title: The Use of Social Media in Interprofessional Education: Systematic Review.

text: BACKGROUND The implementation of interprofessional education (IPE) activities into health care education is a challenge for many training programs owing to time and location constraints of both faculty and learners. The integration of social media into these IPE activities may provide a solution to these problems. OBJECTIVE This review of the published literature aims to identify health care IPE activities using social media. METHODS The authors searched 5 databases (from the beginning coverage date to May 27, 2017) using keywords related to IPE and social media. Teams of 2 authors independently reviewed the search results to identify peer-reviewed, English language papers reporting on IPE activities using social media. They assessed the study quality of identified papers using the Medical Education Research Study Quality Instrument. RESULTS A total of 8 studies met the review's inclusion criteria. Of these 8 papers, 3 had single-group, posttest-only study design; 4 had single-group, pre- and posttest design; and 1 had nonrandomized 3-group design. Qualitative and quantitative outcome measures showed mixed results with the majority of student feedback being positive. CONCLUSIONS Despite a need for additional research, this review suggests that the use of social media may aid the implementation of health care IPE.


title: Evaluation of quality of life in fertile Turkish women with severe endometriosis.

text: We assessed the impact of pain, dysmenorrhoea and dyspareunia on the quality of life among Turkish fertile women with severe endometriosis. A total of 33 patients with histopathologically diagnosed severe endometriosis (Stage IV, revised criteria of the American Fertility Society (rAFS score) were enrolled into the study. Patients reported chronic pelvic pain using a visual analogue scale (VAS) and severity of dysmenorrhoea, dyspareunia and pelvic tenderness using the verbal rating scale (VRS). Quality of life (physical, psychological, social, environmental domains) was evaluated using the World Health Organization Quality of Life Assessment-BREF (WHOQOL-BREF). There were no correlations between quality of life and VRS and VAS scores of chronic pelvic pain in patients with dyspareunia (p > 0.05). VRS in patients with dysmenorrhoea negatively correlated with physical, social and environmental dimensions of quality of life (r = -0.382, r = -0.221, r = -0.373 and p = 0.028, p = 0.013, p = 0.033, respectively). Although the severity of dysmenorrhoea seems to be related with lower quality of life, chronic pelvic pain and dyspareunia due to endometriosis may not have any deleterious effects on the quality of life.


The current effects of the spread of COVID-19 in learning environments involving Japanese college students: What is the state of those environments elsewhere in the world?


What's New in Adult Reconstructive Knee Surgery.


title: [Dynamic Changes of CT Findings in Pneumonia Patients with Coronavirus Disease 19].

text: Objective The chest CT findings of the pneumonia patients with coronavirus disease 19 (COVID-19) were summarized to provide an auxiliary diagnostic basis for the early detection of infected patients. Methods Clinical data and CT images of 23 patients diagnosed with COVID-19 in West China Hospital of Sichuan University were retrospectively collected, and the chest CT findings were summarized and analyzed. Result Of the 23 patients, 56.5% (13/23) had bilateral disease, 69.6% (16/23) had lesions distributed along the bronchovascular bundle, 65.2% (15/23) had lesions distributed periphery, 82.6% (19/23) involved in the basal segment of lower lobe, 82.6% (19/23) had ground-glass opacities, 30.4% (7/23) had ground-glass opacities with consolidation, 26.1% (6/23) had reticular changes. In the stage of disease progression, 54.6% (6/11) had an increased number of lesions, and 63.6% (7/11) had the scope of lesions enlarged and density increased. In the remission stage, 25.0% (4/16) had reduced number of lesions, 81.3% (13/16) had scope of lesions reduced, 62.5% (10/16) had density of lesions decreased, and 37.5% (6/16) had fibrosis. Conclusions As an important diagnostic examination method for COVID-19, CT is conducive to the rapid diagnosis of the disease in patients with epidemiological history.


title: Wearable sensors in intelligent clothing for measuring human body temperature based on optical fiber Bragg grating.

text: Measuring body temperature is considerably important to physiological studies as well as clinical investigations. In recent years, numerous observations have been reported and various methods of measurement have been employed. The present paper introduces a novel wearable sensor in intelligent clothing for human body temperature measurement. The objective is the integration of optical fiber Bragg grating (FBG)-based sensors into functional textiles to extend the capabilities of wearable solutions for body temperature monitoring. In addition, the temperature sensitivity is 150 pm/°C, which is almost 15 times higher than that of a bare FBG. This study combines large and small pipes during fabrication to implant FBG sensors into the fabric. The law of energy conservation of the human body is considered in determining heat transfer between the body and its clothing. The mathematical model of heat transmission between the body and clothed FBG sensors is studied, and the steady-state thermal analysis is presented. The simulation results show the capability of the material to correct the actual body temperature. Based on the skin temperature obtained by the weighted average method, this paper presents the five points weighted coefficients model using both sides of the chest, armpits, and the upper back for the intelligent clothing. The weighted coefficients of 0.0826 for the left chest, 0.3706 for the left armpit, 0.3706 for the right armpit, 0.0936 for the upper back, and 0.0826 for the right chest were obtained using Cramer's Rule. Using the weighting coefficient, the deviation of the experimental result was ± 0.18 °C, which favors the use for clinical armpit temperature monitoring. Moreover, in special cases when several FBG sensors are broken, the weighted coefficients of the other sensors could be changed to obtain accurate body temperature.


title: Pros and cons for intravascular ultrasound in stenting.

text: Intravascular ultrasound is an invaluable tool, necessary for treating patients with venous occlusive disease. The combination of adequate preoperative imaging using duplex ultrasound and axial imaging with computed tomography and/or magnetic resonance allows preoperative identification of extravascular anatomic issues, which may lead to venous obstructive symptoms. During performance of the venous intervention, reliance upon contrast venography alone will lead to frequently missed intravascular pathology which inevitably will lead to inadequate treatment and higher overall failure rates than necessary.


title: Using 3D printed models for planning and guidance during endovascular intervention: a technical advance.

text: Three-dimensional (3D) printing applications in medicine have been limited due to high cost and technical difficulty of creating 3D printed objects. It is not known whether patient-specific, hollow, small-caliber vascular models can be manufactured with 3D printing, and used for small vessel endoluminal testing of devices. Manufacture of anatomically accurate, patient-specific, small-caliber arterial models was attempted using data from a patient's CT scan, free open-source software, and low-cost Internet 3D printing services. Prior to endovascular treatment of a patient with multiple splenic artery aneurysms, a 3D printed model was used preoperatively to test catheter equipment and practice the procedure. A second model was used intraoperatively as a reference. Full-scale plastic models were successfully produced. Testing determined the optimal puncture site for catheter positioning. A guide catheter, base catheter, and microcatheter combination selected during testing was used intraoperatively with success, and the need for repeat angiograms to optimize image orientation was minimized. A difficult and unconventional procedure was successful in treating the aneurysms while preserving splenic function. We conclude that creation of small-caliber vascular models with 3D printing is possible. Free software and low-cost printing services make creation of these models affordable and practical. Models are useful in preoperative planning and intraoperative guidance.


title: Bilateral central vein stenosis: options for dialysis access and renal replacement therapy when all upper extremity access possibilities have been lost.

text: PURPOSE Patients with bilateral central vein stenosis present a unique challenge: treatment options are limited, largely unproven and associated with reputedly poor outcomes. Our aim was to compare patency rates of different access and renal replacement treatment (RRT) modalities in patients with bilateral central vein stenosis/occlusion. MATERIAL AND METHODS Data on all patients presenting to a tertiary referral vascular access centre with end-stage vascular access (defined by bilateral central vein stenosis/occlusion with loss of upper limb access) over a 5-year period were included. 3, 6 and 12-month patencies of translumbar catheters (TLs), tunnelled femoral catheters (Fem), native long saphenous vein loops (SV), prosthetic mid-thigh loop grafts (ThGr), peritoneal dialysis (PD), and expedited donation after cardiac death (DCD) cadaveric renal transplants (Tx) via local allocation policies were compared using log-rank test. Kaplan-Meier survival analysis was used to estimate long-term access survival. RESULTS One hundred forty-six vascular access modalities were attempted in 62 patients (62 Fem, 25 TL, 15 SV, 25 ThGr, 8 PD, 11 Tx). Median follow-up was 876±57 days. Three, 6 and 12-month primary-assisted patencies for each modality were as follows: Fem: 75.4%, 60% and 28%; TL: 88%, 65% and 50%; SV: 87.5%, 60% and 44.6%; ThGr: 64%, 38% and 23.5%; PD: 62.5%, 62.5% and 50%; Tx: 72.7%, 72.7% and 72.7%. SV had better secondary patency at 900 days (76.9%) than ThGr (49.2%) or Fem (35.8%) (p<0.01). No patients died as a result of loss of access. CONCLUSION Patients with bilateral central vein stenosis often require more than one vascular access modality to achieve a "personal access solution." Native long saphenous vein loops provided the best long-term patency. Expedited renal transplantation with priority local allocation of DCD organs to patients with precarious vascular access provides a potential solution to this difficult problem.


title: Value of multiplex PCR to determine the bacterial and viral aetiology of pneumonia in school-age children.

