in subjective measures of sleep.


People have long memories.


title: Potential pitfalls in volume reduction for the treatment of Proteus syndrome.

text: Proteus syndrome is a rare congenital hamartomatous condition that is characterised by a wide range of malformations. Skin and skeletal developmental malformations are common and may manifest as significant physical anomalies. However, few reports have discussed surgical treatment. A 37-year-old woman presented with disproportionate enlargement of the right buttock, which required volume reduction. The overgrown tissue was combined with vascular malformations, which in our patient were extremely thick. The patient experienced massive blood loss during the procedure, due to which a blood transfusion was performed. Pathological findings revealed partial lipohyperplasia with venous malformations. Thus, during operations including incomplete excision, massive bleeding is always a possibility, but is not commonly described in these instances.


title: Postoperative intubation time is associated with acute kidney injury in cardiac surgical patients.

text: INTRODUCTION Acute kidney injury (AKI) is a frequent complication after cardiac surgery and is associated with a poor prognosis. Mechanical ventilation is an important risk factor for developing AKI in critically ill patients. Ventilation with high tidal volumes has been associated with postoperative organ dysfunction in cardiac surgical patients. No data are available about the effects of the duration of postoperative respiratory support in the immediate postoperative period on the incidence of AKI in patients after cardiac surgery. METHOD We performed a secondary analysis of 584 elective cardiac surgical patients enrolled in an observational trial on the association between preoperative cerebral oxygen saturation and postoperative organ dysfunction and analyzed the incidence of AKI in patients with different times to extubation. The latter variable was graded in 4 h intervals (if below 16 h) or equal to or greater than 16 h. AKI was staged according to the AKI Network criteria. RESULTS Overall, 165 (28.3%) patients developed AKI (any stage), 43 (7.4%) patients needed renal replacement therapy. Patients developing AKI had a significantly (P <0.001) lower renal perfusion pressure (RPP) in the first 8 hours after surgery (57.4 mmHg (95% CI: 56.0 to 59.0 mmHg)) than patients with a postoperatively preserved renal function (60.5 mmHg ((95% CI: 59.9 to 61.4 mmHg). The rate of AKI increased from 17.0% in patients extubated within 4 h postoperatively to 62.3% in patients ventilated for more than 16 h (P <0.001). Multivariate logistic regression analysis of variables significantly associated with AKI in the univariate analysis revealed that the time to the first extubation (OR: 1.024/hour, 95% CI: 1.011 to 1.044/hour; P <0.001) and RPP (OR: 0.963/mmHg; 95% CI: 0.934 to 0.992; P <0.001) were independently associated with AKI. CONCLUSION Without taking into account potentially unmeasured confounders, these findings are suggestive that the duration of postoperative positive pressure ventilation is an important and previously unrecognized risk factor for AKI in cardiac surgical patients, independent from low RPP as an established AKI trigger, and that even a moderate delay of extubation increases AKI risk. If replicated independently, these findings may have relevant implications for clinical care and for further studies aiming at the prevention of cardiac surgery associated AKI.


title: Tele-consultations in the wake of COVID-19 - Suggested guidelines for clinical ophthalmology.

text: While telemedicine has been around for a few decades, it has taken great importance and prominence in recent times. With the fear of the virus being transmitted, patients and physicians across specialties are using consultation via a telephone call or video from the safety of their homes. Though tele-ophthalmology has been popular for screening, there are no clear guidelines on how to comprehensively manage patients seeking advice and treatment for a particular eye condition. Some major barriers to diagnosis and management are compromised detailed examination, no measurement of the visual acuity or intraocular pressure and a retinal evaluation not being feasible. Despite these limitations, we do need to help those patients who need immediate care or attention. Hence, this article has put together some guidelines to follow during such consultations. They are important and timely due to the medicolegal and financial implications.


title: The application of a blunt-tip needle to suture the dorsal venous complex in robot-assisted laparoscopic radical prostatectomy.

text: OBJECTIVES Complete haemostasis of the dorsal venous complex (DVC) is of great importance in robot-assisted radical prostatectomy. In this study, we investigated the efficacy of blunt-tip needles in the surgery. METHODS Cases of robot-assisted laparoscopic radical prostatectomy were reviewed. If a blunt-tip needle had been used to suture the DVC, the patient was recruited to the blunt-tip group. If a regular needle was used, the patient was recruited to the control group. Patient characteristics and perioperative outcomes were recorded. RESULTS One hundred and nine cases were reviewed. A blunt-tip needle was used to suture the DVC in 67 cases, and a regular needle in 42 cases. All characteristics of the two groups are comparable (p > 0.05). In 66 cases in the blunt-tip group, no sutures or coagulations were needed when suturing the DVC, Five cases of DVC-related bleeding were observed in the control group, which is higher than in the blunt-tip group (p = 0.031). At the same time, no catheter was sutured in the blunt-tip group. All patients were followed for at least six months. The continence rate in the blunt-tip group is 89.6%, significantly higher than in the control group (73.8%, p = 0.031). CONCLUSIONS Using a blunt-tip needle to suture the DVC may reduce DVC-related bleeding and provide a better surgical field. It may be helpful in improving postoperative continence. However, its effect on positive margin at the apex still needs further investigation.


Pretest-based group forming in advanced cardiovascular life support courses increases acquisition and retention of resuscitation knowledge.


title: Therapeutic antibodies as a treatment option for dengue fever.

text: Dengue fever is the most prevalent mosquito-borne viral disease globally with about 100 million cases of acute dengue annually. Severe dengue infection can result in a life-threatening illness. In the absence of either a licensed vaccine or antiviral drug against dengue, therapeutic antibodies that neutralize dengue virus (DENV) may serve as an effective medical countermeasure against severe dengue. However, therapeutic antibodies would need to effectively neutralize all four DENV serotypes. It must not induce antibody-dependent enhancement of DENV infection in monocytes/macrophages through Fc gamma receptor (FcγR)-mediated phagocytosis, which is hypothesized to increase the risk of severe dengue. Here, we review the strategies and technologies that can be adopted to develop antibodies for therapeutic applications. We also discuss the mechanism of antibody neutralization in the cells targeted by DENV that express Fc gamma receptor. These studies have provided significant insight toward the use of therapeutic antibodies as a potentially promising bulwark against dengue.


title: Clinical trials in the time of a pandemic.

text: The first rumblings about a new coronavirus spreading in China were heard in January 2020. By the end of that month, the World Health Organization, recognizing the severity of the disease and the potential for global spread, had declared a public health emergency. By February 2020, cases had been identified in multiple countries, clinical trials of treatments with some biological plausibility had begun in China, and the initial steps of vaccine development were underway. In mid-March, by which time countries around the world were experiencing rapidly increasing numbers of cases and deaths, the World Health Organization categorized the outbreak as a pandemic. This new coronavirus was designated SARS-COV-2 in recognition of its similarity to the coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002-2003. The race is on to develop treatments that can mitigate the severe consequences of infection and vaccines that can prevent infection and/or diminish the severity of disease in those who do get infected. Many challenges face these development efforts. Some are similar to those faced in the past; others are new. The urgency of finding ways to treat, and ultimately prevent, the consequences of this new and potentially deadly infection has led to unprecedented focus on clinical trials.


