title: Ticagrelor Versus Aspirin in Acute Embolic Stroke of Undetermined Source.

text: BACKGROUND AND PURPOSE Ticagrelor is an effective antiplatelet therapy among patients with atherosclerotic disease and, therefore, could be more effective than aspirin in preventing recurrent stroke and cardiovascular events among patients with embolic stroke of unknown source (ESUS), which includes patients with ipsilateral stenosis <50% and aortic arch atherosclerosis. METHODS We randomized 13 199 patients with a noncardioembolic, nonsevere ischemic stroke or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2-90) or aspirin (300 mg on day 1 followed by 100 mg daily for days 2-90) within 24 hours of symptom onset. In all patients, investigators informed on the presence of ipsilateral stenosis ≥50%, small deep infarct <15 mm, and on cardiac source of embolism detected after enrollment or rare causes, which allowed to construct an ESUS category in all other patients with documented brain infarction. The primary end point was the time to the occurrence of stroke, myocardial infarction, or death within 90 days. RESULTS ESUS was identified in 4329 (32.8%) patients. There was no treatment-by-ESUS category interaction (P=0.83). Hazard ratio in ESUS patients was 0.87 (95% confidence interval, 0.68-1.10; P=0.24). However, hazard ratio was 0.51 (95% confidence interval, 0.29-0.90; P=0.02) in ESUS patients with ipsilateral stenosis <50% or aortic arch atherosclerosis (n=961) and 0.98 (95% confidence interval, 0.76-1.27; P=0.89) in the remaining ESUS patients (n=3368; P for heterogeneity =0.04). CONCLUSIONS In this post hoc, exploratory analysis, we found no treatment-by-ESUS category interaction. ESUS subgroups have heterogeneous response to treatment (Funded by AstraZeneca). CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01994720.


title: Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study.

text: OBJECTIVE Procedural sedation with propofol is widely used in the pediatric population. A well-known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation. METHODS Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark-field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Øbv ), and systemic hemodynamics were analyzed. RESULTS Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Øbv increased but not significantly. CONCLUSIONS Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance.


title: Does red blood cell irradiation and/or anemia trigger intestinal injury in premature infants with birth weight ≤ 1250 g? An observational birth cohort study.

text: BACKGROUND Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality in premature infants. To date, no effective biomarkers exist to predict which premature infants will develop NEC, limiting targeted prevention strategies. Multiple observational studies have reported an association between the exposure to red blood cell (RBC) transfusion and/or anemia and the subsequent development of NEC; however, the underlying physiologic mechanisms of how these factors are independently associated with NEC remain unknown. METHODS In this paper, we outline our prospective, multicenter observational cohort study of infants with a birth weight ≤ 1250 g to investigate the associations between RBC transfusion, anemia, intestinal oxygenation and injury that lead to NEC. Our overarching hypothesis is that irradiation of RBC units followed by longer storage perturbs donor RBC metabolism and function, and these derangements are associated with paradoxical microvascular vasoconstriction and intestinal tissue hypoxia increasing the risk for injury and/or NEC in transfused premature infants with already impaired intestinal oxygenation due to significant anemia. To evaluate these associations, we are examining the relationship between prolonged irradiation storage time (pIST), RBC metabolomic profiles, and anemia on intestinal oxygenation non-invasively measured by near-infrared spectroscopy (NIRS), and the development of NEC in transfused premature infants. DISCUSSION Our study will address a critical scientific gap as to whether transfused RBC characteristics, such as irradiation and metabolism, impair intestinal function and/or microvascular circulation. Given the multifactorial etiology of NEC, preventative efforts will be more successful if clinicians understand the underlying pathophysiologic mechanisms and modifiable risk factors influencing the disease. TRIAL REGISTRATION Our study is registered in ClinicalTrials.gov Identifier: NCT02741648 .


title: Influenza-induced thrombocytopenia is dependent on the subtype and sialoglycan receptor and increases with virus pathogenicity.

text: Thrombocytopenia is a common complication of influenza virus infection, and its severity predicts the clinical outcome of critically ill patients. The underlying cause(s) remain incompletely understood. In this study, in patients with an influenza A/H1N1 virus infection, viral load and platelet count correlated inversely during the acute infection phase. We confirmed this finding in a ferret model of influenza virus infection. In these animals, platelet count decreased with the degree of virus pathogenicity varying from 0% in animals infected with the influenza A/H3N2 virus, to 22% in those with the pandemic influenza A/H1N1 virus, up to 62% in animals with a highly pathogenic A/H5N1 virus infection. This thrombocytopenia is associated with virus-containing platelets that circulate in the blood. Uptake of influenza virus particles by platelets requires binding to sialoglycans and results in the removal of sialic acids by the virus neuraminidase, a trigger for hepatic clearance of platelets. We propose the clearance of influenza virus by platelets as a paradigm. These insights clarify the pathophysiology of influenza virus infection and show how severe respiratory infections, including COVID-19, may propagate thrombocytopenia and/or thromboembolic complications.


title: Single-incision surgery with SILS port for anterior mediastinal lesions: initial experience.

text: Infrasternal mediastinoscopic single-incision surgery is a minimally invasive surgical option for patients with anterior mediastinal lesions. The main drawback of the procedure is difficult when handling the endoscopic instruments through the small infrasternal incision. Herein, we report our initial experience with use of the procedure in 2 patients with bronchogenic cysts in the anterior mediastinum. We found that use of an SILS Port, now widely available for single-incision laparoscopic surgery, can decrease the difficulty of this approach.


title: Human picobirnaviruses identified by molecular screening of diarrhea samples.

text: The global threat of (re)emerging infectious viruses requires a more effective approach regarding virus surveillance and diagnostic assays, as current diagnostics are often virus species specific and not able to detect highly divergent or unknown viruses. A systematic exploration of viruses that infect humans is the key to effectively counter the potential public health threat caused by new and emerging infectious diseases. The human gut is a known reservoir of a wide variety of microorganisms, including viruses. In this study, Dutch clinical diarrhea samples for which no etiological agent could be identified by available cell culture, serological, or nucleic acid-based tests were gathered. Large-scale molecular RNA virus screening based on host nucleic acid depletion, sequence-independent amplification, and sequencing of partially purified viral RNA from a limited number of clinical diarrhea samples revealed four eukaryotic virus species. Among the detected viruses were a rhinovirus and a new picobirnavirus variant. In total, approximately 20% of clinical diarrhea samples contained human picobirnavirus sequences. The Dutch picobirnaviruses belonged to different phylogenetic clades and did not group with other picobirnaviruses according to year of isolation or host species. Interestingly, the average age of patients infected with picobirnavirus was significantly higher than that of uninfected patients. Our data show that sequence-independent amplification of partially purified viral RNA is an efficient procedure for identification of known and highly divergent new RNA viruses in clinical diarrhea samples.


title: The N-terminal region of IFITM3 modulates its antiviral activity by regulating IFITM3 cellular localization.

text: Interferon-inducible transmembrane (IFITM) protein family members IFITM1, -2, and -3 restrict the infection of multiple enveloped viruses. Significant enrichment of a minor IFITM3 allele was recently reported for patients who were hospitalized for seasonal and 2009 H1N1 pandemic flu. This IFITM3 allele lacks the region corresponding to the first amino-terminal 21 amino acids and is unable to inhibit influenza A virus. In this study, we found that deleting this 21-amino-acid region relocates IFITM3 from the endosomal compartments to the cell periphery. This finding likely underlies the lost inhibition of influenza A virus that completes its entry exclusively within endosomes at low pH. Yet, wild-type IFITM3 and the mutant with the 21-amino-acid deletion inhibit HIV-1 replication equally well. Given the pH-independent nature of HIV-1 entry, our results suggest that IFITM3 can inhibit viruses that enter cells via different routes and that its N-terminal region is specifically required for controlling pH-dependent viruses.


docid: uqsipejr

title: Randomized comparison of liposomal amphotericin B versus placebo to prevent invasive mycoses in acute lymphoblastic leukaemia.

text: Objectives To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL). Patients and methods In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB. Results Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB ( n = 237) or placebo ( n = 118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group ( P = 0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group ( P = 0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo ( P = 1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB. Conclusions The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL.


title: Effect of Barrett's esophagus surveillance on esophageal preservation, tumor stage, and survival with esophageal adenocarcinoma.

text: OBJECTIVES Surveillance endoscopy has been recommended for patients with Barrett's esophagus; however, recent studies have questioned the importance owing to the new, lower, estimates of the rate of progression of Barrett's esophagus to cancer. The aim of the present study was to compare the tumor stage, survival, and frequency of esophageal preservation in patients who presented with progression of Barrett's esophagus within a surveillance program versus those who presented with prevalent disease. METHODS A retrospective chart review was performed of all patients treated for high-grade dysplasia or esophageal adenocarcinoma from 2005 to 2010. The surveillance group included patients who had had at least 1 endoscopy and biopsy confirming intestinal metaplasia (with or without low-grade dysplasia) 6 months or more before the endoscopy showing progression. RESULTS A total of 224 patients were included in the present study, 36 in the surveillance group and 188 in the prevalence group. The surveillance patients had significantly earlier stage tumors (P < .0001) and were more likely to undergo endoscopic therapy and to keep their esophagus (44% vs 11%, P < .0001) than were patients with prevalent disease. Furthermore, the patients in the surveillance group were less likely to have lymph node metastases and had better overall and disease-free survival. No patient with high-grade dysplasia or an intramucosal tumor died of cancer. CONCLUSIONS Patients within a surveillance program for Barrett's esophagus had better survival and were less likely to have an esophagectomy than those who presented with prevalent disease. Treatment of intramucosal cancer was curative, and improved survival with surveillance was not secondary to lead time bias. Surveillance endoscopy remains important in patients with Barrett's esophagus.


title: Long-term impact of respiratory viral infection after pediatric lung transplantation.