text: BACKGROUND Conventional methods for the aetiological diagnosis of community-acquired pneumonia (CAP) are often insufficient owing to low sensitivity and the long wait for the results of culture and particularly serology, and it often these methods establish a diagnosis in only half of cases. AIM To evaluate the most common bacterial and viral agents in CAP using a fast responsive PCR method and investigate the relationship between clinical/laboratory features and aetiology, thereby contributing to empirical antibiotic selection and reduction of treatment failure. METHODS In children aged 4-15 years consecutively admitted with a diagnosis of CAP, the 10 most commonly detected bacterial and 12 most commonly detected viral agents were investigated by induced sputum using bacterial culture and multiplex PCR methods. Clinical and laboratory features were compared between bacterial and viral pneumonia. RESULTS In 78 patients, at least one virus was detected in 38 (48.7%) and at least one bacterium in 32 (41%). In addition, both bacteria and viruses were detected in 16 (20.5%) patients. Overall, the agent detection rate was 69.2%. The most common viruses were respiratory syncytial virus and influenza and the most frequently detected bacteria were S. pneumoniae and H. influenzae. PCR was superior to culture for bacterial isolation (41% vs 13%, respectively). Fever, wheezing and radiological features were not helpful in differentiating between bacterial and viral CAP. White blood cell count, CRP and ESR values were significantly higher in the bacterial/mixed aetiology group than in the viral aetiology group. CONCLUSION In CAP, multiplex PCR is highly reliable, superior in detecting multiple pathogens and rapidly identifies aetiological agents. Clinical features are poor for differentiation between bacterial and viral infections. The use of PCR methods allow physicians to provide more appropriate antimicrobial therapy, resulting in a better response to treatment, and it may be possible for use as a routine service if costs can be reduced.


title: Can mesenchymal stem cell therapy be the interim management of COVID-19?

text: COVID-19 pandemic has accounted for ~ 4.3 million confirmed cases and ~ 292,000 deaths (till 12th May, 2020) across the globe since its outbreak. Several anti-viral drugs such as RNA dependent RNA polymerase inhibitors (remdesivir, favipiravir, ribavirin), protease inhibitors (lopinavir, ritonavir) and drugs targeting endocytic pathway (hydroxychloroquine) are being evaluated for COVID-19 but standard therapeutics yet not available. Severe health deterioration in critically ill patients is characterized by pulmonary edema, severe respiratory distress, cytokine storm and septic shock. To combat cytokine storm, immune-therapy targeting IL-1, IL-2, IL-6 and TNFα are being evaluated and one of the promising immune-modulator is the mesenchymal stem cells (MSCs) that can surmount the severity of COVID-19 infections. Recent studies have shown that MSC-therapy significantly dampens the cytokine storm in critically ill COVID-19 patients. This communication endows with the insight of stem cell therapy and summarizes the recent studies on COVID-19 patients.


title: Impact of perfusion lesion in corticospinal tract on response to reperfusion.

text: OBJECTIVES We aimed to examine the impact of corticospinal tract (CST) involvement in acute ischaemic stroke (AIS) patients on functional outcome and the interaction with reperfusion. METHODS We retrospectively examined data in consecutive anterior circulation AIS patients undergoing thrombolysis. MR perfusion (time to maximum of tissue residue function, Tmax) and apparent diffusion coefficient (ADC) images were transformed into standard space and the volumes of CST involvement by Tmax > 6 s (CST-Tmax) and ADC < 620 × 10-6 mm2/s (CST-ADC) lesions were calculated. Good outcome was defined as modified Rankin scale ≤ 2 at 3 months. Reperfusion was defined as a reduction in Tmax > 6 s lesion volume of ≥70% between baseline and 24 h. RESULTS 82 patients were included. Binary logistic regression revealed that both CST-Tmax and CST-ADC volume at baseline were significantly associated with poor outcome (p < 0.05). The 24-h CST-ADC volume was correlated with baseline CST-ADC volume in patients with reperfusion (r = 0.79, p < 0.001) and baseline CST-Tmax volume in patients without reperfusion (r = 0.67, p < 0.001). In patients with CST-Tmax volume > 0 mL and CST-ADC volume < 3 mL, the rate of good outcome was higher in patients with reperfusion than those without (70.4% vs 38.1%, p = 0.04). CONCLUSIONS The use of CST-Tmax in combination with CST-ADC provides prognostic information in patients considered for reperfusion therapies. KEY POINTS • Examine the impact of corticospinal tract involvement in acute ischaemic stroke patients. • Spatially registered Tmax images can identify corticospinal tract hypoperfusion injury. • Corticospinal tract salvage through reperfusion is associated with improved outcome.


title: Experts' Perceptions on China's Capacity to Manage Emerging and Re-emerging Zoonotic Diseases in an Era of Climate Change.

text: Zoonotic diseases transmitted by arthropods and rodents are a major public health concern in China. However, interventions in recent decades have helped lower the incidence of several diseases despite the country's large, frequently mobile population and socio-economic challenges. Increasing globalization, rapid urbanization and a warming climate now add to the complexity of disease control and prevention and could challenge China's capacity to respond to threats of emerging and re-emerging zoonoses. To investigate this notion, face-to-face interviews were conducted with 30 infectious disease experts in four cities in China. The case study diseases under discussion were malaria, dengue fever and haemorrhagic fever with renal syndrome, all of which may be influenced by changing meteorological conditions. Data were analysed using standard qualitative techniques. The study participants viewed the current disease prevention and control system favourably and were optimistic about China's capacity to manage climate-sensitive diseases in the future. Several recommendations emerged from the data including the need to improve health literacy in the population regarding the transmission of infectious diseases and raising awareness of the health impacts of climate change amongst policymakers and health professionals. Participants thought that research capacity could be strengthened and human resources issues for front-line staff should be addressed. It was considered important that authorities are well prepared in advance for outbreaks such as dengue fever in populous subtropical areas, and a prompt and coordinated response is required when outbreaks occur. Furthermore, health professionals need to remain skilled in the identification of diseases for which incidence is declining, so that re-emerging or emerging trends can be rapidly identified. Recommendations such as these may be useful in formulating adaptation plans and capacity building for the future control and prevention of climate-sensitive zoonotic diseases in China and neighbouring countries.


title: Clinical significance of a positive serology for mimivirus in patients presenting a suspicion of ventilator-associated pneumonia.

text: OBJECTIVE A seroconversion to mimivirus has been observed in patients with community-acquired or nosocomial pneumonia. The aim of this study was to determine whether a positive serology for mimivirus was associated with increased morbidity and mortality in patients with a suspicion of ventilator-associated pneumonia (VAP). DESIGN Prospective matched-cohort study. SETTING A 12-bed medical intensive care unit (ICU) in a teaching hospital. PATIENTS Patients ventilated for at least 2 days presenting with a suspicion of VAP. Patients with a positive serology for mimivirus were matched to seronegative patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Matching criteria were: 1) the same main diagnosis on ICU admission, 2) the same age (+/- 10 yrs), 3) the same Simplified Acute Physiology II score (+/-10 points), 4) the same McCabe and Jackson comorbidity score, 5) admission within 1 year, and 6) diagnosis of at least one bacterial VAP during the ICU stay or not. A total of 55 pairs were submitted for analysis. The effectiveness of matching was 94.8%. Patients with a positive serology for mimivirus had longer duration of mechanical ventilation and ICU stay with median excesses of 7 days and 10 days, respectively. There was no difference in ICU mortality. The duration of mechanical ventilation before bronchoalveolar lavage (adjusted odds ratios [OR]1.08, p = 0.02), viral identification other than mimivirus during ICU stay (adjusted OR 0.32, p = 0.05), and enteral nutrition (adjusted OR 0.13, p = 0.01) were associated with positive serology for mimivirus. CONCLUSION A positive serology for mimivirus is associated with a poorer outcome in mechanically ventilated ICU patients.


title: Successful percutaneous access for endovascular aneurysm repair is significantly cheaper than femoral cutdown in a prospective randomized trial.

text: OBJECTIVE Because of its minimally invasive nature, percutaneous femoral access for endovascular aneurysm repair (pEVAR) is currently undergoing rapid popularization. Compared with surgical cutdown for femoral access (cEVAR), it offers the advantage of faster recovery after surgery as well as a reduction in wound complications. Despite proposed advantages, the method is largely considered uneconomical because of its reliance on costly closure devices. METHODS There were 50 patients undergoing EVAR who were enrolled in this randomized prospective single-center trial. Each patient randomly received percutaneous access in one groin and surgical access in the other. The primary end points were access duration and cost. Secondary end points were wound complications and the postoperative pain levels. RESULTS Surgery was performed per protocol in 44 patients. Mean access times for pEVAR and cEVAR were 11.5 ± 3.4 minutes and 24.8 ± 12.1 minutes (P < .001), respectively. Total access costs were €559.65 ± €112.69 for pEVAR and €674.85 ± €289.55 for cEVAR (P = .016). Eight complications in six patients were attributed to cutdown, none to pEVAR (P = .02). The percutaneously accessed groin was significantly less painful at day 1 and day 5 after surgery (P < .001). An intention-to-treat analysis (N = 50 patients) included six cases of pEVAR conversion due to technical failure in three patients (6%) and change of the operative strategy in another three patients (eg, aortouni-iliac stent graft followed by crossover bypass). The intention-to-treat analysis showed shorter mean overall access time for pEVAR (pEVAR, 14.65 ± 10.20 minutes; cEVAR, 25.12 ± 11.77 minutes; P < .001) and no cost difference between the two methods (pEVAR, €651.29 ± €313.49; cEVAR, €625.53 ± €238.29; P = .65). CONCLUSIONS Our data confirm proposed potential benefits attributable to the minimally invasive nature of pEVAR while demonstrating cost-effectiveness despite the additional cost of closure devices. Taking into account pEVAR failures still does not increase pEVAR costs over cEVAR. Further considering reduced postoperative pain and wound complications, the technique deserves consideration in suitable patients.