title: Current national practice patterns for inpatient management of ventral abdominal wall hernia in the United States.

text: BACKGROUND The health-care burden related to ventral hernia management is substantial, with more than 3 billion dollars in expenditures annually in the US. Previous studies have suggested that the utilization of laparoscopic repair remains relatively low although national volume estimates have not been reported. We sought to estimate the inpatient national volume of elective ventral hernia surgery and characterize the proportion of laparoscopic versus open operations. METHODS We analyzed data from the Nationwide Inpatient Sample to identify adults with a diagnosis of an umbilical, incisional, or ventral hernia who underwent an elective inpatient repair between 2009 and 2010. Cases that involved other major abdominal or pelvic operations were excluded. Covariates included patient demographics, surgical approach, and use of mesh. National surgical volume estimates were generated and length of stay and total hospital charges were compared for laparoscopic versus open repairs. RESULTS A total of 112,070 ventral hernia repairs were included in the analysis: 72.1 % (n = 80,793) were incisional hernia repairs, while umbilical hernia repairs comprised only 6.9 % (n = 7,788). Laparoscopy was utilized in 26.6 % (n = 29,870) of cases. Mesh was placed in 85.8 % (n = 96,265) of cases, including 49.3 % (n = 3,841) of umbilical hernia repairs and 90.1 % (n = 72,973) of incisional hernia repairs. Length of stay and total hospital charges were significantly lower for laparoscopic umbilical, incisional, and "other" ventral hernia repairs (p values all <0.001). Total hospital charges during this 2-year period approached 4 billion dollars ($746 million for laparoscopic repair; $3 billion for open repair). CONCLUSIONS Utilization of laparoscopy for elective abdominal wall hernia repair remains relatively low in the US despite its excellent outcomes. Given the substantial financial burden associated with these hernias, future research focused on preventing the development and optimizing the surgical treatment of ventral abdominal wall hernias is warranted.


title: Laparoscopic Bilateral Cervicosacropexy and Vaginosacropexy: New Surgical Treatment Option in Women with Pelvic Organ Prolapse and Urinary Incontinence.

text: OBJECTIVE Sacrocolpopexy (SCP) is the gold standard for apical prolapse treatment. However, the technical performance of each SCP is strongly dependent on the surgeon's own discretion and comparison of clinical outcomes with respect to urinary incontinence (UI) is difficult. We developed a comprehensible laparoscopic surgical technique for the treatment of apical prolapse with UI. METHODS A total of 120 women with UI underwent laparoscopic bilateral SCP for apical prolapse. Thereby, the uterosacral ligaments (USLs) were bilaterally replaced by polyvinylidene fluoride (PVDF) tapes of identical length and shape, which were fixed at defined anatomical landmarks (cervix/vaginal vault and S1). RESULTS The restoration of apical vaginal support was achieved in 116 patients (97%); restoration failed in the first 4 patients owing to the use of fast-absorbable sutures. Seventy-eight patients (65%) with mixed and urgency UI symptoms before surgery achieved continence. The mean hospitalization was 3 days; no major complications were observed intraoperatively. CONCLUSION The advantage of laparoscopic cervicosacropexy (laCESA) and laparoscopic vaginosacropexy (laVASA) lies in the comprehensible surgical technique (clearly defined technique) and the minimal amount of material used (no polypropylenes). The possibility of a short operating time and short hospitalization depicts this laparoscopic bilateral USL replacement as one treatment alternative in patients with apical prolapse suffering from UI.


title: Dexmedetomidine for patients undergoing diagnostic cardiac procedures: a noninferiority study.

text: When anesthetizing children with congenital heart disease for diagnostic cardiac catheterization, anesthesiologists and cardiologists seek to use anesthetic regimens that yield minimal hemodynamic changes and allow for spontaneous ventilations. Recently, dexmedetomidine has been used as an anesthesia adjunct because of its sedative and analgesic properties and minimal ventilatory depressive effects. We tested the hypothesis that the combination of sevoflurane and dexmedetomidine is non-inferior to sevoflurane alone as it refers to hemodynamic measurements during diagnostic cardiac catheterization in children with a transplanted heart, one ventricle (Fontan procedure), or normal cardiac physiology. Patients were anesthetized with inhalation of sevoflurane in nitrous oxide/oxygen and, after baseline hemodynamic measurements, successive boluses of dexmedetomidine followed by continuous infusion were administered. In this study, non-inferiority was shown when differences at steady-state (dexmedetomidine + sevoflurane) compared to baseline (sevoflurane alone) and its associated 95% confidence interval fell completely within the range of plus or minus 20%. Forty-one (26 normal physiology, 9 cardiac transplantation, and 6 Fontan) patients were enrolled. Non-inferiority of sevoflurane + dexmedetomidine compared with sevoflurane alone was shown for heart rate, but not for arterial blood pressure in patients with normal and cardiac transplant physiology. In patients with normal cardiac physiology, non-inferiority was demonstrated for bispectral index. Therefore, while the lack of depressive respiratory effects and non-inferiority for heart rate are desirable, the lack of non-inferiority of dexmedetomidine + sevoflurane combination for arterial blood pressure do not justify the routine use of this combination compared with sevoflurane alone for children with congenital heart disease undergoing cardiac catheterization.


title: Acute Wound Complications After Total Knee Arthroplasty: Prevention and Management.

text: Normal wound healing with avoidance of early wound complications is critical to the success of total knee arthroplasty. The severity of acute complications includes less morbid problems, such as quickly resolved drainage and small superficial eschars, to persistent drainage and full-thickness tissue necrosis, which may require advanced soft-tissue coverage. To achieve proper healing, surgeons must respond to persistent drainage by addressing modifiable patient risk factors, using meticulous surgical technique, and implementing an algorithmic approach to treatment.


title: Efficacy and safety of laparoscopic splenectomy and esophagogastric devascularization for portal hypertension: A single-center experience.

text: Many patients in China have portal hypertension secondary to liver cirrhosis. Splenectomy and devascularization have become an efficacious surgical procedure for portal hypertension, and has been recommended in China as the first choice for the treatment of portal hypertension for a long time. As a result of advances in laparoscopic equipment and techniques, splenectomy and esophagogastric devascularization have been carried out with laparoscope.From January 2012 to December 2017, 453 patients who were diagnosed with portal hypertension and serious gastroesophageal varices received surgical management in our institution. 250 patients chose laparoscopic splenectomy and esophagogastric devascularization and 203 underwent open splenectomy and esophagogastric devascularization.We retrospectively analyzed the perioperative data and follow-up data of these patients. The operation time of laparoscopic group was longer than open group (P ≤ .001). Intraoperative blood loss was less (P ≤ .001), the passing of flatus was earlier (P = .042), and postoperative hospital stay was shorter (P = .001) in the laparoscopic group. During postoperative follow-up of 4 to 75 months, the incidence of esophagogastric variceal rebleeding, encephalopathy, and secondary liver cancer showed no significant differences.Laparoscopic splenectomy and esophagogastric devascularization were safe and more effective than open surgery for portal hypertension and gastroesophageal varices.


Cardiac considerations in patients with COVID-19.