text: To evaluate the epidemiology and to investigate the impact of RVI on chronic allograft rejection after pediatric lung transplantation, a retrospective study of pediatric lung transplant recipients from 2002 to 2007 was conducted. Association between RVI and continuous and categorical risk factors was assessed using Wilcoxon rank-sum tests and Fisher's exact tests, respectively. Association between risk factors and outcomes were assessed using Cox proportional hazards models. Fifty-five subjects were followed for a mean of 674 days (range 14-1790). Twenty-eight (51%) developed 51 RVI at a median of 144 days post-transplant (mean 246; range 1-1276); 41% of infections were diagnosed within 90 days. Twenty-five subjects developed 39 LRI, and eight subjects had 11 URI. Organisms recovered included rhinovirus (n = 14), adenovirus (n = 10), parainfluenza (n = 10), influenza (n = 5), and RSV (n = 4). Three subjects expired secondary to their RVI (two adenovirus, one RSV). Younger age and prior CMV infection were risks for RVI (HR 2.4 95% CI 1.1-5.3 and 17.0; 3.0-96.2, respectively). RVI was not associated with the development of chronic allograft rejection (p = 0.25) or death during the study period. RVI occurs in the majority of pediatric lung transplant recipients, but was not associated with mortality or chronic allograft rejection.


title: Recommendations by the SEPD and AEG, both in general and on the operation of gastrointestinal endoscopy and gastroenterology units, concerning the current SARS-CoV-2 pandemic (March, 18).

text: Infection with SARS-CoV-2 coronavirus, and the disease this agent may induce, are a cause of notable concern for the general population and, of course, among our professionals and patients. Gastrointestinal (GI) endoscopy is a high-risk diagnostic-therapeutic procedure in the case of upper GI examinations, and a moderate to low-risk intervention when involving lower GI explorations. The presence of SARS-CoV-2 RNA in the feces of patients infected with the virus, and occasionally in colonic biopsy samples, has been consistently documented. In fact, viral elimination in the feces may be more prolonged than viral identification in respiratory tract secretions. Furthermore, viral transmission may occur in asymptomatic individuals. However, as of this moment no information has been reported on the possibility of viral transmission, even to professionals, via this route.


title: Contamination of Health Care Personnel During Removal of Personal Protective Equipment.

text: IMPORTANCE Contamination of the skin and clothing of health care personnel during removal of personal protective equipment (PPE) contributes to dissemination of pathogens and places personnel at risk for infection. OBJECTIVES To determine the frequency and sites of contamination on the skin and clothing of personnel during PPE removal and to evaluate the effect of an intervention on the frequency of contamination. DESIGN, SETTING, AND PARTICIPANTS We conducted a point-prevalence study and quasi-experimental intervention from October 28, 2014, through March 31, 2015. Data analysis began November 17, 2014, and ended April 21, 2015. Participants included a convenience sample of health care personnel from 4 Northeast Ohio hospitals who conducted simulations of contaminated PPE removal using fluorescent lotion and a cohort of health care personnel from 7 study units in 1 medical center that participated in a quasi-experimental intervention that included education and practice in removal of contaminated PPE with immediate visual feedback based on fluorescent lotion contamination of skin and clothing. MAIN OUTCOMES AND MEASURES The primary outcomes were the frequency and sites of contamination on skin and clothing of personnel after removal of contaminated gloves or gowns at baseline vs after the intervention. A secondary end point focused on the correlation between contamination of skin with fluorescent lotion and bacteriophage MS2, a nonpathogenic, nonenveloped virus. RESULTS Of 435 glove and gown removal simulations, contamination of skin or clothing with fluorescent lotion occurred in 200 (46.0%), with a similar frequency of contamination among the 4 hospitals (range, 42.5%-50.3%). Contamination occurred more frequently during removal of contaminated gloves than gowns (52.9% vs 37.8%, P = .002) and when lapses in technique were observed vs not observed (70.3% vs 30.0%, P < .001). The intervention resulted in a reduction in skin and clothing contamination during glove and gown removal (60.0% before the intervention vs 18.9% after, P < .001) that was sustained after 1 and 3 months (12.0% at both time points, P < .001 compared with before the intervention). During simulations of contaminated glove removal, the frequency of skin contamination was similar with fluorescent lotion and bacteriophage MS2 (58.0% vs 52.0%, P = .45). CONCLUSIONS AND RELEVANCE Contamination of the skin and clothing of health care personnel occurs frequently during removal of contaminated gloves or gowns. Educational interventions that include practice with immediate visual feedback on skin and clothing contamination can significantly reduce the risk of contamination during removal of PPE.


title: Predicting nurses' acceptance of radiofrequency identification technology.

text: The technology of radiofrequency identification allows for the scanning of radiofrequency identification-tagged objects and individuals without line-of-sight requirements. Healthcare organizations use radiofrequency identification to ensure the health and safety of patients and medical personnel and to uncover inefficiencies. Although the successful implementation of a system incorporating radiofrequency identification technologies requires acceptance and use of the technology, some nurses using radiofrequency identification in hospitals feel like "Big Brother" is watching them. This predictive study used a theoretical model assessing the effect of five independent variables: privacy concerns, attitudes, subjective norms, controllability, and self-efficacy, on a dependent variable, nurses' behavioral intention to use radiofrequency identification. A Web-based questionnaire containing previously validated questions was answered by 106 US RNs. Multiple linear regression showed that all constructs together accounted for 60% of the variance in nurses' intention to use radiofrequency identification. Of the predictors in the model, attitudes provided the largest unique contribution when the other predictors in the model were held constant; subjective norms also provided a unique contribution. Privacy concerns, controllability, and self-efficacy did not provide a significant contribution to nurses' behavioral intention to use radiofrequency identification.


docid: auqhhise

title: The role of primary care in the Brazilian healthcare system: limits and possibilities for fighting COVID-19.


title: Successful ventilation through a Rüsch intubation guide catheter in severe laryngotracheal stenosis.

text: BACKGROUND Providing adequate ventilation may remain complex in patients with severe proximal laryngotracheal stenosis, especially when the airway is shared with the surgeon during tracheal resection surgery. We describe an effective alternative to standard endotracheal intubation using a Rüsch flexible intubation guide catheter. METHODS In two patients undergoing tracheal repair surgery, we failed to insert a 5.0 inner diameter endotracheal tube (6.9 mm outer diameter) or a 6.0 mm outer diameter endoscope through the laryngotracheal stenosis. However, using indirect laryngoscopy, a 6.0 outer diameter Rüsch flexible intubation guide catheter was passed successfully through the vocal cords and then through the stenosis. Controlled ventilation was achieved by means of the Rüsch guide, provided with its two large Murphy's eyes. When the trachea was opened, the Rüsch guide was removed just enough for the surgeons to place a Montandon tracheal tube, at that point taking over ventilation. A 7.0 inner diameter endotracheal cuffed tube had been inserted onto the Rüsch guide and left pending upstream from the vocal cords. Once the posterior tracheal wall was sutured, this endotracheal cuffed tube was slid along the Rüsch guide through the vocal cords with the cuff placed beyond the tracheal sutures. RESULTS Controlled ventilation through the Rüsch flexible intubation guide catheter showed satisfying and stable ventilatory parameters in both patients. Inspiratory pressures of 25-30 mmHg were enough to reach adequate tidal volumes around 450 ml. End tidal CO2 was kept between 35 and 40 mmHg (PaCO2 showed similar values). Standard endotracheal intubation at the end of the tracheal resection was easy and safe thanks to the Rüsch guide still in place between the vocal cords. CONCLUSIONS We suggest an effective and reliable method using a Rüsch flexible intubation guide catheter for airway management in patients suffering from laryngotracheal stenosis in the setting of tracheal repair surgery.


Effect of malnutrition on executive function in older Egyptians in geriatric homes.


Peritoneal Dialysis in the time of COVID-19.


Abdominal Wall: Register & Miscellaneous.


title: Renal Cell Carcinoma Metastasis from Biopsy Associated Hematoma Disruption during Robotic Partial Nephrectomy.

text: We describe a case in which a patient with a past medical history of ovarian cancer received a diagnostic renal biopsy for an incidentally discovered renal mass. During left robotic partial nephrectomy (RPN), a perinephric hematoma was encountered. The hematoma was not present on preoperative imaging and was likely a result of the renal biopsy. The renal cell carcinoma (RCC) and the associated hematoma were widely excised with negative surgical margins. On follow-up imaging at five months postoperatively, a recurrent renal mass at the surgical resection bed and several new nodules in the omentum were detected. During completion left robotic total nephrectomy and omental excision, intraoperative frozen sections confirmed metastatic RCC. We believe that a hematoma seeded with RCC formed as a result of the renal biopsy, and subsequent disruption of the hematoma during RPN caused contamination of RCC into the surrounding structures.


title: Optimal blood pressure after reperfusion therapy in patients with acute ischemic stroke.

text: We investigated the relationship between the mean blood pressure (BP) at 24-72 h and the clinical outcomes after acute ischemic stroke (AIS) in patients treated with reperfusion therapy. The primary outcome was measured using the modified Rankin Scale (mRS) at 3 months after AIS, and was based on the mean systolic BP at 24-72 h post-AIS. Favorable outcome was defined as mRS scores of 0-2. A total of 1,540 patients treated with reperfusion therapy were enrolled in the study. Favorable outcomes occurred more frequently in patients with BP ≤ 130/80 mmHg, and the risks of symptomatic intracranial hemorrhage and early neurological deterioration were lower in this optimal BP group. Multivariable analysis showed a significant association between mean BP ≤ 130/80 mmHg at 24-72 h and favorable outcomes at 3 months after AIS (odds ratio 2.95, 95% confidence interval 2.32-3.77, p < 0.001). Prespecified subgroup analyses showed that BP ≤ 130/80 mmHg had a more significant impact on clinical outcome in patients with recanalization than in those without recanalization. These data indicate that a mean BP of ≤ 130/80 mmHg at 24-72 h post-AIS is independently associated with favorable outcomes in patients treated with reperfusion therapy, particularly in those with recanalization.


title: Single-domain antibodies targeting neuraminidase protect against an H5N1 influenza virus challenge.

