title: The Twin Forceps: A New Instrument for SILS.

text: In the last ten years, the single incision laparoscopic surgery (SILS) is gaining more interest than the traditional laparoscopic surgery (LAP). Many studies make a comparison between the performances of the SILS and the LAP. The results show that the single incision laparoscopic surgery reduces pain, length of period of postoperative hospitalization, and loss of blood. This technique is also able to reduce the infection sites. In spite of many advantages, SILS reveals some problems: laparoscopic instruments triangulation and small workspace. The surgeon has to be more skillful to make a surgery in SILS because the surgeon has only three laparoscopic instruments and only one hole in the abdomen cavity. In this paper, a novel laparoscopic instrument to help the surgeon during a SILS operation is presented. This instrument is innovative forceps with double graspers. Different designs of this instrument are presented, with the final one which greatly simplifies both construction and operation. The initial experience in the laboratory with the innovative instrument is presented. The surgeon experienced in laparoscopic surgery and with the help of assistants performed a training program based on predetermined task performed in simulation box (laparoscopic box-trainer).


Highlights from the first ever virtual American College of Cardiology World Congress of Cardiology 2020 (ACC.20/WCC).


title: Atherosclerosis as a predictor of transient exacerbation of overactive bladder symptoms after robot-assisted laparoscopic radical prostatectomy.

text: OBJECTIVES To assess whether atherosclerosis is involved in the development of overactive bladder and the function of lower urinary tract after robot-assisted radical prostatectomy. METHODS The present cohort consisted of 80 consecutive participants. The preoperative cardio-ankle vascular index was used to evaluate the presence of atherosclerosis. The present cohort was split into two groups, the atherosclerotic group, whose cardio-ankle vascular index was ≥9.0, and the control group, whose index was <9.0. The overactive bladder symptom score and lower urinary tract function were compared for 12 months after surgery. RESULTS The total score of the questionnaire was significantly higher at 6 and 9 months after surgery in the atherosclerosis group (P = 0.04, P = 0.03, respectively). Both the urgency and urgency incontinence subscores of the questionnaire showed a parallel tendency to that of the total score after surgery. At 3 months after surgery, there was a significant increase in the prevalence of de novo overactive bladder in the atherosclerosis group (P = 0.04). At 9 and 12 months after surgery, there was a significant decrease of voided volume in the atherosclerotic group (P < 0.01, P = 0.04, respectively). CONCLUSIONS Atherosclerosis delays the improvement in both overactive bladder symptoms and storage function postoperatively, and it is involved in the transient increase in the prevalence of de novo overactive bladder. Atherosclerosis might be a predictor of the development of overactive bladder after robot-assisted radical prostatectomy.


title: Bispectral index to predict neurological outcome early after cardiac arrest.

text: AIM OF THE STUDY To address the value of continuous monitoring of bispectral index (BIS) to predict neurological outcome after cardiac arrest. METHODS In this prospective observational study in adult comatose patients treated by therapeutic hypothermia after cardiac arrest we measured bispectral index (BIS) during the first 24 hours of intensive care unit stay. A blinded neurological outcome assessment by cerebral performance category (CPC) was done 6 months after cardiac arrest. RESULTS Forty-six patients (48%) had a good neurological outcome at 6-month, as defined by a cerebral performance category (CPC) 1-2, and 50 patients (52%) had a poor neurological outcome (CPC 3-5). Over the 24h of monitoring, mean BIS values over time were higher in the good outcome group (38 ± 9) compared to the poor outcome group (17 ± 12) (p<0.001). Analysis of BIS recorded every 30 minutes provided an optimal prediction after 12.5h, with an area under the receiver operating characteristic curve (AUC) of 0.89, a specificity of 89% and a sensitivity of 86% using a cut-off value of 23. With a specificity fixed at 100% (sensitivity 26%) the cut-off BIS value was 2.4 over the first 271 minutes. In multivariable analyses including clinical characteristics, mean BIS value over the first 12.5h was a predictor of neurological outcome (p = 6E-6) and provided a continuous net reclassification index of 1.28% (p = 4E-10) and an integrated discrimination improvement of 0.31 (p=1E-10). CONCLUSIONS Mean BIS value calculated over the first 12.5h after ICU admission potentially predicts 6-months neurological outcome after cardiac arrest.


title: Abdominal Surgery in Patients with COVID-19: Detection of SARS-CoV-2 in Abdominal and Adipose Tissues.

text: : Multiple tissue samples were obtained during emergent abdominal surgery in four patients with coronavirus disease 2019 (COVID-19) to examine for tissue involvement by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first patient underwent a laparoscopic cholecystectomy for gallbladder empyema and died from severe respiratory failure. The second patient with Crohn's disease underwent emergent laparotomy for a perforation in the terminal ileum and recovered. The third patient underwent an open appendectomy and recovered. The fourth patient underwent emergent laparotomy for a perforated peptic ulcer and died from sepsis. While the SARS-CoV-2 RNA was found in the feces of three patients and in the duodenal wall of the patient with perforated peptic ulcer, RT-PCR examination of abdominal fluid was negative for the virus. The RT-PCR did not detect viral RNA in the wall of small intestine, appendix, and gallbladder, bile, liver, and urine. Visceral fat (omentum) and abdominal subcutaneous fat of four patients were also not infected with the SARS-CoV-2. Although this limited experience did not show direct involvement of abdominal fluid and omentum, assessment in large series is suggested to provide answers about the safety of abdominal surgery in patients with COVID-19.


title: Impact of crossing technique on the incidence of periprocedural myocardial infarction during chronic total occlusion percutaneous coronary intervention.

text: OBJECTIVES We sought to evaluate the impact of crossing strategy on the incidence of periprocedural myocardial infarction (PMI) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND The optimal technique for crossing coronary CTOs remains controversial. METHODS We retrospectively examined the incidence of PMI among 184 consecutive patients who underwent CTO PCI at our institution between 2012 and 2015. Creatine kinase-myocardial band fraction (CK-MB) and troponin were measured before and after PCI in all patients. PMI was defined as CK-MB increase ≥3× upper limit of normal (ULN). RESULTS Mean age was 65 ± 8 years, 98% of patients were men, 57% had diabetes mellitus, 36% were current smokers, 38% had prior heart failure, 31% had prior coronary artery bypass graft surgery (CABG), and 55% had prior PCI. The retrograde approach was used in 38% of cases. As compared with antegrade wire escalation and antegrade dissection/re-entry, use of the retrograde approach was associated with higher J-CTO (Multicenter CTO Registry of Japan) scores (P < 0.0001), higher frequency of moderate or severe calcification (P = 0.0061), longer CTO length (P < 0.0001), more frequent proximal cap ambiguity (P < 0.0001), and lower technical (P = 0.0007) and procedural (P = 0.0014) success. The frequency of PMI for the antegrade-only and retrograde cases was 10% and 33%, respectively (P = 0.0001). On multivariate analysis, use of the retrograde approach and moderate/severe calcification were independently associated with higher incidence of PMI. CONCLUSIONS As compared with antegrade-only crossing techniques, the retrograde approach is used in patients with more complex anatomy but may carry higher risk for PMI. © 2016 Wiley Periodicals, Inc.


title: New device for transrectal trocar placement and rectal sealing for NOTES: a porcine in vivo and human cadaver study.

text: BACKGROUND To date, hybrid NOTES, combining transvaginal and laparoscopic access, represents the most popular clinically applied NOTES approach enabling surgical handling comparable to laparoscopic surgery. The transrectal route could be used in a similar way; however, suitable devices facilitating feasible transrectal access and rectal sealing are lacking. METHODS In collaboration with Karl Storz GmbH, we tailored a rectoscope and trocars to facilitate transrectal trocar placement and rectal sealing for hybrid NOTES procedures using rigid instruments. Five German Landrace pigs underwent transrectal hybrid NOTES cholecystectomy using the new devices. In a second experiment, the transferability to human anatomy was assessed in a human cadaver. RESULTS Using the new devices, transrectal trocar placement and rectal sealing proved to be feasible in both experiments. Transrectal hybrid NOTES cholecystectomy could be performed without complications. CONCLUSION The presented devices provide a tailored operating platform allowing precise transrectal trocar insertion and feasible sealing of the rectotomy. Consequently, these new instruments may pave the way for transrectal hybrid NOTES procedures and could succeed to clinical use in future.


title: Perspective of Oncology Patients During COVID-19 Pandemic: A Prospective Observational Study From India.

text: PURPOSE The coronavirus disease 2019 (COVID-19) pandemic has imposed a unique challenge to oncology patients and their treatment. There is no study related to the patients' preference for systemic therapy during this pandemic. We have conducted a prospective study to analyze that aspect. METHODS All consecutive patients who visited during the lockdown period from April 1-10, 2020, for systemic chemotherapy were included in the study for a questionnaire-based survey to evaluate the willingness to continue chemotherapy during this pandemic and factors influencing the decisions. RESULTS A total of 302 patients were included (median age, 56 years; range, 21-77 years). Most common sites of cancer were breast (n = 114), lung (n = 44), ovary (n = 34), and colon (n = 20). Home address was within the city for 125 patients (42%), outside the city for 138 (46%), and outside the state for 37 (12%). Treatment was curative in 150 patients and palliative in 152. Educational status was primary and above for 231 patients and no formal schooling for 71. A total of 203 patients wanted to continue chemotherapy, 40 wanted to defer, and 56 wanted the physician to decide. Knowledge about COVID-19 strongly correlated with intent of treatment (P = .01), disease status (P = .02), knowledge about immunosuppression (P < .001), home location (P = .02), and education status (P = .003). The worry about catching SARS-CoV-2 was high in those with controlled disease (P = .06) and knowledge about immunosuppression (P = .02). Worry about disease progression was more with palliative intent (P < .001). CONCLUSION This study shows that oncology patients in our country are more worried about disease progression than the SARS-CoV-2 and wish to continue chemotherapy during this pandemic. The treatment guidelines in the COVID-19 scenario should incorporate patients' perspectives.