The Detrimental Impact of the COVID-19 Crisis on Health Equity and Social Determinants of Health.


title: A pattern of cerebral perfusion anomalies between major depressive disorder and Hashimoto thyroiditis.

text: BACKGROUND This study aims to evaluate relationship between three different clinical conditions: Major Depressive Disorders (MDD), Hashimoto Thyroiditis (HT) and reduction in regional Cerebral Blood Flow (rCBF) in order to explore the possibility that patients with HT and MDD have specific pattern(s) of cerebral perfusion. METHODS DESIGN Analysis of data derived from two separate data banks. SAMPLE 54 subjects, 32 with HT (29 women, mean age 38.8 ± 13.9); 22 without HT (19 women, mean age 36.5 ± 12.25). ASSESSMENT Psychiatric diagnosis was carried out by Simplified Composite International Diagnostic Interview (CIDIS) using DSM-IV categories; cerebral perfusion was measured by (99 m)Tc-ECD SPECT. Statistical analysis was done through logistic regression. RESULTS MDD appears to be associated with left frontal hypoperfusion, left temporal hypoperfusion, diffuse hypoperfusion and parietal perfusion asymmetry. A statistically significant association between parietal perfusion asymmetry and MDD was found only in the HT group. CONCLUSION In HT, MDD is characterized by a parietal flow asymmetry. However, the specificity of rCBF in MDD with HT should be confirmed in a control sample with consideration for other health conditions. Moreover, this should be investigated with a longitudinally designed study in order to determine a possible pathogenic cause. Future studies with a much larger sample size should clarify whether a particular perfusion pattern is associated with a specific course or symptom cluster of MDD.


title: Preserved Insulin Secretory Capacity and Weight Loss Are the Predominant Predictors of Glycemic Control in Patients With Type 2 Diabetes Randomized to Roux-en-Y Gastric Bypass.

text: Improvement in type 2 diabetes after Roux-en-Y gastric bypass (RYGB) has been attributed partly to weight loss, but mechanisms beyond weight loss remain unclear. We performed an ancillary study to the Diabetes Surgery Study to assess changes in incretins, insulin sensitivity, and secretion 1 year after randomization to lifestyle modification and intensive medical management (LS/IMM) alone (n = 34) or in conjunction with RYGB (n = 34). The RYGB group lost more weight and had greater improvement in HbA1c. Fasting glucose was lower after RYGB than after LS/IMM, although the glucose area under the curve decreased comparably for both groups. Insulin sensitivity increased in both groups. Insulin secretion was unchanged after LS/IMM but decreased after RYGB, except for a rapid increase during the first 30 min after meal ingestion. Glucagon-like peptide 1 (GLP-1) was substantially increased after RYGB, while gastric inhibitory polypeptide and glucagon decreased. Lower HbA1c was most strongly correlated with the percentage of weight loss for both groups. At baseline, a greater C-peptide index and 90-min postprandial C-peptide level were predictive of lower HbA1c at 1 year after RYGB. β-Cell glucose sensitivity, which improved only after RYGB, and improved disposition index were associated with lower HbA1c in both groups, independent of weight loss. Weight loss and preserved β-cell function both predominantly determine the greatest glycemic benefit after RYGB.


title: Major thoracic surgery in Jehovah's witness: A multidisciplinary approach case report.

text: INTRODUCTION A bloodless surgery can be desirable also for non Jehovah's witnesses patients, but requires a team approach from the very first assessment to ensure adequate planning. PRESENTATION OF THE CASE Our patient, a Jehovah's witnesses, was scheduled for right lower lobectomy due to pulmonary adenocarcinoma. Her firm denies to receive any kind of transfusions, forced clinicians to a bloodless management of the case. DISCUSSION Before surgery a meticulous coagulopathy research and hemodynamic optimization are useful to prepare patient to operation. During surgery, controlled hypotension can help to obtain effective hemostasis. After surgery, clinicians monitored any possible active bleeding, using continuous noninvasive hemoglobin monitoring, limiting the blood loss due to serial in vitro testing. The optimization of cardiac index and delivery of oxygen were continued to grant a fast recovery. CONCLUSION Bloodless surgery is likely to gain popularity, and become standard practice for all patients. The need for transfusion should be targeted on individual case, avoiding strictly fixed limit often leading to unnecessary transfusion.


title: Selection of an appropriate left-sided double-lumen tube size for one-lung ventilation among Asians.

text: CONTEXT Selecting an appropriate size double-lumen tube (DLT) for one-lung ventilation has always been a challenge as most choose it based on experience or using the existing guidelines based on gender and height. AIMS The aim of this study was to determine if the appropriate choice of this tube could be based on the patients' height, weight, tracheal diameter (TD), or the left main stem bronchus diameter (LMBD) and also to determine the relationship between height and depth of insertion among Asians. SUBJECTS AND METHODS This was a retrospective review of 179 patients who were intubated with a left-sided DLT and also had a posterior-anterior view of a digital chest radiograph for tracheal and left main bronchus diameter measurements. Additional data collected included patients' demographics and DLT size used. RESULTS There were 123 (68.7%) males and 56 (31.3%) females with an overall mean age of 33.3 ± 16.3 years. Majority of the males (48.8%) used a size 39 Fr while females (46.4%) used a 35 Fr. There were weak correlations between DLT size with height (male: R2 = 0.222; female: R2 = 0.193), DLT size with weight (male: R2 = 0.109; female: R2 = 0.211), DLT size with TD (male: R2 = 0.027); female: R2 = 0.016), and DLT size with LMBD (male: R2 = 0.222; female: R2 = 0.193). There was a good correlation between depth of DLT inserted with patient's height for both genders. CONCLUSION The appropriate size of the left-sided DLT could not be predicted based on patients' height, weight, tracheal or left main bronchus diameter alone in Asians; however, the depth of insertion of the tube was dependent on the height in both genders.


The Importance of Addressing Advance Care Planning and Decisions About Do-Not-Resuscitate Orders During Novel Coronavirus 2019 (COVID-19).


title: Extracorporeal membrane oxygenation circuitry.

text: The extracorporeal membrane oxygenation circuit is made of a number of components that have been customized to provide adequate tissue oxygen delivery in patients with severe cardiac and/or respiratory failure for a prolonged period of time (days to weeks). A standard extracorporeal membrane oxygenation circuit consists of a mechanical blood pump, gas-exchange device, and a heat exchanger all connected together with circuit tubing. Extracorporeal membrane oxygenation circuits can vary from simple to complex and may include a variety of blood flow and pressure monitors, continuous oxyhemoglobin saturation monitors, circuit access sites, and a bridge connecting the venous access and arterial infusion limbs of the circuit. Significant technical advancements have been made in the equipment available for short- and long-term extracorporeal membrane oxygenation applications. Contemporary extracorporeal membrane oxygenation circuits have greater biocompatibility and allow for more prolonged cardiopulmonary support time while minimizing the procedure-related complications of bleeding, thrombosis, and other physiologic derangements, which were so common with the early application of extracorporeal membrane oxygenation. Modern era extracorporeal membrane oxygenation circuitry and components are simpler, safer, more compact, and can be used across a wide variety of patient sizes from neonates to adults.