text: UNLABELLED Influenza virus neuraminidase (NA) is an interesting target of small-molecule antiviral drugs. We isolated a set of H5N1 NA-specific single-domain antibodies (N1-VHHm) and evaluated their in vitro and in vivo antiviral potential. Two of them inhibited the NA activity and in vitro replication of clade 1 and 2 H5N1 viruses. We then generated bivalent derivatives of N1-VHHm by two methods. First, we made N1-VHHb by genetically joining two N1-VHHm moieties with a flexible linker. Second, bivalent N1-VHH-Fc proteins were obtained by genetic fusion of the N1-VHHm moiety with the crystallizable region of mouse IgG2a (Fc). The in vitro antiviral potency against H5N1 of both bivalent N1-VHHb formats was 30- to 240-fold higher than that of their monovalent counterparts, with 50% inhibitory concentrations in the low nanomolar range. Moreover, single-dose prophylactic treatment with bivalent N1-VHHb or N1-VHH-Fc protected BALB/c mice against a lethal challenge with H5N1 virus, including an oseltamivir-resistant H5N1 variant. Surprisingly, an N1-VHH-Fc fusion without in vitro NA-inhibitory or antiviral activity also protected mice against an H5N1 challenge. Virus escape selection experiments indicated that one amino acid residue close to the catalytic site is required for N1-VHHm binding. We conclude that single-domain antibodies directed against influenza virus NA protect against H5N1 virus infection, and when engineered with a conventional Fc domain, they can do so in the absence of detectable NA-inhibitory activity. IMPORTANCE Highly pathogenic H5N1 viruses are a zoonotic threat. Outbreaks of avian influenza caused by these viruses occur in many parts of the world and are associated with tremendous economic loss, and these viruses can cause very severe disease in humans. In such cases, small-molecule inhibitors of the viral NA are among the few treatment options for patients. However, treatment with such drugs often results in the emergence of resistant viruses. Here we show that single-domain antibody fragments that are specific for NA can bind and inhibit H5N1 viruses in vitro and can protect laboratory mice against a challenge with an H5N1 virus, including an oseltamivir-resistant virus. In addition, plant-produced VHH fused to a conventional Fc domain can protect in vivo even in the absence of NA-inhibitory activity. Thus, NA of influenza virus can be effectively targeted by single-domain antibody fragments, which are amenable to further engineering.


title: High CD3+ Cells in Intracranial Thrombi Represent a Biomarker of Atherothrombotic Stroke.

text: BACKGROUND AND PURPOSE Approximately 30% of strokes are cryptogenic despite an exhaustive in-hospital work-up. Analysis of clot composition following endovascular treatment could provide insight into stroke etiology. T-cells already have been shown to be a major component of vulnerable atherosclerotic carotid lesions. We therefore hypothesize that T-cell content in intracranial thrombi may also be a biomarker of atherothrombotic origin. MATERIALS AND METHODS We histopathologically investigated 54 consecutive thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fibrin-dominant, erythrocyte-dominant or mixed pattern. We then performed quantitative analysis of CD3+ cells on immunohistochemically-stained thrombi and compared T-cell content between "atherothrombotic", "cardioembolism" and "other causes" stroke subtypes. RESULTS Fourteen (26%) thrombi were defined as fibrin-dominant, 15 (28%) as erythrocyte-dominant, 25 (46%) as mixed. The stroke cause was defined as "atherothrombotic" in 10 (18.5%), "cardioembolism" in 25 (46.3%), and "other causes" in 19 (35.2%). Number of T-cells was significantly higher in thrombi from the "atherothrombotic" group (53.60 ± 28.78) than in the other causes (21.77 ± 18.31; p<0.0005) or the "cardioembolism" group (20.08 ± 15.66; p<0.0003). CONCLUSIONS The CD3+ T-cell count in intracranial thrombi was significantly higher in "atherothrombotic" origin strokes compared to all other causes. Thrombi with high content of CD3+ cells are more likely to originate from an atherosclerotic plaque.


title: Medical intelligence, security and global health: the foundations of a new health agenda.

text: Medical intelligence, security and global health are distinct fields that often overlap, especially as the drive towards a global health security agenda gathers pace. Here, we outline some of the ways in which this has happened in the recent past during the recent Ebola epidemic in West Africa and in the killing of Osama Bin laden by US intelligence services. We evaluate medical intelligence and the role it can play in global health security; we also attempt to define a framework that illustrates how medical intelligence can be incorporated into foreign policy action in order delineate the boundaries and scope of this growing field.


title: Stroke Neurologist's Perspective on the New Endovascular Trials.

text: Before December 2014, the only proven effective treatment for acute ischemic stroke was recombinant tissue-type plasminogen activator (r-tPA). This has now changed with the publication of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE), Extending the Time for Thrombolysis in Emergency Neurological Deficits--Intra-Arterial (EXTEND IA), Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment Trial (SWIFT PRIME), and Randomized Trial of Revascularization With the Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) studies. We review the main results of these studies and how they inform stroke patient management going forward. The main take home points for neurologists are (1) intra-arterial thrombectomy is a potently effective treatment and should be offered to patients who have documented occlusion in the distal internal carotid or the proximal middle cerebral artery, have a relatively normal noncontrast head computed tomographic scan, severe neurological deficit, and can have intra-arterial thrombectomy within 6 hours of last seen normal; (2) benefits are clear in patients receiving r-tPA before intra-arterial thrombectomy; r-tPA should not be withheld if the patient meets criteria, and benefit in patients who do not receive r-tPA or have r-tPA exclusions requires further study; and (3) these favorable results occur when intra-arterial thrombectomy is performed in an endovascular stroke center by a coordinated multidisciplinary team that extends from the prehospital stage to the endovascular suite, minimizes time to recanalization, uses stent-retriever devices, and avoids general anesthesia. In conclusion, stroke teams, including practicing neurologists caring for patients with stroke should now provide the option for intra-arterial thrombectomy for a subset of patients with acute stroke.


title: A rare complication of chronic granulomatous disease in a child: constrictive aspergillus pericarditis.

text: A 3-year-old girl with the diagnosis of chronic granulomatous disease (CGD) was hospitalized for bronchopneumonia and congestive heart failure. Her medical history included methylprednisolone medication for autoimmune gastric outlet obstruction. Computed tomography revealed pneumonic infiltrations and pericardial thickening. A pulsed-wave Doppler recording revealed E/A >1. During a pericardiectomy, multiple islands of thick, firm-walled, fibrinous exudate-containing, small abscess formations were observed. Histopathological evaluation of pericardial tissue revealed granulomatous inflammation. Aspergillus fumigatus was cultured from the abscess. In conclusion, development of constrictive aspergillus pericarditis should be considered in patients with CGD because immediate initiation of antifungal management with aggressive surgical treatment is life-saving.


title: Assembling viral channel forming proteins: Vpu from HIV-1.

text: Different routes of assembly are probed for the transmembrane domain (TMD) of the bitopic membrane protein Vpu from HIV-1. Vpu is responsible for the amplification of viral release from the host cell. The mode of action includes (i) heteroassembly with host factors and (ii) the formation of homo-oligomers, which are able to conduct ions across the lipid membrane. Two different routes of assembling short sequences of the N terminus, including the TMD of Vpu, Vpu1-32, and Vpu8-26, are presented by using a combination of classical molecular dynamics (MD) simulations combined with a docking approach. The rim of alanines (Ala-8, -11, -15, and -19) resembles an interlocking motif for the sequential assembly into a dimer and trimer. Simultaneous assembly results in oligomeric bundles (trimers to pentamers) with either tryptophans (Trp-23) or purely hydrophobic residues facing the center. Bundles, with serines facing the pore (Ser-24), are energetically not the lowest structures. For pentameric bundles with Ser-24 facing the pore, no water column develops during a short 25 ns MD simulation.


docid: yvmuiiux

title: Third nerve palsy following carotid artery dissection and posterior cerebral artery thrombectomy: Case report and review of the literature.

text: BACKGROUND Common causes of oculomotor nerve palsy are diabetes, aneurysmal compression, and uncal herniation. A lesser-known cause of third nerve dysfunction is ischemia, often due to carotid artery dissection. CASE DESCRIPTION An 80-year-old man presented with an acute ischemic stroke with a National Institutes of Health Stroke Scale score of >20 from a high cervical internal carotid artery (ICA) dissection and a tandem ICA terminus embolic occlusion with extension of clot into the adjacent fetal posterior cerebral artery (PCA). We used a stentriever to perform selective PCA thrombectomy, with immediate postthrombectomy development of ipsilateral anisocoria. The anisocoria progressed into complete oculomotor nerve palsy over 8 h after the procedure. CONCLUSIONS The clinical course described in this case is consistent with injury to the third nerve due to mechanical injury or occlusion of perforator supply to the nerve during thrombectomy. Oculomotor nerve palsy is a rare but known complication after ischemia; however, to our knowledge, this is the first case after thrombectomy for a PCA embolus.


title: Clipless and sutureless laparoscopic adrenalectomy carried out with the LigaSure device in 32 patients.

text: BACKGROUND Laparoscopic adrenalectomy has become the standard procedure for treating patents with adrenal masses. The purpose of this study was to evaluate the use of the LigaSure vessel closure system during laparoscopic adrenalectomy. METHODS The LigaSure device was used in 32 patients undergoing laparoscopic adrenalectomy for adrenal masses. Adrenalectomy was carried out without the use of clips or sutures for vessel closure. In 1 patient the adrenal tumor had invaded the ipsilateral kidney, so laparoscopic nephrectomy was also carried out during the same operation. In another patient, a renal cell carcinoma in the left kidney had metastasized to the right adrenal gland. Both the kidney and the contralateral adrenal gland were removed laparoscopically during the same operation. RESULTS Adrenal masses had a mean greatest diameter of 3.48 cm (range 2 to 11 cm). Mean operative time was 83.2 minutes (range 30 to 190 min). Mean blood loss was 36.2 mL (range 10 to 140 mL). No conversions to open surgery were necessary. No patients experienced major bleeding intraoperatively or postoperatively. Adrenal tumor types included adrenocortical adenoma (16 patients), pheochromocytoma (13 patients), malignant pheochromocytoma (1 patient), chromophobic carcinoma (1 patient), and metastasis from a renal cell carcinoma (1 patient). CONCLUSIONS For vessel closure during laparoscopic adrenalectomy, the LigaSure device seems to be safe and effective. For patients with conditions such as renal cell carcinoma combined with metastasis to the contralateral adrenal gland, nephrectomy, and contralateral adrenalectomy can be carried out during the same laparoscopic operation.


title: Effect of scapular dyskinesis on supraspinatus repair healing in a rat model.