title: Laparoscopic liver packing to protect surrounding organs during thermal ablation.

text: PURPOSE To evaluate the feasibility of liver packing for the prevention of injury to adjacent organs during thermal ablation of liver tumors. MATERIAL AND METHODS Between January 2005 and March 2010, 47 (52 sessions) patients with non-resectable liver tumors were treated and their tumors (55 primary carcinomas and 65 metastases, 1-12) were isolated from adjacent organs by laparoscopic liver mobilization and packing. Stereotactic radiofrequency ablation (SRFA) comprised body fixation, contrast-enhanced CT, 3-D planning, navigation, needle placement, control CT of needle positions (with image fusion), thermal ablation and control CT (with image fusion). Liver packing was removed laparoscopically thereafter. Complications, primary success and local recurrence rates were analyzed. RESULTS A total of 120 liver lesions with a median size of 2.4 cm (range 1-15 cm) were treated. Laparoscopic packing could be performed in all patients. The primary success rate of ablation was 91.6% (110/120) and the local recurrence rate was 4.5% (5/110). There was one perioperative death (1.9%). All remaining complications could be managed by radiological interventions. Despite broad surface contact thermal injury of surrounding organs could be prevented in all patients. CONCLUSION Liver packing presents a viable and safe option for RFA of tumors with broad surface contact to surrounding organs with excellent local tumor control.


Survival of the fittest.


Role of rehabilitation medicine in the COVID-19 pandemic: an Iranian consensus.


title: Endovascular Treatment Versus Intravenous Thrombolysis for Acute Ischemic Stroke: a Quantitative Review and Meta-Analysis of 21 Randomized Trials.

text: Emerging studies suggest that endovascular treatment (EVT) may be superior to intravenous thrombolysis for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) to assess the efficacy and safety of endovascular treatment in patients with acute ischemic stroke as compared with intravenous thrombolysis. We assessed RCTs investigating EVT versus intravenous thrombolysis (IVT) published up to June 2015. In total, 21 studies of 4473 patients were included in the systematic review and meta-analysis. EVT significantly improved functional outcome at 90 days (risk ratio (RR) 1.35, 95 % confidence interval (CI) 1.18 to 1.55, I 2 = 61 %) and reduced the mortality (RR 0.81, 95 % CI 0.68 to 0.95, I 2 = 0 %), with similar symptomatic hemorrhagic transformation (SHT) rate (RR 1.12, 95 % CI 0.88 to 1.44, I 2 = 0 %). Based on the current data, endovascular therapy may produce good clinical outcomes with similar symptomatic hemorrhage and mortality as compared with intravenous thrombolysis in acute ischemic stroke. This advancing intervention is a landmark change in stroke treatment and could be of huge potential benefit to patients worldwide.


title: Heartland Virus and Hemophagocytic Lymphohistiocytosis in Immunocompromised Patient, Missouri, USA.

text: Heartland virus is a suspected tickborne pathogen in the United States. We describe a case of hemophagocytic lymphohistiocytosis, then death, in an immunosuppressed elderly man in Missouri, USA, who was infected with Heartland virus.


Endosonography for lung cancer staging: one scope fits all?


title: Structural analysis of the evolutionary origins of influenza virus hemagglutinin and other viral lectins.

text: Influenza virus and other viruses use host cell surface sugars as receptors. Here we show that the sugar-binding domains in influenza virus hemagglutinin and other viral lectins share the same structural fold as human galectins (host lectins). Unlike the easily accessible sugar-binding sites in human galectins, the sugar-binding sites in viral lectins are hidden in cavities. We propose that these viral lectins originated from host lectins but have evolved to use hidden sugar-binding sites to evade host immune attacks.


title: The global dimensions of public health preparedness and implications for US action.

text: The globalization of public health is both real and relevant throughout the United States and to Americans traveling or residing abroad. US public policy responses are evolving, but a crisper and more comprehensive global perspective is needed. I suggest four timely US actions to address today's competing realities of globalization and economic austerity: raise awareness among clinicians and local health departments; capture and share exemplary disaster management practices across countries; ensure that US global health investments are effective, efficient, and sustainable; and think globally while acting locally to enhance US health security. The reauthorization of the Pandemic and All-Hazards Preparedness Act of 2006 provides an opportunity to more clearly address the global dimensions of domestic preparedness.


title: Respiratory care year in review 2011: long-term oxygen therapy, pulmonary rehabilitation, airway management, acute lung injury, education, and management.

text: For the busy clinician, educator, or manager, it is becoming an increasing challenge to filter the literature to what is relevant to one's practice and then update one's practice based on the current evidence. The purpose of this paper is to review the recent literature related to long-term oxygen therapy, pulmonary rehabilitation, airway management, acute lung injury and acute respiratory distress syndrome, respiratory care education, and respiratory care management. These topics were chosen and reviewed in a manner that is most likely to have interest to the readers of Respiratory Care.


title: Consensus on current management of endometriosis.

text: STUDY QUESTION Is there a global consensus on the management of endometriosis that considers the views of women with endometriosis? SUMMARY ANSWER It was possible to produce an international consensus statement on the current management of endometriosis through engagement of representatives of national and international, medical and non-medical societies with an interest in endometriosis. WHAT IS KNOWN ALREADY Management of endometriosis anywhere in the world has been based partially on evidence-based practices and partially on unsubstantiated therapies and approaches. Several guidelines have been developed by a number of national and international bodies, yet areas of controversy and uncertainty remain, not least due to a paucity of firm evidence. STUDY DESIGN, SIZE, DURATION A consensus meeting, in conjunction with a pre- and post-meeting process, was undertaken. PARTICIPANTS/MATERIALS, SETTING, METHODS A consensus meeting was held on 8 September 2011, in conjunction with the 11th World Congress on Endometriosis in Montpellier, France. A rigorous pre- and post-meeting process, involving 56 representatives of 34 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. MAIN RESULTS AND THE ROLE OF CHANCE A total of 69 consensus statements were developed. Seven statements had unanimous consensus; however, none of the statements were made without expression of a caveat about the strength of the statement or the statement itself. Only two statements failed to achieve majority consensus. The statements covered global considerations, the role of endometriosis organizations, support groups, centres or networks of expertise, the impact of endometriosis throughout a woman's life course, and a full range of treatment options for pain, infertility and other symptoms related to endometriosis. LIMITATIONS, REASONS FOR CAUTION This consensus process differed from that of formal guideline development. A different group of international experts from those participating in this process would likely have yielded subtly different consensus statements. WIDER IMPLICATIONS OF THE FINDINGS This is the first time that a large, global, consortium, representing 34 major stake-holding organizations from five continents, has convened to systematically evaluate the best available current evidence on the management of endometriosis, and to reach consensus. In addition to 18 international medical organizations, representatives from 16 national endometriosis organizations were involved, including lay support groups, thus generating input from women who suffer from endometriosis.


title: Evolution of technique in performance of minimally invasive colectomies.

text: BACKGROUND Hand-assisted laparoscopic surgery is commonly used in colorectal surgery and provides benefit in complex cases. OBJECTIVE This study examined the minimally invasive surgical trends, patient characteristics, and operative variables unique to patients undergoing hand-assisted laparoscopic surgery. DESIGN This was a retrospective medical chart review. SETTINGS The study was conducted in a tertiary care medical center. PATIENTS Patients included in the study were those who underwent pure laparoscopic colectomies, hand-assisted laparoscopic colectomies, and traditional open surgery for elective treatment of diverticular disease, colorectal cancer, IBD, and benign polyp disease. MAIN OUTCOME MEASURES Primary outcomes included patient characteristics and operative variables unique to patients undergoing hand-assisted laparoscopic surgery and documentation of operative technique trends within an experienced colorectal group. RESULTS Diverticular disease characteristics specific to hand-assisted laparoscopic surgery included the presence of dense inflammatory adhesions (p < 0.0001), diverticular fistulas (p < 0.0001), and unresolved phlegmon (p = 0.0003). Characteristics specific for colorectal cancer included intraoperative tumor bulk (p < 0.0001) and the inability to achieve appropriate surgical resection margins (p < 0.001). Similarly, variables identified for benign polyp disease included adhesions (p < 0.0001) and the ability to gain adequate exposure (p < 0.0001). Limited use of hand-assisted laparoscopic surgery was observed in patients with IBD. LIMITATIONS This was a retrospective, observational study from a single center. CONCLUSIONS Conversion to hand-assisted laparoscopic surgery provides benefit in surgical scenarios where dense inflammatory adhesions, diverticular fistulas, and intra-abdominal postdiverticulitis phlegmon are present. In addition, benefit is observed in patients with colorectal cancer where laparoscopic dissection of bulky tumor proves to be difficult and where the technical ability to obtain margins using pure laparoscopy is compromised. Although our practice has changed to favor pure laparoscopy, hand-assisted laparoscopic surgery continues to play an important role in complex colorectal cases that otherwise would require open surgery (see video, Supplemental Digital Content 1, http://links.lww.com/DCR/A146).


title: Association between respiratory viruses and exacerbation of COPD: a case-control study.

