title: Endotherapy in case of relapse of neoplastic Barrett's esophagus after successful initial endoscopic resection.

text: BACKGROUND Endotherapy in cases of neoplastic Barrett esophagus (BE) relapse after successful initial endoscopic management is commonly accepted, but few studies analyze this topic and also take into account the metachronous lesions. AIMS To evaluate the efficiency of endotherapy in the case of neoplastic BE relapse after successful complete endoscopic eradication of neoplastic BE and metaplastic BE. METHODS Retrospective review of medical records was collected in a computerized and prospective manner between 2000 and 2015, in a single tertiary care center. Recurrence was defined by histological presence of high-grade dysplasia or superficial adenocarcinoma at least 6 months after the end of successful initial endotherapy. RESULTS Eighteen patients were assessed (1F/17 M). Delay between initial treatment and relapse was 16.6 months (range 6-33). Endotherapy for relapse obtained a sustained and complete remission for 8/18 (44%) patients, with an average endoscopic follow-up of 28 months. The complication rate of endotherapy was 6%. Surgical management was required in 33% (2 pT2N0M0, 2 pTisN0M0, 1 pTm2N0M0 and 1 pTm3N0M0) and salvage radiochemotherapy in 17% (3/18). One patient treated by 6 sessions of ER was considered as a failure given the multiple sessions of endotherapy. Multivariate analysis showed that length of BE (>5 cm), late stenosis adverse events and the quality of vertical margin during initial ER are predictive factors for disease-free survival (p value < 0.01, Hazard Ratio up to 0.076). CONCLUSION Endotherapy could be a treatment for management of neoplastic BE relapse, but should be carefully used, with strict follow-up.


title: Epicardial adipose tissue and carotid artery disease: Protocol for systematic review and meta-analysis.

text: BACKGROUND Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex. METHODS This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators. RESULTS We propose the current protocol to evaluate the evaluation of EAT with ED. CONCLUSION This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. ETHICS AND DISSEMINATION Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER PROSPERO (CRD42018083458).


Ebola and ethics.


A young male with bilateral chest pain.


Stability and Viability of SARS-CoV-2.


title: A rare type of double aortic arch diagnosed by echocardiography in an asymptomatic 9-year-old patient.

text: A case of double aortic arch with an atretic left arch distal to the origin of the left subclavian artery was suspected by echocardiography (ECHO) in an asymptomatic 9-year-old girl and confirmed by magnetic resonance imaging (MRI). The authors report their ECHO findings, which could be an important diagnostic tool for symptomatic patients because confusion exists in the literature regarding the differentiation of the aforementioned rare malformation from a right arch with mirror image branching. The authors support their ECHO proposal with an explanation based on the hypothetical double aortic arch plan set by Edwards.


title: A one-step conversion from gastric banding to laparoscopic Roux-en-Y gastric bypass is as safe as a two-step conversion: A comparative analysis of 885 patients.

text: AIMS To achieve additional weight loss or to resolve band-related problems, a laparoscopic adjustable gastric banding (LAGB) can be converted to a laparoscopic Roux-en-Y gastric bypass (RYGB). There is limited data on the feasibility and safety of routinely performing a single-step conversion. We assessed the efficacy of this revisional approach in a large cohort of patients operated in a high-volume bariatric institution. METHODS Between October 2004 and December 2015, a total of 885 patients who underwent LAGB removal with RYGB were identified from a prospectively collected database. In all cases, a single-stage conversion procedure was planned. The feasibility of this approach and peri-operative outcomes of these patients were evaluated and analyzed. RESULTS A single-step approach was successfully achieved in 738 (83.4%) of the 885 patients. During the study period, there was a significant increase in performing the conversion from LAGB to RYGB single-staged. No mortality or anastomotic leakage was observed in both groups. Only 45 patients (5.1%) had a 30-d complication: most commonly hemorrhage (N = 20/45), with no significant difference between the groups. CONCLUSION Converting a LAGB to RYGB can be performed with a very low morbidity and zero-mortality in a high-volume revisional bariatric center. With increasing experience and full standardization of the conversion, the vast majority of operations can be performed as a single-stage procedure. Only a migrated band remains a formal contraindication for a one-step approach.


title: Middle East respiratory syndrome coronavirus: five years later.

text: INTRODUCTION In the past five years, there have been 1,936 laboratory-confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 35.6%. Most cases have arisen in the Middle East, particularly the Kingdom of Saudi Arabia, however there was a large hospital-associated outbreak in the Republic of Korea in 2015. Exposure to dromedary camels has been recognized by the World Health Organization (WHO) as a risk factor in primary cases, but the exact mechanisms of transmission are not clear. Rigorous application of nationally defined infection prevention and control measures has reduced the levels of healthcare facility-associated outbreaks. There is currently no approved specific therapy or vaccine available. Areas covered: This review presents an overview of MERS-CoV within the last five years, with a particular emphasis on the key areas of transmission, infection control and prevention, and therapies and vaccines. Expert commentary: MERS-CoV remains a significant threat to public health as transmission mechanisms are still not completely understood. There is the potential for mutations that could increase viral transmission and/or virulence, and zoonotic host range. The high mortality rate highlights the need to expedite well-designed randomized clinical trials for direct, effective therapies and vaccines.


Coagulopathy associated with COVID-19.


title: Radiofrequency ablation: technique and clinical applications.

text: Radiofrequency ablation is the most commonly used percutaneous ablation technique and well-documented in the literature on focal therapies. It has become the image-guided ablation method of choice because of its efficacy, safety, and ease of use. Radiofrequency ablation has shown promise in treating selected solid tumors, particularly those involving the liver, kidneys, lungs, and the musculoskeletal system. It is a minimally invasive technique often used in inoperable patients with other comorbidities. Radiofrequency ablation requires a minimal hospital stay or can be performed on an outpatient basis. The aim of this article is to review radiofrequency ablation techniques and their clinical applications.


title: Drivers of disease emergence and spread: is wildlife to blame?

text: The global focus on wildlife as a major contributor to emerging pathogens and infectious diseases (EIDs) in humans and domestic animals is not based on field, experimental or dedicated research, but mostly on limited surveys of literature, opinion and the assumption that biodiversity harbours pathogens. The perceived and direct impacts of wildlife, from being a reservoir of certain human and livestock pathogens and as a risk to health, are frequently overstated when compared to the Global burden of disease statistics available from WHO, OIE and FAO. However organisms that evolve in wildlife species can and do spill-over into human landscapes and humans and domestic animal population and, where these organisms adapt to surviving and spreading amongst livestock and humans, these emerging infections can have significant consequences. Drivers for the spill-over of pathogens or evolution of organisms from wildlife reservoirs to become pathogens of humans and domestic animals are varied but almost without exception poorly researched. The changing demographics, spatial distribution and movements, associated landscape modifications (especially agricultural) and behavioural changes involving human and domestic animal populations are probably the core drivers of the apparent increasing trend in emergence of new pathogens and infectious diseases over recent decades.


title: Determining the microbiological cause of a chest infection.

text: Over recent years non-culture techniques such as specific viral and bacterial nucleic acid amplification, serology and antigen detection have considerably developed and been applied within research studies to clinical samples, significantly increasing pathogen detection in pneumonia. There are promising signs of improved diagnostic yields for pneumococcal pneumonia when using molecular techniques to detect pneumococcal gene sequences in blood or by combining serum biomarkers with rapid pneumococcal urinary antigen testing. Pathogens have traditionally been difficult to detect in pneumonia and treatment is usually successful with empiric antibiotics. However, directed antibiotic treatment has significant benefits in terms of antibiotic stewardship and these new technologies make this goal a possibility, though not yet a reality.


title: Unusual venous route of pulmonary artery catheter in a liver transplant recipient: pericardiophrenic or highest intercostal vein?: a case report.

text: We report an extraordinary case in which the venous route for pulmonary artery catheterization was unusual. A 41 year-old woman with an end-stage liver disease underwent a living-donor liver transplantation. After induction of anesthesia, the pulmonary artery catheter was revealed to be advanced into the left brachiocephalic vein and then slipped into another vein that drains into the left brachiocephalic vein. In this case, we assumed that the catheter had most likely slipped into the left pericardiophrenic vein since the catheter follows the left heart border similarly to the route of this vein according to the chest X-ray. Patients with liver cirrhosis develop many collateral vessels and have enlarged veins due to portal hypertension, which makes this vascular route possible. We present this case for anesthesiologists to be aware of the possibilities of unusual venous route due to dilated collateral vessels especially in liver transplant patients.


title: Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn's disease patients.