text: BACKGROUND Rotator cuff tears are common conditions that often require surgical repair to improve function and to relieve pain. Unfortunately, repair failure remains a common problem after rotator cuff repair surgery. Several factors may contribute to repair failure, including age, tear size, and time from injury. However, the mechanical mechanisms resulting in repair failure are not well understood, making clinical management difficult. Specifically, altered scapular motion (termed scapular dyskinesis) may be one important and modifiable factor contributing to the risk of repair failure. Therefore, the objective of this study was to determine the effect of scapular dyskinesis on supraspinatus tendon healing after repair. METHODS A rat model of scapular dyskinesis was used. Seventy adult male Sprague-Dawley rats (400-450 g) were randomized into 2 groups: nerve transection of the accessory and long thoracic nerves (SD) or sham nerve transection (Sham control). After this procedure, all rats underwent unilateral detachment and repair of the supraspinatus tendon. All rats were sacrificed at 2, 4, and 8 weeks after surgery. Shoulder function, passive joint mechanics, and tendon properties (mechanical, histologic, organizational, and compositional) were evaluated. RESULTS Scapular dyskinesis alters joint function and may lead to compromised supraspinatus tendon properties. Specifically, diminished mechanical properties, altered histology, and decreased tendon organization were observed for some parameters. CONCLUSION This study identifies scapular dyskinesis as one underlying mechanism leading to compromise of supraspinatus healing after repair. Identifying modifiable factors that lead to compromised tendon healing will help improve clinical outcomes after repair.


title: Type 2 Diabetes Remission Rates After Laparoscopic Gastric Bypass and Gastric Banding: Results of the Longitudinal Assessment of Bariatric Surgery Study.

text: OBJECTIVE The goals of this study were to determine baseline and postbariatric surgical characteristics associated with type 2 diabetes remission and if, after controlling for differences in weight loss, diabetes remission was greater after Roux-en-Y gastric bypass (RYGBP) than laparoscopic gastric banding (LAGB). RESEARCH DESIGN AND METHODS An observational cohort of obese participants was studied using generalized linear mixed models to examine the associations of bariatric surgery type and diabetes remission rates for up to 3 years. Of 2,458 obese participants enrolled, 1,868 (76%) had complete data to assess diabetes status at both baseline and at least one follow-up visit. Of these, 627 participants (34%) were classified with diabetes: 466 underwent RYGBP and 140 underwent LAGB. RESULTS After 3 years, 68.7% of RYGBP and 30.2% of LAGB participants were in diabetes remission. Baseline factors associated with diabetes remission included a lower weight for LAGB, greater fasting C-peptide, lower leptin-to-fat mass ratio for RYGBP, and a lower hemoglobin A1c without need for insulin for both procedures. After both procedures, greater postsurgical weight loss was associated with remission. However, even after controlling for differences in amount of weight lost, relative diabetes remission rates remained nearly twofold higher after RYGBP than LAGB. CONCLUSIONS Diabetes remission up to 3 years after RYGBP and LAGB was proportionally higher with increasing postsurgical weight loss. However, the nearly twofold greater weight loss-adjusted likelihood of diabetes remission in subjects undergoing RYGBP than LAGB suggests unique mechanisms contributing to improved glucose metabolism beyond weight loss after RYGBP.


title: Sub-diffusion decays in fluorescence correlation spectroscopy: dye photophysics or protein dynamics?

text: Transitions between bright and dark fluorescent states of several rhodamine dyes were investigated by fluorescence correlation spectroscopy. We resolved two sub-diffusion exponential decays for free rhodamines in aqueous solutions, of which the slower component scales linearly with the viscosity of the solution. Correlation data for proteins and DNA labeled with tetramethylrhodamine were fitted with three to four exponential decays describing flickering dynamics on a time scale between 0.5 and 100 μs. We investigated the nature of these processes by performing experiments under different experimental conditions and for different samples. On the basis of how their population and lifetime change with viscosity, the oxygen content of the solution, the laser irradiance, and the detection geometry, we assigned these states, in the order of increasing lifetimes, to a triplet state, a hybrid between twisted-intramolecular-charge-transfer state and a ground state lactonic state, a lactonic state, and a photoionized state, respectively. Our data suggests that none of the observed sub-diffusion correlation decays can be directly assigned to the intramolecular dynamics of the labeled biomolecules. However, we found evidence that the intrinsic conformational dynamics of the biomolecule appears in the correlation curves as a modulation of the photophysics of the dye label. This shows the importance of accurate control measurements and appropriate modeling of the dye photophysics in fluorescence correlation studies, and it cautions against direct assignments of dark-state relaxation times to folding kinetics in proteins and nucleic acids.


title: The effect of intraoperative administration of dexamethasone for PONV prophylaxis on perioperative blood glucose level in obese and normal weight children.

text: BACKGROUND The incidence of postoperative nausea and vomiting (PONV) can be reduced by dexamethasone. Single-dose administration may cause elevated blood glucose levels in obese adults. No data are available for children. OBJECTIVE The aim was to evaluate perioperative blood glucose changes related to body weight in children who received dexamethasone. PATIENTS AND METHODS This prospective observational study included 62 children. All patients received total intravenous anesthesia and a single dose of dexamethasone (0.15 mg/kg, maximum 8 mg). Blood glucose levels were measured up to 6 h. Standard deviation scores (SDS) were calculated using age- and gender-specific body mass index (BMI) percentiles, p<0.05. RESULTS A total of 62 children (11.5±2.9 years, median SDS 0.43, 29% overweight/obese) were included. Blood glucose levels increased from 5.52±0.52 to 6.74±0.84 mmol/L 6 h after dexamethasone without correlation to the BMI-SDS. CONCLUSIONS This study showed an increase of perioperative blood glucose (normoglycemic ranges) after single dose of dexamethasone, but no BMI-dependent effect was observed in children. Therefore, low-dose dexamethasone may be used in obese children for PONV prophylaxis.


title: Randomized sham-controlled trial evaluating efficacy and safety of endoscopic gastric plication for primary obesity: The ESSENTIAL trial.

text: OBJECTIVE Evaluate safety and efficacy of the pose™ procedure for obesity treatment. METHODS Subjects with Class I to II obesity were randomized (2:1) to receive active or sham procedure, after each investigator performed unblinded lead-in cases. All subjects were provided low-intensity lifestyle therapy. Efficacy end points were the mean difference in percent total body weight loss (%TBWL) at 12 months between randomized groups, and responder rate achieving ≥5% TBWL. The primary safety end point was incidence of reported adverse events. RESULTS Three hundred thirty-two subjects were randomized (active, n = 221; sham, n = 111); thirty-four subjects were included in the unblinded lead-in cohort. Twelve-month results were mean TBWL 7.0 ± 7.4% in lead-in, 4.95 ± 7.04% in active, and 1.38 ± 5.58% in sham groups, respectively. Responder rate was 41.55% in active and 22.11% in sham groups, respectively (P < 0.0001); mean responder result was 11.5% TBWL. The differences observed between active and sham groups for co-primary end points were statistically significant (P < 0.0001); however, super superiority margin as set forth in the study design was not met. No unanticipated adverse events or deaths occurred. Procedure-related serious adverse event rates were 5.0% (active) and 0.9% (sham), P = 0.068. CONCLUSIONS The pose procedure was safe and resulted in statistically significant and clinically meaningful weight loss over sham through 1 year.


title: Effectiveness of Fatigue Management Interventions in Reducing Severity and Impact of Fatigue in People with Progressive Multiple Sclerosis: A Systematic Review.

text: Background Rehabilitation interventions are recommended to manage multiple sclerosis (MS)-related fatigue. However, existing research has largely been generalized to those with relapsing-remitting MS, making it difficult to determine the effectiveness of these interventions in people with progressive MS. Therefore, this study aimed to systematically review the evidence related to the effectiveness of fatigue management interventions in reducing the severity and impact of fatigue in people with progressive MS. Methods Six electronic databases (CINAHL, Cochrane Library, MEDLINE, PEDro, ProQuest, and Web of Science Core Collections) were searched for relevant articles up until November 2017. Randomized controlled trials and quasi-experimental studies that examined the effects of exercise, behavioral interventions, and rehabilitation on fatigue in people with progressive MS using self-reported fatigue outcome measures were included in this review. Results Eight exercise, two rehabilitation, and two behavioral interventions were investigated in the 13 articles included in this review. Heterogeneous effects were reported between studies, with only two exercise, one behavioral, and two rehabilitation interventions recording significant improvements in postintervention fatigue severity or impact. However, most studies were underpowered, only two used fatigue as the primary outcome, and only one specifically recruited participants with predefined levels of fatigue. Conclusions Evidence from this review is inconclusive regarding the effectiveness of nonpharmacologic interventions in reducing the severity and impact of fatigue in progressive MS populations. Adequately powered randomized controlled trials are required to evaluate fatigue management interventions in people with progressive MS experiencing high levels of fatigue and using fatigue as the primary outcome.


docid: mararpjl

title: Controlled transient hypercapnia: a novel approach for the treatment of delayed cerebral ischemia after subarachnoid hemorrhage?

text: OBJECT The authors undertook this study to investigate whether the physiological mechanism of cerebral blood flow (CBF) regulation by alteration of the arterial partial pressure of carbon dioxide (PaCO₂) can be used to increase CBF after aneurysmal subarachnoid hemorrhage (aSAH). METHODS In 6 mechanically ventilated patients with poor-grade aSAH, the PaCO₂ was first decreased to 30 mm Hg by modification of the respiratory rate, then gradually increased to 40, 50 and 60 mm Hg for 15 minutes each setting. Thereafter, the respirator settings were returned to baseline parameters. Intracerebral CBF measurement and brain tissue oxygen saturation (StiO₂), measured by near-infrared spectroscopy (NIRS), were the primary and secondary end points. Intracranial pressure (ICP) was controlled by external ventricular drainage. RESULTS A total of 60 interventions were performed in 6 patients. CBF decreased to 77% of baseline at a PaCO₂ of 30 mm Hg and increased to 98%, 124%, and 143% at PaCO₂ values of 40, 50, and 60 mm Hg, respectively. Simultaneously, StiO₂ decreased to 94%, then increased to 99%, 105%, and 111% of baseline. A slightly elevated delivery rate of cerebrospinal fluid was noticed under continuous drainage. ICP remained constant. After returning to baseline respirator settings, both CBF and StiO₂ remained elevated and only gradually returned to pre-hypercapnia values without a rebound effect. None of the patients developed secondary cerebral infarction. CONCLUSIONS Gradual hypercapnia was well tolerated by poor-grade SAH patients. Both CBF and StiO₂ reacted with a sustained elevation upon hypercapnia; this elevation outlasted the period of hypercapnia and only slowly returned to normal without a rebound effect. Elevations of ICP were well compensated by continuous CSF drainage. Hypercapnia may yield a therapeutic potential in this state of critical brain perfusion. Clinical trial registration no.: NCT01799525 ( ClinicalTrials.gov ).


title: A Randomized Controlled Trial Comparing Laparoscopic Lens Defogging Techniques through Simulation Model.