text: BACKGROUND Respiratory viral infection is the main cause of exacerbations of chronic obstructive pulmonary disease (COPD) in all age groups. The present study aimed to find out the association between viral infection in exacerbated and stable patients with COPD as well as evaluating the frequency of respiratory viruses in the Iranian exacerbated patients. METHODS The study included 170 patients as the sample group with acute exacerbations and a control group consisting of 96 stable patients over a period of 3 years. Reverse transcription- nested polymerase chain reaction (RT-nested PCR) and nested PCR methods were used to diagnose the presence of 16 respiratory viruses. RESULTS Viral infection was detected in 81 (47.6%) exacerbations and 24 (25%) stable patients (p < 0.05). Adenovirus was more frequent among the exacerbated patients than the stable patients (p < 0.05). Furthermore, influenza virus, respiratory syncytial virus, and enterovirus turned out to be the most common viruses in both groups. Moreover, respiratory viral co-infection has a possible role in exacerbation, severity, and longer hospitalization. Muscle pain and fever were found as significant symptoms in the infected patients with exacerbations. CONCLUSIONS The current study investigated the probable roles of the respiratory viruses, and dual infections during acute exacerbations of COPD. Since climate-dependent respiratory viral incidence patterns in Iran are often dissimilar, preparing a comprehensive global model of respiratory infections with seasonal details in different geographical zones might decrease the morbidity and mortality rate in exacerbations of COPD.


title: Selective arterial embolization of symptomatic and asymptomatic renal angiomyolipomas: a retrospective study of safety, outcomes and tumor size reduction.

text: BACKGROUND Angiomyolipoma (AML) is the most common renal benign tumor. Treatment should be considered for symptomatic patients or for those at risk for complications, especially retroperitoneal bleeding which is correlated to tumor size, grade of the angiogenic component and to the presence of tuberous sclerosis complex (TSC). This study reports our single-center experience with the use of selective arterial embolization (SAE) in the management of symptomatic and asymptomatic renal AMLs. METHODS In this retrospective mono-centric study, all demographic and imaging data, medical records, angiographic features, outpatient charts and follow-up visits of patients who underwent prophylactic or emergency SAE for AMLs between January 2005 and July 2016 were reviewed. Tumor size and treatment outcomes were assessed at baseline and after the procedure during follow-up. Computed tomography (CT), magnetic resonance imaging (MRI) or ultrasonography was used to evaluate AML shrinkage. Renal function was measured pre- and post-procedure. RESULTS Twenty-three patients (18 females, 5 males; median age, 45 years; range, 19-85 years) who underwent SAE either to treat bleeding AML (n=6) or as a prophylactic treatment (n=17) were included. Overall, 34 AMLs were embolized. TSC status was confirmed for 6 patients. Immediate technical success rate was 96% and 4 patients benefitted from an additional procedure. Major complications occurred in 3 patients and minor post-embolization syndrome (PES) in 14 patients. The mean AML size reduction rate was 26.2% after a mean follow-up was 20.5 months (range, 0.5-56 months), and only non-TSC status was significantly associated with better shrinkage of tumor (P=0.022). Intralesional aneurysms were significantly more frequent in patients with hemorrhagic presentation (P=0.008). There was no change in mean creatinine level after SAE. CONCLUSIONS SAE is a safe and effective technique to manage renal AMLs as a preventive treatment as well as in emergency setting, with significant reduction in tumor size during follow-up. A multidisciplinary approach remains fundamental, especially for TSC patients. In addition to size, the presence of intralesional aneurysms should be considered in any prophylactic treatment decision.


title: Intraoperative Frontal Alpha-Band Power Correlates with Preoperative Neurocognitive Function in Older Adults.

text: Each year over 16 million older Americans undergo general anesthesia for surgery, and up to 40% develop postoperative delirium and/or cognitive dysfunction (POCD). Delirium and POCD are each associated with decreased quality of life, early retirement, increased 1-year mortality, and long-term cognitive decline. Multiple investigators have thus suggested that anesthesia and surgery place severe stress on the aging brain, and that patients with less ability to withstand this stress will be at increased risk for developing postoperative delirium and POCD. Delirium and POCD risk are increased in patients with lower preoperative cognitive function, yet preoperative cognitive function is not routinely assessed, and no intraoperative physiological predictors have been found that correlate with lower preoperative cognitive function. Since general anesthesia causes alpha-band (8-12 Hz) electroencephalogram (EEG) power to decrease occipitally and increase frontally (known as "anteriorization"), and anesthetic-induced frontal alpha power is reduced in older adults, we hypothesized that lower intraoperative frontal alpha power might correlate with lower preoperative cognitive function. Here, we provide evidence that such a correlation exists, suggesting that lower intraoperative frontal alpha power could be used as a physiological marker to identify older adults with lower preoperative cognitive function. Lower intraoperative frontal alpha power could thus be used to target these at-risk patients for possible therapeutic interventions to help prevent postoperative delirium and POCD, or for increased postoperative monitoring and follow-up. More generally, these results suggest that understanding interindividual differences in how the brain responds to anesthetic drugs can be used as a probe of neurocognitive function (and dysfunction), and might be a useful measure of neurocognitive function in older adults.


docid: zrzqdpxx

title: Recombinant Human Bone Morphogenetic Protein 6 Delivered Within Autologous Blood Coagulum Restores Critical Size Segmental Defects of Ulna in Rabbits.

text: BMP2 and BMP7, which use bovine Achilles tendon-derived absorbable collagen sponge and bovine bone collagen as scaffold, respectively, have been approved as bone graft substitutes for orthopedic and dental indications. Here, we describe an osteoinductive autologous bone graft substitute (ABGS) that contains recombinant human BMP6 (rhBMP6) dispersed within autologous blood coagulum (ABC) scaffold. The ABGS is created as an injectable or implantable coagulum gel with rhBMP6 binding tightly to plasma proteins within fibrin meshwork, as examined by dot-blot assays, and is released slowly as an intact protein over 6 to 8 days, as assessed by ELISA. The biological activity of ABGS was examined in vivo in rats (Rattus norvegicus) and rabbits (Oryctolagus cuniculus). In a rat subcutaneous implant assay, ABGS induced endochondral bone formation, as observed by histology and micro-CT analyses. In the rabbit ulna segmental defect model, a reproducible and robust bone formation with complete bridging and restoration of the defect was observed, which is dose dependent, as determined by radiographs, micro-CT, and histological analyses. In ABGS, ABC scaffold provides a permissive environment for bone induction and contributes to the use of lower doses of rhBMP6 compared with BMP7 in bovine bone collagen as scaffold. The newly formed bone undergoes remodeling and establishes cortices uniformly that is restricted to implant site by bridging with host bone. In summary, ABC carrier containing rhBMP6 may serve as an osteoinductive autologous bone graft substitute for several orthopedic applications that include delayed and nonunion fractures, anterior and posterior lumbar interbody fusion, trauma, and nonunions associated with neurofibromatosis type I.


title: Comparison of the Physiological Effect of Billroth-I and Roux-en-Y Reconstruction Following Laparoscopic Distal Gastrectomy.

text: BACKGROUND Laparoscopic distal gastrectomy (LDG) is a widely used minimally invasive surgery. Following LDG, Billroth-I (B-I) provides physiological reconstruction by preserving the duodenal passage but results in a high incidence of reflux esophagitis that decreases postoperative quality of life. Because of this, Roux-en-Y (R-Y) reconstruction is often considered the first choice after LDG. However, very few studies have investigated differences in physiological function between B-I and R-Y after LDG. We hypothesized that B-I would outperform R-Y in clinical and physiological outcomes, including nutrition parameters. METHODS We compared hemoglobin, ferritin, serum iron, Vitamin B12, 25(OH)-Vitamin D (V-D), body weight, and gastric emptying after LDG in patients with either B-I or R-Y reconstruction. RESULTS The levels of hemoglobin in the B-I group were significantly higher than that in the R-Y group at all time points later than 6 months postsurgery. The ferritin levels were significantly higher in the B-I group at all time points later than 9 months postsurgery. The concentration of serum V-D in the B-I group was significantly higher than that in the R-Y group at 1 year 6 months, 1 year 9 months, and 2 years after surgery. Gastric emptying in the R-Y group was significantly slower than in the B-I group. CONCLUSIONS Our data indicate that B-I leads to less postsurgical iron deficiency anemia and V-D deficiency compared with R-Y reconstruction. Furthermore, gastric emptying was preserved in B-I reconstruction compared with R-Y reconstruction. In conclusion, after LDG, B-I reconstruction seems to cause fewer nutritional complications than R-Y reconstruction.


title: Fixation versus no fixation in laparoscopic totally extraperitoneal repair of primary inguinal hernia-a systematic review and meta-analysis of randomized controlled trials.

text: INTRODUCTION The necessity of mesh fixation in laparoscopic totally extraperitoneal (TEP) inguinal hernia repair remains controversial. We performed a systematic review and meta-analysis to compare the effectiveness of mesh fixation versus no fixation in laparoscopic TEP repair for primary inguinal hernia. MATERIALS AND METHODS PubMed, EMBASE, and Cochrane databases were searched for relevant articles from January 1992 until May 2020. All trials that compared fixation versus no fixation in TEP repairs for inguinal herniae were included. Recurrent and femoral herniae were excluded from the current analysis. The primary outcome measure was recurrence while secondary outcomes included postoperative pain at 24 h, mean operative time, urinary retention, and seroma rates. Random effects models were used to calculate pooled effect size estimates. Sensitivity analyses were also carried out. RESULTS Eight randomized controlled trials were included capturing 557 patients and 715 inguinal herniae. On random effects analysis, there were no significant differences between fixation and no fixation with respect to recurrence (RD 0.00, 95% CI = - 0.01 to 0.01, p = 1.00), operative time (MD 1.58 min, 95% CI = - 0.22 to 3.37, p = 0.09), seroma (OR = 0.70, 95% CI = 0.28 to 1.74, p = 0.44), or urinary retention (RD 0.09, 95% CI = - 0.18 to 0.36, p = 0.53). However, fixation was associated with more pain at 24 h (MD 0.93, 95% CI = 0.20 to 1.66, p = 0.01). CONCLUSIONS Mesh fixation in laparoscopic TEP repair for primary inguinal herniae is associated with increased postoperative pain at 24 h but similar recurrence, seroma, and urinary retention. Therefore, it may be omitted.