title: Retroperitoneal fibrosis in feline renal transplant recipients: 29 cases (1998-2011).

text: OBJECTIVE To evaluate features, treatment, and prognosis associated with retroperitoneal fibrosis that developed after renal transplantation in cats. DESIGN Retrospective case series. ANIMALS 29 cats. PROCEDURES Medical records of cats that developed retroperitoneal fibrosis after renal transplantation at the College of Veterinary Medicine, University of Pennsylvania, between 1998 and 2011 were reviewed for signalment, date of transplantation, age, results of urine and blood analyses, blood pressure at the time of diagnosis, infectious disease and medication anamneses, anesthetic protocols, and intraoperative complications. RESULTS Of 138 transplant recipients, 29 (21%) developed clinically important retroperitoneal fibrosis. Nineteen (66%) were male, and median age at the time of renal transplantation was 8 years (range, 4 to 13 years). Median number of days after transplantation to diagnosis of retroperitoneal fibrosis was 62 (range, 4 to 730 days; mean, 125 days). The most common clinical signs were lethargy and anorexia. All affected cats were azotemic (BUN concentration > 32 mg/dL; creatinine concentration > 2.0 mg/dL) and anemic (PCV < 35%) at the time of retroperitoneal fibrosis diagnosis, although cats were nonazotemic at the time of discharge following transplantation, and anemia was less pronounced. Twenty-five cats successfully underwent surgical ureterolysis in which scar tissue was dissected away from the allograft ureter to relieve extraluminal compression. Retroperitoneal fibrosis recurred in 6 (22%) cats a median of 180 days (range, 8 to 343 days) following the original diagnosis and was treated successfully by repeated ureterolysis. CONCLUSIONS AND CLINICAL RELEVANCE Retroperitoneal fibrosis occurred in a substantial percentage of feline renal transplant recipients and should be considered a differential diagnosis in any feline renal transplant recipient with clinicopathologic findings, imaging abnormalities, or signs suggestive of obstructive uropathy.


title: Photoplethysmography-based algorithm for detection of cardiogenic output during cardiopulmonary resuscitation.

text: Detecting return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR) is challenging, time consuming, and requires interrupting chest compressions. Based on automated-CPR porcine data, we have developed an algorithm to support ROSC detection, which detects cardiogenic output during chest compressions via a photoplethysmography (PPG) signal. The algorithm can detect palpable and impalpable spontaneous pulses. A compression-free PPG signal which estimates the spontaneous pulse waveform, was obtained by subtracting the compression component, modeled by a harmonic series. The fundamental frequency of this series was the compression rate derived from the transthoracic impedance signal measured between the defibrillation pads. The amplitudes of the harmonic components were obtained via a least mean-square algorithm. The frequency spectrum of the compression-free PPG signal was estimated via an autoregressive model, and the relationship between the spectral peaks was analyzed to identify the pulse rate (PR). Resumed cardiogenic output could also be detected from a decrease in the baseline of the PPG signal, presumably caused by a redistribution of blood volume to the periphery. The algorithm indicated cardiogenic output when a PR or a redistribution of blood volume was detected. The algorithm indicated cardiogenic output with 94% specificity and 69% sensitivity compared to the retrospective ROSC detection of nine clinicians. Results showed that ROSC detection can be supported by combining the compression-free PPG signal with an indicator based on the detected PR and redistribution of blood volume.


An uncertain future for cardiovascular drug development?


title: Allosteric Regulation of Phosphatidylinositol 4-Kinase III Beta by an Antipicornavirus Compound MDL-860.

text: MDL-860 is a broad-spectrum antipicornavirus compound discovered in 1982 and one of the few promising candidates effective in in vivo virus infection. Despite the effectiveness, the target and the mechanism of action of MDL-860 remain unknown. Here, we have characterized antipoliovirus activity of MDL-860 and identified host phosphatidylinositol-4 kinase III beta (PI4KB) as the target. MDL-860 treatment caused covalent modification and irreversible inactivation of PI4KB. A cysteine residue at amino acid 646 of PI4KB, which locates at the bottom of a surface pocket apart from the active site, was identified as the target site of MDL-860. This work reveals the mechanism of action of this class of PI4KB inhibitors and offers insights into novel allosteric regulation of PI4KB activity.


Clinical Features and Chest CT Manifestations of Coronavirus Disease (COVID-19).


title: Comparison of the Contact Force Exerted on Teeth by Conventional Macintosh Laryngoscope Versus Video Laryngoscopes.

text: During laryngoscopy, the laryngoscope blade sometimes comes in contact with the teeth, fracturing or dislocating them. However, no studies have compared the effects of newly marketed video laryngoscopes and the Macintosh laryngoscope (Mac) on teeth. In this study, we measured and compared the force exerted on the teeth of an intubating manikin by the Mac, the Airway Scope (Pentax), and the McGrath MAC (Covidien). The mean force exerted was 141.1 ± 15.7 kg by the Mac, 39.2 ± 10.3 kg by the Airway Scope, and 48.7 ± 6.7 kg by the McGrath MAC. No significant difference was observed between the Airway Scope and the McGrath MAC. When the Mac is inserted, the glottis has to be visually located from outside the oral cavity. However, a significant force is not necessary when inserting video laryngoscopes because a camera is mounted on the blade tip. In this laboratory model, the lower force exerted by the video laryngoscopes should contribute to a reduction in their impact on fracture or dislocation of teeth.


title: Does β2-adrenergic stimulation attenuate fluid extravasation during hypothermic cardiopulmonary bypass? An experimental study in pigs.

text: OBJECTIVES Hypothermic cardiopulmonary bypass (CPB) is associated with increased fluid filtration, edema formation and, occasionally, organ dysfunction. Cold-induced reduction in endothelial barrier function may play a role. β(2)-adrenergic activation elevates cellular cyclic adenosine monophosphate (cAMP) which maintains endothelial barrier properties. In this study, we tested whether β-adrenergic stimulation could influence the increase in fluid extravasation observed during hypothermic CPB. MATERIALS AND METHODS Fourteen pigs randomly received terbutaline infusion (T-group) (n=7) or a control infusion (C-group) (n=7). All animals were given 60 min of normothermic CPB, followed by 90 min of hypothermic CPB. Fluid input and losses, plasma volume, colloid osmotic pressures (plasma, interstitial fluid), hematocrit, serum proteins and total tissue water content were measured and the fluid extravasation rates (FER) calculated. STATISTICS by SPSS. Values presented as mean ± SD. Repeated measure analysis of variance was performed and a t-test used when appropriate. RESULTS The commencement of normothermic CPB resulted in a 20% hemodilution, with an abrupt increase in fluid requirements during the first 10 min. FER increased from 0.18 (0.06) pre-bypass to 0.78 (0.27) ml/kg/min (T-group) (p=0.002) and from 0.16 (0.05) to 0.93 (0.26) ml/kg/min (C-group) (p<0.001) with no between-group differences. Thereafter, FER stabilized at a level of 0.32 (0.13) and 0.27 (0.14) ml/kg/min in the T-group and C-group, respectively. After the start of cooling, FER increased in the T-group to 0.55 (0.12) ml/kg/min (P=0.046) and in the C-group to 0.54 (0.13) ml/kg/min (P=0.006), with no between-group differences (P=0.738). CONCLUSION In the present experimental study, we were unable to demonstrate any clinically relevant modulating effect of terbutaline on fluid extravasation during hypothermic cardiopulmonary bypass.