text: Context Current literature demonstrates a lack of comparative studies regarding effective techniques for reducing laparoscopic lens fogging. Aim Our primary objective is to determine the efficacy of various laparoscopic defogging techniques (LDT) through a randomized controlled trial that employs a novel simulation model of the abdominopelvic cavity. Settings and Design This study was conducted at academic community hospital. This study design was a randomized controlled trial through simulation. Subjects and Methods A chamber was constructed that simulated the abdominopelvic cavity. We used 5 and 10 mm 0° laparoscopes. A 10 cm visual analog scale was developed to assign visual clarity (VC) scores. The 10 cm mark indicated perfect VC. We employed the following LDTs: (1) glove warming (GLOVE), (2) surfactant solution (Fog Reduction and Elimination Device [FRED]), (3) chlorhexidine solution (SOAP), (4) warm saline (SALINE), and (5) control. Three observers were blinded to the LDT used. Primary outcomes included VC scores at designated time intervals (5, 30, and 60 s) for each LDT. A minimum of 10 observations per time interval were required to achieve adequate power based on a 2.5 cm difference in VC scores. Results For the 10 mm laparoscope, FRED, SOAP, and SALINE had a VC score at 60 s (VC60) higher than control (4.8 ± 2.2, 7.8 ± 0.8, 7.9 ± 0.7 vs. 2.4 ± 0.72, P < 0.05). Both SOAP and SALINE VC60 scores were higher than FRED (7.8 ± 0.8, 7.9 ± 0.7 vs. 4.8 ± 2.2, P < 0.05). No differences were noted in VC60 scores between control and GLOVE (2.4 ± 0.72 vs. 3.1 ± 2.2, P > 0.05) and between SOAP and SALINE (7.8 ± 0.8 vs. 7.9 ± 0.7, P > 0.05). Similar results were noted with the 5 mm laparoscope. Conclusions Common LDTs such as SALINE and SOAP were more effective than FRED, while GLOVE was no different than control. These results demonstrate that the use of effective LDTs can potentially translate into improved patient care and operative outcomes during surgery.


title: Pre-bent instruments used in single-port laparoscopic surgery versus conventional laparoscopic surgery: comparative study of performance in a dry lab.

text: BACKGROUND Different types of single-incision laparoscopic surgery (SILS) have become increasingly popular. Although SILS is technically even more challenging than conventional laparoscopy, published data of first clinical series seem to demonstrate the feasibility of these approaches. Various attempts have been made to overcome restrictions due to loss of triangulation in SILS by specially designed SILS-specific instruments. This study involving novices in a dry lab compared task performances between conventional laparoscopic surgery (CLS) and single-port laparoscopic surgery (SPLS) using newly designed pre-bent instruments. METHODS In this study, 90 medical students without previous experience in laparoscopic techniques were randomly assigned to undergo one of three procedures: CLS, SPLS using two pre-bent instruments (SPLS-pp), or SPLS using one pre-bent and one straight laparoscopic instrument (SPLS-ps). In the dry lab, the participants performed four typical laparoscopic tasks of increasing difficulty. Evaluation included performance times or number of completed tasks within a given time frame. All performances were videotaped and evaluated for unsuccessful attempts and unwanted interactions of instruments. Using subjective questionnaires, the participants rated difficulties with two-dimensional vision and coordination of instruments. RESULTS Task performances were significantly better in the CLS group than in either SPLS group. The SPLS-ps group showed a tendency toward better performances than the SPLS-pp group, but the difference was not significant. Video sequences and participants` questionnaires showed instrument interaction as the major problem in the single-incision surgery groups. CONCLUSIONS Although SILS is feasible, as shown in clinical series published by laparoscopically experienced experts, SILS techniques are demanding due to restrictions that come with the loss of triangulation. These can be compensated only partially by currently available SILS-designed instruments. The future of SILS depends on further improvements in the available equipment or the development of new approaches such as needlescopically assisted or robotically assisted procedures.


ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging: A Report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the American Society of Nuclear Cardiology, the American College of Radiology, the American Heart Associa


Sleep Health Service in China During the COVID-19 Outbreak.


title: Effects of alveolar recruitment maneuver on end-expiratory lung volume during one-lung ventilation.

text: PURPOSE To investigate the effects of alveolar recruitment maneuver (ARM) during one-lung ventilation (OLV) on end-expiratory lung volume (EELV) of the dependent lung. METHODS Patients who were planned to undergo lung resection surgery for lung tumors and needed OLV for at least 1 h were included in the study. After turning the patients into the lateral position under total intravenous anesthesia, OLV was commenced using a double-lumen endobronchial tube. EELV was measured using the nitrogen washout technique at 20 min after OLV started (baseline) and 15, 30, 45, 60 min after ARM was performed on the dependent lung. RESULTS Among 42 patients who completed the study, EELV increased at 15 min after ARM by 20% or greater compared with baseline in 21 patients (responders). Responders were significantly shorter in height (158 vs. 165 cm, p = 0.01) and had smaller preoperative functional residual capacity (2.99L vs. 3.65L, p = 0.02) than non-responders. Before ARM, responders had significantly higher driving pressure (14.2 vs. 12.4 cmH2O, p = 0.01) and lower respiratory system compliance (23.6 vs. 31.4 ml/cmH2O, p = 0.0002) than non-responders. Driving pressure temporarily dropped after ARM in responders, while no significant change was observed in non-responders. Fourteen out of 21 responders kept EELV 20% or more increased EELV than baseline at 60 min after ARM. CONCLUSION EELV of the dependent lung was increased by 20% or greater in half of the patients responding to ARM. The increased volume of the dependent lung caused by ARM was maintained for 60 min in two-thirds of the responders.


title: [Suggestions for disinfection of ophthalmic examination equipment and protection of ophthalmologist against 2019 novel coronavirus infection].

text: At present, the prevention and treatment of 2019 Novel Coronavirus (2019-nCoV) in China has reached a critical stage. It is extremely important to disinfect ophthalmic examination instruments and protect ophthalmic medical care during the epidemic period to reduce cross-infection in clinical practice and reduce the infection risk of ophthalmic medical staff. (Chin J Ophthalmol, 2020, 56: 0001).


title: Radiolabeling of fab and f(ab')2 antibody fragments with 99mTc(I) tricarbonyl core using a new bifunctional tridentate ligand.

text: The objective of this study was to design and evaluate a new histidine-modified tridentate chelator for labeling antimesothelin fab and f(ab')2 antibody fragments with the Tc(I) tricarbonyl ([Tc(CO)3]) core. N-(ortho-phenol)-histidine chelator was synthesized by modifying the single amino acid L-histidine, a natural amino acid, with an additional phenol group to obtain the bifunctional tridentate ligand after reductive amination. Bioconjugation was based on the carbodiimide activation of the carboxylate of chelator and on further reaction with the amine groups present on the antibody fragments. Radiolabeling was accomplished by replacing the three aqua ligands of the complex precursor [Tc(CO)3(H2O)3] with the tridentate chelator. The antibody fragments radiolabeled with [Tc(CO)3] core were tested for stability by the cysteine challenge test. The immunoreactivity and binding affinity of the radiolabeled fragments were studied using in-vitro cell-binding assays. Radiochemical yields achieved for [Tc(CO)3] core labeling of fab and f(ab')2 were 91.6±9.1% and 80.7±8.5%, respectively. Stability studies of radiolabeled antibody fragments showed that the Tc label was stable to transchelation by cysteine. Both Tc-fab and Tc-f(ab')2 retained their reactivity and affinity to the mesothelin antigen. From our studies, it can be concluded that the newly synthesized N-(ortho-phenol)-histidine chelator is a promising candidate for [Tc(CO)3] labeling of biomolecules and for developing other novel Tc radiopharmaceuticals.


title: Removing vascular obstructions: a challenge, yet an opportunity for interventional microdevices.

text: Cardiovascular diseases are the leading cause of death worldwide; they are mainly due to vascular obstructions which, in turn, are mainly caused by thrombi and atherosclerotic plaques. Although a variety of removal strategies has been developed for the considered obstructions, none of them is free from limitations and conclusive. The present paper analyzes the physical mechanisms underlying state-of-art removal strategies and classifies them into chemical, mechanical, laser and hybrid (namely chemo-mechanical and mechano-chemical) approaches, while also reviewing corresponding commercial/research tools/devices and procedures. Furthermore, challenges and opportunities for interventional micro/nanodevices are highlighted. In this spirit, the present review should support engineers, researchers active in the micro/nanotechnology field, as well as medical doctors in the development of innovative biomedical solutions for treating vascular obstructions. Data were collected by using the ISI Web of Knowledge portal, buyer's guides and FDA databases; devices not reported on scientific publications, as well as commercial devices no more for sale were discarded. Nearly 70% of the references were published since 2006, 55% since 2008; these percentages respectively raise to 85% and 65% as regards the section specifically reviewing state-of-art removal tools/devices and procedures.


title: Laparoscopic Inguinal Hernia Repair With a Novel Hernia Mesh Incorporating a Nitinol Alloy Frame Compared With a Standard Lightweight Polypropylene Mesh.

text: BACKGROUND Numerous mesh materials are available for laparoscopic inguinal hernia repair. The role of fixation of mesh in laparoscopic inguinal hernia repair remains controversial. Mesh materials have been engineered to anatomically conform to the pelvis to potentially reduce or eliminate the need for fixation. This study evaluates the outcomes of laparoscopic inguinal hernia utilizing a device consisting of a lightweight polypropylene mesh with a nitinol frame (Rebound HRD) compared with repair with lightweight polypropylene mesh with permanent tack fixation. METHODS A prospective randomized trial evaluating the outcomes of laparoscopic inguinal hernia repair with a lightweight polypropylene mesh with a nitinol frame (N-LWM) compared with standard lightweight polypropylene mesh (LWM) was conducted. Randomization was performed at an N-LWM to LWM ratio of 2:1. Repairs were standardized to a laparoscopic extraperitoneal approach without fixation for N-LWM and titanium tack fixation for LWM repairs. Follow-up assessments were performed at 7 days, 6 months, and 1 year. Outcome measures include visual analog pain scale (VAS), Short Form 36 (SF-36), Carolinas Comfort Scale (CCS), operative details, complications, and recurrences. RESULTS There were 47 patients that underwent laparoscopic inguinal hernia repair and adhered to study protocol (31 N-LWM, 16 LWM). The groups did not differ significantly in age, body mass index, ethnicity, or employment. The N-LWM group had bilateral mesh placed in 51.6% and LWM 43.8% (P = .76). Operative duration was similar, 59.6 ± 23.1 minutes for LWM and 62.4 ± 26.7 minutes for N-LWM (P = .705) as was mesh handling time was 5.4 ± 3.1 minutes LWM versus 7.3 ± 3.9 minutes N-LWM (P = .053). VAS, CCS, and SF-36 survey results were similar between groups. There was one recurrence (0.03%) in the N-LWM group. CONCLUSIONS Nitinol-framed lightweight polypropylene mesh may be safely used during laparoscopic inguinal hernia repair with outcomes comparable to LWM at 1 year. N-LWM does not impact operating room time, mesh handling time, pain, recurrences, or complications.