text: Objectives: Anti-TNF agents are effective to treat perianal Crohn's disease (CD). Evidence suggests that Crohn's disease patients with perianal fistulas need higher infliximab (IFX) serum concentrations compared to patients without perianal CD to achieve complete disease control. Our aim was to compare anti-TNF serum concentrations between patients with actively draining and closed perianal fistulas. Methods: A retrospective survey was performed in CD patients with perianal disease treated with IFX or adalimumab (ADL). Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging. Results: We identified 66 CD patients with a history of perianal fistulas treated with IFX (n = 47) and ADL (n = 19). Median IFX serum trough concentrations ([interquartile range]) were higher in patients with closed fistulas (n = 32) compared to patients with actively draining fistulas (n = 15): 6.0 µg/ml [5.4-6.9] versus 2.3 µg/ml [1.1-4.0], respectively (p < .001)). A similar difference was seen in patients treated with ADL: median serum concentrations were 7.4 µg/ml [6.5-10.8] in 13 patients with closed fistulas versus 4.8 µg/ml [1.7-6.2] in 6 patients with producing fistulas (p = .003). Serum concentrations of ≥5.0 µg/ml for IFX (area under the curve of 0.92; 95% CI: 0.82-1.00)) and 5.9 µg/ml for ADL (area under the curve of 0.89; 95% CI 0.71-1.00) were associated with fistula closure. Conclusion: Cut-off serum concentrations ≥5.0 µg/ml for IFX and ≥5.9 µg/ml for ADL were associated with perianal fistula closure. Hence, patients with producing perianal fistulas may benefit from anti-TNF dose intensification to achieve fistula closure.


title: Sports: The Infectious Hazards.

text: Although the medical complications of sports are usually traumatic in nature, infectious hazards also arise. While blood-borne pathogens such as HIV, hepatitis B, and hepatitis C, cause significant illness, the risk of acquiring these agents during sporting activities is minimal. Skin infections are more commonplace, arising from a variety of microbial agents including bacterial, fungal, and viral pathogens. Sports involving water contact can lead to enteric infections, eye infections, or disseminated infections such as leptospirosis. Mumps, measles, and influenza are vaccine-preventable diseases that have been transmitted during sporting events, both in players and in spectators. Prevention is the key to many of these infections. Players should be vaccinated and should not participate in sports if their infection can be spread by contact, airborne, or droplet transmission.


Community Obstetrical Units Less Likely than Academic Units to Have Universal COVID-19 Testing.


title: An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

text: The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed.


title: Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry.

text: Introduction Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.


title: A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens.

text: We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N=44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N=44, age 1-8 years). These longitudinal data were analyzed with a novel method, using a mathematical model to describe the observed responses, and their variation among subjects. This allowed us to estimate biologically meaningful characteristics of the serum antibody response, like peak level and decay rate, and to compare these among natural infections and vaccine responses. Compared to natural infection, responses to PT after vaccination with the tested vaccines are smaller in magnitude and tend to decay slightly faster. When present in vaccines, FHA and Prn tend to produce high peak levels, higher than those in naturally infected patients, but these decay faster. As expected, the Dutch whole cell vaccine produced lower antibody responses than the acellular vaccines. This model allows a better comparison of the kinetics of vaccine induced antibody responses and after natural infection over a long follow up period.


title: Single-port access total laparoscopic hysterectomy with Korean-made OCTO Port: Turkish surgeons' initial experience.

text: We present our initial experience with single-port access total laparoscopic hysterectomy (TLH) surgery using a Korean-made laparoscopic port (OCTO™ Port). In a retrospective study, single-port access TLH (SPA-TLH) with the OCTO Port was performed on 34 patients with benign gynaecological indications from July 2013 to May 2014 by two surgeons (Ahmet Kale and Hasan Terzi). All patients were divided into two groups. The first 15 patients who underwent SPA-TLH were classified as Group 1, and the second 19 patients who underwent SPA-TLH were classified as Group 2. Patient data were analyzed for age, body mass index (BMI, kg/m(2)), weight of uterus, vaginal cuff suturation time, estimated blood loss, operation time, hysterectomy indications and operative outcomes. The median time needed for the surgery was 75 min in both groups. The duration of suturing of the vaginal cuff was shorter in Group 2 compared with that in Group 1. The estimated blood loss was less in Group 2 compared with Group 1: Four patients in Group 1 required blood transfusion while none of the patients in Group 2 required blood transfusion. The OCTO Port has soft and flexible instrumental movements, which can reduce crowding of instruments during surgery, and the cap rotates 360 degrees. The OCTO Port might facilitate the learning curve of single-port laparoscopic hysterectomy surgery.


title: Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists.

text: OBJECTIVES To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. MATERIALS AND METHODS A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. RESULTS Among 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p< 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95%CI 1.74-10.54, p=0.012). CONCLUSIONS COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties. Available at. .


title: Incidence of iatrogenic ureteral injury after laparoscopic colectomy.

text: OBJECTIVE To compare the incidence of iatrogenic ureteral injury between laparoscopic and open colectomies at a single institution. DESIGN From June 1, 2005, through July 31, 2010, patients were identified from a prospectively maintained database and hospital records were retrospectively reviewed. SETTING Mount Sinai Medical Center. PATIENTS Fourteen patients who underwent colectomy complicated by a ureteral injury. MAIN OUTCOME MEASURES A significant increase in ureteral injuries occurred after laparoscopic vs open procedures (0.66% vs 0.15%, P = .007). RESULTS A total of 5729 colectomies were performed during the study period. Fourteen ureteral injuries occurred, resulting in a 0.244% incidence of iatrogenic ureteral injury. Patient demographics demonstrated that 9 injuries (64%) occurred in females and 7 patients (50%) had undergone prior abdominal operations. Operative indications were inflammatory bowel disease (n = 7), diverticulitis (n = 2), and malignant neoplasm (n = 4). Thirteen operations (87%) in this study were elective colectomies, and 7 patients (50%) underwent laparoscopic procedures, with 2 open conversions. Of the 5729 colectomies, 4669 were open and 1060 laparoscopic. Regarding ureteral injuries, no difference was observed in intraoperative identification of ureteral injury in patients who underwent preoperative ureteral stent placement (n = 4) vs those who did not (50% [2 of 4] vs 50% [5 of 10]). CONCLUSIONS A significant increase was found in the incidence of iatrogenic ureteral injuries with laparoscopy compared with open colectomies. Preoperative stent placement did not ensure intraoperative identification of injury. Female sex and increased operative blood loss appear to predispose patients to injury.


title: Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial.

text: BACKGROUND There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.


title: Clinical presentation and course of COVID-19.

text: Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.


title: Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea.

text: RATIONALE Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear. OBJECTIVES We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a result, there is a surge in pulmonary O(2) uptake that rapidly depletes the finite alveolar O(2) store, thereby accelerating arterial O(2) desaturation. METHODS Recurrent apneas were simulated in an experimental lamb model. Pulmonary O(2) uptake was calculated from continuously measured arterial and mixed-venous O(2) saturation and cardiac output. MEASUREMENTS AND MAIN RESULTS Direct measurements revealed that asynchrony in the desaturation and resaturation of arterial and venous blood gave rise to dips and surges in O(2) uptake. After desaturation to 50%, a typical nadir in preterm infants, O(2) uptake surged to a peak of 176.9 ± 7.8% of metabolic rate. During subsequent apneas, desaturation rate was increased two- to threefold greater than during isolated apneas, in direct proportion to the magnitude of the surge in O(2) uptake (P < 0.001; R(2) = 0.897). Application of our mathematical model to a published recording of cyclic apneas in a preterm infant precisely reproduced the accelerated desaturation rates of up to 15% · s(-1) observed clinically. CONCLUSIONS Rapid depletion of alveolar O(2) stores by surges in O(2) uptake almost completely explains the acceleration of desaturation that occurs during recurrent apnea. This powerful mechanism is likely to explain the severity of intermittent hypoxemia that is associated with neurocognitive and cardiovascular morbidities in preterm infants and adults.


title: Vaccines for the common cold.

text: BACKGROUND The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat and fever (usually < 37.8˚C). The widespread morbidity it causes worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. OBJECTIVES To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS We searched CENTRAL (2012, Issue 12), MEDLINE (1948 to January week 1, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013) and LILACS (1982 to January 2013). SELECTION CRITERIA Randomised controlled trials (RCTs) of any virus vaccines to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS Two review authors independently evaluated methodological quality and extracted trial data. Disagreements were resolved by discussion or by consulting a third review author. MAIN RESULTS This review included one RCT with 2307 healthy participants; all of them were analysed. This trial compared the effect of an adenovirus vaccine against a placebo. No statistically significant difference in common cold incidence was found: there were 13 events in 1139 participants in the vaccines group and 14 events in 1168 participants in the placebo group; risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 2.02, P = 0.90). No adverse events related to the live vaccine were reported. AUTHORS' CONCLUSIONS This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine.