title: Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1.

text: Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A, and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIβ (PI4KB) at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB-dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we demonstrate AiV hijacking of the cellular cholesterol transport system involving oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein. AiV RNA replication was inhibited by silencing cellular proteins known to be components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP-A/B), the PI4P-phosphatase SAC1, and PI-transfer protein β. OSBP, VAP-A/B, and SAC1 were present at RNA replication sites. We also found various previously unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3, OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein interaction-based OSBP recruitment has not been reported for other picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP-mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA replication. Electron microscopy showed that AiV-induced vesicle-like structures were close to ER membranes. Altogether, we conclude that AiV directly recruits the cholesterol transport machinery through protein-protein interactions, resulting in formation of membrane contact sites between the ER and AiV ROs and cholesterol supply to the ROs.IMPORTANCE Positive-strand RNA viruses utilize host pathways to modulate the lipid composition of viral RNA replication sites for replication. Previously, we demonstrated that Aichi virus (AiV), a picornavirus, forms a complex comprising certain proteins of AiV, the Golgi apparatus protein ACBD3, and the lipid kinase PI4KB to synthesize PI4P lipid at the sites for AiV RNA replication. Here, we confirmed cholesterol accumulation at the AiV RNA replication sites, which are established by hijacking the host cholesterol transfer machinery mediated by a PI4P-binding cholesterol transfer protein, OSBP. We showed that the component proteins of the machinery, OSBP, VAP, SAC1, and PITPNB, are all essential host factors for AiV replication. Importantly, the machinery is directly recruited to the RNA replication sites through previously unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3. Consequently, we propose a specific strategy employed by AiV to efficiently accumulate cholesterol at the RNA replication sites via protein-protein interactions.


title: First CT characteristic appearance of patients with coronavirus disease 2019.

text: OBJECTIVES To investigate imaging features of the coronavirus disease 2019 (COVID-19), and to provide concrete evidences for diagnosis of COVID-19. METHODS Imaging data of the first chest CT examination and clinical data (age, sex, clinical history, epidemiological history, and laboratory tests) of 163 patients with COVID-19 from 2 hospitals were collected for retrospective analysis. Imaging features of the first chest CT examination and the correspondence between CT manifestations and the nucleic acid test results of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were analyzed. RESULTS The first chest CT images of 163 COVID-19 patients showed that 92.02% of lesions were ground-glass opacity (GGO), 76.69% were consolidation, and 73.62% were GGO together with consolidation. Multiple lesions were found in 71.17% patients and multiple lobules in 86.50% patients. Lesions in 53.37% patients were found with bronchial inflation signs and those in 36.20% patients presented with "crazy paving" pattern, while only 7.36% were found with hilar node enlargement and pleural effusion. First CT findings of 18 patients were found to be inconsistent with the results of pathogen examination. CONCLUSIONS COVID-19 patients showed specific features in the first chest CT examination. The combination of the first chest CT imaging features and SARS-CoV-2 nucleic acid test results as well as reexamination if necessary can help to make the diagnosis of SARS-CoV-2 infection accurately.


title: Local production of inflammatory mediators during childhood parainfluenza virus infection.

text: OBJECTIVE To describe the clinical manifestations of parainfluenza virus (PIV) infection and to characterize biochemical markers of PIV disease severity. PATIENTS AND METHODS We reviewed the medical records of 165 children who had a nasal wash culture positive for PIV at our institution between 1998 and 2008. Nasal wash samples were assayed for 26 inflammatory mediators using Luminex bead proteomics. RESULTS A total of 153 patients, ages 2 weeks to 12 years, with single virus infection were included in our final analysis. Fifty-two patients were infected with PIV1, 19 with PIV2, 74 with PIV3, and 8 with PIV4. Lower respiratory tract infection (LRTI) was diagnosed in 67 (44%) patients, 21 (14%) had laryngotracheobronchitis, and 49 (32%) had an upper respiratory infection other than laryngotracheobronchitis. LRTI was diagnosed in 54% of patients infected with PIV3, 35% of those infected with PIV1, 26% of those with PIV2, and 50% of those with PIV4. Compared with uninfected control patients, PIV-infected patients had higher nasal wash concentrations of interleukin-6, CX-chemokine ligand 8 (CXCL8 or interleukin-8), CCL3 (macrophage inflammatory protein-1alpha), CCL4 (macrophage inflammatory protein-1beta), CXCL9 (monokine induced by interferon gamma), and CCL5 (regulated upon activation, normal T cell expressed and secreted (RANTES). Patients with LRTI, moderate or severe illness, and PIV 1 or 3 (respirovirus) infection had higher nasal wash concentrations of CXCL8 when compared with patients with upper respiratory infection, mild illness, or PIV 2 and 4 (rubulavirus) infection (P < 0.05). CONCLUSIONS PIV infection causes a spectrum of illnesses associated with the expression and release of several proinflammatory mediators. Of note, elevated concentrations of CXCL8 in nasal wash samples are associated with more severe forms of PIV disease.


SUZY forceps™ for the removal of an esophageal coin from a child.


title: Global inequities in dietary calcium intake during pregnancy: a systematic review and meta-analysis.

text: BACKGROUND Evidence shows that adequate calcium intake during pregnancy reduces the risk of hypertensive disorders of pregnancy. In most low- and middle-income countries (LMICs) the daily calcium intake is well below recommendations. Mapping calcium intake during pregnancy worldwide and identifying populations with low calcium intake will provide the evidence base for more targeted actions to improve calcium intake. OBJECTIVE To assess dietary calcium intake during pregnancy worldwide. SEARCH STRATEGY MEDLINE and EMBASE (from July 2004 to November 2017). SELECTION CRITERIA Cross-sectional, cohort, and intervention studies reporting calcium intake during pregnancy. DATA COLLECTION AND ANALYSIS Five reviewers working in pairs independently performed screening, extraction, and quality assessment. We reported summary measures of calcium intake and calculated the weighted arithmetic mean for high-income countries (HICs) and LMICs independently, and for geographic regions, among studies reporting country of recruitment, mean intake, and total number of participants. When available, inadequate intakes were reported. MAIN RESULTS From 1880 citations 105 works met the inclusion criteria, providing data for 73 958 women in 37 countries. The mean calcium intake was 948.3 mg/day (95% CI 872.1-1024.4 mg/day) for HICs and 647.6 mg/day (95% CI 568.7-726.5 mg/day) for LMICs. Calcium intakes below 800 mg/day were reported in five (29%) countries from HICs and in 14 (82%) countries from LMICs. CONCLUSION These results are consistent with a lack of improvement in calcium dietary intake during pregnancy and confirm the gap between HICs and LMICs, with alarmingly low intakes recorded for pregnant women in LMICs. From the public health perspective, in the absence of specific local data, calcium supplementation of pregnant women in these countries should be universal. TWEETABLE ABSTRACT Despite dietary recommendations, women in LMICs face pregnancy with diets low in calcium.


title: Capnography sensor use is associated with reduction of adverse outcomes during gastrointestinal endoscopic procedures with sedation administration.

text: BACKGROUND Evidence to date suggests that capnography monitoring during gastrointestinal endoscopic procedures (GEP) reduces the incidence of hypoxemia, but the association of capnography monitoring with the incidence of other adverse outcomes surrounding these procedures has not been well studied. Our aims were to estimate the incidence of pharmacological rescue events and death at discharge from an inpatient or outpatient hospitalization where GEP was performed with sedation, and to determine if capnography monitoring was associated with reduced incidence of these adverse outcomes. METHODS This retrospective Premier Database analysis included medical inpatients and all outpatients undergoing GEP with sedation. Patients were grouped as follows: (1) pulse oximetry (SpO2) only, (2) capnography only, (3) SpO2 with capnography, and (4) neither SpO2 nor capnography. Multivariable logistic regression and propensity-score matching were used to compare patients with capnography sensor use to patients with only SpO2 sensor use. Outcome measures included the incidence of pharmacological rescue events, as defined by administration of naloxone and/or flumazenil, and death. RESULTS Two hundred fifty eight thousand and two hundred sixty two inpatients and 3,807,151 outpatients were analyzed. For inpatients, capnography monitoring was associated with a 47% estimated reduction in the odds of death at discharge (OR: 0.53 [95% CI: 0.40-0.70]; P < 0.0001) and a non-significant 10% estimated reduction in the odds of pharmacological rescue event at discharge (0.91 [0.65-1.3]; P = 0.5661). For outpatients, capnography monitoring was associated with a 61% estimated reduction in the odds of pharmacological rescue event at discharge (0.39 [0.29, 0.52]; P < 0.0001) and a non-significant 82% estimated reduction in the odds of death at discharge (0.18 [0.02, 1.99]; P = 0.16). CONCLUSIONS In hospital medical inpatients and all outpatients undergoing GEP performed with sedation, capnography monitoring was associated with a reduced likelihood of pharmacological rescue events in outpatients and death in inpatients when assessed at discharge. Despite the limitations of the retrospective data analysis methodology, the use of capnography during these procedures is recommended.


title: Natural history and metabolic consequences of morbid obesity for patients denied coverage for bariatric surgery.