[Renal sympathetic denervation: still to follow after Symplicity HTN-3? No].


title: Public Perceptions of Advance Care Planning, Palliative Care, and Hospice: A Scoping Review.

text: Background: Although access to advance care planning (ACP), palliative care, and hospice has increased, public attitudes may still be barriers to their optimal use. Purpose: To synthesize empirical research from disparate sources that describes public perceptions of ACP, palliative care, and hospice in ways that could inform public messaging. Data Sources: Searches of PubMed and other databases were made from January 2011 to January 2020. Study Selection: Studies reporting survey or interview data with the public that asked specifically about awareness and attitudes toward ACP, palliative care, or hospice were included. Data Extraction and Synthesis: Two reviewers independently screened citations, read full texts, and performed data abstraction. Twelve studies met inclusion criteria and included >9800 participants. For ACP, 80% to 90% of participants reported awareness, and a similar proportion considered it important, but only 10% to 41% reported having named a proxy or completed a written document. For palliative care, 66% to 71% of participants reported no awareness of palliative care, and those who reported awareness often conflated it with end-of-life care. However, after being prompted with a tested definition, 95% rated palliative care favorably. For hospice, 86% of participants reported awareness and 70% to 91% rated it favorably, although 37% held significant misconceptions. Limitations: A limited number of studies met inclusion criteria, and some were published in nonpeer reviewed sources. The studies reflect public perceptions pre-COVID-19. Conclusion: Consumer perceptions of ACP, palliative care, and hospice each have a distinct profile of awareness, perceptions of importance, and reports of action taking, and these profiles represent three different challenges for public messaging.


title: Home mechanical ventilation for COPD: high-intensity versus target volume noninvasive ventilation.

text: BACKGROUND High-intensity noninvasive ventilation (HI-NIV) is the most effective means of improving several physiological and clinical parameters in subjects with chronic hypercapnic COPD. Whether the newer hybrid mode using target tidal volume noninvasive ventilation (target V(T) NIV) provides additional benefits remains unclear. METHODS Subjects with COPD successfully established on long-term HI-NIV were switched to target V(T) NIV. Optimal target V(T) settings according to nocturnal transcutaneous P(CO2) measurements were achieved following a randomized crossover trial using 8 mL/kg ideal body weight and 110% of individual V(T) during HI-NIV, respectively. The following parameters were compared at the beginning of the trial while subjects were on HI-NIV, and after 3 months on optimal target V(T) NIV: sleep quality by polysomnography, overnight gas exchange, subjects' tolerance, overnight pneumotachygraphic measurements during NIV, health-related quality of life (severe respiratory insufficiency questionnaire), exercise capacity (6-min walk test), and lung function. RESULTS Ten of 14 subjects completed the study. There were no differences between HI-NIV and target V(T) NIV in any of the above-mentioned parameters. Specifically, the mean overnight transcutaneous P(CO2) was equivalent under each form of ventilation (both 45 ± 5 mm Hg, P = .75). CONCLUSIONS Switching subjects from well-established HI-NIV to target V(T) NIV shows no clinical benefits in chronic hypercapnic COPD. In particular, sleep quality, the control of nocturnal hypoventilation, daytime hypercapnia, overnight ventilation patterns, subjects' tolerance, health-related quality of life, lung function, and exercise capability were all similar in subjects who underwent HI-NIV and target V(T) NIV. Nevertheless, target V(T) NIV might offer some physiological advantages in breathing pattern and might be beneficial in some individual patients. (German Clinical Trials Register [www.drks.de] Registration DRKS00000450.).


title: Crouzon's Syndrome with Life-Threatening Ear Bleed: Ruptured Jugular Vein Diverticulum Treated by Endovascular Embolization.

text: Crouzon's syndrome is the commonest variety of syndromic craniosynostosis. Life-threatening ear bleed due to ruptured jugular venous diverticulum in Crouzon's syndrome has not been described previously. In patients with syndromic craniosynostosis, definitive repair of jugular diverticulum by open surgery is fraught with high risk of bleeding, poor functional outcomes, and even death. A 24-year-old woman with Crouzon's syndrome presented with conductive hearing loss and recurrent episodes of torrential bleeding from her left ear. On computed tomography, a defect in the roof of jugular fossa containing jugular venous diverticulum immediately inferior to the bony external auditory canal was seen. The clinical presentation, imaging features, and endovascular management of Crouzon's syndrome due to a ruptured jugular venous diverticulum is described.


title: The safety and efficacy of radiofrequency ablation following endoscopic submucosal dissection for Barrett's neoplasia.

text: The current standard of treating early Barrett's neoplasia is resection of visible lesions using endoscopic mucosal resection (EMR) followed by ablative therapy to the Barrett's segment. There is increasing evidence to support the use of endoscopic submucosal dissection (ESD) where en-bloc resection and lower recurrence rates may be achieved. However, ESD is associated with deep submucosal dissection when compared to EMR. This may increase the risk of complications including stricture formation with subsequent radiofrequency ablation (RFA) therapy. The aim of this study is to compare the safety and efficacy of RFA following EMR and ESD as well as when RFA was used without prior endoscopic resection. The primary outcome measure was complication rates. Clearance of dysplasia (CRD) and clearance of intestinal metaplasia (CRIM) were secondary outcomes. A retrospective analysis of a cohort of 91 patients referred for RFA from a single academic tertiary center was performed. The choice of endoscopic resection method was tailored according to the lesion type and morphology. Focal and circumferential ablation was performed after initial follow up endoscopy postresection. Patients proceeded straight to RFA in the absence of any visible lesions. In this study, the ESD group had a higher proportion of cancers compared to the EMR cohort (74.1% vs. 30.2%, P < 0.01) prior to RFA. All complications post RFA occurred in the groups with previous endoscopic resection. There was no significant difference in the total complication rate (7.4% vs. 9.3%, P = 0.78) and stricture formation rate (3.7% vs. 9.3%, P = 0.38) between the ESD and EMR groups. CRD was achieved in 96.3% in the ESD group, 88.4% in the EMR group, and all patients in the RFA alone group. CRIM rates were similar in the EMR and ESD groups (81.4% vs. 85.2%) but higher in the RFA alone group (90.5%). In conclusion, RFA following ESD is very effective and not associated with an increased risk of complications compared to EMR. This supports the application of RFA in the treatment algorithm of patients undergoing ESD for Barrett's neoplasia.


title: Comparative study of NOTES rectosigmoidectomy in a swine model: E-NOTES vs. P-NOTES.

text: BACKGROUND AND STUDY AIMS Several reports have demonstrated the safety of pure natural-orifice transluminal endoscopic surgery (P-NOTES) using transanal endoscopic microsurgery (TEM) and embryonic NOTES (E-NOTES; laparoscopic surgery through the umbilicus). This study was performed to compare the safety and applicability of NOTES rectosigmoidectomy between E-NOTES and P-NOTES in a swine model. PATIENTS AND METHODS E-NOTES was conducted through a single port using laparoscopic instruments (n = 11). P-NOTES was performed using TEM with transgastric endoscopic assistance (n = 11). Gastrotomies were created using a needle knife and the balloon dilatation technique, and closed using T-anchors. Blood samples were collected to evaluate changes in systemic cytokine levels during the preoperative and postoperative periods; operative outcomes were also evaluated and compared between the groups. The necropsy findings were recorded after sacrifice at 1 week after the procedure. RESULTS The mean operative time for P-NOTES was significantly longer than that for E-NOTES (239 vs. 103 minutes, P < 0.001). The mean distance from the anal verge to colorectal anastomosis in the P-NOTES group was significantly less than that in the E-NOTES group (2.9 vs. 17.6 cm, P < 0.001). On necropsy, the complication rate of P-NOTES was higher than that of E-NOTES, but without statistical significance (54.5 % vs. 18.2 %, P = 0.091). The differences in changes in TNF-α, C-reactive protein, interleukin-6, and interleukin-1β between P-NOTES and E-NOTES were not significant. CONCLUSIONS E-NOTES rectosigmoidectomy in the swine model is safe, but remains challenging for use in pelvic dissection. P-NOTES rectosigmoidectomy using TEM may be a promising tool for pelvic dissection, but the transgastric approach involves a high degree of risk.