Too much information, too little evidence: is waste in research fuelling the covid-19 infodemic?


title: Coronary vein defibrillator coil placement in patients with high defibrillation thresholds.

text: Background Elevated defibrillation threshold (DFT) occurs in 2%-6% of patients undergoing implantable cardioverter defibrillator (ICD) implantation. Adding a defibrillation coil in the coronary sinus (CS) or its branches can result in substantial reductions in the mean DFT. However, data regarding acute success and long-term stability remain lacking. We report our experience with this bailout strategy. Methods Patients with elevated DFT at implantation (safety margin at implantation <10 J) and those with failed ICD shocks for ventricular arrhythmias (VA) referred for high DFT underwent placement of an additional defibrillation coil in the CS. DFT testing was performed at the completion of the implantation procedure. External potentially reversible factors were excluded. High-output devices were systematically used. Results Four patients with high DFT at implantation and two with several failed shock attempts underwent placement of a defibrillation coil in the CS. Mean age was 41.8 (23-78). They presented a mean LVEF of 21% (15-30), QRS-complex duration of 109.8 milliseconds (87-168), body surface area of 1.96 m2 (1.45-2.58), and a mean R wave of 16.3 mV (8-27). Defibrillation coil implantation in the CS (final shocking configuration of right ventricle as anode and left ventricle (LV) plus can as cathode) was associated with successful DFT testing in all. Three patients had a concomitant LV lead for biventricular pacing. During a mean follow-up of 54.67 months (10-118), two patients experienced successful ICD shocks for VA (one of them also presented inappropriate shocks because of the fast conducting atrial fibrillation). Conclusions Positioning of a defibrillation coil in the CS can result in a substantial reduction in mean DFT and associates with optimal long-term stability.


title: Evolved variants of the membrane protein can partially replace the envelope protein in murine coronavirus assembly.

text: The coronavirus small envelope (E) protein plays a crucial, but poorly defined, role in the assembly of virions. To investigate E protein function, we previously generated E gene point mutants of mouse hepatitis virus (MHV) that were defective in growth and assembled virions with anomalous morphologies. We subsequently constructed an E gene deletion (ΔE) mutant that was only minimally viable. The ΔE virus formed tiny plaques and reached optimal infectious titers many orders of magnitude below those of wild-type virus. We have now characterized highly aberrant viral transcription patterns that developed in some stocks of the ΔE mutant. Extensive analysis of three independent stocks revealed that, in each, a faster-growing virus harboring a genomic duplication had been selected. Remarkably, the net result of each duplication was the creation of a variant version of the membrane protein (M) gene that was situated upstream of the native copy of the M gene. Each different variant M gene encoded an expressed protein (M*) containing a truncated endodomain. Reconstruction of one variant M gene in a ΔE background showed that expression of the M* protein markedly enhanced the growth of the ΔE mutant and that the M* protein was incorporated into assembled virions. These findings suggest that M* proteins were repeatedly selected as surrogates for the E protein and that one role of E is to mediate interactions between transmembrane domains of M protein monomers. Our results provide a demonstration of the capability of coronaviruses to evolve new gene functions through recombination.


title: High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial.

text: PURPOSE Intubation of hypoxemic patients is associated with life-threatening adverse events. High-flow therapy by nasal cannula (HFNC) for preoxygenation before intubation has never been assessed by randomized study. Our objective was to evaluate the efficiency of HFNC for preoxygenation, compared to high fraction-inspired oxygen facial mask (HFFM). METHODS Multicenter, randomized, open-labelled, controlled PREOXYFLOW trial (NCT 01747109) in six French intensive care units. Acute hypoxemic adults requiring intubation were randomly allocated to HFNC or HFFM. Patients were eligible if PaO2/FiO2 ratio was below 300 mmHg, respiratory rate at least 30/min and if they required FiO2 50% or more to obtain at least 90% oxygen saturation. HFNC was maintained throughout the procedure, whereas HFFM was removed at the end of general anaesthesia induction. Primary outcome was the lowest saturation throughout intubation procedure. Secondary outcomes included adverse events related to intubation, duration of mechanical ventilation and death. RESULTS A total of 124 patients were randomized. In the intent-to-treat analysis, including 119 patients (HFNC n = 62; HFFM n = 57), the median (interquartile range) lowest saturation was 91.5% (80-96) for HFNC and 89.5% (81-95) for the HFFM group (p = 0.44). There was no difference for difficult intubation (p = 0.18), intubation difficulty scale, ventilation-free days (p = 0.09), intubation-related adverse events including desaturation <80% or mortality (p = 0.46). CONCLUSIONS Compared to HFFM, HFNC as a preoxygenation device did not reduce the lowest level of desaturation.


Human Coronavirus OC43 Associated with Fatal Encephalitis.


title: Active Reperfusion Hemorrhage during Thrombectomy: Angiographic Findings and Real-Time Correlation with the CT "Spot Sign".

text: Introduction Symptomatic intracranial hemorrhage represents one of the most feared complications of endovascular reperfusion. We aim to describe a series of patients that experienced immediate reperfusion injury with active intraprocedural extravasation within the territory of the deep penetrating arteries and provide real-time correlation with CT "spot sign." Methods This was a retrospective analysis of patients that suffered reperfusion injury with active arterial extravasation during endovascular stroke treatment in two tertiary care centers. Results Five patients were identified. Median age was 63 (58-71) years, 66% were male. Median NIHSS was 13.5 (9.5-23.0), platelet level 212,000 (142,000-235,000), baseline systolic blood pressure 152 (133-201) mm Hg, and non-contrast CT ASPECTS 7.0 (6.5-9.0). Two patients were taking aspirin and one had received intravenous thrombolysis. There were three middle cerebral artery M1, one internal carotid artery terminus, and one vertebrobasilar junction occlusion. Three patients had anterior circulation tandem occlusions. Stroke etiology was extracranial atherosclerosis (n = 2), intracranial atherosclerosis (n = 2), and cervical dissection (n = 1). The median time from onset to puncture was 5.5 (3.9-8.6) h. Intravenous heparin was administered in all patients (median dose of 4,750 [3,250-6,000] units) and intravenous abciximab in four. All tandem cases had the cervical lesion addressed first. Four lenticulostriates and one paramedian pontine artery were involved. Intraprocedural flat-panel CT was performed in four (80%) cases and provided real-time correlation between the active contrast extravasation and the "spot sign." The bailout included use of protamine, blood pressure control, and balloon guide catheter or intracranial compliant balloon inflation plus coiling of targeted vessel. All patients had angiographic cessation of bleeding at the end of the procedure with parenchymal hemorrhage type 1 in one case and type 2 in four. Three patients had modified Rankin score of 4 and two were dead at 90 days. Conclusions Active reperfusion hemorrhage involving perforator arteries was observed to correlate with the CT "spot sign" and to be associated with poor outcomes.