title: Assessment of perioperative stress in colorectal cancer by use of in vitro cell models: a systematic review.

text: Background The perioperative period is important for patient outcome. Colorectal cancer surgery can lead to metastatic disease due to release of disseminated tumor cells and the induction of surgical stress response. To explore the overall effects on surgically-induced changes in serum composition, in vitro model systems are useful. Methods A systematic search in PubMed and EMBASE was performed to identify studies describing in vitro models used to investigate cancer cell growth/proliferation, cell migration, cell invasion and cell death of serum taken pre- and postoperatively from patients undergoing colorectal tumor resection. Results Two authors (MG and TK) independently reviewed 984 studies and identified five studies, which fulfilled the inclusion criteria. Disagreements were solved by discussion. All studies investigated cell proliferation and cell invasion, whereas three studies investigated cell migration, and only one study investigated cell death/apoptosis. One study investigated postoperative peritoneal infection due to anastomotic leak, one study investigated mode of anesthesia (general anesthesia with volatile or intravenous anesthetics), and one study investigated preoperative intervention with granulocyte macrophage colony stimulating factor (GMCSF). In all studies an increased proliferation, cell migration and invasion was demonstrated after surgery. Anesthetics with propofol and intervention with GMCSF significantly reduced postoperative cell proliferation, whereas peritoneal infection enhanced the invasive capability of tumor cells. Conclusion This study suggests that in vitro cell models are useful and reliable tools to explore the effect of surgery on colorectal cancer cell proliferation and metastatic ability. The models should therefore be considered as additional tests to investigate the effects of perioperative interventions.


title: Effectiveness of Endovenous Radiofrequency Ablation for Elderly Patients with Varicose Veins of Lower Extremities.

text: Objective: The purpose of this study was to evaluate safety and effectiveness of endovenous radiofrequency ablation (RFA) for elderly patients. Materials and Methods: We enrolled 140 patients (194 limbs) who underwent RFA for varicose veins of lower extremities. Patients were divided into two groups; elderly patients (more than 75 years old, E-group, n=36) and young patients (under 75 years old, Y-group, n=104), and perioperative data were analyzed and compared between two groups. Results: In E-group, there were more than patients with hypertension, ischemic heart disease, malignant tumor, and cerebrovascular disease. A partial recanalization was observed in only one limb (0.6%) in Y-group. Endovenous heat induced thrombosis (EHIT) was identified four limbs (2.8%) in Y-group and two limbs (4.1%) in E-group. All EHITs were class 1 by Kabnick classification, and they disappeared within one month after interventions, without antithrombotic therapy. No other major complications were observed. There were no significantly differences for preoperative mean venous clinical severity scores (VCSS) (Y : E=4.84 : 4.47) and postoperative VCSS (Y : E=1.16 : 1.19, 0.35 : 0.58, 0.15 : 0.06, 0.05 : 0.06 at 1, 3, 6, 12 months after) in both groups. Conclusion: RFA for elderly patients is a safe and effective strategy for varicose veins of lower extremities.


title: Vacuum suction fixation versus staple fixation in TAPP laparoscopic hernia repair: introduction of a new technique for mesh fixation.

text: BACKGROUND Proper mesh fixation is critical for successful TAPP laparoscopic hernia repair. Conventional mesh fixation may cause chronic neuralgia, groin paresthesia or other complications. This study aimed at introducing a new vacuum suction technique for mesh fixation and evaluating its efficacy and safety compared with traditional staple fixation way. METHODS Clinical data of 242 patients undergoing TAPP from July 2011 to March 2014 were retrospectively analyzed. Patients were divided into vacuum suction fixation group and staple fixation group. The operation time, hospital stay, complications, recurrence, visual analogue scale pain score and cost were evaluated. RESULTS All surgeries were successful. The operation time of staple group was (42.34 ± 10.15) min for unilateral hernia and (64.08 ± 16.01) min for bilateral hernias. The postoperative hospital stay was (2.76 ± 0.84) days. One recurrence was observed (0.90%). For vacuum group, the operation time was (42.66 ± 7.76) min and (63.92 ± 10.49) min, and hospital stay was (2.60 ± 0.74) days. No recurrence was observed. There was no significant difference in recurrence, operation time, postoperative pain and hospital stay between two groups (P > 0.05). Average cost were (11,714 ± 726) RMB for vacuum group which was lower than staple group (14,837 ± 1568) RMB (P < 0.05). The top three complications of staple group were scrotal emphysema (10.81%), scrotal seroma (6.31%) and temporary nerve paresthesia (4.50%) while for vacuum group, they were scrotal seroma (3.82%), temporary nerve paresthesia (3.05%), scrotal emphysema (1.53%) and uroschesis (1.53%). The incidence of scrotal emphysema was lower in vacuum group (P < 0.05). No significant difference was observed in other complications (P > 0.05). CONCLUSION Both techniques for mesh fixation are safe and effective. There is no significant difference in recurrence, operation time, postoperative pain or hospital stay. The vacuum suction fixation technique is more economical with lower incidence of scrotal emphysema.


title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

text: The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.


title: COVID-19 Pandemic: Can Maintaining Optimal Zinc Balance Enhance Host Resistance?

text: The novel coronavirus disease 2019 (COVID-19) is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Millions around the world are wondering, if there is anything that could be done, other than maintaining high personal hygiene, and be vigilant of the symptoms, to reduce the spread of the disease and chances of getting infected, or at least to lessen the burden of the disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this article, I will briefly discuss, why keeping adequate zinc balance might enhance the host response and be protective of viral infections.


title: Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in adults.

text: BACKGROUND The epidemiology of respiratory viruses and their potential clinical impact when recovered in lower respiratory specimens has not been established in the hospital setting. A study was performed to investigate the association between positive viral detection and respiratory infection in an at-risk population. METHODS 299 adult patients who underwent bronchoalveolar lavage (BAL) procedures were enrolled in a hospital-based prospective cohort study. Descriptive epidemiology is presented of 17 different respiratory viruses detected by reverse transcription-polymerase chain reaction assays in BAL fluid specimens. Multivariate analysis was conducted to identify the clinical characteristics independently associated with the presence of virus. RESULTS Of 522 BAL fluid specimens analysed, 81% were collected in adult transplant recipients or other immunocompromised patients. Overall, PCR assays identified viral nucleic acid in 91 BAL fluid samples (17.4%). Similar rates of virus-positive BAL fluid were found in the different subpopulations studied (p = 0.113). Coronaviruses were the most frequent (32.3%), followed by rhinovirus (22.6%), parainfluenza (19.5%), influenza (9.7%), respiratory synctial virus (8.6%), human metapneumovirus (4.2%) and bocavirus (3.1%). Multivariate analysis using mixed models showed that respiratory viral infections were associated with a lack of antibiotic treatment response (OR 2.2, 95% CI 1.2 to 4.1) and the absence of radiological infiltrate (OR 0.3, 95% CI 0.2 to 0.8). In lung transplant recipients in whom a respiratory infection was suspected, the respiratory viral detection rate was 24.4% compared with 13.8% overall in other patients (p = 0.02). CONCLUSIONS In this cohort of hospitalised adults, respiratory viruses detected in BAL fluid specimens were associated with respiratory symptoms, absence of radiological infiltrates and a poor response to antibiotic therapy.


title: Proteolytic activation of the porcine epidemic diarrhea coronavirus spike fusion protein by trypsin in cell culture.

text: Isolation of porcine epidemic diarrhea coronavirus (PEDV) from clinical material in cell culture requires supplementation of trypsin. This may relate to the confinement of PEDV natural infection to the protease-rich small intestine of pigs. Our study focused on the role of protease activity on infection by investigating the spike protein of a PEDV isolate (wtPEDV) using a reverse genetics system based on the trypsin-independent cell culture-adapted strain DR13 (caPEDV). We demonstrate that trypsin acts on the wtPEDV spike protein after receptor binding. We mapped the genetic determinant for trypsin-dependent cell entry to the N-terminal region of the fusion subunit of this class I fusion protein, revealing a conserved arginine just upstream of the putative fusion peptide as the potential cleavage site. Whereas coronaviruses are typically processed by endogenous proteases of the producer or target cell, PEDV S protein activation strictly required supplementation of a protease, enabling us to study mechanistic details of proteolytic processing. Importance: Recurring PEDV epidemics constitute a serious animal health threat and an economic burden, particularly in Asia but, as of recently, also on the North-American subcontinent. Understanding the biology of PEDV is critical for combatting the infection. Here, we provide new insight into the protease-dependent cell entry of PEDV.