Viral infections and atherothrombosis: Another caution in the wake of COVID-19?


title: New insights into the nuclear localization of retroviral Gag proteins.

text: Retroviruses assemble new virus particles that are released by budding from the plasma membranes of infected cells. Gag proteins, encoded by retroviruses, orchestrate the assembly of virus particles in close collaboration with host cell machinery. The earliest steps in retrovirus assembly-those immediately following synthesis of Gag on cytosolic ribosomes-are poorly understood. Rous sarcoma virus (RSV) offers a unique model system for dissecting these early steps because the RSV Gag protein undergoes transient nuclear trafficking prior to plasma membrane transport. Other Gag proteins, including those of human immunodeficiency virus (HIV), murine leukemia virus (MLV), foamy virus and retrotransposons in Schizosaccharomyces pombe and Drosophila, have also been detected in the nucleus, suggesting that nuclear trafficking of Gag proteins is a common property of retroviruses and retrotransposons. In addition to retroviruses, many structural proteins of unrelated viruses, including influenza M1, NEP and NP proteins,38 Borna disease virus N and P proteins28,56 and coronavirus N protein,23,57 undergo nuclear localization and bind viral RNAs to form viral ribonuclear protein (RNP) complexes that are exported from the nucleus for packaging into virus particles. Similarly, nuclear trafficking of the RSV Gag protein is required for efficient encapsidation of the viral genomic RNA (gRNA) into assembling virus particles.19 Recently, we reported that the viral RNA itself appears to be a key factor in controlling the nucleus/cytosol distribution of RSV Gag.22 Our data demonstrate that binding of RSV RNA to the Gag protein promotes Gag-CRM1-RanGTP binding, resulting in export of the retroviral RNP from the nucleus. We propose that association of the viral RNA induces a conformational change in Gag that reveals its nuclear export signal (NES) and prepares that complex for its journey to the plasma membrane for budding. This work challenges existing dogmas regarding the molecular basis of Gag-mediated selection of gRNA for packaging and may lead to novel paradigms for the mechanism of retroviral genome encapsidation.


title: Surgical Swine Model of Chronic Cardiac Ischemia Treated by Off-Pump Coronary Artery Bypass Graft Surgery.

text: Chronic cardiac ischemia that impairs cardiac function, but does not result in infarct, is termed hibernating myocardium (HM). A large clinical subset of coronary artery disease (CAD) patients have HM, which in addition to causing impaired function, puts them at higher risk for arrhythmia and future cardiac events. The standard treatment for this condition is revascularization, but this has been shown to be an imperfect therapy. The majority of pre-clinical cardiac research focuses on infarct models of cardiac ischemia, leaving this subset of chronic ischemia patients largely underserved. To address this gap in research, we have developed a well-characterized and highly reproducible model of hibernating myocardium in swine, as swine are ideal translational models for human heart disease. In addition to creating this unique disease model, we have optimized a clinically relevant treatment model of coronary artery bypass surgery in swine. This allows us to accurately study the effects of bypass surgery on heart disease, as well as investigate additional or alternate therapies. This model surgically induces single vessel stenosis by implanting a constrictor on the left anterior descending (LAD) artery in a young pig. As the pig grows, the constrictor creates a gradual stenosis, resulting in chronic ischemia with impaired regional function, but preserving tissue viability. Following the establishment of the hibernating myocardium phenotype, we perform off-pump coronary artery bypass graft surgery to revascularize the ischemic region, mimicking the gold-standard treatment for patients in the clinic.


title: Differentiation of biologic scaffold materials through physicomechanical, thermal, and enzymatic degradation techniques.

text: OBJECTIVE The objective of this study was to characterize the physicomechanical, thermal, and degradation properties of several types of biologic scaffold materials to differentiate between the various materials. BACKGROUND As more biologic scaffold materials arrive on the market, it is critical that surgeons understand the properties of each material and are provided with resources to determine the suitability of these products for specific applications such as hernia repair. METHODS Twelve biologic scaffold materials were evaluated, including crosslinked and non-crosslinked; those of bovine, human, and porcine origin; and derivatives of pericardium, dermis, and small intestine submucosa. Physicomechanical, thermal, and degradation properties were evaluated through biomechanical testing, modulated differential scanning calorimetry, and collagenase digestion assays, respectively. Biomechanical testing included suture retention, tear strength, uniaxial tensile, and ball burst techniques. RESULTS All scaffolds exhibited suture retention strengths greater than 20 N, but only half of the scaffolds exhibited tear resistance greater than 20 N, indicating that some scaffolds may not provide adequate resistance to tearing. A wide range of burst strengths were observed ranging from 66.2 ± 10.8 N/cm for Permacol to 1,028.0 ± 199.1 N/cm for X-Thick AlloDerm, and all scaffolds except SurgiMend, Strattice, and CollaMend exhibited strains in the physiological range of 10% to 30% (at a stress of 16 N/cm). Thermal analysis revealed differences between crosslinked and non-crosslinked materials with crosslinked bovine pericardium and porcine dermis materials exhibiting a higher melting temperature than their non-crosslinked counterparts. Similarly, the collagenase digestion assay revealed that crosslinked bovine pericardium materials resisted enzymatic degradation significantly longer than non-crosslinked bovine pericardium. CONCLUSIONS Although differences were observed because of cross-linking, some crosslinked and non-crosslinked materials exhibited very similar properties. Variables other than cross-linking, such as decellularization/sterilization treatments or species/tissue type also contribute to the properties of the scaffolds.


docid: rlqvlemt

title: An epidemiological study to assess the prevalence of diabetic peripheral neuropathic pain among adults with diabetes attending private and institutional outpatient clinics in South Africa.

text: OBJECTIVE To determine the prevalence of diabetic peripheral neuropathic pain (DPNP) among South African adults with type 1 or type 2 diabetes. METHODS This cross-sectional study recruited patients with diabetes from 50 institutional/private clinics. DPNP was diagnosed using Douleur Neuropathique 4 (DN4) questionnaire (score ≥4). Health-related quality-of-life (HRQoL) and sleep were assessed with EQ-5D and Daily Sleep Interference Scale (DSIS), respectively. RESULTS Prevalence of DPNP was 30.3% (n = 1046). Risk of DPNP was significantly increased in people aged 50-64 years (odds ratio [OR] 1.71, 95% confidence intervals [CI] 1.21, 2.41), with diabetes for ≥10 years (OR 1.55, 95% CI 1.15, 2.08), female patients (OR 1.58, 95% CI 1.18, 2.12), and black patients (OR 1.71, 95% CI 1.19, 2.46). Mean ± SD EQ-5D and DSIS scores were 0.84 ± 0.16 and 0.83 ± 1.90, respectively, in participants without DPNP versus 0.64 ± 0.25 and 3.62 ± 2.96, respectively, in those with DPNP. CONCLUSIONS DPNP is widely prevalent in South Africa. Despite its negative impact on HRQoL and sleep, DPNP is inadequately treated. DN4 is an easy-to-use, validated questionnaire that can be used widely as a DPNP screening tool in clinical practice.


title: Correlation between nucleotide mutation and viral loads of human bocavirus 1 in hospitalized children with respiratory tract infection.

text: The human bocavirus 1 (HBoV1) parvovirus causes respiratory disease and primarily affects children. Despite its worldwide prevalence, the mechanisms of HBoV1 replication and pathogenesis remain largely undefined. In this study of 846 children hospitalized at the Children's Hospital of Chongqing Medical University in China for respiratory tract infection between June 2009 and May 2011, HBoV1 was detected in 112 (13.2%) by real-time quantitative PCR. The median age of HBoV1-positive patients was 10 months old. Forty-five (40.2%) of the HBoV1 cases were monoinfections, and 67 (59.8%) were viral co-infections. Genotyping of all 112 HBoV1-positive cases yielded 27 full HBoV1 sequences, as well as two NS1 gene sequences, 15 NP1 gene sequences and 10 VP1/VP2 gene sequences harbouring 24, 10 and 43 mutations, respectively. Statistical analysis revealed no relationship between genetic mutations and clinical manifestations of HBoV1-positive patients. However, the viral loads were significantly lower in samples with mutations G236A or A447G in NP1, or G1461A in VP1/VP2, than in samples with wild-type HBoV1. Future studies should investigate whether these mutations in the HBoV1 gene may represent useful markers of disease pathogenesis.


title: State-of-the-art medical prevention of postoperative recurrence of Crohn's disease.

text: Postoperative recurrence of Crohn's disease is a frequent and often severe sequela of the disease. Until a few years ago it was deemed inescapable, as all the conventional medications used to treat the disease have been proven of little benefit in preventing recurrence after surgical treatment. In the past few years, anti-TNF agents given immediately after surgery have shown a remarkable efficacy in the prevention of disease recurrence. Large, randomized, controlled trials are currently underway to confirm these findings. Anti-TNF treatment of endoscopic lesions that occur after surgery seems to be less effective than using TNF antagonists to prevent recurrence. However, although the data are limited, this treatment strategy seems to be still superior to all the other prevention strategies that are not based on anti-TNF agents. Limited data are available on long-term outcomes of patients treated with anti-TNF agents after surgery. They suggest that these medications are safe and effective after many years of treatment. In addition, these agents might prevent recurrence even at doses lower than those used in patients with Crohn's disease who have not had surgery.


title: Liver abscess as a complication of laparoscopic gastric banding bariatric surgery.

text: BACKGROUND The World Health Organization has identified the rapidly growing prevalence of obesity as one of today's serious health problems. Various surgical interventions categorized collectively as bariatric surgery now play an ever-increasing important role as the only known effective treatment for severe obesity. Laparoscopic gastric bypass is currently the most frequent bariatric surgical procedure performed. However, the laparoscopic adjustable gastric band (LAGB) is rapidly gaining in popularity as a minimally invasive surgical option with anticipated similarly efficacious outcomes. Gastric band erosion following LAGB is an uncommon yet potentially serious complication unique to this form of weight loss surgery. METHODS Case report and literature review. RESULTS We report a case of a pyogenic liver abscess related to a LAGB procedure. Apropos to this case, we review the presumed pathophysiologic mechanism of this particular infectious process, and discuss this and other complications associated with LAGB operations. CONCLUSIONS As LAGB bariatric procedures become more popular, clinicians need to be aware of uncommon, but potentially serious complications unique to this form of weight loss surgery.


Challenges to dementia care during COVID-19: Innovations in remote delivery of group Cognitive Stimulation Therapy.


Authors' reply to Kremer and Van de Perre.