Covid-19 is threatening the survival of US primary care.


docid: pubxhmvm

title: Accuracy of neutrophil gelatinase-associated lipocalin for acute kidney injury diagnosis in children: systematic review and meta-analysis.

text: OBJECTIVE To estimate the accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a biomarker for acute kidney injury (AKI) in children. METHODS A systematic review of the literature was performed. The review protocol was registered at PROSPERO (CRD 42015024153). We conducted searches in the following databases: Medline (PubMed), LILACS (BVS), SCOPUS (Elsevier), Embase (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, and ISI Web of Science, from January 1990 to October 2016. For inclusion, studies measured NGAL levels in plasma and urine for AKI in children. For each study, 2 × 2 contingency tables were developed. For statistical analysis we calculated the sensitivity, specificity and diagnostic odds ratio. For methodological assessment, we used Quality Assessment of Diagnostic Accuracy Studies-2. Software used for analysis was Stata 14, and RevMan 5.3. RESULTS In total 13 studies were analyzed, which included 1629 children. For urinary NGAL, the pooled sensitivity was 0.76 (95% CI 0.62-0.85) and a pooled specificity 0.93 (95% CI 0.88-0.96). The diagnostic odds ratio (DOR) for the detection of AKI was 43 (95% CI 16-115) and the Area under the curve (AUC) was 0.94 (95% CI 0.92-0.96). For plasma NGAL the combined sensitivity was 0.80 (95% CI 0.64-0.90) and a combined specificity was 0.87 (95% CI 0.74-0.94). The DOR was 26 (95% CI 8.0-82) and AUC was 0.90 (95% CI 0.87-0.94) for the detection of AKI in children. CONCLUSION The data suggest that NGAL levels can be an important biomarker for the early detection of AKI in children.


Law as a Social Medicine: Enhancing International Inter-regime Regulatory Coopetition as a Means for the Establishment of a Global Health Governance Framework.


Responding to COVID-19: Agile Use of Information Technology to Serve Patients With Diabetes.


title: Impact of the COVID-19 pandemic on orthopedic trauma workload in a London level 1 trauma center: the "golden month".

text: Background and purpose - The COVID-19 pandemic has been recognized as an unprecedented global health crisis. This is the first observational study to evaluate its impact on the orthopedic workload in a London level 1 trauma center (i.e., a major trauma center [MTC]) before (2019) and during (2020) the "golden month" post-COVID-19 lockdown.Patients and methods - We performed a longitudinal observational prevalence study of both acute orthopedic trauma referrals, operative and anesthetic casemix for the first "golden" month from March 17, 2020. We compared the data with the same period in 2019. Statistical analyses included median (median absolute deviation), risk and odds ratios, as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05.Results - Acute trauma referrals in the post-COVID period were almost halved compared with 2019, with similar distribution between pediatric and adult patients, requiring a significant 19% more admissions (RR 1.3, OR 2.6, p = 0.003). Hip fractures and polytrauma cases accounted for an additional 11% of the modal number of injuries in 2020, but with 19% reduction in isolated limb injuries that were modal in 2019. Total operative cases fell by a third during the COVID-19 outbreak. There was a decrease of 14% (RR 0.85, OR 0.20, p = 0.006) in aerosol-generating anesthetic techniques used.Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute trauma referrals, admissions (but increased risk and odds ratio), operations, and aerosolizing anesthetic procedures since implementing social distancing and lockdown measures during the "golden month."


docid: yvxvhlqm

title: Healing the suffering of the lonely heart.


title: Closed-loop mechanical ventilation for lung injury: a novel physiological-feedback mode following the principles of the open lung concept.

text: Adherence to low tidal volume (VT) ventilation and selected positive end-expiratory pressures are low during mechanical ventilation for treatment of the acute respiratory distress syndrome. Using a pig model of severe lung injury, we tested the feasibility and physiological responses to a novel fully closed-loop mechanical ventilation algorithm based on the "open lung" concept. Lung injury was induced by surfactant washout in pigs (n = 8). Animals were ventilated following the principles of the "open lung approach" (OLA) using a fully closed-loop physiological feedback algorithm for mechanical ventilation. Standard gas exchange, respiratory- and hemodynamic parameters were measured. Electrical impedance tomography was used to quantify regional ventilation distribution during mechanical ventilation. Automatized mechanical ventilation provided strict adherence to low VT-ventilation for 6 h in severely lung injured pigs. Using the "open lung" approach, tidal volume delivery required low lung distending pressures, increased recruitment and ventilation of dorsal lung regions and improved arterial blood oxygenation. Physiological feedback closed-loop mechanical ventilation according to the principles of the open lung concept is feasible and provides low tidal volume ventilation without human intervention. Of importance, the "open lung approach"-ventilation improved gas exchange and reduced lung driving pressures by opening atelectasis and shifting of ventilation to dorsal lung regions.


title: Identify, isolate, inform: a 3-pronged approach to management of public health emergencies.

text: During an evolving public health emergency, a simple algorithm for initial patient identification and management is essential for providers on the front lines. This article recommends a 3-pronged system of Identify, Isolate, Inform to describe the actions necessary in the first few minutes of encountering a potential Ebola patient. Application of the "vital sign zero" triage concept of early recognition of potential threats coupled with this novel algorithm will optimize protection of health care workers and the public health while concurrently providing a safe method for individual patient care.


docid: nshgfavp

title: Imaging of EGFR expression in murine xenografts using site-specifically labelled anti-EGFR 111In-DOTA-Z EGFR:2377 Affibody molecule: aspect of the injected tracer amount.

text: INTRODUCTION Overexpression of epidermal growth factor receptor (EGFR) is a prognostic and predictive biomarker in a number of malignant tumours. Radionuclide molecular imaging of EGFR expression in cancer could influence patient management. However, EGFR expression in normal tissues might complicate in vivo imaging. The aim of this study was to evaluate if optimization of the injected protein dose might improve imaging of EGFR expression in tumours using a novel EGFR-targeting protein, the DOTA-Z(EGFR:2377) Affibody molecule. METHODS An anti-EGFR Affibody molecule, Z(EGFR:2377), was labelled with (111)In via the DOTA chelator site-specifically conjugated to a C-terminal cysteine. The affinity of DOTA-Z(EGFR:2377) for murine and human EGFR was measured by surface plasmon resonance. The cellular processing of (111)In-DOTA-Z(EGFR:2377) was evaluated in vitro. The biodistribution of radiolabelled Affibody molecules injected in a broad range of injected Affibody protein doses was evaluated in mice bearing EGFR-expressing A431 xenografts. RESULTS Site-specific coupling of DOTA provided a uniform conjugate possessing equal affinity for human and murine EGFR. The internalization of (111)In-DOTA-Z(EGFR:2377) by A431 cells was slow. In vivo, the conjugate accumulated specifically in xenografts and in EGFR-expressing tissues. The curve representing the dependence of tumour uptake on the injected Affibody protein dose was bell-shaped. The highest specific radioactivity (lowest injected protein dose) provided a suboptimal tumour-to-blood ratio. The results of the biodistribution study were confirmed by gamma-camera imaging. CONCLUSION The (111)In-DOTA-Z(EGFR:2377) Affibody molecule is a promising tracer for radionuclide molecular imaging of EGFR expression in malignant tumours. Careful optimization of protein dose is required for high-contrast imaging of EGFR expression in vivo.


title: Rationale for prescription, and effectiveness of, upper limb orthotic intervention for children with cerebral palsy: a systematic review.

text: PURPOSE To explore (i) reasons for upper limb orthosis prescription for children with cerebral palsy (CP), (ii) the link between reason and effect according to intended outcome and outcome measure utilized and (iii) to classify the prescribed orthoses using standard terminology. METHOD A prospectively registered (center for reviews and dissemination: 42015022067) systematic review searched for experimental and observational studies investigating rigid/thermoplastic upper limb orthotic intervention for children aged 0-18 with CP. The Cochrane central register, MEDLINE, CINAHL, Embase, SCOPUS and Web of Science databases were searched. Included studies were assessed for risk of bias. RESULTS Sixteen studies met selection criteria. Two studies described a specific reason for orthosis prescription, six prescribed orthoses to manage a clinical symptom and eight did not describe a reason. Eight studies were analyzed for effect according to intended outcome with no clear connection found between reasons for prescription, outcome measures utilized and effect reported. INTERPRETATION The lack of evidence for upper limb orthotic intervention for children with CP leads to uncertainty when considering this treatment modality. Future research is needed to evaluate the effect of orthosis wear in relation to intended outcome utilizing robust methods and valid and reliable outcome measures. Implications for rehabilitation: Insufficient evidence exists about the reason for prescription of upper limb orthoses. The connection between reason for orthosis prescription, intended outcome, outcome measure utilized and observed effect is unclear. Recommend orthosis prescription to be accompanied by clear documentation of the aim of the orthosis and description using orthosis classification system terminology. Outcome measures consistent with the reason for orthosis prescription and intended outcome of the intervention are essential to measure effectiveness of the intervention.