text: BACKGROUND Patients satisfying the National Institutes of Health criteria and deemed appropriate candidates often do not undergo bariatric surgery for insurance-related reasons. Our objective was to explore the natural history of these patients compared with that of those who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS The medical records of the patients evaluated for LRYGB from 2001 to 2007 were retrospectively reviewed. The presence of co-morbidities was assessed at the initial evaluation and within a 3-year follow-up period for patients who had undergone LRYGB and those denied surgery. The statistical analysis included chi-square tests. RESULTS A total of 189 patients were in the denied cohort and 587 in the LRYGB cohort. The age, gender, and body mass index were similar between the 2 cohorts at the initial evaluation. The percentage of patients with a diagnosis of a co-morbidity in the denied and LRYGB cohorts at the initial evaluation was 20% and 25% with diabetes mellitus, 51% and 43% with hypertension, 20% and 22% with obstructive sleep apnea, 34% and 24% with lipid disorders, and 62% and 49% with gastroesophageal reflux disease, respectively. The body mass index at the initial evaluation and during follow-up was 47.3 and 46.8 kg/m(2) in the denied cohort (n = 165, P = .236) and 48.5 and 30.5 kg/m(2) in the LRYGB cohort (n = 544, P <.001), respectively. During the follow-up period, a greater incidence of new-onset diabetes (P <.001), hypertension (P <.001), obstructive sleep apnea (P <.001), gastroesophageal reflux disease (P <.001), and lipid disorders (P <.001) was observed in the denied cohort. CONCLUSION Patients denied LRYGB had a greater incidence of new co-morbidities diagnosed within a short follow-up period, without a significant change in their body mass index.


title: A Case for Targeting Th17 Cells and IL-17A in SARS-CoV-2 Infections.

text: SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.


title: Commentary on the coronavirus pandemic: Anticipating a fourth wave in the opioid epidemic.

text: Experiencing the COVID-19 pandemic simultaneously with the U.S. opioid epidemic is anticipated to have a profound mental health impact on some of our most vulnerable populations. Recent federal and state regulatory changes have been made under the state of emergency in order to ameliorate the some of the challenges faced in maintaining access to substance use and addiction services during such times. There are currently considerable limitations in quantifying the impact of COVID-19 among those with substance use disorders, however, it is imperative that health care systems continue to serve this population in order to prevent associated morbidity and mortality. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Treatment of Angio-Seal-Related Femoral Artery Occlusion Using Directional Atherectomy-Primary Results and Midterm Follow-Up.

text: OBJECTIVE We describe a novel approach for the endovascular treatment of femoral artery occlusion as a result of Angio-Seal closure device deployment. BACKGROUND Angio-Seal is the most commonly used vascular closure device following percutaneous coronary and peripheral catheterizations worldwide. A rare complication of Angio-Seal deployment is an occlusion of the femoral artery leading to limb ischemia requiring revascularization. Given its unique ability to cut both atherosclerotic plaque and the Angio-Seal anchor with a collagen plug at operator-directed planes, TurboHawk/HawkOne atherectomy device can be a fast and effective approach to treat Angio-Seal-associated femoral artery occlusions. METHODS We studied 13 consecutive patients who developed Angio-Seal-associated femoral artery occlusions that occurred from 3 hours to several weeks after catheterization. These patients were successfully treated with TurboHawk/HawkOne directional atherectomy followed by balloon angioplasty with no complications. During a mean follow-up period of 20.4 ± 17.3 months, 12 patients remained claudication free with no evidence of obstructive arterial disease of the treated segment on imaging studies. One patient developed restenosis that was treated with repeat atherectomy and balloon angioplasty following which he was asymptomatic at follow-up. CONCLUSION The use of directional atherectomy followed by balloon angioplasty is a quick, safe, and effective endovascular approach to treating Angio-Seal-associated femoral artery occlusions. It is associated with an excellent success rate, no complications, and good midterm outcomes.


title: Retreatment and outcomes of recurrent intracranial vertebral artery dissecting aneurysms after stent assisted coiling: a single center experience.

text: BACKGROUND AND PURPOSE The retreatment of recurrent intracranial vertebral artery dissecting aneurysms (VADAs) after stent assisted coiling (SAC) has not yet been studied. The purpose of this study was to evaluate the strategies and outcomes for retreatment of recurrent VADAs after SAC. METHODS Between September 2009 and November 2013, six consecutive patients presenting with recurrent intracranial VADAs after SAC were enrolled in this study. They were all male with age ranging from 29 to 54 years (mean age, 46.2 years). The procedures of treatments and angiographic and clinical follow-up were reviewed retrospectively. Retreatment modalities were selected individually according to the characteristics of recurrence. The outcomes of retreatment were evaluated by angiographic and clinical follow-up. RESULTS Six patients with recurrent intracranial VADAs after SAC were retreated, with second SAC in three patients, coil embolization, double overlapping stents placement and endovascular occlusion with aneurysm trapping in one patient, respectively. Immediate angiographic outcomes of retreatment were: complete occlusion in three patients, nearly complete occlusion in two patients, and contrast medium retention in dissecting aneurysm in one patient. All cases were technically successful. No complications related to endovascular procedures occurred. Angiographic follow-up was available in all five patients treated with second SAC or double overlapping stents, which was complete occlusion in four patients, obliteration of parent artery in one patient, showing no recurrence at 4-11 months (mean: 8.6 months). Clinical follow-up was performed in all six patients at 11-51 months after initial endovascular treatment and at 9-43 months after retreatment. The mRS of last clinical follow-up was excellent in five patients and mild disability in only one patient. CONCLUSIONS Endovascular retreatment is feasible and effective for recurrent intracranial VADAs after SAC. Individualized strategies of retreatment should be enacted according to the characteristics and reasons for the recurrence.


title: Laparoendoscopic single-site combined cholecystectomy and hysterectomy.

text: Laparoendoscopic single-site (LESS) surgery has gained increased acceptance among surgeons in various specialties. The universal nature of port placement in the umbilicus during LESS surgery may enable concomitant procedures to be performed in these surgical specialties via this single incision. This case report presents a 37-year-old woman who underwent concomitant LESS cholecystectomy and hysterectomy to treat a symptomatic fibroid uterus and symptoms of cholelithiasis. The surgical procedure was performed in approximately 3 hours without any complications, and the patient was discharge to home 18 hours after the procedure. This case demonstrates that increasingly complex concomitant procedures can be performed using a LESS surgical approach.


Mentoring during the COVID-19 pandemic.


title: SARS-CoV-2 in urine. - Should Endourologists be concerned and what PPE measures should be taken to protect the Endourologist when in theatre ?

text: SARS-CoV-2 is usually transmitted through air however several recent reports have found the virus in urine. Only 187 urine samples have been reported to have been tested in the literature to date despite over 4 million cases of respiratory Covid 19 positive cases being reported worldwide. Of these 187 urine tests 6 were positive for the virus and this persisted in urine in once case for up to 42 days. The urine sample was still positive for Covid 19 despite respiratory swabs being negative. There is a potential concern therefore that Endourologists who generally perform a high number of urine prone procedures could be at risk of exposure to the virus peri operatively. There is still confusion as to the type of PPE Endourologists should use and in what circumstances. Until it is proven that urine is not a potential source for transmission of the Virus Endourologists should have a clear knowledge of the different types of PPE available and what they should use when performing procedures.


title: Evaluating the effects of the COVID-19 pandemic on the physical and mental well-being of obstetricians and gynecologists in Turkey.

text: OBJECTIVE To apply online surveying to assess the general physical and mental well-being of obstetricians/gynecologists (OB/GYNs) working in COVID-19 designated hospitals in Turkey. METHODS A prospective survey-based study using an online survey platform. Three hundred participants working at COVID-19 designated hospitals in Turkey identified from a hospital database were sent a link to the survey by email between April 29 and May 20, 2020. RESULTS A total of 253 OB/GYNs (31 consultants and 222 residents) completed the survey, for a response rate of 84.3%. Of respondents, 191 (76.4%) were anxious about coming into contact with pregnant women infected with COVID-19. 74.4% stated that they were afraid of getting sick. 64.8% reported that they had fallen into despair at times because of the pandemic. 66.5% stated that their family lives were affected. 72.4% started living separately from their families because of the pandemic. CONCLUSION Despite the difficulties in patient care during the pandemic, OB/GYNs continued providing for their patients, which reflected positively on their perceptions of the profession. The importance of trust in the national healthcare system, presence of adequate PPE, finding a suitable coping mechanism, and family support were essential for Turkish OB/GYNs during the COVID-19 pandemic.


title: Two in One: Endovascular Treatment of Acute Tandem Occlusions in the Anterior Circulation.

text: PURPOSE Acute major stroke with high-grade stenosis or occlusion of the extracranial internal carotid artery (ICA) and additional intracranial large artery occlusion is increasingly treated with a mechanical endovascular approach by extracranial stenting and intracranial thrombectomy due to poor response to systemic thrombolysis with recombinant tissue plasminogen activator (rtPA). This article presents a single centre cohort of this challenging subtype of stroke, describing the technical procedure and analysing the angiographic and clinical outcome. METHODS Clinical and imaging data of all consecutive patients between July 2008 and March 2013 with intracranial artery occlusion in the anterior circulation and additional occlusion or pseudo-occlusion of the cervical ICA were retrospectively analysed with respect to demographical and clinical characteristics. Technical approach, recanalization rate, recanalization time and short-term clinical outcome were determined. RESULTS A total of 43 patients with tandem occlusion in the anterior circulation met the inclusion criteria. Out of these, 32 (74.4%) occlusions and 11 (25.6%) pseudo-occlusions of the extracranial ICA with additional occlusion of the distal segment of the ICA in 7.0% (3/43), the M1-segment of the middle cerebral artery (MCA) in 81.4% (35/43) or the M2-segment of the MCA in 11.6% (5/43) of cases were treated with combined endovascular approach including extracranial stenting with angioplasty and intracranial mechanical thrombectomy. In 76.7% of cases, an angiographic recanalization result of 2b or 3 using the Thrombolysis in Cerebral Infarction (TICI) score was achieved. Mean time from first angiographic series to recanalization was 103 min. A modified Rankin Scale (mRS) score of ≤ 2 was achieved in 32.6% at the time of discharge. CONCLUSION Endovascular therapy of patients with tandem occlusion in the anterior circulation with emergency extracranial stenting and intracranial mechanical thrombectomy appears to be safe and may lead to a satisfactory angiographic result and clinical outcome.