The hemagglutinin-esterase gene in human coronaviruses SARS-CoV-2, HKU1 and OC43.


title: Primary dysmenorrhea with and without premenstrual syndrome: variation in quality of life over menstrual phases.

text: PURPOSE The majority of studies on quality of life (QoL) of women with menstrual disturbances have not taken menstrual cycle phase into account. We aimed to determine the size of changes in QoL score during perimenstrual week compared to those during late follicular phase in women suffering from dysmenorrhea with or without premenstrual syndrome (PMS) and also to compare the two groups. METHODS In this observational analytical study, participants were selected purposively from among single students aged 18-30 years, who were residing at university dormitories in Tabriz, Iran, and had moderate or severe dysmenorrhea. They reported quality of their life during the past week using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) at two time points, days 3-4 and 11-12, of their menstrual cycle. RESULTS Among 52 participants with PMS and 64 without PMS, about half reported severe dysmenorrhea. The mean total quality score was significantly lower during perimenstrual week than during late follicular phase in both group with PMS [48 vs 79, mean difference - 31 (95% confidence interval - 37 to - 26)] and group without PMS [56 vs 78, - 1 (- 27 to - 18)]. The score was significantly lower in the group with PMS than in those without PMS during perimenstrual week [- 8 (- 13 to - 2)] but not during late follicular phase [2.1 (- 2.9 to 7.0)]. CONCLUSIONS Dysmenorrhea with or without PMS significantly reduces QoL of women during perimenstrual week. The QoL is slightly lower in group with PMS during perimenstrual week but not during late follicular phase.


title: Laparoscopic pyeloplasty: Initial experience with 3D vision laparoscopy and articulating shears.

text: INTRODUCTION Laparoscopic reconstructive surgery is associated with a steep learning curve related to the use of two-dimensional (2D) vision and rigid instruments. With the advent of robotic surgery, three-dimensional (3D) vision, and articulated instruments, this learning curve has been facilitated. We present a hybrid alternative to robotic surgery, using laparoscopy with 3D vision and articulated shears. OBJECTIVE To compare outcomes of children undergoing pyeloplasty using 3D laparoscopy with articulated instruments with those undergoing the same surgery using standard laparoscopy with 2D vision and rigid instruments. STUDY DESIGN Medical charts of 33 consecutive patients with ureteropelvic junction obstruction who underwent laparoscopic pyeloplasty by a single surgeon from 2006 to 2013 were reviewed in a retrospective manner. The current 3D cohort was compared with the previous 2D cohort. Data on age, weight, gender, side, operative time, dimension (2D = 19 patients, 3D = 8 patients), presence of a crossing vessel, length of hospital stay, and complication rate were compared between the two groups. Articulating shears were used for pelvotomy and spatulation of the ureter in the 3D group. Statistical tests included linear regression models and chi square tests for trends using STATA software. RESULTS Operative time per case was decreased by an average of 48 min in the group undergoing 3D laparoscopic pyeloplasty compared with the group undergoing 2D laparoscopic pyeloplasty (p = 0.02) (Figure). Complication rate and length of hospital stay were not significantly affected by the use of 3D laparoscopy. DISCUSSION These favorable results are in accordance with previous literature emphasizing the importance of 3D vision in faster and more precise execution of complex surgical maneuvers. The use of flexible instruments has also helped overcome the well-described delicate step of a dismembered pyeloplasty, namely the pelvotomy and ureteral spatulation. Limitations of this study are those inherent to the retrospective study design. CONCLUSION The use of 3D vision endoscopy with articulating instruments blurs the distinction between current robotic-assisted and conventional laparoscopic technology, and provides a hybrid alternative deserving further attention.


title: [Exploration of fire needling therapy on coronavirus disease 2019].

text: Combined with previous clinical experience in anti-epidemic and acupuncture, the prevention program of fire needling therapy for coronavirus disease 2019 (COVID-19) was drawn out. Fire needling therapy has the effects of clearing heat, removing dampness, replenishing for the deficiency, removing stasis and detoxifying, which is mainly aimed at preventing populations, light and common types cases, and cases in the recovery period. Acupoints of governor vessel, lung meridian, bladder meridian and stomach meridian are mainly used in this program. For the special groups, such as children, elderly and weak, and pregnant women, Shenzhu (GV 12), Danshu (BL 19), Geshu (BL 17), Zhigou (TE 6), etc. are added. It is hoped that fire needling therapy will be applied in the community and square cabin hospitals as an effective supplement to anti-epidemic of traditional Chinese medicine (TCM).


Feasibility of bedside open lung biopsy in patients treated with extracorporeal membrane oxygenation.


title: Dynamics in a simple evolutionary-epidemiological model for the evolution of an initial asymptomatic infection stage.

text: Pathogens exhibit a rich variety of life history strategies, shaped by natural selection. An important pathogen life history characteristic is the propensity to induce an asymptomatic yet productive (transmissive) stage at the beginning of an infection. This characteristic is subject to complex trade-offs, ranging from immunological considerations to population-level social processes. We aim to classify the evolutionary dynamics of such asymptomatic behavior of pathogens (hereafter "latency") in order to unify epidemiology and evolution for this life history strategy. We focus on a simple epidemiological model with two infectious stages, where hosts in the first stage can be partially or fully asymptomatic. Immunologically, there is a trade-off between transmission and progression in this first stage. For arbitrary trade-offs, we derive different conditions that guarantee either at least one evolutionarily stable strategy (ESS) at zero, some, or maximal latency of the first stage or, perhaps surprisingly, at least one unstable evolutionarily singular strategy. In this latter case, there is bistability between zero and nonzero (possibly maximal) latency. We then prove the uniqueness of interior evolutionarily singular strategies for power-law and exponential trade-offs: Thus, bistability is always between zero and maximal latency. Overall, previous multistage infection models can be summarized with a single model that includes evolutionary processes acting on latency. Since small changes in parameter values can lead to abrupt transitions in evolutionary dynamics, appropriate disease control strategies could have a substantial impact on the evolution of first-stage latency.


title: Efficacy of uniportal video assisted thoracoscopic surgery in management of primary spontaneous hemopneumothorax.

text: INTRODUCTION Primary spontaneous hemopneumothorax (PSHP) is an accumulation of blood and air in the pleural space without trauma or obvious etiology. It is a rare surgical emergency and may lead to hypovolemic shock if not treated. Early and fast recognition will improve patient outcomes. PRESENTATION OF THE CASE We present a case of PSHP in a young male utilizing the uniportal video-assisted thoracoscopic surgery (VATS) through the same incisional site of the thoracostomy tube. The patient made an uneventful recovery. DISCUSSION VATS has become the first line and the gold standard surgical management of most thoracic surgeries. In case of PSHP, some thoracic surgeons still skeptical about the minimal invasive approach in such emergency. Applying the concept of uniportal technique, which can be used for diagnostic as well as major therapeutic purposes. There is vast literature that support the notion that it reduces postoperative pain and paresthesia and lead to fast patient recovery. CONCLUSION As demonstrated in our case, uniportal VATS is safe and effective in the management of PSHP.


title: Dynamics of HBV surface antigen related endpoints in chronic hepatitis B infection: a systematic review and meta-analysis.

text: BACKGROUND In chronic hepatitis B (CHB) treatment, hepatitis B virus surface antigen (HBsAg) is regarded as a promising clinical endpoint associated with long-term clinical outcomes. We performed a meta-analysis to characterize the dynamics and influencing factors of HBsAg. METHODS Literature search was conducted through PubMed from January 1995 to May 2015 for papers reporting HBsAg in patients receiving various anti-viral treatments. We conducted weighted linear regression to select for potential influencing factors on maximum HBsAg loss percentage, and subgroup analysis to calculate the pooled estimates of maximum HBsAg loss and seroconversion percentage following treatment of interferon (IFN), nucleoside analogue (NUC), or combination therapies (NUC+IFN), respectively. Study heterogeneity was assessed through sensitivity test and I-square statistics. RESULTS We collected data from 24 papers involving 6674 adult CHB patients. In most studies, average HBsAg level decreased during treatment but relapsed after treatment cessation, while HBsAg loss or seroconversion percentage continued to increase or remain stable after treatment cessation. No strong relationship was observed between maximum HBsAg change and its baseline level. The pooled estimates of maximum HBsAg loss percentage for IFN (5.3%, 2.7%-7.9%) and NUC+IFN (5.2%, 3.1%-7.4%) were significantly higher than that of NUC (0.93%, 0.29%-1.6%). Higher maximum HBsAg loss percentage is associated with longer peak time. Pooled maximum HBsAg seroconversion percentage estimates were 1.6%, 0.56% and 6.2% for IFN, NUC and NUC+IFN. CONCLUSIONS With respect to HBsAg lowering, this meta-analysis confirmed the importance of longer treatment duration and addition of IFN, which revealed the potential value of immune-based therapies.


title: Supra-Annular Mitral Implantation of Melody Valve: Minimizing Left Ventricular Outflow Tract Obstruction.

text: Utilization of the Melody valve for mitral valve replacement has been previously reported; however, left ventricular outflow tract obstruction is a frequent concern. In this report, a technique for supra-annular placement of the Melody valve in the mitral position is described which will minimize the risk of left ventricular outflow tract obstruction.