title: Pronounced inflammatory response to endotoxaemia during nighttime: a randomised cross-over trial.

text: BACKGROUND Circadian variation in bodily functions has been shown to impact health in acute and chronic medical conditions. Little is known about the relationship between circadian rhythm and sepsis in humans. We aimed to investigate circadian variations in the host response in a human endotoxaemia model. DESIGN AND METHODS A cross-over study, where 12 healthy young men received E. coli endotoxin (lipopolysaccharide, LPS) 0.3 ng/kg at 12 noon and, on another day, at 12 midnight. Blood samples were analysed for pro- and anti-inflammatory cytokines: tumour-necrosis factor (TNF)-alpha, soluble TNF receptors (sTNF-R)-1 and -2, interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-6, and IL-10 as well as YKL-40 and the oxidative stress markers malondialdehyde (MDA), ascorbic acid (AA) and dehydroascorbic acid (DHA) before and at 2, 4, 6 and 8 hours after LPS administration. RESULTS The levels of MDA and IL-10 where significantly higher during the day time (P<0.05) whereas levels of TNF-alpha, sTNF-RI, sTNF-RII, IL-1Ra, IL-6, and YKL-40 were higher (P<0.01 for all comparisons) during the night time. No significant differences were seen in the levels of AA and DHA. CONCLUSION A day-night difference in the acute phase response to endotoxaemia exists in healthy volunteers with a more pronounced inflammatory response during the night time. This circadian difference in the response to endotoxaemia may play an important role in the clinical setting and should be investigated further.


title: Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke.

text: OBJECTIVE To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). METHODS All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). RESULTS HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). CONCLUSIONS IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.


title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of Adjunctive Pimavanserin in Patients With Major Depressive Disorder and an Inadequate Response to Therapy (CLARITY).

text: OBJECTIVE Pimavanserin is a 5-hydroxytryptamine-2A antagonist and inverse receptor agonist. This phase 2 study examined the efficacy and safety of pimavanserin as adjunctive therapy in patients with major depressive disorder (MDD). METHODS This was a multicenter, randomized, double-blind, placebo-controlled study in patients with DSM-5-defined MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI). Using a 2-stage sequential parallel-comparison design, patients were initially randomized in a 3:1 ratio to placebo or pimavanserin added to ongoing SSRI or SNRI therapy; at 5 weeks, placebo nonresponders were re-randomized to placebo or pimavanserin for an additional 5 weeks. Key endpoints were change from baseline to the end of each stage in 17-item Hamilton Depression Rating Scale (HDRS-17) total score and Sheehan Disability Scale (SDS) score. RESULTS Between December 2016 and October 2018, 207 patients were randomized. For the prespecified pooled Sequential Parallel Comparison Design analyses of Stages 1 and 2, the least squares (LS) mean (SE) difference for the HDRS-17 total score was -1.7 (0.85) (P = .039) and for the SDS score was -0.8 (0.29) (P = .004). At week 5 of Stage 1, LS mean (SE) difference for pimavanserin versus placebo was significant for changes on the HDRS-17 (-4.0 [1.09], P = .0003) and SDS (-1.2 [0.40], P = .0036) with effect sizes of 0.626 and 0.498, respectively. Early and sustained separation of pimavanserin from placebo (P < .05) occurred at 1 week. The most common adverse events with pimavanserin were dry mouth, nausea, and headache. CONCLUSIONS Pimavanserin demonstrated robust efficacy in patients with MDD and an inadequate response to an SSRI or SNRI. Tolerability was consistent with previous experience. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03018340.


Two for one with split- or co-ventilation at the peak of the Covid-19 tsunami: is there any role for communal care when the resources for personalised medicine are exhausted?


docid: kszpfusf

title: Apical loop-internal loop RNA pseudoknots: a new type of stimulator of -1 translational frameshifting in bacteria.

text: Nearly all members of a widespread family of bacterial transposable elements related to insertion sequence 3 (IS3), therefore called the IS3 family, very likely use programmed -1 ribosomal frameshifting to produce their transposase, a protein required for mobility. Comparative analysis of the potential frameshift signals in this family suggested that most of the insertion sequences from the IS51 group contain in their mRNA an elaborate pseudoknot that could act as a recoding stimulator. It results from a specific intramolecular interaction between an apical loop and an internal loop from two stem-loop structures. Directed mutagenesis, chemical probing, and gel mobility assays of the frameshift region of one element from the IS51 group, IS3411, provided clear evidences of the existence of the predicted structure. Modeling was used to generate a three-dimensional molecular representation of the apical loop-internal loop complex. We could demonstrate that mutations affecting the stability of the structure reduce both frameshifting and transposition, thus establishing the biological importance of this new type of RNA structure for the control of transposition level.


title: Comparative study of safety and outcomes of single-port access versus conventional laparoscopic colorectal surgery.

text: BACKGROUND Single-port access (SPA) offers cosmetic advantages in addition to the well-recognised benefits of conventional multi-port laparoscopic (CL) surgery, and can be carried out using standard straight instruments. We report the outcomes of our early experience with SPA colorectal resections in comparison with CL surgery. METHODS We compared the following data, patient characteristics, operating time, morbidity, operative mortality, length of hospital stay and tumour variables, of patients who underwent SPA right, left, sigmoid and total colon resections, as well as high anterior resections and panproctocolectomies, with that of patients who underwent equivalent conventional laparoscopic (CL) operations. The 40 SPA and 78 CL patients studied underwent surgery between February 2008 and September 2011. RESULTS There was no difference between the SPA and CL operations, as regards the patient's sex (55.0 vs. 62.8% males, p = 0.411), comorbidity (ASA I 10.0 vs. 12.8%; ASA II 57.5 vs. 59.0%; ASA III 32.5 vs. 25.6%; ASA IV 0 vs. 2.6%, p = 0.722) and body mass index (26.2 vs. 28.0 kg/m(2), p = 0.073). However, SPA patients were younger (mean age 54.1 vs. 64.8 years, p = 0.001), and malignancy was a less common indication for surgery (25.0 vs. 71.8%, p < 0.001). There were no conversions to open surgery, and one death occurred in the CL group (1.3%). Mean operating time (162 vs. 170 min, p = 0.547), median post-operative hospital stay (4 vs. 4 days, p = 0.255) and morbidity (7.5 vs. 12.8%, p = 0.538) were comparable. CONCLUSIONS SPA laparoscopic surgery appears safe in the hands of experienced laparoscopic surgeons, with no increase in operating time, length of stay, morbidity and mortality. Selection of patients with indications for surgery for benign disease may be of importance to ensure an oncologically safe initial uptake of SPA colorectal practice.


title: Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial.

text: BACKGROUND Present mechanical devices are unable to achieve recanalisation in up to 20-40% of large vessel occlusion strokes. We compared efficacy and safety of the Trevo Retriever, a new stent-like device, with its US Food and Drug Administration-cleared predecessor, the Merci Retriever. METHODS In this open-label randomised controlled trial, we recruited patients at 26 sites in the USA and one in Spain. We included adults aged 18-85 years with angiographically confirmed large vessel occlusion strokes and US National Institutes of Health Stroke Scale (NIHSS) scores of 8-29 within 8 h of symptom onset. We randomly assigned patients (1:1) with sequentially numbered sealed envelopes to thrombectomy with Trevo or Merci devices. Randomisation was stratified by age (≤68 years vs 69-85 years) and NIHSS scores (≤18 vs 19-29) with alternating blocks of various sizes. The primary efficacy endpoint, assessed by an unmasked core laboratory, was thrombolysis in cerebral infarction (TICI) scores of 2 or greater reperfusion with the assigned device alone. The primary safety endpoint was a composite of procedure-related adverse events. Analyses were done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01270867. FINDINGS Between Feb 3, 2011, and Dec 1, 2011, we randomly assigned 88 patients to the Trevo Retriever group and 90 patients to Merci Retriever group. 76 (86%) patients in the Trevo group and 54 (60%) in the Merci group met the primary endpoint after the assigned device was used (odds ratio 4·22, 95% CI 1·92-9·69; p(superiority)<0·0001). Incidence of the primary safety endpoint did not differ between groups (13 [15%] patients in the Trevo group vs 21 [23%] in the Merci group; p=0·1826). INTERPRETATION Patients who have had large vessel occlusion strokes but are ineligible for (or refractory to) intravenous tissue plasminogen activator should be treated with the Trevo Retriever in preference to the Merci Retriever. FUNDING Stryker Neurovascular.