title: Double aortic arch in an adult.

text: We present the case of a 60-year old man who complained of severe dysphagia caused by a double aortic arch (DAA) with a right-sided descending thoracic aorta. The left-sided aortic arch had a compressive segment located between the left subclavian artery and the descending thoracic aorta. Using left third thoracotomy, the segment, which caused compression of the oesophagus, was ligated and divided. After the operation, the patient was completely relieved of his symptoms. We concluded that the removal of the compressive portion of the left aortic arch and the ligation of the ligamentum arteriosum are the only treatment measures needed in such cases.


title: Rupture Resemblance Score (RRS): toward risk stratification of unruptured intracranial aneurysms using hemodynamic-morphological discriminants.

text: OBJECTIVE We have previously developed three logistic regression models for discriminating intracranial aneurysm rupture status from 119 aneurysms based on hemodynamic-morphological parameters. In this study we exploit their use as a tool for predicting the risk of rupture of aneurysms with a defined Rupture Resemblance Score (RRS). METHODS We collected three-dimensional images of 85 consecutive aneurysms, applied the three regression models and compared model performance at predicting rupture status against anecdotal metrics (aneurysm size and aspect ratio). We then reinterpreted the model-predicted probability as RRS, where the higher the score the closer the resemblance to previously known rupture components, and applied the RRS prospectively to four unruptured aneurysms with borderline treatment decisions. RESULTS All three models yielded excellent sensitivity (0.78-0.83) and specificity (0.78-0.84) at a cutoff score of 50%, whereas aneurysm size and aspect ratio showed poor sensitivities (0.28 and 0.33, respectively). Lowering the cutoff score to 30% improved sensitivity to 0.90. The RRS identified most of the ruptured aneurysms and also some unruptured ones that closely resembled ruptured aneurysms hemodynamically and/or morphologically. The prospective application of the RRS to unruptured aneurysms shows that it could provide additional insights for treatment decisions. CONCLUSIONS Previous regression models based on hemodynamic-morphological parameters are able to discriminate rupture in a new cohort in the same population. A higher probability of rupture is associated with larger size ratio, lower normalized wall shear stress and higher oscillatory shear index. The RRS could potentially stratify rupture risk and assist in treatment decision-making for unruptured aneurysms.


title: A breath of fresh air: a quality-improvement study comparing an air-circulating technique versus conventional technique to prevent nasogastric tube dysfunction.

text: BACKGROUND Nasogastric tubes are an important component of care in patients with gastrointestinal obstructions. However, they are prone to malfunction despite conventional flushing techniques, with potentially severe consequences. There is no widely accepted, gold-standard way to ensure that a nasogastric tube succeeds in maintaining an empty stomach following flushing. METHODS We have developed a flushing technique to better ensure successful tube function. We compared this technique to conventional flushing both in vitro (using a plastic stomach model) and in vivo (in a pig model), and we provide a didactic video. RESULTS The mean gastric residual volume following our novel flushing technique is nearly 25-fold lower than following conventional flushing (13 mL vs. 330 mL). CONCLUSIONS Our simple technique is more effective than conventional techniques in maintaining nasogastric tube function and therefore should prevent dangerous vomiting and aspiration pneumonia better than conventional techniques.


title: Laparoscopic pancreaticoduodenectomy: single-surgeon experience.

text: BACKGROUND Innovations in surgical strategies and technologies have facilitated laparoscopic pancreaticoduodenectomy (LPD). However, data regarding the short-term and long-term results of LPD are sparse, and this procedure is the primary focus of the current study. METHODS Between October 2010 and October 2013, a total of 31 consecutive patients received LPD, including hand-assisted laparoscopic pancreaticoduodenectomy, total laparoscopic pancreaticoduodenectomy, and laparoscopic pylorus-preserving pancreaticoduodenectomy. Data regarding short-term surgical outcomes and long-term oncological results were collected prospectively. RESULTS The median operative time was 515.0 min (interquartile range 465.0-585.0 min). The median intraoperative estimated blood loss was 260.0 mL (interquartile range 150.0-430.0 mL). Conversion to open pancreaticoduodenectomy was required in three patients (9.7%) due to intraoperative pneumoperitoneum intolerance (n = 1, 3.2%) and tumor adherence to the superior mesenteric vein (n = 2, 6.5%). No significant differences between the surgical approaches were observed in regard to intraoperative and postoperative data. Postoperative severe complications (Clavien ≥ III) were detected in three (9.7%) patients, including one grade C pancreatic fistula, one grade B postoperative bleeding event, and one afferent loop obstruction. There were no deaths within 30 days following LPD. The final pathological results revealed duodenal adenocarcinoma in 14 (45.2%) patients, ampullary adenocarcinoma in four (12.9%) patients, distal common bile duct cancer in six (19.4%) patients, pancreatic ductal adenocarcinoma in five (16.1%) patients, gastrointestinal stroma tumor in one (3.2%) patient, and chronic pancreatitis in one (3.2%) patient. All patients suffering from tumors underwent R0 resection (n = 30, 100.0%), with the optimal number of collected lymph nodes (median: 13, interquartile range 11-19). At the most recent follow-up, 20 patients were still alive, and the 1-, and 3-year overall survival for patients with duodenal adenocarcinoma were 100.0 and 71.4%, respectively. CONCLUSIONS According to this study, LPD is feasible and technically safe for highly selected patients and can offer acceptable oncological outcomes and long-term survival.


title: Scandinavian SSAI clinical practice guideline on pre-hospital airway management.

text: BACKGROUND The Scandinavian society of anaesthesiology and intensive care medicine task force on pre-hospital airway management was asked to formulate recommendations following standards for trustworthy clinical practice guidelines. METHODS The literature was systematically reviewed and the grading of recommendations assessment, development and evaluation (GRADE) system was applied to move from evidence to recommendations. RESULTS We recommend that all emergency medical service (EMS) providers consider to: apply basic airway manoeuvres and airway adjuncts (good practice recommendation); turn unconscious non-trauma patients into the recovery position when advanced airway management is unavailable (good practice recommendation); turn unconscious trauma patients to the lateral trauma position while maintaining spinal alignment when advanced airway management is unavailable [strong recommendation, low quality of evidence (QoE)]. We suggest that intermediately trained providers use a supraglottic airway device (SAD) or basic airway manoeuvres on patients in cardiac arrest (weak recommendation, low QoE). We recommend that advanced trained providers consider using an SAD in selected indications or as a rescue device after failed endotracheal intubation (ETI) (good practice recommendation). We recommend that ETI should only be performed by advanced trained providers (strong recommendation, low QoE). We suggest that videolaryngoscopy is considered for ETI when direct laryngoscopy fails or is expected to be difficult (weak recommendation, low QoE). We suggest that advanced trained providers apply cricothyroidotomy in 'cannot intubate, cannot ventilate' situations (weak recommendation, low QoE). CONCLUSION This guideline for pre-hospital airway management includes a combination of techniques applied in a stepwise fashion appropriate to patient clinical status and provider training.


title: Effects of arterial load variations on dynamic arterial elastance: an experimental study.

text: Background. Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . Methods. Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. Results. After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. Conclusions. Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.


title: Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19 disease.

text: BACKGROUND Some people with SARS-CoV-2 infection remain asymptomatic, whilst in others the infection can cause mild to moderate COVID-19 disease and COVID-19 pneumonia, leading some patients to require intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever or cough, and signs such as oxygen saturation or lung auscultation findings, are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19 disease, or select patients for further diagnostic testing. OBJECTIVES To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19 disease or COVID-19 pneumonia. SEARCH METHODS On 27 April 2020, we undertook electronic searches in the Cochrane COVID-19 Study Register and the University of Bern living search database, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. SELECTION CRITERIA Studies were eligible if they included patients with suspected COVID-19 disease, or if they recruited known cases with COVID-19 disease and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards including reverse transcription polymerase chain reaction (RT-PCR), clinical expertise, imaging, serology tests and World Health Organization (WHO) or other definitions of COVID-19. DATA COLLECTION AND ANALYSIS Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the QUADAS-2 checklist. Analyses were descriptive, presenting sensitivity and specificity in paired forest plots, in ROC (receiver operating characteristic) space and in dumbbell plots. We did not attempt meta-analysis due to the small number of studies, heterogeneity across studies and the high risk of bias. MAIN RESULTS We identified 16 studies including 7706 participants in total. Prevalence of COVID-19 disease varied from 5% to 38% with a median of 17%. There were no studies from primary care settings, although we did find seven studies in outpatient clinics (2172 participants), and four studies in the emergency department (1401 participants). We found data on 27 signs and symptoms, which fall into four different categories: systemic, respiratory, gastrointestinal and cardiovascular. No studies assessed combinations of different signs and symptoms and results were highly variable across studies. Most had very low sensitivity and high specificity; only six symptoms had a sensitivity of at least 50% in at least one study: cough, sore throat, fever, myalgia or arthralgia, fatigue, and headache. Of these, fever, myalgia or arthralgia, fatigue, and headache could be considered red flags (defined as having a positive likelihood ratio of at least 5) for COVID-19 as their specificity was above 90%, meaning that they substantially increase the likelihood of COVID-19 disease when present. Seven studies carried a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional four studies, we were unable to assess the risk for selection bias. These factors make it very difficult to determine the diagnostic properties of these signs and symptoms from the included studies. We also had concerns about the applicability of these results, since most studies included participants who were already admitted to hospital or presenting to hospital settings. This makes these findings less applicable to people presenting to primary care, who may have less severe illness and a lower prevalence of COVID-19 disease. None of the studies included any data on children, and only one focused specifically on older adults. We hope that future updates of this review will be able to provide more information about the diagnostic properties of signs and symptoms in different settings and age groups. AUTHORS' CONCLUSIONS The individual signs and symptoms included in this review appear to have very poor diagnostic properties, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out disease. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19 disease, are urgently needed. Results from such studies could inform subsequent management decisions such as self-isolation or selecting patients for further diagnostic testing. We also need data on potentially more specific symptoms such as loss of sense of smell. Studies in older adults are especially important.