The emergence of the novel H1N1 virus: implications for global mental health.


title: Repeat-dose steady-state pharmacokinetic evaluation of once-daily hydromorphone extended-release (OROS(®) hydromorphone ER) in patients with chronic pain.

text: OBJECTIVE To characterize the steady-state pharmacokinetic profile of hydromorphone extended-release (ER) in patients with chronic pain taking concomitant medications. METHODS This open-label repeat-dose study enrolled 22 patients (mean age, 51.4 years; 81.8% female). All patients were receiving at least one concomitant medication; 86.4% were receiving at least two concomitant medications and 81.8% were receiving at least three. Patients receiving a stable dose of an opioid were converted to hydromorphone ER at a 5:1 ratio (morphine equivalent:hydromorphone). The dose was titrated to adequate analgesia over 3-14 days and stabilized between 8-48 mg. Oral morphine immediate-release was permitted for breakthrough pain. Area under the concentration-time curve from 0-24 hours (AUC(0-24)), maximum plasma concentration (C(max)), trough plasma concentration (C(min)), average plasma concentration (C(avg)), and degree of fluctuation (100 × [(C(max) - C(min)) ÷ C(avg)]) were calculated based on data from 14 patients. RESULTS Dose-normalized to 16 mg, mean pharmacokinetic parameter values were: AUC(0-24), 41.1 ng · h/mL; C(max), 2.6 ng/mL; C(min), 1.1 ng/mL; C(avg), 1.7 ng/mL; and the degree of fluctuation was 99.6%. The pharmacokinetic profile of hydromorphone ER was linear and consistent with dose proportionality. Mean pain intensity difference scores showed statistically significant improvement from 2-21 hours after dosing. Sixteen (72.7%) patients reported at least one adverse event (AE). The most common were constipation (31.8%), headache (22.7%), and vomiting (13.6%). One patient discontinued treatment due to vomiting. No deaths, serious AEs, or unexpected AEs occurred. CONCLUSION These findings replicate and extend the steady-state pharmacokinetic profile of hydromorphone ER, previously characterized in healthy volunteers, to a population of chronic pain patients taking numerous concomitant medications.


title: Ubiquitin-like protein modifiers and their potential for antiviral and anti-HCV therapy.

text: All viral infections subvert the host immune response. Targeting the host mechanisms that are modulated by viral infection offers new avenues for antiviral drug development. Host ubiquitin and multiple ubiquitin-like modifiers (Ubls) are commonly altered by, or important for, viral infection. Protein modification by ubiquitin or Ubls contributes to numerous cellular processes, such as protein degradation, signal transduction, protein relocalization and pathogen-host interactions. This post-translational modification plays an essential role for viral life cycles and host antiviral mechanisms. Some Ubls, such as ISG15 and SUMO, have been shown to modulate virus infections and are potential targets for therapeutic manipulation. Hepatitis C virus (HCV) is a positive-stranded RNA virus that predominantly infects hepatocytes. Recent data suggest that ISG15 might be a potential drug target for anti-HCV therapy. Inhibition of ISG15 expression and/or ISG15 conjugation (ISGylation) provides a rationale for the design of new anti-HCV drugs.


title: Tolerance and efficacy of tribasic manganese chloride in growing broiler chickens.

text: These studies were designed to determine the relative bioavailability and tolerance of tribasic Mn chloride (TBMC) for growing broiler chickens. In experiment 1, birds were fed a basal diet (starter, 102 ppm; grower, 209 ppm) or the basal diet supplemented with 3,600, 4,500, or 5,400 ppm Mn from either TBMC or manganese sulfate (MnSO(4)), and BW, feed intake, and plasma Mn were measured. In experiments 2 and 3, diets included the basal diet (45 and 43 ppm Mn, respectively) and the basal diet supplemented with graded levels of either TBMC or MnSO(4) ranging from 30 to 240 ppm Mn. Body weight and feed intake were measured and tibia, bile, and liver were collected for mineral analysis; heart samples were taken for manganese superoxide dismutase activity, protein, and relative mRNA abundance. In experiment 1, BW differed among treatments, with higher Mn leading to lower BW (P < 0.05). Birds from all treatments showed higher plasma Mn than birds fed the basal diet. Birds supplemented with the highest level of MnSO(4) had the highest level of plasma Mn (P < 0.05). In experiment 2, tibia and liver Mn increased with higher dietary Mn regardless of source (P < 0.05). Liver Mn increased up to the 60 ppm diets whereas Mn in the tibia was highest with the 130 ppm diets. Bile Mn increased with increasing dietary Mn, but these differences were not significant. In experiment 3, manganese superoxide dismutase activity, protein, and relative mRNA abundance were not affected by diet. The calculated bioavailabilities of TBMC and MnSO(4) did not differ significantly (P > 0.20). Together, these results indicate that TBMC is as effective as and better tolerated than MnSO(4) and that supplementing Mn at the lowest level used in this study may be sufficient for normal development of broiler chickens.


title: Curved Microneedle Array-Based sEMG Electrode for Robust Long-Term Measurements and High Selectivity.

text: Surface electromyography is widely used in many fields to infer human intention. However, conventional electrodes are not appropriate for long-term measurements and are easily influenced by the environment, so the range of applications of sEMG is limited. In this paper, we propose a flexible band-integrated, curved microneedle array electrode for robust long-term measurements, high selectivity, and easy applicability. Signal quality, in terms of long-term usability and sensitivity to perspiration, was investigated. Its motion-discriminating performance was also evaluated. The results show that the proposed electrode is robust to perspiration and can maintain a high-quality measuring ability for over 8 h. The proposed electrode also has high selectivity for motion compared with a commercial wet electrode and dry electrode.


title: Radially expanding laparoscopic trocar ports significantly reduce postoperative pain in all age groups.

text: BACKGROUND Trocar entry points have been identified as a significant source of pain after laparoscopic surgery. This is particularly true of the larger 12-mm ports that require deep fascial closure to avoid port-site herniation. We investigated whether using radially expanding trocars not requiring fascial closure compared to conventional cutting trocars for the 12-mm port in transabdominal preperitoneal (TAPP) hernia repairs had any effect on postoperative analgesic requirements and return to work or normal activity. METHODS The number of days analgesia was required postoperatively and the number of days taken to return to normal activity was recorded for 143 consecutive patients who underwent TAPP hernia repair by a single experienced laparoscopic surgeon. Exactly the same operative technique was used in these patients with the exception of the 12-mm port site entry. In group 1 (104 patients), a conventional cutting trocar was used requiring deep fascial closure. In group 2 (39 patients), a radially expanding trocar was used and the fascial defect was not closed. RESULTS Analgesia was required for an average of 10.5 days in group 1 and 2.4 days in group 2 (P < 0.001). The average time to return to work or to normal activity was 23.4 days in group 1 and 15.6 days in group 2 (P = 0.004). There was no significant difference between the two groups with respect to the patients' age, sex, or operating time. CONCLUSION Using the laparoscopic TAPP hernia repair as a standardised operation, changing from 12-mm fascial port closure to a technique that uses port dilation (not requiring a potentially "tight" deeper fascial closure) in a similar group of patients shows that there is a significant reduction in postoperative analgesic requirement and an earlier return to productive work or normal lifestyle. Perhaps dilating ports should replace those larger 10-, 12-, and 15-mm ports that require deeper sutures in all laparoscopic surgical operations.


title: COVID-19 and the Future of Long-Term Care: The Urgency of Enhanced Federal Financing.

text: The economic threat posed by responses to COVID 19 endangers financing for long-term care across the states that is already inadequate and inequitable. Increasing the federal share of Medicaid spending as unemployment rises would mitigate fiscal pressure on states and preserve public services. But unlike the demand for Medicaid's health care protections, which rises when economic activity declines, the demand for long-term care protections will grow even in a healthy economy as the population ages. Enhanced federal support is urgent not only to cope with the virus today but also to meet the long-term care needs of the nation's aging population in the years to come. Long-term care financing policy should be modified to either adjust federal matching funds by the age of each state's population, or fully federalize the funding of LTC expenses of Medicaid beneficiaries who are also eligible for Medicare.


title: Irreversible electroporation in porcine liver: acute computed tomography appearance of ablation zone with histopathologic correlation.

text: OBJECTIVE The objective of this study was to define acute computed tomography (CT) characteristics of ablation zone created by irreversible electroporation (IRE) in porcine liver, with histopathologic correlation. METHODS Twenty-three IRE ablation zones were created in 4 Yorkshire pig livers percutaneously under image guidance. A prototype generator was used (Ethicon Endo-surgery, Cincinnati, Ohio). Variable spacing of paired electrodes between 1 and 2.0 cm was used. Contrast-enhanced multiphasic CT scans were obtained. Pigs were killed after 5 to 6 hours for gross pathology sectioning with routine and vital histological stains. Computed tomography images were analyzed using 3-dimensional software, and ablation zone size measured on CT was correlated with pathologically determined size. RESULTS Nineteen of 19 ablation zones created with up to 1.5-cm spacing showed fusion between individual ablation zones generated by each electrode. Ablation zones were isodense precontrast and hypodense to liver postcontrast, with best delineation in the portal phase. Nine of these had nondistorted circumferential margins on both CT and gross pathology suitable for correlation, and among these, size measurements on CT were closely correlated with pathologically determined ablation zone size. Most importantly, on the delayed venous phase, there is internal enhancement within the ablation zone itself, except for small perielectrode zones that remained hypodense. On histopathology, IRE ablation zones showed preserved microvasculature with congestion of sinusoids, except for small perielectrode zones where coagulative changes were suggested. CONCLUSION Portal phase contrast-enhanced CT scans correlate well with liver IRE ablation size and shape on histopathology.


Flattening the curve on Covid-19.


title: Experience With Transitioning From Laparoscopic to Robotic Right Colectomy.

text: Background and Objectives The number of robotic colorectal procedures performed has rapidly increased, but there are only sparse data available about the robotic learning curve of expert laparoscopic colorectal surgeons. Methods In this retrospective study, we reviewed 101 minimally invasive right colectomies consecutively performed by a single surgeon with 20 years of clinical practice fully dedicated to laparoscopic surgery. Thus, the last 59 laparoscopic resections were compared with the first 42 robotic resections. Results The duration of the procedure was longer in the robotic group, but the conversion rate was the same in both groups. There was no difference between groups in rates of overall and severe postoperative complications, reoperation, hospital length of stay, and readmission. Number of harvested lymph nodes and oncological quality of resection defined by the pathologist were the same. Conclusions This study suggests that the transition from the right laparoscopic colectomy with extracorporeal anastomosis to the robot-assisted right colectomy with intracorporeal anastomosis when performed by a surgeon with experience in laparoscopic colorectal surgery may not entail any increase on the morbidity rate or reduce the oncologic quality of the resection.


title: Pediatric SARS, H1N1, MERS, EVALI, and Now Coronavirus Disease (COVID-19) Pneumonia: What Radiologists Need to Know.

text: OBJECTIVE. The purpose of this article is to review new pediatric lung disorders-including disorders that have occurred in recent years years such as severe acute respiratory syndrome (SARS), swine-origin influenza A (H1N1), Middle East respiratory syndrome (MERS), e-cigarette or vaping product use-associated lung injury (EVALI), and coronavirus disease (COVID-19) pneumonia-to enhance understanding of the characteristic imaging findings. CONCLUSION. Although the clinical symptoms of SARS, H1N1, MERS, EVALI, and COVID-19 pneumonia in pediatric patients may be nonspecific, some characteristic imaging findings have emerged or are currently emerging. It is essential for radiologists to have a clear understanding of the characteristic imaging appearances of these lung disorders in pediatric patients to ensure optimal patient care.


docid: uowoayrt

title: Understanding the Singapore COVID-19 Experience: Implications for Hospital Medicine.