title: Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

text: BACKGROUND Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (> 16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G <400 mg/dl, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (p= 0.03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.


docid: edemjaey

title: High hematocrit resulting from administration of erythropoiesis-stimulating agents is not fully predictive of mortality or toxicities in preclinical species.

text: We conducted a retrospective analysis of publicly available preclinical toxicology studies with erythropoiesis-stimulating agents (ESAs) to examine common adverse events in rats, Beagle dogs, and cynomolgus monkeys. Mortality and/or thrombotic events were reported sporadically in a subset of studies and attributed to the high hematocrit (HCT) achieved in the animals. However, similarly high HCT was achieved in both high-dose and low-dose groups, but there were no reported adverse events in the low-dose group suggesting HCT was not the sole contributing factor leading to toxicity. Our analysis indicated that increased dose, dose frequency, and dosing duration in addition to high HCT contributed to mortality and thrombosis. To further evaluate this relationship, the incidence of toxicities was compared in rats administered an experimental hyperglycosylated analog of recombinant human erythropoietin (AMG 114) at varying dosing schedules in 1-month toxicity studies. The incidence of mortality and thrombotic events increased in higher dose groups and when dosed more frequently, despite a similarly high HCT in all animals. The results from the investigative study and retrospective analysis demonstrate that ESA-related toxicities in preclinical species are associated with dose level, dose frequency, and dosing duration, and not solely dependent upon a high HCT.


Much on early intervention, some thoughts on COVID-19 and a paradox to ponder on.


An immunopathogenic perspective of interleukin-1 signaling.


title: Surgical technique for allogeneic uterus transplantation in macaques.

text: No study has reported an animal model of uterus transplantation (UTx) using cynomolgus macaques. We aimed to establish a surgical technique of allogeneic UTx assuming the recovery of a uterus from a deceased donor in cynomolgus macaques. Four allogeneic UTxs were performed in female cynomolgus macaques. Donor surgeries comprised en bloc recovery of organs with iliac vessels on both sides, and/or abdominal aorta/vena cava after sufficient perfusion from one femoral artery or external iliac artery. Before perfusion, 150 mL of whole blood was obtained from the donor for subsequent blood transfusion to the recipient. Four uterine grafts were orthotopically transplanted to recipients. End-to-side anastomosis was performed to the iliac vessels on one side in case 1 and iliac vessels on both sides in case 2; aorto-aorto/cavo-caval anastomosis was performed in cases 3 and 4. Arterial blood flow of the uterine grafts was determined by intraoperative indocyanine green (ICG) angiography. ICG angiography results showed sufficient blood flow to all uterine grafts, and anaemia did not progress. Under appropriate immune suppression, all recipients survived for more than 90 days post-transplantation, without any surgical complications. We describe a surgical technique for allogeneic UTx in cynomolgus macaques.


docid: iqexnomp

title: Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers.

text: PURPOSE To investigate the effects of repeated glycyrrhizin ingestion on the oral pharmacokinetics of talinolol, a probe drug for P-glycoprotein (P-gp) activity in humans. METHODS Fourteen healthy adult male subjects were enrolled in a two-phase randomized crossover-design study. In each phase the volunteers received placebo or compound glycyrrhizin tablets (75 mg glycyrrhizin three times daily) for 6 days. On the seventh day, a single oral dose of 100 mg talinolol was administered, and blood samples were obtained to determine plasma talinolol concentrations, measured in plasma by high-performance liquid chromatography with an ultraviolet detector. Non-compartmental analysis was used to characterize talinolol plasma concentration-time profiles. All pharmacokinetics parameters were calculated using DAS ver. 2.1 software, and statistical analyses were performed with SPSS ver. 13.0 software. Analysis of variance was used to check the difference of the means of the pharmacokinetic parameters between the two treatments at a significance level of 0.05. RESULTS All treatments were well tolerated during the study period. The geometric mean ± standard deviation of the AUC(0-∞) for talinolol treated by glycyrrhizin and talinolol treated by placebo was 2,218.3 ± 724.3 and 1,988.2 ± 649.2 ng·h/mL, respectively. The 90 % confidence intervals for the ratio of adjusted geometric means (glycyrrhizin:placebo) for AUC(0-∞) and C (max) fell wholly within the interval [80, 125]. Six days of glycyrrhizin treatment resulted in no significant alterations in the pharmacokinetic parameters (AUC(0-∞), AUC(0-24), C (max), t (max), t (½)) for talinolol. CONCLUSIONS Continuous glycyrrhizin administration had no induction effect on the expression of P-gp in our trial. Further research is needed to study the direct inhibition effect of glycyrrhizin on the function of P-gp with the simultaneous administration of both glycyrrhizin and P-gp substrate.


title: What use are words at a time like this?

text: What use are words at a time like this? I am writing this on 27th March as the world is plunging further into the coronavirus crisis. Like many worldwide, I am in virtual 'lockdown' in Australia while the exponential spread of the virus continues. At a follow-up tele-consult with my medical consultant recently, he said that he was apprehensive about the 'calm before the storm' that our health services face. He was deadly serious.


title: Functional properties and genetic relatedness of the fusion and hemagglutinin-neuraminidase proteins of a mumps virus-like bat virus.

text: UNLABELLED A bat virus with high phylogenetic relatedness to human mumps virus (MuV) was identified recently at the nucleic acid level. We analyzed the functional activities of the hemagglutinin-neuraminidase (HN) and the fusion (F) proteins of the bat virus (batMuV) and compared them to the respective proteins of a human isolate. Transfected cells expressing the F and HN proteins of batMuV were recognized by antibodies directed against these proteins of human MuV, indicating that both viruses are serologically related. Fusion, hemadsorption, and neuraminidase activities were demonstrated for batMuV, and either bat-derived protein could substitute for its human MuV counterpart in inducing syncytium formation when coexpressed in different mammalian cell lines, including chiropteran cells. Cells expressing batMuV glycoproteins were shown to have lower neuraminidase activity. The syncytia were smaller, and they were present in lower numbers than those observed after coexpression of the corresponding glycoproteins of a clinical isolate of MuV (hMuV). The phenotypic differences in the neuraminidase and fusion activity between the glycoproteins of batMuV and hMuV are explained by differences in the expression level of the HN and F proteins of the two viruses. In the case of the F protein, analysis of chimeric proteins revealed that the signal peptide of the bat MuV fusion protein is responsible for the lower surface expression. These results indicate that the surface glycoproteins of batMuV are serologically and functionally related to those of hMuV, raising the possibility of bats as a reservoir for interspecies transmission. IMPORTANCE The recently described MuV-like bat virus is unique among other recently identified human-like bat-associated viruses because of its high sequence homology (approximately 90% in most genes) to its human counterpart. Although it is not known if humans can be infected by batMuV, the antigenic relatedness between the bat and human forms of the virus suggests that humans carrying neutralizing antibodies against MuV are protected from infection by batMuV. The close functional relationship between MuV and batMuV is demonstrated by cooperation of the respective HN and F proteins to induce syncytium formation in heterologous expression studies. An interesting feature of the glycoproteins of batMuV is the downregulation of the fusion activity by the signal peptide of F, which has not been reported for other paramyxoviruses. These results are important contributions for risk assessment and for a better understanding of the replication strategy of batMuV.


docid: rrwufozf

title: Tibialis anterior muscle fascicle dynamics adequately represent postural sway during standing balance.

text: To maintain a stable, upright posture, the central nervous system (CNS) must integrate sensory information from multiple sources and subsequently generate corrective torque about the ankle joint. Although proprioceptive information from the muscles that cross this joint has been shown to be vital in this process, the specific source of this information remains questionable. Recent research has been focused on the potential role of tibialis anterior (TA) muscle during standing, largely due to the lack of modulation of its activity throughout the sway cycle. Ten young, healthy subjects were asked to stand normally under varying conditions, for periods of 60 s. During these trials, intramuscular electromyographic (EMG) activity and the fascicle length of three distinct anatomical regions of TA were sampled synchronously with kinematic data regarding sway position. In the quiet standing conditions, TA muscle activity was unmodulated and fascicle length changes in each region were tightly coupled with changes in sway position. In the active sway condition, more EMG activity was observed in TA and the fascicle length changes were decoupled from sway position. No regional specific differences in correlation values were observed, contrasting previous observations. The ability of the fascicles to follow sway position builds upon the suggestion that TA is well placed to provide accurate, straightforward sensory information to the CNS. As previously suggested, through reciprocal inhibition, afferent information from TA could help to regulate plantar flexor torque at relevant phases of the sway cycle. The proprioceptive role of TA appears to become complicated during more challenging conditions.