Mobilizing animal models against a pandemic.


title: Short-term outcomes of local correction of stoma prolapse with a stapler device.

text: BACKGROUND The aim of the present study was to classify the short-term outcomes of local correction of stoma prolapse with a stapler device. METHODS The medical records of 11 patients undergoing local correction of stoma prolapse using a stapler device were retrospectively reviewed. RESULTS No mortality or morbidity was observed after the surgery. Median operative time was 35 min (range 15-75 min), and blood loss was minimal. Median duration of follow-up was 12 months (range 6-55 months). One of the 11 patients had a recurrent stoma prolapse. CONCLUSIONS This technique can be a feasible, safe and minimally invasive correction procedure for stoma prolapse.


title: Three-Port Versus Five-Port Laparoscopic Distal Gastrectomy for Early Gastric Cancer Patients: A Propensity Score Matched Case-Control Study.

text: AIM The aim of this study was to evaluate the feasibility and safety of three-port laparoscopic distal gastrectomy (TP-LDG) as a reduced port laparoscopic gastrectomy. MATERIALS AND METHODS We retrospectively identified 146 patients preoperatively diagnosed with early gastric cancer who underwent five-port laparoscopic distal gastrectomy (FP-LDG) or TP-LDG between May 2013 and July 2016. A propensity score matching analysis was used to create patient groups (48 patients in each group) matched for sex, age, body mass index, previous abdominal surgery history, and American Society of Anesthesiologist score. The short-term surgical outcomes between TP-LDG and FP-LDG were compared. RESULTS The TP-LDG group had a statistically shorter umbilical wound length [3.4 (range, 3.0-4.0) cm vs. 3.9 (range, 3.7-4.0) cm, p = .000], shorter operative time [230 (range, 190-310) min vs. 250 (range, 180-320) min, p = .036], and lower estimated blood loss [68 (range, 20-180) mL vs. 80 (range, 40-150) mL, p = .005] compared to that in the FP-LDG group. However, there was no specific superiority regarding inflammatory profiles. Complication rates were also similar (8.4% TP-LDG vs. 12.6% FP-LDG, p = .504). CONCLUSIONS TP-LDG is a feasible and safe surgical procedure for the patients with early gastric cancer and provides the benefit of better cosmesis.


title: Retroperitoneal single-site robot-assisted partial nephrectomy using Lapsingle Vision advanced access platform: initial three case reports.

text: Robot-assisted partial nephrectomy is currently the standard for treatment of small renal mass. Recently, robot-assisted single site surgery has been introduced. However, there have been few reports of retroperitoneal approaches. Herein, we report initial case series of retroperitoneal single-site robot-assisted partial nephrectomy using the da Vinci Xi surgical system using the Lapsingle Vision advanced access platform. Three patients have undergone retroperitoneal single-site robot-assisted partial nephrectomy due to incidental finding of renal mass. Operation duration, estimated blood loss, warm ischemia time, estimated glomerular filtration rate (eGFR) change, and complication were evaluated. Renal cell carcinoma of the two clear cell type and one chromophobe was diagnosed based on the pathological examination. Initial two cases were successfully completed with minimal bleeding and warm ischemic time within 25 minutes. The last 3rd case has been converted to multiport operation due to limited retroperitoneal space and difficulty in managing upper pole renal mass. Retroperitoneal single-site robot-assisted partial nephrectomy is a feasible treatment modality for treatment of posterior or lateral renal masses. Additional cases are needed to confirm the safety and efficacy of this technique.


title: Rapid pulmonary fibrosis induced by acute lung injury via a lipopolysaccharide three-hit regimen.

text: Based on the common characteristic of severe acute respiratory syndrome (SARS) and highly pathogenic avian influenza and the mechanism of inflammation and fibrosis, it is speculated that there should exist a fundamental pathological rule that severe acute lung injury (ALI)-induced rapid pulmonary fibrosis is caused by various etiological factors, such as SARS coronavirus, H5N1-virus, or other unknown factors, and also by lipopolysaccharide (LPS), the most common etiological factor. The investigation employed intratracheally, and intraperitoneally and intratracheally applied LPS three-hit regimen, compared with bleomycin-induced chronic pulmonary fibrosis. Inflammatory damage and fibrosis were evaluated, and the molecular mechanism was analyzed according to Th1/Th2 balance, Sma- and MAD-related proteins (Smads) and signal transducer and activator of transcriptions (STATs) expression. The results suggested that rapid pulmonary fibrosis could be induced by ALI via LPS three-hits. The period from 3-7 days in the LPS group was the first rapid pulmonary fibrosis stage, whereas the second fast fibrosis stage occurred on days 14-21. Th2 cell polarization, Smad4 and Smad7 should be the crucial molecular mechanism of ALI-induced rapid fibrosis. The investigation was not only performed to establish a new rapid pulmonary fibrosis model, but also to provide the elicitation for mechanism of ALI changed into the rapid pulmonary fibrosis.


title: Comparison of a paediatric emergency ruler with a digital algorithm for weight and age estimation.

text: BACKGROUND Emergency tapes like the "Paediatric-Emergency-Ruler" (PaedER) provide drug dosing and recommend medical airway equipment based on estimated patient bodyweight and age. Previous studies have revealed unsatisfactory accuracy in bodyweight estimation, due to the tapes' length-based weight categories. Therefore, we developed a digital algorithm allowing continuous length-based estimation of weight and age. The aim of this study was to compare the new algorithm with the PaedER regarding accuracy in estimating bodyweight and recommendation of medical airway equipment. METHODS Patients with a body length suitable for the PaedER were included in this single centre, prospective clinical observation trial after obtaining informed written parental consent. Bodyweight estimations by the algorithm and PaedER within ± 10% and ± 20% of the actual bodyweight were compared. Furthermore, medical airway equipment suggested by the PaedER and algorithm were compared with the equipment actually used for anaesthesia. Wilcoxon- and McNemar-Tests were used for statistical analysis. Results are median (interquartiles), P < 0.05 was considered significant. RESULTS In total, 489 patients aged 2.0 years (0.4-5.9), with a body length of 89.0 cm (63.5-114.5), weighing 12.8 kg (6.3-19.6), were included. The algorithm's precision of bodyweight estimation within ± 10%/± 20% was significantly higher at 64.0%/91.6% than the PaedER at 55.4%/81.8% (P < 0.001). Compared to PaedER the algorithm showed a higher incidence of correctly recommended medical airway equipment based on its accuracy for age and bodyweight estimation. CONCLUSION The new digital algorithm is an alternative to conventional emergency tapes, showing improved accuracy regarding length-based estimation of bodyweight and recommendation of medical airway equipment.


title: Stroke: Stroke prevention--time to say goodbye to the ABCD2 score?

text: The ABCD2 score was developed to triage patients with transient ischaemic attack according to the risk of experiencing a stroke in the next few hours or days. However, a new systematic review and meta-analysis on the ABCD2 score gives us considerable cause to rethink its value for clinical situations.