docid: hwhkimpe

title: E-Health in Norway Before and During the Initial Phase of the Covid-19 Pandemic.

text: The use of e-health services has for many years gradually increased in Norway as in most European countries. Searching for information about health and illness has previously by far been the most popular service. In this study, we review the literature with the aim of examining any changes in e-health use during the Covid-19 pandemic. We find that there has been a marked change in Norway, with an extreme increase in video consultations, especially in primary care and in the mental health field. The government has also released an app for tracking the illness, which so far has been downloaded by approximately 1/4 of the population. These changes are likely to impact the use of e-health also after the pandemic.


title: Immediate versus delayed surgery for hip fractures in the elderly patients: a protocol for a systematic review and meta-analysis.

text: BACKGROUND Hip fractures are a major public health problem in elderly populations and are accompanied by high-mortality rates. Whether timing of surgery has an impact on morbidity and mortality has been discussed controversially, numerous studies suggest that the delay of surgery can significantly increase the risk of morbidity and mortality; others report that achieving a stable medical condition is more important than early surgery. The goal of our systematic review is to assess the impact of timing of surgery on health outcomes in patients aged 60 years or older with acute hip fracture. In addition, we will investigate differences in beneficial or harmful effects of timing of surgery in subgroups of patients based on demographic characteristics, physical status, and the use of anticoagulant medications. METHODS We will systematically search MEDLINE via Ovid, the Cochrane Library, Embase, PubMed, and clinical trial registries (from 1997 to 2017). In addition, we will search reference lists of pertinent reviews, archives of annual meetings of orthopaedic societies, and contact experts. We will include randomized controlled trials and non-randomized studies assessing the impact of timing of surgery after hip fracture in patients 60 years or older, published in English or German. Our outcomes of interest include health outcomes such as mortality, perioperative complications, functional capacity, and quality of life. We plan to perform meta-analyses if we have at least three sufficiently similar studies. If data are sufficient, we will conduct subgroup-analyses testing for differences between age groups, sex, patients' physical status as assessed with ASA (American Society of Anesthesiologists) scores, and the use of anticoagulation. DISCUSSION Since this is the first systematic review on this topic since 2010, our findings will help to inform clinical practice guidelines concerning timing of surgery in hip fractures. Furthermore, our findings could contribute to define an optimal time period for surgery for different groups of patients with acute hip fracture. SYSTEMATIC REVIEW REGISTRATION PROSPERO 2017 CRD42017058216.


The morbidity and mortality of COVID-19 are associated with ABO and Rh blood groups.


docid: axokercv

title: Preliminary results of antiscarring therapy in the prevention of postendoscopic esophageal mucosectomy strictures.

text: BACKGROUND Esophageal endoscopic submucosal dissection (ESD) is an effective minimally invasive therapy for early esophageal cancer and high-grade Barrett dysplasia. However, esophageal stricture formation after circumferential or large ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and transforming growth factor β3 (TGF-β3) exhibits antiscarring effects that may prevent post-ESD stricture formation. METHODS Using endoscopic mucosectomy (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment was excised in a porcine model. The site was either untreated (control, n = 6) or received 40 evenly distributed injections of antiscarring agent immediately and at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2); Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-β3 2 μg (n = 2), 0.5 μg (n = 2). The degree of stricture formation was determined by the percentage reduction of the esophageal lumen on weekly fluoroscopic examination. Animals were euthanized when strictures exceeded 80 % or the animals were unable to maintain weight. RESULTS The control group had a luminal diameter reduction of 78.2 ± 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks, the Hal group showed a decrease in mean stricture formation (68.4 % low dose, 57.7 % high dose), while both TGF-β3 dosage groups showed no significant change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall treated with high-dose MMC appeared to be necrotic and eventually led to perforation. In contrast, low dose MMC, TGF-β3 and Hal treated areas appeared re-epithelialized and healthy. CONCLUSIONS Preliminary data on MMC and Hal demonstrated promise in reducing esophageal stricture formation after EEM. More animal data are needed to perform adequate statistical analysis in order to determine overall efficacy of antiscarring therapy.


Adapting to the impact of COVID-19 on mental health: an international perspective.


title: Association between cannabis use and treatment outcomes in patients receiving methadone maintenance treatment: a systematic review protocol.

text: BACKGROUND With the non-medical use of prescription opioids increasingly becoming a method of abuse in Canada, the number of patients requiring methadone maintenance treatment (MMT) for opioid use disorder has increased dramatically. The rate of cannabis use in this population is disproportionately high (~50 %). Because its use is generally perceived as harmless, cannabis use is often not monitored during MMT. Current literature regarding the effects of cannabis use on MMT is conflicting, and the presence and nature of an association has not been clearly established. The primary objective of this review will be to conduct a systematic review of the literature and, if appropriate, a meta-analysis to determine whether there is an association between cannabis use and MMT outcomes. A secondary objective will be to perform subgroup analyses (by age, sex, method of cannabis measurement, and country) to determine whether cannabis use differentially influences MMT outcomes within these subgroups. METHODS/DESIGN The search will be conducted on the following electronic databases using a predefined search strategy: MEDLINE, EMBASE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Two authors (LZ and MB) will independently screen articles using predetermined inclusion/exclusion criteria and will extract data from included articles using a pilot-tested data extraction form. Disagreements at all stages of the screening process will be settled through discussion, and when consensus cannot be reached, a third author (ZS) will be consulted. An assessment of quality and risk of bias will be conducted on all included articles, and a sensitivity analysis will be used to compare results of studies with high and low risk of bias. We will perform random- and fixed-effects meta-analyses, if appropriate, with heterogeneity calculated using the I (2) statistic and formal evaluation of publication bias. DISCUSSION Results of this systematic review will elucidate the association between cannabis use and methadone maintenance treatment outcomes. We will provide evidence that will be useful to clinicians regarding whether monitoring cannabis use during MMT is advantageous for optimizing MMT outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015029372.


title: Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation.

text: Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they "snatch" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.


title: Increased Need for Gastrointestinal Surgery and Increased Risk of Surgery-Related Complications in Patients with Ehlers-Danlos Syndrome: A Systematic Review.

text: BACKGROUND/AIMS Ehlers-Danlos syndromes (EDSs) constitute a rare group of inherited connective tissue diseases, characterized by multisystemic manifestations and general tissue fragility. Most severe complications include vascular and gastrointestinal (GI) emergencies requiring acute surgery. The purpose of this systematic review was to assess the causes of GI-related surgery and related mortality and morbidity in patients with EDSs. METHODS A systematic search was conducted in PubMed, Embase, and Scopus to identify relevant studies. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines for systematic reviews were followed. According to eligibility criteria, data were extracted and systematically screened by 2 authors. RESULTS Screening process identified 11 studies with a total of 1,567 patients. Findings indicated that patients with EDSs had a higher occurrence of surgery demanding GI manifestations, including perforation, hemorrhage, rupture of intra-abdominal organs, and rectal prolapse. Most affected was the vascular subtype, of which up to 33% underwent GI surgery and suffered from a lowered average life expectancy of 48 years (range 6-78). Secondary complications of surgery were common in all patients with EDSs. CONCLUSION Studies suggested that patients with EDSs present an increased need for GI surgery, but also an increased risk of surgery-related complications, most predominantly seen in the vascular subtype.


title: siRNAs: their potential as therapeutic agents--Part II. Methods of delivery.

text: RNA interference (RNAi) is a sequence-specific mechanism to control the expression of target genes. This technique has proven potentials both in vivo and in vitro. The main hurdle for using RNAi-based therapy is the effective delivery of RNAi-based drugs to the target cells or tissues in vivo. The aspects of off-target effects, delivery methods, induction of immune response and dose determination for delivery should, however, be considered carefully. If these challenges associated with siRNA can be met, then the potentials of RNAi could be exploited to the full for the development of therapeutic tools and drugs.


title: Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats.

text: Bats harbor many emerging and reemerging viruses, several of which are highly pathogenic in other mammals but cause no clinical signs of disease in bats. To determine the role of interferons (IFNs) in the ability of bats to coexist with viruses, we sequenced the type I IFN locus of the Australian black flying fox, Pteropus alecto, providing what is, to our knowledge, the first gene map of the IFN region of any bat species. Our results reveal a highly contracted type I IFN family consisting of only 10 IFNs, including three functional IFN-α loci. Furthermore, the three IFN-α genes are constitutively expressed in unstimulated bat tissues and cells and their expression is unaffected by viral infection. Constitutively expressed IFN-α results in the induction of a subset of IFN-stimulated genes associated with antiviral activity and resistance to DNA damage, providing evidence for a unique IFN system that may be linked to the ability of bats to coexist with viruses.