title: Impact of renal impairment on long-term retention of gadolinium in the rodent skin following the administration of gadolinium-based contrast agents.

text: OBJECTIVE Several publications have suggested a possible association between Gd-based contrast agents (GBCAs) and the development of nephrogenic systemic fibrosis, a rare but serious disease. To date, nephrogenic systemic fibrosis has been observed only in patients with severe renal insufficiency.The aim of this study was to determine the impact of a prolonged circulation time of GBCAs caused by reduced renal clearance on the long-term retention of Gd in the skin of rats after administration of different GBCAs. MATERIAL AND METHODS Renally impaired Han Wistar Rats (5/6-nephrectomized rats) were injected with Omniscan, OptiMARK, Magnevist, or Gadovist. The contrast agents were administered once daily for 5 consecutive days into the tail vein at a dose of 2.5 mmol Gd/kg b.w. Skin biopsies were taken at various time points, and the gadolinium (Gd) concentration was determined by inductive coupled plasma mass spectrometry (ICP-MS) over an observation period of 168 days post injection (p.i.). RESULTS Differences in the skin Gd concentrations were observed between the 4 investigated GBCAs. For the nonionic linear compounds, Omniscan and OptiMARK, high Gd concentrations were maintained in the skin over the observation period of up to 168 days p.i. For the ionic linear compound, Magnevist, comparatively lower Gd retention in the skin was observed over time. For the macrocyclic compound, Gadovist, the Gd values in the skin were even lower, and significantly lower than Gd values in the skin in Omniscan and OptiMARK treated animals. CONCLUSION The results of this preclinical study support the use of 5/6-nephrectomized rats as a model for prolonged circulation time of GBCAs as seen in patients with severe renal impairment. Surgically induced severe renal impairment resulted in delayed clearance of the administered GBCAs in the study animals. The highest amount of Gd was observed in the skin after treatment with the nonionic linear GBCAs, whereas the lowest Gd values were observed after treatment with the macrocyclic agent. This suggests that the difference in the Gd values observed in rat skin tissue after treatment with the different GBCAs is caused of a different propensity of the different GBCAs to release Gd in vivo. However, the analytical method used does not distinguish between chelated and unchelated Gd.


title: Comparison of long-term survival and immediate postoperative liver function after laparoscopic and open distal gastrectomy for early gastric cancer patients with liver cirrhosis.

text: BACKGROUND Several studies have suggested no difference in the liver function of early gastric cancer (EGC) patients with liver cirrhosis (LC) between laparoscopic and open distal gastrectomy. However, the number of patients and comparison of long-term survival rates between the two groups are limited. The purpose of this study was to compare the long-term survival and immediate postoperative liver function of EGC patients with LC after laparoscopic and open distal gastrectomy. MATERIALS AND METHODS The clinical data of EGC patients with LC who had no other malignancy and underwent distal gastrectomy at Asan Medical Center between January 2005 and April 2013 were investigated retrospectively. All patients were divided into two groups: the open group (OG) and laparoscopic group (LG). The clinicopathologic data of the two groups were compared. RESULTS The number of patients in each group was 48 and 27 in the OG and LG, respectively. There were no significant differences in the age, sex ratio, ASA score, cause of liver cirrhosis, preoperative Child-Pugh classification, tumor location, TNM stage, total postoperative drain amount, albumin, total bilirubin, alkaline phosphatase, alanine aminotransferase, prothrombin time, morbidity and recurrence rate. Shorter hospital stay, longer operative time and more retrieved lymph nodes were observed in LG. The long-term overall survival rate was not different between the two groups (P = 0.356). CONCLUSIONS For EGC patients with liver cirrhosis, especially Child A cirrhosis, laparoscopic or laparoscopy-assisted distal gastrectomy can be a safe surgical procedure in comparison to open distal gastrectomy in terms of the long-term survival rate and immediate postoperative liver function.


title: Membrane fusion-mediated autophagy induction enhances morbillivirus cell-to-cell spread.

text: In the context of viral infections, autophagy induction can be beneficial or inhibitory. Within the Paramyxoviridae family, only morbilliviruses have been investigated and are reported to induce autophagy. Here we show that morbilliviruses rapidly induce autophagy and require this induction for efficient cell-to-cell spread. Coexpression of both glycoproteins in cells expressing one of the cellular receptors was required for autophagy induction, and LC3 punctum formation, indicative of autophagy, was mainly observed in syncytia. A similar correlation between syncytium formation and autophagy induction was also observed for other paramyxovirus glycoproteins, suggesting that membrane fusion-mediated autophagy may be common among paramyxoviruses and possibly other enveloped viruses.


title: Hepatocellular carcinoma tumor thrombus entering the inferior vena cava treated with percutaneous RF ablation: a case report.

text: PURPOSE Hepatocellular carcinoma (HCC) is the most common form of liver cancer. In advanced cancer stages (metastatic disease and/or vascular invasion), the generally accepted standard of care is systemic therapy using sorafenib as first-line treatment and, recently, regorafenib and nivolumab as second-line treatment, but the quality of life and the prognosis of patients remain very poor. Our paper reports a case of US-guided radiofrequency ablation (RFA) of both intraparenchymal HCC and inferior vena cava tumor thrombus. METHODS We treated a patient with HCC associated with tumor thrombus extending into vena cava after failure of sorafenib therapy using US-guided radiofrequency ablation (RFA). RESULTS A good radiological and clinical response was observed in association with excellent tolerability. The patient has been followed up for 15 months from the ablation, is alive, and is in a good clinical condition without evidence of tumor recurrence. CONCLUSION This is the first case in which this minimally invasive percutaneous procedure has been successfully used to treat an HCC thrombus entering the vena cava.


title: Reproductive outcomes following robotic-assisted laparoscopic myomectomy (RALM).

text: Uterine myomas are the most common type of benign tumor in women of reproductive age and are commonly associated with menorrhagia, dysmenorrhea, dyspareunia, and urinary symptoms. Uterine fibroids have been also linked to infertility and pregnancy loss. Women wishing to preserve or restore their fertility are best treated by myomectomy. Robotic-assisted laparoscopic myomectomy is one of the latest technological applications of minimally invasive surgery. Limited data exist regarding the feasibility of robotic-assisted laparoscopic myomectomy (RALM) in terms of pregnancy and surgical outcomes, and more studies are needed. The goal of this study is to assess reproductive outcomes following RALM in a private practice setting. The study was performed in the form of a retrospective chart review. Female patients 22-44 years old diagnosed with intramural myoma were eligible for inclusion. Presence of a myoma was a necessary but not necessarily the presenting symptom. All patients underwent RALM between January 2006 and May 2009 under the care of one surgeon at two clinical sites. Patients were selected postsurgically via chart review based on inclusion parameters outlined above. Median values for pregnancy rate, number of myomas, diameter of largest myoma, surgery duration, and blood loss were calculated and used for subsequent statistical analysis. Clinically useful markers for pregnancy outcomes evaluation following RALM were identified. Thirty patients were enrolled, of whom 16 were interested in conception due to infertility. A pregnancy rate of 75 % was recorded. Among those who conceived, eight patients (67 %) reported natural conception within 6 months of unprotected intercourse, while four patients (33 %) utilized assisted reproductive technologies to conceive. One patient (8 %) miscarried. Two patients (17 %) experienced premature delivery, at 28 and 32 weeks, respectively. All deliveries were performed via Cesarean section. No surgical complications were reported following RALM. There were no cases of scar dehiscence or rupture. The median number of myomas in those who delivered was estimated at 1.0 compared with 3.5 in those unable to conceive (p < 0.05). In addition, median age was 34 compared with 42.5 years, respectively (p < 0.05). This retrospective study assessed pregnancy outcomes following RALM. Our pregnancy rate of 75 % combined with a low incidence of complications contributes to the limited pool of data available on this topic, and supports the need for a multicenter trial to further evaluate effectiveness and safety of RALM in terms of pregnancy outcomes.


title: Examination of Hospital Workers' Emotional Responses to an Infectious Disease Outbreak: Lessons From the 2015 MERS Co-V Outbreak in South Korea.

text: ABSTRACTHospital workers are critical for a successful response to an infectious disease outbreak and for preventing disease transmission to the community. Therefore, hospital crisis management should implement efforts to improve hospital workers' preparedness in responding to public health emergencies caused by infectious diseases. Traditionally, preparedness and skill of hospital workers have been emphasized, but awareness of the importance of the emotional mindset of hospital workers in dealing with disease outbreaks has only recently increased; therefore, empirical approaches to examining emotional responses of hospital workers has been limited. This study analyzed qualitative data of the 2015 Middle East Respiratory Syndrome outbreak in South Korea. In particular, negative emotions and stress experienced by hospital workers who treated patients were characterized, as were the events that triggered such experiences. These events were categorized into four themes (eg, Mistake, Missing, Delay Due to Communication Failure). Identifying events that trigger negative emotions in hospital workers has important implications for hospitals' management guidance in relation to an infectious disease outbreak. (Disaster Med Public Health Preparedness. 2018;page 1 of 7).