Women and children first: the need for ringfencing during the COVID-19 pandemic.


title: Quantification and visualisation methods of data-driven chronic care delivery pathways: protocol for a systematic review and content analysis.

text: INTRODUCTION Chronic conditions require long periods of care and often involve repeated interactions with multiple healthcare providers. Faced with increasing illness burden and costs, healthcare systems are currently working towards integrated care to streamline these interactions and improve efficiency. To support this, one promising resource is the information on routine care delivery stored in various electronic healthcare databases (EHD). In chronic conditions, care delivery pathways (CDPs) can be constructed by linking multiple data sources and extracting time-stamped healthcare utilisation events and other medical data related to individual or groups of patients over specific time periods; CDPs may provide insights into current practice and ways of improving it. Several methods have been proposed in recent years to quantify and visualise CDPs. We present the protocol for a systematic review aiming to describe the content and development of CDP methods, to derive common recommendations for CDP construction. METHODS AND ANALYSIS This protocol followed the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. A literature search will be performed in PubMed (MEDLINE), Scopus, IEEE, CINAHL and EMBASE, without date restrictions, to review published papers reporting data-driven chronic CDPs quantification and visualisation methods. We will describe them using several characteristics relevant for EHD use in long-term care, grouped into three domains: (1) clinical (what clinical information does the method use and how was it considered relevant?), (2) data science (what are the method's development and implementation characteristics?) and (3) behavioural (which behaviours and interactions does the method aim to promote among users and how?). Data extraction will be performed via deductive content analysis using previously defined characteristics and accompanied by an inductive analysis to identify and code additional relevant features. Results will be presented in descriptive format and used to compare current CDPs and generate recommendations for future CDP development initiatives. ETHICS AND DISSEMINATION Database searches will be initiated in May 2019. The review is expected to be completed by February 2020. Ethical approval is not required for this review. Results will be disseminated in peer-reviewed journals and conference presentations. PROSPERO REGISTRATION NUMBER CRD42019140494.


title: Recovery of gastric ileus following laparoscopic ventral rectopexy within an enhanced recovery protocol.

text: PURPOSE The enhanced recovery after surgery (ERAS) protocol has had limited adoption in laparoscopic ventral rectopexy (LVR), and the extent of gastric ileus shortly after LVR remains unknown. This study was designed to assess the degree of gastric emptying shortly after LVR within an ERAS protocol. METHODS From August 2012 to June 2014, 40 patients diagnosed with external or internal rectal prolapse were recruited. All patients underwent LVR within an ERAS protocol. Carbohydrate solution (CS) was administered before and 5 h after surgery on the same day. The pyloric area (PA) was measured using ultrasonography before and after each CS intake. RESULTS The PA was measured in 34 patients. The PA measured prior to CS intake, before surgery, was not significantly different from that after surgery. The rate of increase in the PA, which was calculated by the PA measured 1 h after CS intake divided by the PA measured prior to CS intake before surgery, was not significantly different from that after surgery. The postoperative hospital stay was 1 (1-2) day, and 36 patients (90 %) were discharged on the first postoperative afternoon. CONCLUSION Postoperative gastric ileus was resolved in most cases within 5 h after LVR under an ERAS protocol.


Cochrane Corner: Coronavirus (COVID-19): remote care through telehealth.


Totally intracorporeal robotic en bloc resection for deep infiltrating endometriosis of the rectovaginal wall with natural orifice specimen extraction.


title: [Smell disorders at COVID-19 - the current level of knowledge].

text: Early reports of SARS-CoV-2 infections only rarely mentioned smell and taste disorders. Several studies, particularly from Europe and the USA, have now confirmed these symptoms as an early key feature of COVID-19. About 70 % of patients seem to experience a reduction of smell and taste in the course of the disease, with most of the studies published to date based on questionnaires and anamnestic data. Validated smell tests have so far only been used in a few studies. A distinction between taste and taste disorders, i. e. a distinction between retronasal aroma taste and the olfactory system from the dysfunction of taste capsules and the further cranial nerves, was mostly not made in the studies available to date. Some reports associate olfactory disorders with a milder clinical course. At the same time, the olfactory system via the olfactory bulb represents an entry point into the central nervous system, and an olfactory disorder could be a predisposing factor for central neurological symptoms. The clinical significance of smell and taste disorders in COVID-19 patients is currently still unclear. Further open questions concern the exact prevalence and the prognosis, so that overall higher quality studies with validated smell tests and larger numbers of patients are required.


title: COVID-19 Prevention and Control Public Health Strategies in Shanghai, China.

text: CONTEXT COVID-19 was characterized as a pandemic by the World Health Organization on March 11, 2020. This research aims to analyze the public health strategies to prevent and control COVID-19 in Shanghai, China, and provide recommendations for public health policy and interventions in the United States. PROGRAM Based on the Social-Ecological Model, this research collected information for public health strategies from the Shanghai Municipal Health Commission and various Chinese websites. EVALUATION The daily confirmed new cases of COVID-19 decreased from 27 to 0 in 53 days since the first case of COVID-19 was confirmed in Shanghai on January 20, 2020. DISCUSSION The pattern of daily confirmed new cases suggests the effectiveness of public health strategies. This research also provides recommendations on the development and improvements of public health strategies in the U.S. by acknowledging the differences in political and social systems between the two countries.


title: Safety profile of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis.

text: PURPOSE To evaluate the safety of endovascular treatment of chronic cerebrovascular insufficiency (CCSVI) in patients with multiple sclerosis (MS). METHODS In a 1-year period, 461 MS patients (261 women; mean age 45.4 years, range 21-79) with CCSVI underwent endovascular treatment of 1012 venous lesions during 495 procedures [34 (6.9%) reinterventions]. While balloon angioplasty was preferred, 98 stents were implanted in 76 patients for lesion recoil, restenosis, or suboptimal dilation. The procedures were analyzed for incidences of major adverse events (death, major bleeding, or clinical deterioration of MS), access site complications, procedure-related complications, and procedural safety-related variables (fluoroscopy and contrast times). The complication rates were compared to published data for similar endovascular methods. RESULTS There were no deaths, major bleeding events, or clinical deterioration of MS. Access site complications included limited groin hematoma (5, 1.0%); there were no arteriovenous fistulas or puncture site infections. Systemic complications included only rare cardiac arrhythmias (6, 1.2%). Procedure-related complications included vein rupture (2, 0.4%), vein dissection (15, 3.0%), acute in-stent/in-segment thrombosis (8, 1.6%), and acute recoil (1, 0.2%); there was no stent migration or fracture or distal embolization. Mean fluoroscopy time was 22.7 minutes, and mean contrast volume was 136.3 mL. CONCLUSION Endovascular therapy appears to be a safe and reliable method for treating CCSVI. Innovations such as purpose-specific materials and devices are needed, as are case-controlled and randomized data to establish efficacy in ameliorating MS symptoms.


title: [The CoViD-19 epidemic is posing entirely new problems for home cancer care services.]

text: We report on the protocol adopted by the Oncological Home Care Service of the Tuscany Cancer Association during the CoViD-19 pandemic. Based on the experience in home cancer care gained during the 2009 earthquake, we have developed strategies to ensure continuity of care, non-abandonment and protection of operators. In this context, the double triage protocol plays a central role, aimed at identifying patients at risk for CoViD-19 infection and rationalizing home access. we describe the protocol and present the preliminary data.


COVID-19 in the maritime setting: the challenges, regulations and the international response.