Possible Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in a Public Bath Center in Huai'an, Jiangsu Province, China.


title: Copper intrauterine device use and HIV acquisition in women: a systematic review.

text: OBJECTIVES To review systematically copper intrauterine device (Cu-IUD) use and HIV acquisition in women. METHODS We searched Pubmed, Embase and the Cochrane Library between database inception and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using an unspecified IUD or Cu-IUD compared with non-hormonal or no contraceptive users, or hormonal contraceptive users. We extracted information from included studies, assessed study quality, and summarised study findings. RESULTS From 2494 publications identified, seven met our inclusion criteria. One randomised controlled trial (RCT), judged "informative with few limitations", found no statistically significant differences in HIV risk between users of the Cu-IUD and either intramuscular depot medroxyprogesterone acetate (DMPA-IM) or levonorgestrel implant. One observational study, deemed "informative but with important limitations", found no statistically significant difference in HIV incidence among IUD users compared with women who had tubal ligation or who were not using any contraception. Another "informative but with important limitations" observational study found no difference in HIV incidence between Cu-IUD users and DMPA or norethisterone enanthate injectable, or implant users. An RCT considered "unlikely to inform the primary question" also found no difference in HIV risk between Cu-IUD and progestogen-only injectable users. Findings from the other three "unlikely to inform the primary question" cohort studies were consistent with the more robust studies suggesting no increased risk of HIV acquisition among Cu-IUD users. CONCLUSION The collective evidence, including that from a large high-quality RCT, does not indicate an increased risk of HIV acquisition among users of Cu-IUDs.


title: Age ≥80 Years Is Not a Contraindication for Intra-Arterial Therapy after Ischemic Stroke.

text: BACKGROUND Clinical trials confirmed the safety and efficacy of intra-arterial therapy (IAT) in the management of ischemic stroke. At a community hospital, we compared outcomes in patients aged ≥80 and patients in the age range 55-79 years receiving IAT following ischemic stroke. METHODS Data were retrospectively abstracted for ischemic stroke patients ≥55 years treated with IAT at an urban comprehensive stroke center between 2010 and 2013. Baseline demographics, incidence of symptomatic intracranial hemorrhage (sICH), in-hospital mortality, discharge modified Rankin scale (mRS) score (favorable ≤2) and improvement in National Institutes of Health Stroke Scale Score (NIHSS; decreased score at discharge) were compared between patients in the age range 55-79 and patients ≥80 years. Data were analyzed using univariate analyses and multivariate logistic regression. RESULTS IAT was performed in 239 patients with ischemic stroke; 63 (26.4%) were ≥80 years. When compared to patients aged 55-79, the elderly patients were more often female and non-smokers, with a history of atrial fibrillation. No differences were observed in those ≥80 years compared to patients in the age range 55-79 years for sICH (10 vs. 5%, p = 0.23), mortality (24 vs. 18%, p = 0.28), favorable discharge mRS score (13 vs. 19%, p = 0.27), or improvement in NIHSS (83 vs. 92%, p = 0.10). The nonsignificant association of age with the outcomes persisted after adjusting for covariates and when analyzing the subset of patients who received IAT only. CONCLUSIONS These findings suggest that in a cohort not subject to the criteria of a clinical trial, age ≥80 years should not be a contraindication to IAT.


title: A Field-Based Method for Determination of Dissolved Inorganic Carbon in Water Based on CO2 and Carbonate Equilibria.

text: The processing, storage, and flux of inorganic carbon in rivers and streams play an influential role in the lateral transfer of atmospheric and terrestrial carbon to the marine environment. Quantifying and understanding this transfer requires a rapid and accurate means of measuring representative concentrations of dissolved inorganic carbon (DIC) and CO2 in field settings. This paper describes a field method for the determination of DIC based on the direct measurement of dissolved CO2 using a commercial carbonation meter. A 100-mL water sample is combined with 10 mL of a high ionic strength, low-pH, citrate buffer, mixed well, and the dissolved CO2 concentration is measured directly. The DIC is then calculated based on the dissolved CO2 concentration, buffer-controlled ionic strength, pH, and temperature of the mixture. The method was accurate, precise, and comparable to standard laboratory analytical methods when tested using prepared sodium bicarbonate solutions up to 40 mM DIC, North Atlantic seawater, commercial bottled waters, and carbonate spring waters. Coal mine drainage waters were also tested and often contained higher DIC concentrations in the field than in subsequent laboratory measurements; the greatest discrepancy was for the high-CO2 samples, suggesting that degassing occurred after sample collection. For chemically unstable waters and low-pH waters, such as those from high-CO2 mine waters, the proposed field DIC method may enable the collection of DIC data that are more representative of natural settings.


title: SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020.

text: Respiratory disease and increased mortality occurred in minks on two farms in the Netherlands, with interstitial pneumonia and SARS-CoV-2 RNA in organ and swab samples. On both farms, at least one worker had coronavirus disease-associated symptoms before the outbreak. Variations in mink-derived viral genomes showed between-mink transmission and no infection link between the farms. Inhalable dust contained viral RNA, indicating possible exposure of workers. One worker is assumed to have attracted the virus from mink.


title: Postoperative Mesh Infection-Still a Concern in Laparoscopic Era.

text: Introduction of synthetic mesh was a landmark breakthrough in the management of hernia repair and has significantly reduced recurrence rates. But in addition to the benefits, some more problems have come in picture major being 'mesh infection'. Prolene mesh has shown promise when used in abdominal and inguinal hernia repair, especially when used in planned surgeries. This material, derived from monofilament polypropelene, is found to be biologically inert in almost every person. Being a foreign material, a slightest breach in asepsis can lead to favourable environment for bacterial proliferation and form a 'biofilm'. This phenomenon especially after laparoscopic surgeries gives rise to chronic discharging sinus at the port site, abscess formation around mesh and even sepsis. It appears that laparoscopic hernia repair is a promising method but having chances of mesh infection owing to difficult approach and lack of uniformity in sterilization of laparoscopic instruments. Slightest breach in sterility or protocols might lead to such a large ventral wall sinus, increasing morbidity and cost of treatment. Treatment of infected mesh is possible by local debridement, irrigation, mesh removal and systemic antibiotics culminating in increased morbidity over duration of disease, but still it would be worth emphasizing-'Prevention is better than cure'.


title: Northern Ireland disease surveillance report for January to March 2014.

text: Listerial encephalitis in adult cattle Oxalate nephrosis in Zwartble ewes and lambs Histomonosis in chickens Feline tuberculosis caused by Mycobacterium bovis These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for January to March 2014.


title: Present and Future Application of Energy Devices in Thoracic Surgery.

text: In the last decade, many energy devices have entered day-to-day practice in thoracic surgery. Some have proven and recognized applications, whereas others still require further trials. Nevertheless, currently used devices continue to be improved on and new applications for current devices will be evaluated. Ultimately, novel applications of energy in thoracic surgery and refinement in technology will hopefully allow for safer and less invasive techniques for patients requiring thoracic surgical procedures. In this article, we review the present and future applications of energy devices in thoracic surgery.


What's next now that the WHO has declared a COVID-19 pandemic?


title: SARS-CoV-2 infection of the nervous system: A review of the literature on neurological involvement in novel coronavirus disease (COVID-19).

text: The novel coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is believed to have emerged from an animal source and has been spreading rapidly among humans. Recent evidence shows that SARS-CoV-2 exhibits neurotropic properties and causes neurological diseases. Here we review the literature on neurological involvement in SARS-CoV-2 infections and the possible mechanisms of invasion of the nervous system by this virus, to provide a summary and critical analysis of the early reporting of neurological involvement in COVID-19. An exhaustive search of scientific articles on neurological involvement in COVID-19 was performed in the Web of Science, Scopus, Medline/PubMed, and several other databases. Nineteen relevant articles that had been published or were in preprint were carefully selected according to the inclusion and exclusion criteria. Based on our research, we found that patients with COVID-19 can present with neurological symptoms that can be broadly divided into central nervous system involvement, such as headache, dizziness, altered mental state, and disorientation, and peripheral nervous system involvement, such as anosmia and hypogeusia. Most of these patients are in the older age group and exhibit comorbidities, especially hypertension, and severe infection. In extreme presentations of COVID-19, some patients exhibit seizures, stroke, flaccid paraparesis, corticospinal weakness, and even coma. Moreover, the neurological manifestations can occur independently of the respiratory system. In conclusion, SARS-CoV-2 infection can cause multiple neurological syndromes in a more complex presentation. Therefore, this review elucidated the involvement of the nervous system in SARS-CoV-2 infection and will hopefully help improve the management of COVID-19.


title: Clinical Classification and Severity Scoring Systems in Chronic Pancreatitis: A Systematic Review.