title: Leg hammock for closed reduction of tibial shaft fractures.

text: Tibial shaft fractures are common injuries in emergency departments (EDs). Although many of these fractures require surgery, nearly all are stabilized in the ED with a long leg splint or bivalved cast. Long leg splinting is often challenging for a single health care provider. Further, even with assistance or previously described techniques for fracture reduction and stabilization, fracture angulation may occur, potentially leading to pain for the patient, fracture displacement, or further soft tissue injury. The authors propose a method for splinting tibial fractures that avoids fracture angulation, is cost-effective and quick, and can be easily performed by a single health care provider.


title: Relationship between the magnetic resonance imaging appearance of adenomyosis and endometriosis phenotypes.

text: STUDY QUESTION What is the relationship between endometriosis phenotypes superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA), deep infiltrating endometriosis (DIE) and the adenomyosis appearance by magnetic resonance imaging (MRI)? SUMMARY ANSWER Focal adenomyosis located in the outer myometrium (FAOM) was observed more frequently in women with endometriosis, and was significantly associated with the DIE phenotype. WHAT IS KNOWN ALREADY An association between endometriosis and adenomyosis has been reported previously, although data regarding the association between MRI appearance of adenomyosis and the endometriosis phenotype are currently still lacking. STUDY DESIGN, SIZE, DURATION This was an observational, cross-sectional study using data prospectively collected from non-pregnant patients who were between 18 and 42 years of age, and who underwent surgery for symptomatic benign gynecological conditions between January 2011 and December 2014. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRIs were retained for this study. PARTICIPANTS/MATERIALS, SETTING, METHODS Surgery was performed on 292 patients with signed consent and available preoperative MRIs. After a thorough surgical examination of the abdomino-pelvic cavity, 237 women with histologically proven endometriosis were allocated to the endometriosis group and 55 symptomatic women without evidence of endometriosis to the endometriosis free group. The existence of diffuse or FAOM was studied in both groups and according to surgical endometriosis phenotypes (SUP, OMA and DIE). MAIN RESULTS AND THE ROLE OF CHANCE Adenomyosis was observed in 59.9% (n = 175) of the total sample population (n = 292). Based on MRI, the distribution of adenomyosis was as follows: isolated diffuse adenomyosis (53 patients; 18.2%), isolated FAOM (74 patients; 25.3%), associated diffuse and FAOM (48 patients; 16.4%). Diffuse adenomyosis (isolated and associated to FAOM) was observed in one-third of the patients regardless of whether they were endometriotic patients or endometriosis free women taken as controls (34.2% (81 cases) versus 36.4% (20 cases)); P = 0.764. Among endometriotic women, diffuse adenomyosis (isolated and associated to FAOM) failed to reach significant correlation with the endometriosis phenotypes (SUP, 20.0% (8 cases); OMA, 45.2% (14 cases) and DIE, 35.5% (59 cases); P = 0.068). In striking contrast, there was a significant increase in the frequency of FAOM in endometriosis-affected women than in controls (119 cases (50.2%) versus 5.4% (3 cases); P < 0.001). FAOM correlated with the endometriosis phenotypes, significantly with DIE (SUP, 7.5% (3 cases); OMA, 19.3% (6 cases) and DIE, 66.3% (110 cases); P < 0.001). LIMITATIONS, REASONS FOR CAUTION There was a possible selection bias due to the specificity of the study design, as it only included surgical patients in a referral center that specializes in endometriosis surgery. Therefore, women referred to our center may have suffered from particularly severe forms of endometriosis. This could explain the high number of women with DIE (166/237-70%) in our study group. This referral bias for women with severe lesions may have amplified the difference in association of FAOM with the endometriosis-affected patients compared to women without endometriosis. Furthermore, according to inclusion criteria, women in the endometriosis free group were symptomatic women. This may introduce some bias as symptomatic women may be more prone to have associated adenomyosis that in turn could have been overrepresented in the endometriosis free group. Whether this selection could have introduced a bias in the relationship between endometriosis and adenomyosis remains unknown. WIDER IMPLICATIONS OF THE FINDINGS This study opens the door to future epidemiological, clinical and mechanistic studies aimed at better characterizing diffuse and focal adenomyosis. Further studies are necessary to adequately determine if diffuse and focal adenomyosis are two separate entities that differ in terms of pathogenesis. STUDY FUNDING/COMPETING INTEREST(S) No funding supported this study. The authors have no conflict of interest to declare.


title: The pain quality response profile of a corticosteroid injections and heated lidocaine/tetracaine patch in the treatment of shoulder impingement syndrome.

text: OBJECTIVES To describe the effects of 2 pain treatments for shoulder impingement syndrome (SIS), and illustrate how investigators can use pain quality information to understand treatment response differences. MATERIALS AND METHODS This study presents pain quality data from a randomized open-label study comparing the effects of an injection of triamcinolone and up to twice daily application of a heated lidocaine/tetracaine (Trilexis) patch in individuals with SIS. Study participants completed a measure of pain quality at baseline and again on study days 14, 28, and 42 following initiation of 2 treatments for SIS. Baseline and posttreatment pain quality scores were graphed to provide a visual representation of treatment-associated changes. Analyses of variance were used to examine the differences between treatment conditions in changes in pain quality with treatment. RESULTS Both treatments resulted in substantial (and similar) pretreatment to posttreatment improvements in many pain qualities. However, differences in the time course of treatment effects were observed for itchy and heavy qualities. DISCUSSION Although 2 different pain treatments appear to have the same effects when only pretreatment to posttreatment changes are examined, treatment differences emerged when the time course of treatment is examined. The findings support the importance of assessing both pain qualities and time course of treatment as outcome domains. The results illustrate how investigators can use data from clinical trials to provide a more fine-tuned description of treatment effects, providing knowledge that could be helpful in selecting treatment options at the individual patient level. SUMMARY Examination of the effects of pain treatments on pain qualities over time will help researchers and clinicians understand if certain pain quality domains respond faster to one treatment versus another, and may identify differences between treatments that would not be observed by measures of global pain intensity alone.


docid: gglkvpiy

title: Percutaneous CT-guided thermal ablation as salvage therapy for recurrent non-small cell lung cancer after external beam radiotherapy: A retrospective study.

text: PURPOSE The aim of this study was to evaluate radiofrequency ablation (RFA) and microwave ablation (MWA) as a viable salvage option for patients with locally recurrent non-small cell lung cancer (NSCLC) after radiotherapy. MATERIALS AND METHODS This retrospective study was conducted on patients who had received thermal ablation for recurrent NSCLC post-curative radiotherapy. Medical records and follow-up imaging with computed tomography (CT) and PET-CT were analysed to determine time to local progression (TTLP) and overall survival (OS). TTLP was determined according to the modified RECIST criteria. RESULTS Twelve patients, mean age 71 ± 7 years, received 17 thermal ablation sessions, with RFA performed for four lesions and MWA for 13. Nine tumours were squamous cell cancers (SCC) and eight were adenocarcinomas. Eleven tumours had recurred post-external beam radiation and one post-stereotactic body radiation therapy. Mean tumour size was 34.2 ± 12.8 mm, tumour stages prior to radiotherapy were Ia (2), Ib (3), IIa (4), IIb (1) and III (2). Follow-up period was 19 ± 11 months. Overall median TTLP was 14 months (95% CI: 8, 19), and median OS was 35 months (95% CI: 12, 58). Mean TTLP for tumours <30 mm was 23 months and for tumours >30 mm 14 months (p = 0.20). Recurrence rates reduced from 50% after initial ablation to 20% with a second ablation. Complication rate for pneumothorax requiring intervention was 17%. CONCLUSION Both RFA and MWA ablation prolonged local tumour control with minimal morbidity in this study group of recurrent NSCLC after radiotherapy.


title: Assessing groundwater quality for drinking water supply using hybrid fuzzy-GIS-based water quality index.