Measles in the UK: a test of public health competency in a crisis.


RECOVERY trial: the UK covid-19 study resetting expectations for clinical trials.


title: Endoluminal surgical triangulation 2.0: A new flexible surgical robot. Preliminary pre-clinical results with colonic submucosal dissection.

text: BACKGROUND Complex intraluminal surgical interventions of the gastrointestinal tract are challenging due to the limitation of existing instruments. Our group has developed a master-slave robotic flexible endoscopic platform that provides instrument triangulation in an endoluminal environment. MATERIALS AND METHODS Colonic endoscopic submucosal dissections (ESD) were carried out in eight pigs. The robot was introduced transanally. A combination of adapted tele-operated instruments was used. Specimens were inspected and measured. RESULTS Out of 18 ESDs in total, 12 were successfully completed. Among the completed procedures, two perforations and one system failure occurred and were managed intraoperatively. There was no major bleeding. Mean size of the removed specimens was 18.2 ± 9.8 cm2 and mean total procedure time was 73 ± 35.5 min. CONCLUSIONS Experimental colorectal ESDs using the flexible surgical robot were feasible and reflected a short learning curve. After some technical improvements the system might allow for a wider adoption of complex endoluminal surgical procedures.


Reimagining healthcare after covid-19: a new normal for medicine.


title: Diurnal fluctuations in polybrominated diphenyl ether concentrations during and after a severe dust storm episode in Kuwait City, Kuwait.

text: Concentrations of polybrominated diphenyl ethers (PBDEs) were quantified in four-hour integrated air samples obtained serially over a five day period in May 2007 in Kuwait City during and after a severe dust storm. The ∑PBDE concentrations ranged from 51 to 1307 pg m(-3) for the first two days of sampling and 20 to 148 pg m(-3) for the rest of the sampling period. The first two days of sampling occurred during a severe dust storm episode when the total suspended particulates (TSP) in air exceeded 1000 μg/m(3) with concentrations peaking during the day and decreasing at night. During this dust episode, the peak nighttime PBDE concentration was 30 times higher than the minimum daytime concentration. Although ∑PBDE concentrations peaked at night during the first two sampling days, the fluctuations in the BDE 47:99 ratio tracked changes in ambient temperature remarkably well, following a clear diurnal pattern. The fraction of congeners in the gas phase varied inversely with solar flux and was lower on days with a high number of hours of sunshine, suggesting that photolytic degradation of gas-phase PBDEs was occurring.


Huge retroperitoneal complicated pseudotumour in haemophilia B with inhibitor.


Fallacies and Facts Around COVID-19: The Multifaceted Infection.


title: Reduced blood flow in normal white matter predicts development of leukoaraiosis.

text: The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61±11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval=0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.


In reply: Assessment of fluid responsiveness with end-tidal carbon dioxide using a simplified passive leg-raising maneuver: a prospective observational study.


title: Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.


title: Comparison of the Accula SARS-CoV-2 Test with a Laboratory-Developed Assay for Detection of SARS-CoV-2 RNA in Clinical Nasopharyngeal Specimens.

text: Background: Several point-of-care (POC) molecular tests have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) for diagnosis of SARS-CoV-2. The test performance characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test need to be evaluated to inform its optimal use.Objectives: The aim of this study was to assess test performance of the Accula SARS-CoV-2 test.Study design: The performance of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT) targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa coefficient.Results: Overall percent agreement between the assays was 84.0% (95% confidence interval [CI] 75.3 to 90.6%), PPA was 68.0% (95% CI 53.3 to 80.5%) and the kappa coefficient was 0.68 (95% CI 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test, and showed low viral load burden with a median cycle threshold value of 37.7. NPA was 100% (95% CI 94.2 to 100%).Conclusion: Compared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false negative rate of the Accula POC test calls for a more thorough evaluation of POC test performance characteristics in clinical settings, and for confirmatory testing in individuals with moderate to high pre-test probability of SARS-CoV-2 who test negative on Accula.


title: Effect of Methotrexate or Salpingectomy for Ectopic Pregnancy on Subsequent In Vitro Fertilization-Embryo Transfer Outcomes.

text: OBJECTIVE To investigate the effect of methotrexate (MTX) or salpingectomy for ectopic pregnancy on the outcomes of subsequent in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN Retrospective cohort study (Canadian Task Force Classification II-3). SETTING Academic center. PATIENTS All patients undergoing fresh IVF-ET between January 2004 and July 2013 after treatment of an ectopic pregnancy with MTX or salpingectomy in the preceding IVF-ET cycle were analyzed for potential inclusion. INTERVENTION MTX or laparoscopic salpingectomy for an ectopic pregnancy followed by a subsequent IVF-ET cycle. MEASUREMENTS AND MAIN RESULTS A total of 144 patients with sonographically confirmed ectopic pregnancies were identified during the study period. Of these, 107 (74.3%) patients were treated with MTX and 37 (25.7%) were treated with laparoscopic salpingectomy. Eighty-eight patients (82.2%) in the MTX group and 22 patients (59.4%) patients in the salpingectomy group underwent a subsequent IVF-ET cycle. There were no significant differences in demographic data or baseline cycle characteristics between the 2 groups. No difference was observed in basal follicle-stimulating hormone (FSH) level before and after MTX or salpingectomy treatment. Indicators of ovarian responsiveness, including total days of stimulation, total dosage of gonadotropins, and number of mature oocytes before and after either treatment, were comparable in the 2 groups. The number of doses of MTX (1 vs > 1) did not correlate with changes in ovarian response. The pregnancy outcomes, specifically live birth, were equivalent in the 2 groups. Comparing post-MTX cycles and post-salpingectomy cycles, patients in the latter group required higher doses of gonadotropins (+705 IU vs +221.5 IU; p < .01), although the number of mature oocytes remained similar in the 2 groups. CONCLUSION Treatment of ectopic pregnancies with MTX or salpingectomy might not adversely affect ovarian reserve, ovarian responsiveness, or subsequent IVF cycle outcomes. However, in our study cohort, patients treated with MTX, those s treated with laparoscopic salpingectomy required higher gonadotropin doses in a subsequent cycle to attain the same number of mature oocytes.


title: Phosphonic Acid Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase, Tomato Acidic Leucine Aminopeptidase and Aminopeptidase from Barley Seeds.

text: The inhibitory activity of 14 racemic phosphonic acid analogs of phenylglycine, substituted in aromatic rings, towards porcine aminopeptidase N (pAPN) and barley seed aminopeptidase was determined experimentally. The obtained patterns of the inhibitory activity against the two enzymes were similar. The obtained data served as a basis for studying the binding modes of these inhibitors by pAPN using molecular modeling. It was found that their aminophosphonate fragments were bound in a highly uniform manner and that the difference in their affinities most likely resulted from the mode of substitution of their phenyl rings. The obtained binding modes towards pAPN were compared, with these predicted for bovine lens leucine aminopeptidase (blLAP) and tomato acidic leucine aminopeptidase (tLAPA). The performed studies indicated that the binding manner of the phenylglycine analogs to biLAP and tLAPA are significantly similar and differ slightly from that predicted for pAPN.


Ebola: controlling the nightmare.