text: INTRODUCTION Chronic pancreatitis (CP) is characterised by pain, functional deficits, nutritional and mechanical complications. Frequently managed in out-patient settings, the clinical course is unpredictable and requires multi-disciplinary care. There remains substantial variation in management. In contrast to acute pancreatitis, there are no globally accepted classification or severity scores to predict the disease course or compare interventions. We conducted a systematic review to determine the scope and clinical use of existing scoring systems. METHODS A systematic search was developed with a medical librarian using the Embase, Medline and Cochrane databases. Original articles and conference abstracts describing an original or modified classification or scoring system in CP that stratified patients into clinical and/or severity categories were included. To assess clinical application/validation, studies using all or part of a score as a stratification tool to measure another parameter or outcome were selected. Studies reporting on diagnosis or aetiology only were excluded. Four authors performed the search in independent pairs and conflicts were resolved by a fifth author using CovidenceTM systematic review software. RESULTS Following screening 6,652 titles and 235 full-text reviews, 48 papers were analysed. Eleven described original scores and 6 described modifications of published scores. Many were comprehensive but limited in capturing the full spectrum of disease. In 31 studies, a score was used to categorise patients to compare or correlate various outcome measures. Exocrine and endocrine dysfunction and pain were included in 6, 5, and 4 scoring systems, respectively. No score included other nutrition parameters, such as bone health, malnutrition, or nutrient deficiency. Only one score has been objectively validated prospectively and independently for monitoring clinical progression and prognosis, but this had been applied to an in-patient population. CONCLUSION Available systems and scores do not reflect recent advances and guidelines in CP and are not commonly used. A practical clinical classification and scoring system, validated prospectively for prognostication would be useful for the meaningful analysis in observational and interventional studies in CP.


title: Reinterventions after fenestrated or branched endovascular aortic aneurysm repair.

text: OBJECTIVE Reinterventions after fenestrated or branched endovascular aneurysm repair (F/B-EVAR) are sometimes necessary to maintain aneurysm exclusion or endograft and target artery patency. These reinterventions are nontrivial, potentially associated with morbidity, mortality, and resource utilization. Whereas rates, types, and outcomes of reintervention after infrarenal EVAR have been well described, they have not been well described for F/B-EVAR. We sought to characterize the morbidity, mortality, and resource utilization due to reinterventions after F/B-EVAR. METHODS All F/B-EVAR variables collected prospectively through a single-institution, Institutional Review Board-approved registry, which included patients enrolled in a physician-sponsored investigational device exemption trial (G130210), were reviewed (November 2010-December 2016). Reinterventions were defined as any procedure that was aneurysm related, device related, or target artery related. For patients with more than one reintervention, each intervention occurrence was treated as a discrete event. Reintervention type, indication, timing (perioperative, days 0-30; short term, days 31-180; midterm, >180 days), inpatient/outpatient, length of stay, and morbidity/mortality were recorded. Reintervention success was defined as resolution of the indication. RESULTS Among 123 consecutive F/B-EVARs (mean follow-up, 25 months), 32 patients (25%) underwent 54 reinterventions (one reintervention, 20 (63%) patients; two reinterventions, 6 (19%) patients; three reinterventions, 4 (13%) patients; four reinterventions, 1 (3.1%) patient; and six reinterventions, 1 (3.1%) patient). The most frequent indications were type III endoleaks (n = 15 [28%]), target artery occlusions (n = 7 [13%]), and stenoses (n = 6 [11%]). These were performed in the perioperative, short-term, and midterm time frames 17%, 41%, and 43% of the time, respectively. Reinterventions were percutaneous (67%), inpatient procedures (61%), with median length of stay of 5 days. Of the 32 reintervention patients, 4 experienced access site complications and 4 died <30 days after reintervention (3 were adjudicated as not aneurysm related/not reintervention related). In 31 of 32 (97%) patients, reintervention success was achieved. CONCLUSIONS Reinterventions after F/B-EVAR were necessary in 26% of patients, most commonly for type III endoleaks and target artery complications. Whereas all but one reintervention was successful, many of these required complex procedures with significant morbidity and mortality. Development of strategies to eliminate type III endoleaks by improving component junction integrity and to ensure target artery primary patency are key next steps in the evolution of F/B-EVAR.


title: [Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].

text: The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.


title: Periprosthetic Anesthetic for Postoperative Pain After Laparoscopic Ventral Hernia Repair: A Randomized Clinical Trial.

text: IMPORTANCE Laparoscopic ventral hernia repair (LVHR) using mesh is a well-established intervention for ventral hernia, but pain control can be challenging. OBJECTIVE To determine whether instillation of a long-acting local anesthetic between the mesh and the peritoneum after LVHR reduces pain or narcotic requirements. DESIGN, SETTING, AND PARTICIPANTS A prospective, double-blind, randomized clinical trial with data collection during a brief hospital stay in a tertiary care, community teaching hospital over 3 years between December 15, 2011, and March 28, 2014. Of 120 screened patients undergoing LVHR in this intention-to-treat analysis, 99 eligible patients were randomized. Forty-two patients received the study drug, and 38 patients received placebo. Patients with a history of chronic narcotic use were excluded. INTERVENTION After mesh placement, a long-acting local anesthetic (bupivacaine hydrochloride, 0.50%) or placebo (0.9% normal saline) was injected between the mesh and the peritoneum. MAIN OUTCOMES AND MEASURES Postoperative pain (on a standard scale ranging from 0 to 10), and narcotic medication use (intravenous morphine equivalents). There were no adverse events. RESULTS Baseline and operative characteristics were similar except that the treatment group was older (61.8 vs 52.3 years, P = .001). After surgery, pain scores in the recovery room (3.2 vs 4.7, P = .003), interval total narcotic use (6.7 vs 12.5 mg, P = .003 at <4 hours and 0 vs 2.7 mg, P = .01 at 8-12 hours), and total intravenous narcotic use (9.2 vs 17.2 mg of morphine sulfate equivalents, P = .03) were significantly less in the treatment group. CONCLUSIONS AND RELEVANCE Administration of a long-acting local anesthetic between the mesh and the peritoneum significantly reduces postoperative pain and narcotic use after LVHR. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01530815.


title: Measurement of endotracheal tube secretions volume by micro computed tomography (MicroCT) scan: an experimental and clinical study.

text: BACKGROUND Biofilm accumulates within the endotracheal tube (ETT) early after intubation. Contaminated secretions in the ETT are associated with increased risk for microbial dissemination in the distal airways and increased resistance to airflow. We evaluated the effectiveness of micro computed tomography (MicroCT) for the quantification of ETT inner volume reduction in critically ill patients. METHODS We injected a known amount of gel into unused ETT to simulate secretions. We calculated the volume of gel analyzing MicroCT scans for a length of 20 cm. We then collected eleven ETTs after extubation of critically ill patients, recording clinical and demographical data. We assessed the amount of secretions by MicroCT and obtained ETT microbiological cultures. RESULTS Gel volumes assessed by MicroCT strongly correlated with injected gel volumes (p < 0.001, r2 = 0.999).MicroCT revealed the accumulation of secretions on all the ETTs (median 0.154, IQR:0.02-0.837 mL), corresponding to an average cross-sectional area reduction of 1.7%. The amount of secretions inversely correlated with patients' age (p = 0.011, rho = -0.727) but not with days of intubation, SAPS2, PaO2/FiO2 assessed on admission. Accumulation of secretions was higher in the cuff region (p = 0.003). Microbial growth occurred in cultures from 9/11 ETTs, and did not correlate with secretions amount. In 7/11 cases the same microbes were identified also in tracheal aspirates. CONCLUSIONS MicroCT appears as a feasible and precise technique to measure volume of secretions within ETTs after extubation. In patients, secretions tend to accumulate in the cuff region, with high variability among patients.


David Oliver: Doughnut deliveries, hospital staff, and the pandemic.


title: Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits.

text: INTRODUCTION Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties. METHODS The PEEP level (8 cmH2O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA. RESULTS PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated. CONCLUSIONS Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.


title: Radiofrequency ablation of hepatic tumours: effect of post-ablation margin on local tumour progression.

text: PURPOSE The purpose of this study was to retrospectively evaluate the relationship between post-ablation margins and local tumour progression following radiofrequency ablation (RFA) of hepatocellular carcinomas and colorectal liver metastases. METHODS Eighty-three patients with 107 hepatic tumours who underwent RFA were divided into two groups: the hepatocellular carcinoma (HCC) group (55 patients with 69 lesions) and the colorectal liver metastases group (28 patients with 38 lesions). Post-ablation margins were calculated on 1-month follow-up contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) studies. Efficacy was evaluated at 1-month post-ablation, then at 3-month intervals for the first year and biannually thereafter. RESULTS The results of the log-rank test showed that the minimum threshold post-ablation margin of 0.4 cm (P = 0.020) and tumour size smaller than 2.5 cm (P = 0.001) significantly correlated with local control for the HCC group. In the colorectal liver metastases group, the results of the log-rank test showed that the minimum threshold post-ablation margin of 0.4 cm (P = 0.345) and tumour size smaller than 2.5 cm (P = 0.168) did not correlate with local control. CONCLUSION Percutaneous RFA is more effective in achieving local control in patients with HCCs than with colorectal liver metastases.


title: Real-Time Fluorescence Imaging Using Indocyanine Green to Assess Therapeutic Effects of Near-Infrared Photoimmunotherapy in Tumor Model Mice.

text: BACKGROUND Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment. METHODS In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour. RESULTS Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg-1 and 0.3 mg kg-1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly. CONCLUSIONS Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.


Confusion over CPR in patients with covid-19.