text: Groundwater is a vital source of freshwater in both urban and rural regions of the world. However, its injudicious abstraction and rapidly increasing contamination are posing a severe threat for sustainable water supply worldwide. Geographical Information System (GIS)-based groundwater quality evaluation using Groundwater Quality Index (GQI) has been proved to be a cost-effective tool for assessing groundwater quality and its variability at a larger scale. However, the conventional GQI approach is unable to deal with uncertainties involved in the assessment of environmental problems. To overcome this limitation, a novel hybrid framework integrating Fuzzy Logic with the GIS-based GQI is proposed in this study for assessing groundwater quality and its spatial variability. The proposed hybrid framework is demonstrated through a case study in a hard-rock terrain of Southern India using ten prominent groundwater-quality parameters measured during pre-monsoon and post-monsoon seasons. Two conventional GIS-based GQI models GQI-10 (using all the ten groundwater-quality parameters) and GQI-7 (using seven 'concerned/critical' groundwater-quality parameters) as well as hybrid Fuzzy-GIS-based GQI (FGQI) models (using seven critical parameters) were developed for the two seasons and the results were compared. The Trapezoidal membership functions classified the model input parameters into 'desirable', 'acceptable' and 'unacceptable' classes based on the experts' knowledge and water quality standards for drinking purposes. The concentrations of Ca2+, Mg2+, and SO42- in groundwater were found within the WHO desirable limits for drinking water throughout the year, while the concentrations of seven parameters (TDS, NO3--N, Na+, Cl-, K+, F- and Hardness) exceed their permissible limits during pre-monsoon and post-monsoon seasons. A comparative evaluation of GQI models revealed that the FGQI model predicts groundwater quality better than the conventional GQI-10 and GQI-7 models. GQI modeling results suggest that the groundwater of most of eastern and southern parts (∼60% in pre-monsoon season; ∼90% in post-monsoon season) of the study area is unsuitable for drinking. Further, the groundwater quality deteriorates during post-monsoon seasons compared to pre-monsoon seasons, which indicates an increased influx of contaminants from different industries, mining areas, waste disposal sites and agricultural fields during monsoon seasons. This finding calls for the strict enforcement of regulations for proper handling of effluents from various contamination sources in the study area. It is concluded that the fuzzy logic-based decision-making approach (FGQI) is more reliable and pragmatic for groundwater-quality assessment and analysis at a larger scale. It can serve as a useful tool for the water planners and decision makers in efficiently monitoring and managing groundwater quality at watershed or basin scales.


The Italian dermatologic community facing COVID-19 pandemic: recommendation from the Italian society of dermatology and venereology.


title: Thiazolides: a new class of antiviral drugs.

text: BACKGROUND Thiazolides have emerged as a new class of broad-spectrum antiviral drugs, and the first thiazolide, nitazoxanide, is in late-stage clinical trials for treating chronic hepatitis C. OBJECTIVE To review the chemistry, pharmacology, toxicology and efficacy of thiazolides as antiviral agents with emphasis on clinical development of nitazoxanide in treating chronic hepatitis C. METHODS Literature search, information from Romark Laboratories and my personal experience with the discovery and development of thiazolides serve as the sources for this review. CONCLUSIONS Thiazolides are metabolically stable, highly bound to plasma proteins and are associated with a favorable toxicology profile. Phase II clinical trials have demonstrated efficacy and safety of nitazoxanide added to peginterferon with or without ribavirin in treating patients with chronic hepatitis C. More limited clinical data indicated potential in treating chronic hepatitis B, and three randomized controlled trials have demonstrated efficacy in reducing the duration of viral gastroenteritis. New generation thiazolides with the nitro group of nitazoxanide replaced by a non-reducible group are not active against anaerobes but retain broad-spectrum activity against viruses. Further studies are needed. Research indicates that these drugs may play an important and complementary role in combination with other classes of antiviral drugs.


Combined Use of Intra-aortic Balloon Pump and Venoarterial Extracorporeal Membrane Oxygenation Support With Femoral Arterial Cannulation Impairs Cerebral Microcirculation: Evaluation With Laser Speckle Flowgraphy.


title: Tracheal Microbiota in Patients With a Tracheostomy Before, During and After an Acute Respiratory Infection.

text: Examining tracheal microbiota before, during and after acute respiratory infection in patients with a tracheostomy demonstrated large baseline intrapatient microbiota variability and a significant bloom of Haemophilus and Moraxella on day 1 of acute respiratory infection symptoms. The tracheal microbiota community composition changed significantly from baseline to 1 month after acute respiratory infection.


title: Discovery of swine as a host for the Reston ebolavirus.

text: Since the discovery of the Marburg and Ebola species of filovirus, seemingly random, sporadic fatal outbreaks of disease in humans and nonhuman primates have given impetus to identification of host tropisms and potential reservoirs. Domestic swine in the Philippines, experiencing unusually severe outbreaks of porcine reproductive and respiratory disease syndrome, have now been discovered to host Reston ebolavirus (REBOV). Although REBOV is the only member of Filoviridae that has not been associated with disease in humans, its emergence in the human food chain is of concern. REBOV isolates were found to be more divergent from each other than from the original virus isolated in 1989, indicating polyphyletic origins and that REBOV has been circulating since, and possibly before, the initial discovery of REBOV in monkeys.


title: Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese.

text: BACKGROUND Obesity and its related comorbidities are significant risk factors for nonalcoholic fatty liver disease (NAFLD). Liver fibrosis is the major determinant of long-term outcomes in NAFLD. A non-invasive tool that accurately identifies obese patients at elevated risk of liver fibrosis would be of significant value. Fibrosis risk scores in patients with NAFLD have been proposed but have not been validated in obese populations. We aimed to validate established simple fibrosis scores in bariatric surgical patients. METHODS We conducted a prospective study of 107 consecutive high-risk obese patients undergoing primary bariatric surgery. Proposed fibrosis scores (NAFLD fibrosis score; body mass index (BMI), aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT), and diabetes (BARD); Fibrosis-4 (FIB-4); Forn; and AST to platelet ratio index) were calculated and compared hepatic fibrosis determined by histology of intraoperative liver biopsies. Accuracy was determined, and fibrosis score thresholds were optimized. These modified thresholds were then validated in an independent bariatric surgical population. RESULTS Liver biopsies were available in 101 patients. Sixty-eight patients had some degree of fibrosis, with 23 patients (23 %) having significant fibrosis (F2-4). The Forn score best predicted significant fibrosis (area under the receiver operator characteristic curve (AUROC) 0.724, p = 0.001). With standard thresholds, the sensitivity for the Forn score for identification of significant fibrosis (F2-4) was 0 %. Using modified thresholds of 3.5, the sensitivity and negative predictive value increased to 85.7 and 94.7 %. This threshold was applied to an independent validation cohort with good accuracy. CONCLUSIONS Fibrosis risk scores using simple markers have moderate success at delineating obese patients with significant NAFLD-related fibrosis. Thresholds, however, need to be lowered to maximize diagnostic accuracy in this cohort.


title: The laboratory tests and host immunity of COVID-19 patients with different severity of illness.

text: BACKGROUND The Coronavirus Disease-2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak in China. The host immunity of COVID-19 patients is unknown. METHODS The routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission. RESULTS A total of 65 SARS-CoV-2-positive patients were classified as mild (n=30), severe (n=20), and extremely severe (n=15) illness. Many routine laboratory tests such as ferritin, lactate dehydrogenase and D-dimer were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells and B cells were all gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The co-stimulatory molecule CD28 had opposite results. The percentage of natural regulatory T cells was decreased in extremely severe patients. The percentage of IFN-γ producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ producing CD4+ T cells was increased in extremely severe patients. The IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients. CONCLUSIONS The number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.


SARS-CoV-2 Does Not Spread Through ECMO or Dialysis Membranes.


title: Prevalence of Cerebral Palsy in Indian Children: A Systematic Review and Meta-Analysis.

text: OBJECTIVE To determine the pooled-prevalence of cerebral palsy in Indian children. METHODS The authors searched the published literature from different databases (PubMed, Ovid SP and EMBASE) and also tried to acquire information from the unpublished literature about the prevalence of cerebral palsy. They screened prospective/retrospective, cross-sectional, and cohort studies of children with cerebral palsy in the Indian population. Data were extracted from the included studies, and quality assessment was performed. Data were analysed using STATA MP12 (Texas, College Station). RESULTS Of the 862 publications searched, eight studies were qualified and included for quantitative analysis. The overall pooled prevalence of cerebral palsy per 1000 children surveyed was 2.95 (95% CI 2.03-3.88). Sub-group analysis for rural, urban and mixed rural-urban study population demonstrated the pooled prevalence as 1.83 (95% CI 0.41-3.25), 2.29 (95% CI 1.43-3.16) and 4.37 (95% CI 2.24-6.51) respectively. CONCLUSIONS This systematic review observed a paucity of high-quality, prevalence studies of cerebral palsy in India, which is a limitation to estimate the inferences for a national estimate. The observed prevalence of cerebral palsy in India is near similar to global estimates. There is a need to re-allocate resources and revisit the implementation of the existing policies for the prevention and management of cerebral palsy, taking into account the current disease burden.