title: Clinical Manifestations Associated with Peripheral Joint Involvement in Patients with Acute Chikungunya Virus Infection.

text: AbstractChikungunya virus (CHIKV) causes an acute febrile illness usually accompanied by severe polyarthralgia and polyarthritis. Previous studies have shown that older age, female gender, and some comorbid conditions are associated with chronic CHIKV arthritis. However, the factors associated with acute arthralgia and arthritis are not well known. Thus, we studied the clinical manifestations associated with acute peripheral joint involvement in a group of CHIKV patients from Puerto Rico. Patients with a history of fever for < 7 days evaluated at the emergency department of a university-based hospital were tested for several pathogens including CHIKV. All patients with laboratory-positive CHIKV infection were studied. Demographic features, clinical manifestations, and comorbidities were determined. Patients with and without peripheral joint involvement were compared using bivariable and multivariable analyses. In total, 172 patients with CHIKV fever were evaluated; 52.9% were women. The mean (standard deviation) age was 21.1 years (19.3). Peripheral arthralgia and/or arthritis were seen in 156 (90.7%) patients. In the multivariable analysis adjusted for age and gender, peripheral joint involvement was associated with myalgia (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.48-14.72), back pain (OR = 16.77, 95% CI = 3.07-313.82), ocular pain (OR = 8.88, 95% CI = 1.65-165.19), headache (OR = 3.63, 95% CI = 1.06-12.53), anorexia (OR = 5.68, 95% CI = 1.87-18.97), and nausea (OR = 6.88, 95% CI = 2.05-31.49). In conclusion, in this population of patients with acute CHIKV infection, peripheral joint involvement was associated with myalgia and back pain as well as nonmusculoskeletal manifestations such as headache, ocular pain, anorexia, and nausea.


docid: slayfvip

title: Special Issue: Digital Health in Times of COVID-19.


title: Transmembrane Protein pUL50 of Human Cytomegalovirus Inhibits ISGylation by Downregulating UBE1L.

text: Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that can be conjugated to proteins via an enzymatic cascade involving the E1, E2, and E3 enzymes. ISG15 expression and protein ISGylation modulate viral infection; however, the viral mechanisms regulating the function of ISG15 and ISGylation are not well understood. We recently showed that ISGylation suppresses the growth of human cytomegalovirus (HCMV) at multiple steps of the virus life cycle and that the virus-encoded pUL26 protein inhibits protein ISGylation. In this study, we demonstrate that the HCMV UL50-encoded transmembrane protein, a component of the nuclear egress complex, also inhibits ISGylation. pUL50 interacted with UBE1L, an E1-activating enzyme for ISGylation, and (to a lesser extent) with ISG15, as did pUL26. However, unlike pUL26, pUL50 caused proteasomal degradation of UBE1L. The UBE1L level induced in human fibroblast cells by interferon beta treatment or virus infection was reduced by pUL50 expression. This activity of pUL50 involved the transmembrane (TM) domain within its C-terminal region, although pUL50 could interact with UBE1L in a manner independent of the TM domain. Consistently, colocalization of pUL50 with UBE1L was observed in cells treated with a proteasome inhibitor. Furthermore, we found that RNF170, an endoplasmic reticulum (ER)-associated ubiquitin E3 ligase, interacted with pUL50 and promoted pUL50-mediated UBE1L degradation via ubiquitination. Our results demonstrate a novel role for the pUL50 transmembrane protein of HCMV in the regulation of protein ISGylation.IMPORTANCE Proteins can be conjugated covalently by ubiquitin or ubiquitin-like proteins, such as SUMO and ISG15. ISG15 is highly induced in viral infection, and ISG15 conjugation, termed ISGylation, plays important regulatory roles in viral growth. Although ISGylation has been shown to negatively affect many viruses, including human cytomegalovirus (HCMV), viral countermeasures that might modulate ISGylation are not well understood. In the present study, we show that the transmembrane protein encoded by HCMV UL50 inhibits ISGylation by causing proteasomal degradation of UBE1L, an E1-activating enzyme for ISGylation. This pUL50 activity requires membrane targeting. In support of this finding, RNF170, an ER-associated ubiquitin E3 ligase, interacts with pUL50 and promotes UL50-mediated UBE1L ubiquitination and degradation. Our results provide the first evidence, to our knowledge, that viruses can regulate ISGylation by directly targeting the ISGylation E1 enzyme.


title: Simple, Rapid and Sensitive Portable Molecular Diagnosis of SFTS Virus Using Reverse Transcriptional Loop-Mediated Isothermal Amplification (RT-LAMP).

text: Recently, human infections caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which can lead to fatality, have dramatically increased in East Asia. With the unavailability of vaccines or antiviral drugs to prevent and/or treat SFTSV infection, early rapid diagnosis is critical for prevention and control of the disease. Here, we report the development of a simple, rapid and sensitive portable detection method for SFTSV infection applying reverse transcription-loop mediated isothermal amplification (RT-LAMP) combined with one-pot colorimetric visualization and electro-free reaction platform. This method utilizes a pocket warmer to facilitate diagnosis in a resource-limited setting. Specific primers were designed to target the highly-conserved region of L gene of SFTSV. The detection limit of the RT-LAMP assay was approximately 100 viral genome copies from three different SFTSV strains. This assay exhibited comparable sensitivity to qRT-PCR and 10-fold more sensitivity than conventional RT-PCR, with a rapid detection time of 30 to 60 minutes. The RT-LAMP assay using SFTSV clinical specimens has demonstrated a similar detection rate to qRT-PCR and a higher detection rate compared to conventional RT-PCR. Moreover, there was no observed cross-reactive amplification of other human infectious viruses including Japanese Encephalitis Virus (JEV), Dengue, Enterovirus, Zika, Influenza and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This highly sensitive, electro- and equipment-free rapid colorimetric visualization method is feasible for resource-limited SFTSV field diagnosis.


Randomized controlled trials for everything?


title: The Effect of a Synthetic Heparan Sulfate on the Healing of Colonic Anastomoses.

text: BACKGROUND The mimetic compound OTR4120 may replace endogenous-degraded heparan sulfates that normally maintain the bioactivity of growth factors that are important for tissue repair. Herein, we investigated the effect of OTR4120 on the healing of normal colonic anastomoses. METHODS We evaluated the following two treatment groups of male Sprague Dawley rats (220-256 g): control-treated colonic anastomoses (n = 25) and OTR4120-treated colonic anastomoses (n = 25). We resected 10 mm of the left colon and then applied either saline alone (control) or OTR4120 (100 μg/mL) in saline to the colonic ends before an end-to-end single-layer anastomosis was constructed and again on the anastomosis before the abdomen and skin were closed. RESULTS On postoperative day 3, the anastomotic breaking strengths were 1.47 ± 0.32 N (mean ± SD) in the control group and 1.52 ± 0.27 N in the OTR4120-treated animals (P = 0.622). We also found that the hydroxyproline concentration (indicator of collagen) in the anastomotic wounds did not differ (P = 0.571) between the two groups. CONCLUSIONS Our data demonstrate that a single local application of OTR4120 intraoperatively did not increase the biomechanical strength of colonic anastomoses at the critical postoperative day 3 when the anastomoses are the weakest.


title: Flat detector angio-CT following intra-arterial therapy of acute ischemic stroke: identification of hemorrhage and distinction from contrast accumulation due to blood-brain barrier disruption.

text: BACKGROUND AND PURPOSE Flat panel detector CT in the angiography suite may be valuable for the detection of intracranial hematomas; however, abnormal contrast enhancement frequently mimics hemorrhage. We aimed to assess the accuracy of flat panel detector CT in detecting/excluding intracranial bleeding after endovascular stroke therapy and whether it was able to reliably differentiate hemorrhage from early blood-brain barrier disruption. MATERIALS AND METHODS Seventy-three patients were included for retrospective evaluation following endovascular stroke therapy: 32 after stent-assisted thrombectomy, 14 after intra-arterial thrombolysis, and 27 after a combination of both. Flat panel CT images were assessed for image quality and the presence and type of intracranial hemorrhage and BBB disruption by 2 readers separately and in consensus. Follow-up by multisection head CT, serving as the reference standard, was evaluated by a single reader. RESULTS Conventional head CT revealed intracranial hematomas in 12 patients (8 subarachnoid hemorrhages, 7 cases of intracerebral bleeding, 3 SAHs plus intracerebral bleeding). Image quality of flat panel detector CT was considered sufficient in all cases supratentorially and in 92% in the posterior fossa. Regarding detection or exclusion of intracranial hemorrhage, flat panel detector CT reached a sensitivity, specificity, positive and negative predictive values, and accuracy of 58%, 85%, 44%, 91%, and 81%, respectively. Maximum attenuation measurements were not valuable for the differentiation of hemorrhage and BBB disruption. CONCLUSIONS Flat panel CT after endovascular stroke treatment was able to exclude the rare event of an intracranial hemorrhage with a high negative predictive value. Future studies should evaluate the predictive value of BBB disruptions in flat panel detector CT for the development of relevant hematomas.


title: Diagnostic Ultrasound Services During the Coronavirus Disease (COVID-19) Pandemic.

text: OBJECTIVE. Nosocomial transmission of coronavirus disease (COVID-19) to frontline health care workers is well known, and health care workers may inadvertently become vectors for onward transmission. Ultrasound (US) service providers are at significant risk because scanning usually requires prolonged close patient contact. The bulky US equipment may also facilitate fomite transmission of disease. With increasing use of point-of-care and portable diagnostic US services, the risk is substantial. CONCLUSION. Our experience and protocols may help service providers with their own effective response against COVID-19.