Ultrasound-guided tracheal intubation: a novel intubation technique.


title: Successful treatment of coronavirus disease 2019 in a patient with asthma.

text: Underlying lung disease, especially asthma, has recently been found to be associated with a higher risk of hospitalization with coronavirus disease 2019 (COVID-19) infection. Inhaled corticosteroids (ICS) are the most commonly used controller medications in patients with asthma. It is unclear whether ICS use increases the risk for severe COVID-19 infection. At the current time, asthma organizations are still recommending the continued use of ICS and other asthma medications to minimize the risk of uncontrolled asthma. However, for patients with asthma and who have recovered from COVID-19 infection, the timing of resumption of asthma therapy is equally uncertain. Pulmonary function testing and exhaled oral nitric oxide testing are aerosol-generating procedures and are currently being severely restricted at most health-care facilities. We presented a case of a patient with cough-variant asthma who developed severe COVID-19 associated acute respiratory distress syndrome with the need for intubation and prolonged mechanical ventilation. We highlighted the potential utility of using COVID-19 RNA detection as well as immunoglobulin G antibody testing to help guide the timing of resumption of asthma therapy.


title: Histopathology and the detection of avian bornavirus in the nervous system of birds diagnosed with proventricular dilatation disease.

text: Avian bornavirus (ABV) is currently considered a probable etiologic agent of proventricular dilatation disease (PDD) of psittacines. We tested 24 stored avian brain samples, processed for histopathology and retained following their submission for necropsy or histopathology to the Schubot Exotic Bird Center diagnostic laboratory in 1992. Thirteen of these samples were from birds diagnosed at that time as suffering from PDD. The remaining 11 samples were diagnosed as suffering from diseases other than PDD. Immunohistochemistry was performed using an antiserum directed against the ABV nucleoprotein (N-protein). Stained slides were read by an investigator unaware of their prior histopathology results. Cells containing ABV N-protein were present in the nervous tissues of all 13 PDD cases. One bird not previously diagnosed with PDD also had ABV N-protein in its brain. A review of this bird's necropsy report indicated that it was, most probably, also suffering from PDD. The remaining 10 non-PDD birds had no detectable N-protein in their brains. The N-protein was present in the cerebrum, cerebellum and spinal cord. These findings support other studies that indicate that ABV is an etiological agent of PDD.


[Urgent research agenda for the novel coronavirus epidemic: transmission and non-pharmaceutical mitigation strategies].


title: Hydrophilic pyrazine dyes as exogenous fluorescent tracer agents for real-time point-of-care measurement of glomerular filtration rate.

text: Various hydrophilic pyrazine-bis(carboxamides) derived from 3,5-diamino-pyrazine-2,5-dicarboxylic acid bearing neutral and anionic groups were prepared and evaluated for use as fluorescent glomerular filtration rate (GFR) tracer agents. Among these, the dianionic d-serine pyrazine derivatives 2d and 2j, and the neutral dihydroxypropyl 2h, exhibited favorable physicochemical and clearance properties. In vitro studies show that 2d, 2h, and 2j have low plasma protein binding, a necessary condition for renal excretion. In vivo animal model results show that these three compounds exhibit a plasma clearance equivalent to iothalamate (a commonly considered gold standard GFR agent). In addition, these compounds have a higher urine recovery compared to iothalamate. Finally, the plasma clearance of 2d, 2h, and 2j remained unchanged upon blockage of the tubular secretion pathway with probenecid, a necessary condition for establishment of clearance via glomerular filtration only. Hence, 2d, 2h, and 2j are promising candidates for translation to the clinic as exogenous fluorescent tracer agents in real-time point-of-care monitoring of GFR.


title: Allopurinol reduces brachial and central blood pressure, and carotid intima-media thickness progression after ischaemic stroke and transient ischaemic attack: a randomised controlled trial.

text: OBJECTIVE Central blood pressure (CBP) and carotid intima-media thickness (CIMT) are surrogate measures of cardiovascular risk. Allopurinol reduces serum uric acid and oxidative stress and improves endothelial function and may therefore reduce CBP and CIMT progression. This study sought to ascertain whether allopurinol reduces CBP, arterial stiffness and CIMT progression in patients with ischaemic stroke or transient ischaemic attack (TIA). METHODS We performed a randomised, double-blind, placebo-controlled study, examining the effect of 1-year treatment with allopurinol (300 mg daily), on change in CBP, arterial stiffness and CIMT progression at 1 year and change in endothelial function and circulating inflammatory markers at 6 months. Patients aged over 18 years with recent ischaemic stroke or TIA were eligible. RESULTS Eighty participants were recruited, mean age 67.8 years (SD 9.4). Systolic CBP [-6.6 mm Hg (95% CI -13.0 to -0.3), p=0.042] and augmentation index [-4.4% (95% CI -7.9 to -1.0), p=0.013] were each lower following allopurinol treatment compared with placebo at 12 months. Progression in mean common CIMT at 1 year was less in allopurinol-treated patients compared with placebo [between-group difference [-0.097 mm (95% CI -0.175 to -0.019), p=0.015]. No difference was observed for measures of endothelial function. CONCLUSIONS Allopurinol lowered CBP and reduced CIMT progression at 1 year compared with placebo in patients with recent ischaemic stroke and TIA. This extends the evidence of sustained beneficial effects of allopurinol to these prognostically significant outcomes and to the stroke population, highlighting the potential for reduction in cardiovascular events with this treatment strategy. TRIAL REGISTRATION NUMBER ISRCTN11970568.


title: Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis.

text: This guideline is a revision of the clinical practice guideline, "Diagnosis and Management of Bronchiolitis," published by the American Academy of Pediatrics in 2006. The guideline applies to children from 1 through 23 months of age. Other exclusions are noted. Each key action statement indicates level of evidence, benefit-harm relationship, and level of recommendation. Key action statements are as follows:


title: In vivo comparison of two navigation systems for abdominal percutaneous needle intervention.

text: PURPOSE To compare the accuracy of a Kinect-Optical navigation system with an electromagnetic (EM) navigation system for percutaneous liver needle intervention. MATERIALS AND METHODS Five beagles with nine artificial tumors were used for validation. The Veran IG4 EM navigation system and a custom-made Kinect-Optical navigation system were used. Needle insertions into each tumor were conducted with these two guidance methods. The target positioning error (TPE) and the time cost of the puncture procedures were evaluated. RESULTS A total of 18 needle insertions were performed to evaluate the navigation accuracy of the two guidance approaches. The targeting error was 6.78 ± 3.22 mm and 8.72 ± 3.5 mm for the Kinect-Optical navigation system and the EM navigation system, respectively. There is no statistically significant difference in the TPE between the Kinect-Optical navigation system and the EM navigation system (p = 0.229). The processing time with the Kinect-Optical system (10 min) is similar to that of the Veran IG4 system (12 min). CONCLUSIONS The accuracy of the Kinect-Optical navigation system is comparable to that of the EM navigation system.


title: Safety of Intra-articular Hyaluronic Acid Injections in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

text: BACKGROUND Some controversy exists regarding the safety of intra-articular hyaluronic acid (IAHA) in the management of osteoarthritis (OA). OBJECTIVE The objective of this study was to re-assess the safety profile of IAHA in patients with OA, through a comprehensive meta-analysis of randomized, placebo-controlled trials. METHODS A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with IAHA in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, cardiac, vascular, respiratory, nervous system, skin and subcutaneous tissue disorders, musculoskeletal, renal and urinary disorders, infections and infestations, and hypersensitivity reaction. RESULTS Database searches initially identified 1481 records. After exclusions according to the selection criteria, 22 studies were included in the qualitative synthesis, and nine studies having adequate data were ultimately included in the meta-analysis. From the studies excluded according to the pre-specified selection criteria, 21 with other pharmacological OA treatments permitted during the trials were a posteriori included in a parallel qualitative synthesis, from which eight studies with adequate data were finally included in a parallel meta-analysis. Since this meta-analysis was designed to assess safety, the exclusion criterion on concomitant anti-OA medication was crucial. However, due to the high number of studies that allowed mainly concomitant oral non-steroidal anti-inflammatory drugs (NSAIDs), we decided to include them in a post hoc parallel analysis in order to compare the results from the two analyses. No statistically significant difference in odds was found between IAHA and placebo for all types of SOC-related disorders, except for infections and infestations, for which significantly lower odds were found with IAHA compared with placebo, both overall (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.40-0.93; I2 = 0%) and in studies without concomitant anti-OA medication (OR = 0.49, 95% CI 0.27-0.89). There were significant increased odds of reporting serious AEs with IAHA compared with placebo, both overall (OR = 1.78, 95% CI 1.21-2.63; I2 = 0%) and in studies with concomitant anti-OA medication (OR = 1.78, 95% CI 1.10-2.89), but not in studies without concomitant anti-OA medication (OR = 1.78, 95% CI 0.92-3.47). CONCLUSIONS Using the available data on studies without any concomitant anti-OA medication permitted during clinical trials, IAHA seems not to be associated with any safety issue in the management of OA. However, this evidence was associated with only a "low" to "moderate" certainty. A possible association with increased risk of serious AEs, particularly when used with concomitant OA medications, requires further investigation.


title: Development of a rapid, sensitive TaqMan real-time RT-PCR assay for the detection of Rose rosette virus using multiple gene targets.

text: Rose rosette virus (RRV), belonging to the genus Emaravirus, is a highly destructive pathogen that causes rose rosette disease. The disease is a major concern for the rose industry in the U.S. due to the lack of highly sensitive methods for early detection of RRV. This is critical, as early identification of the infected plants and eradication is necessary in minimizing the risks associated with the spread of the disease. A highly reliable, specific and sensitive detection assay is thus required to test and confirm the presence of RRV in suspected plant samples. In this study a TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for the detection of RRV from infected roses, utilizing multiple gene targets. Four pairs of primers and probes; two of them (RRV_2-1 and RRV_2-2) based on the consensus sequences of the glycoprotein gene (RNA2) and the other two (RRV_3-2 and RRV_3-5) based on the nucleocapsid gene (RNA3) were designed. The specificity of the primers and probes was evaluated against other representative viruses infecting roses, belonging to the genera Alfamovirus, Cucumovirus, Ilarvirus, Nepovirus, Tobamovirus, and Tospovirus and one Emaravirus (Wheat mosaic virus). Dilution assays using the in vitro transcripts (spiked with total RNA from healthy plants, and non-spiked) showed that all the primers and probes are highly sensitive in consistently detecting RRV with a detection limit of 1 fg. Testing of the infected plants over a period of time (three times in monthly intervals) indicated high reproducibility, with the primer/probe RRV_3-5 showing 100% positive detection, while RRV_2-1, RRV_2-2 and RRV_3-2 showed 90% positive detection. The developed real-time RT-PCR assay is reliable, highly sensitive, and can be easily used in diagnostic laboratories for testing and confirmation of RRV.


title: Tocotrienol-rich vitamin E improves diabetic nephropathy and persists 6-9 months after washout: a phase IIa randomized controlled trial.

text: Chronic hyperglycemia in type 2 diabetes mellitus increases oxidative stress and inflammation which contributes to long-term diabetic kidney disease. Tocotrienol-rich vitamin E, as Tocovid, has been shown to reduce oxidative stress and inflammation to ameliorate diabetes in rat models and human subjects. In this prospective, multicenter, double-blinded, placebo-controlled clinical trial, 54 patients (duration = 18.4 years, HbA1c = 8.8%) with diabetic nephropathy were randomized to receive Tocovid 200 mg or placebo for 12 weeks. Fasting blood samples were taken to measure HbA1c, serum creatinine, estimate glomerular filtration rate (eGFR), urine albumin:creatinine ratio, malondialdehyde, tumor necrosis factor receptor-1, vascular cell adhesion molecule-1 (VCAM-1), and thromboxane-B2. Patients were reassessed 6-9 months post-washout. After 12 weeks of supplementation, Tocovid significantly decreased serum creatinine levels (mean difference: -3.3 ± 12.6 versus 5.4 ± 14.2, p = 0.027) and significantly increase eGFR (mean difference: 1.5 ± 7.6 versus -2.9 ± 8.0, p = 0.045) compared with placebo. There were no significant changes in HbA1c, blood pressure, and other parameters. Subgroup analysis revealed that in patients with low serum vitamin E concentrations at baseline, Tocovid reduced serum creatinine, eGFR, and VCAM-1 significantly. After 6-9 months of washout, persistent difference in serum creatinine remained between groups (mean difference: 0.82 ± 8.33 versus 11.26 ± 15.47, p = 0.031), but not eGFR. Tocovid at 400 mg/day significantly improved renal function in 12 weeks of supplementation, as assessed by serum creatinine and eGFR, which remained significant 6-9 months post-washout.


Diabetes and Technology in the Covid-19 Pandemic Crisis.


U.S. 'Warp Speed' vaccine effort comes out of the shadows.


title: Renal denervation after Symplicity HTN-3: an update.

text: After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial--Symplicity HTN-3--to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25-30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity-mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already "knocking at the door", the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.


title: Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon.

text: Porcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in the pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics, but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using an activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or small interfering RNA (siRNA) led to a decrease in virus yields. Further analysis revealed that inhibition of EGFR produced augmentation of type I interferon genes. We next observed that the EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in decreased PEDV RNA levels, and vice versa. The data on STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires activation of the STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of the type I interferon response and provides a novel therapeutic target for virus infection.IMPORTANCE EGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR in PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of the EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.


title: AACR Calls on Congress to Take Immediate Action Against COVID-19 and Protect Patients with Cancer During the Pandemic.

text: On March 30, 2020 the AACR Board of Directors provided a letter to US Congressional leadership on behalf of its members in response to the COVID-19 public health emergency.


To-go medications as a means to treat discharged emergency department patients during COVID-19.


title: Activated Mesenchymal Stem Cells Interact with Antibiotics and Host Innate Immune Responses to Control Chronic Bacterial Infections.

text: Chronic bacterial infections associated with biofilm formation are often difficult to resolve without extended courses of antibiotic therapy. Mesenchymal stem cells (MSC) exert antibacterial activity in vitro and in acute bacterial infection models, but their activity in chronic infection with biofilm models has not been previously investigated. Therefore, we studied the effects of MSC administration in mouse and dog models of chronic infections associated with biofilms. Mice with chronic Staphylococcus aureus implant infections were treated by i.v. administration of activated or non-activated MSC, with or without antibiotic therapy. The most effective treatment protocol was identified as activated MSC co-administered with antibiotic therapy. Activated MSC were found to accumulate in the wound margins several days after i.v. administration. Macrophages in infected tissues assumed an M2 phenotype, compared to untreated infections which contained predominately M1 macrophages. Bacterial killing by MSC was found to be mediated in part by secretion of cathelicidin and was significantly increased by antibiotics. Studies in pet dogs with spontaneous chronic multi drug-resistant wound infections demonstrated clearance of bacteria and wound healing following repeated i.v. administration of activated allogeneic canine MSC. Thus, systemic therapy with activated MSC may be an effective new, non-antimicrobial approach to treatment of chronic, drug-resistant infections.


Minimally Invasive Ivor-Lewis Esophagectomy: Use of the OrVIL Device for the EEA Intrathoracic Anastomosis.


title: [Thoughts on the reform of preventive medicine education in the context of new medicine].

text: Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.


title: Commentary: Challenges to Achieve Conceptual Clarity in the Definition of Pandemics.

text: From a scientific standpoint, the world is more prepared than ever to respond to infectious disease outbreaks; paradoxically, globalization and air travel, antimicrobial resistance, the threat of bioterrorism, and newly emerging pathogens driven by ecological, socioeconomic, and environmental factors, have increased the risk of global epidemics.1,2,3 Following the 2002-2003 severe acute respiratory syndrome (SARS), global efforts to build global emergency response capabilities to contain infectious disease outbreaks were put in place.4,5,6 But the recent H1N1, Ebola, and Zika global epidemics have shown unnecessary delays and insufficient coordination in response efforts.7,8,9,10 In a thoughtful and compelling essay,11 Thana C. de Campos argues that greater clarity in the definition of pandemics would probably result in more timely effective emergency responses, and pandemic preparedness. In her view, a central problem is that the definition of pandemics is based solely on disease transmission across several countries, and not on spread and severity together, which conflates two very different situations: emergency and nonemergency disease outbreaks. A greater emphasis on severity, such that pandemics are defined as severe and rapidly spreading infectious disease outbreaks, would make them "true global health emergencies," allowing for priority resource allocation and effective collective actions in emergency response efforts. Sympathetic to the position taken by de Campos, here I highlight some of the challenges in the definition of severity during an infectious disease outbreak.


title: A Real-life Population Pharmacokinetic Study Reveals Factors Associated with Clearance and Immunogenicity of Infliximab in Inflammatory Bowel Disease.

text: BACKGROUND Several factors influencing the pharmacokinetics of infliximab (IFX) in inflammatory bowel disease (IBD) have been identified. We studied the impact of patient, disease, and treatment characteristics on clearance and immunogenicity of IFX in a real-world patient-with-IBD cohort. METHODS Serum concentrations of IFX and antibodies to IFX (ATIs) were measured in patients with IBD at a single center using an enzyme-linked immunosorbent assay and radioimmunoassay. Patient, disease, and treatment characteristics were retrospectively collected along with laboratory values. Pharmacokinetics and ATI titer were analyzed simultaneously by nonlinear mixed-effects modeling. RESULTS Nine hundred ninety-seven IFX concentrations and 756 ATI measurements from 332 patients with IBD (253 Crohn's disease and 79 ulcerative colitis) were included. Mean (SD) IFX dose was 5.47 ± 1.33 mg/kg. ATIs were detected in 75/332 (23%) patients; insufficient exposure below an IFX trough level of 3 μg/mL was the most predictive factor of developing ATI and resulted in a 4-fold increased risk of ATI development. ATI titer was a better predictor of IFX clearance than ATI as a dichotomous parameter. ATI titers >30 AU/mL were consistently associated with undetectable IFX concentrations. IFX clearance was affected by body weight (40-149 kg) ranging from 0.27 to 0.53 L/d, serum albumin (2-5.4 g/dL) from 0.93 to 0.24 L/d, and titers of ATIs (0-53,000 AU/mL) from 0.36 L/d to 15.93 L/d (P < 0.001). Previously biologic-treated patients exhibited a higher clearance of IFX. CONCLUSIONS IFX exposure below 3 μg/mL increases risk of ATIs. Identification of influential pharmacokinetics and ATI factors improves prediction of IFX levels, potentially allowing individualized dosing and cost reduction.