Three Decades Single Center Experience of Airway Complications After Lung Transplantation

Post lung transplantation airway complications like necrosis, stenosis, malacia and dehiscence cause significant morbidity, and are most likely caused by post-operative hypo perfusion of the anastomosis. Treatment can be challenging, and airway stent placement can be necessary in severe cases. Risk factors for development of airway complications vary between studies. In this single center retrospective cohort study, all lung transplant recipients between November 1990 and September 2020 were analyzed and clinically relevant airway complications of the anastomosis or distal airways were identified and scored according to the ISHLT grading system. We studied potential risk factors for development of airway complications and evaluated the impact on survival. The treatment modalities were described. In 651 patients with 1,191 airway anastomoses, 63 patients developed 76 clinically relevant airway complications of the airway anastomoses or distal airways leading to an incidence of 6.4% of all anastomoses, mainly consisting of airway stenosis (67%). Development of airway complications significantly affects median survival in post lung transplant patients compared to patients without airway complication (101 months versus 136 months, p = 0.044). No significant risk factors for development of airway complication could be identified. Previously described risk factors could not be confirmed. Airway stents were required in 55% of the affected patients. Median survival is impaired by airway complications after lung transplantation. In our cohort, no significant risk factors for the development of airway complications could be identified.</jats:p&gt

Influence of Reoperations on Long-Term Quality of Life After Restrictive Procedures: A Prospective Study

Quality of life improves after bariatric surgery. However, long-term results and the influence of reoperations are not well known. A prospective quality of life assessment before, 1 and 7 years after laparoscopic adjustable gastric banding (LAGB) and vertical banded gastroplasty (VBG) was performed in order to determine the influence of reoperations during follow-up. One hundred patients were included in the study. Fifty patients underwent VBG and 50 LAGB. Patients completed the quality of life questionnaires prior to surgery and two times during follow-up. Health-related quality of life (HRQoL) questionnaires included the Nottingham Health Profile I and II and the Sickness Impact Profile 68. Follow-up was 84% with a mean duration of 84 months (7 years). During follow-up, 65% of VBG patients underwent conversion to Roux-en-Y gastric bypass while 44% of LAGB patients underwent a reoperation or conversion. One year after the procedure, nearly all quality-of-life parameters significantly improved. After 7 years, the Nottingham Health Profile (NHP)-I domain “physical ability”, the NHP-II and the SIP-68 domains “mobility control”, “social behavior”, and “mobility range” were still significantly improved in both groups. The domains “emotional reaction”, “social isolation” (NHP-I), and “emotional stability” (SIP-68) remained significantly improved in the VBG group while this was true for the domain “energy level” (NHP-I) in the LAGB group. Both the type of procedure and reoperations during follow-up were not of significant influence on the HRQoL results. Weight loss and decrease in comorbidities were the only significant factors influencing quality of life. Restrictive bariatric surgery improves quality of life. Although results are most impressive 1 year after surgery, the improvement remains significant after long-term follow-up. Postoperative quality of life is mainly dependent on weight loss and decrease in comorbidities and not on the type of procedure or surgical complications

773Triple elimination of mother-to-child transmission of HIV, syphilis and hepatitis B in the Pacific Islands

Abstract Background Without intervention, HIV, hepatitis B virus and syphilis can be transmitted from mother-to-child during pregnancy, birth and breastfeeding and these can cause adverse pregnancy and longer-term outcomes. The 22 Pacific Island countries and territories (PICTs) have among the highest global prevalence of syphilis and hepatitis B. Mother-to-child transmission remains a concern, particularly hepatitis B. Global and regional elimination targets have been set to eliminate mother-to-child transmission (EMTCT) however progress of PICTs towards meeting targets is unknown. Methods Data from 2000-2019 relating to EMTCT epidemiological, process and impact targets were extracted from peer reviewed literature, online data repositories and grey literature. Results 27 peer reviewed reports, data from online data repositories for 19 countries and twelve national demographic and/or health reports were collated. Existing online databases report data for only small number of EMTCT indicators and there are few peer-reviewed studies that report EMTCT coverage estimates for PICTs. Availability of data varied between countries and available data suggests that few countries are meeting EMTCT indicator targets. Conclusions Based on the current trach trajectory, PICTs will not reach triple elimination by 2030. Both interventions to improve EMTCT activity coverage and strengthened surveillance, monitoring and evaluation systems are required. Key messages Mother-to-child transmission of HIV, hepatitis B and syphilis is a major concern in the Pacific and increased efforts are required, including strengthened monitoring and evaluation systems. </jats:sec

Proteomic Profiling of Plasmodium Sporozoite Maturation Identifies New Proteins Essential for Parasite Development and Infectivity

Plasmodium falciparum sporozoites that develop and mature inside an Anopheles mosquito initiate a malaria infection in humans. Here we report the first proteomic comparison of different parasite stages from the mosquito—early and late oocysts containing midgut sporozoites, and the mature, infectious salivary gland sporozoites. Despite the morphological similarity between midgut and salivary gland sporozoites, their proteomes are markedly different, in agreement with their increase in hepatocyte infectivity. The different sporozoite proteomes contain a large number of stage specific proteins whose annotation suggest an involvement in sporozoite maturation, motility, infection of the human host and associated metabolic adjustments. Analyses of proteins identified in the P. falciparum sporozoite proteomes by orthologous gene disruption in the rodent malaria parasite, P. berghei, revealed three previously uncharacterized Plasmodium proteins that appear to be essential for sporozoite development at distinct points of maturation in the mosquito. This study sheds light on the development and maturation of the malaria parasite in an Anopheles mosquito and also identifies proteins that may be essential for sporozoite infectivity to humans

Evaluating Multimedia Features and Fusion for Example-Based Event Detection

Multimedia event detection (MED) is a challenging problem because of the heterogeneous content and variable quality found in large collections of Internet videos. To study the value of multimedia features and fusion for representing and learning events from a set of example video clips, we created SESAME, a system for video SEarch with Speed and Accuracy for Multimedia Events. SESAME includes multiple bag-of-words event classifiers based on single data types: low-level visual, motion, and audio features; high-level semantic visual concepts; and automatic speech recognition. Event detection performance was evaluated for each event classifier. The performance of low-level visual and motion features was improved by the use of difference coding. The accuracy of the visual concepts was nearly as strong as that of the low-level visual features. Experiments with a number of fusion methods for combining the event detection scores from these classifiers revealed that simple fusion methods, such as arithmetic mean, perform as well as or better than other, more complex fusion methods. SESAME’s performance in the 2012 TRECVID MED evaluation was one of the best reported

High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients

BACKGROUND: : Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression. METHODS: : The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. RESULTS: : Humoral responses to COVID-19 vaccination were observed in 41/103 (40%) LTR at 28 days after the second vaccination. 62/103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. CONCLUSIONS: : This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2x)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

BACKGROUND: During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. AIM: The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. DESIGN: Seventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out

Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit

We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose-α1-3-glucose and xylose-α1-3-xylose-α1-3-glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O-glucosylation. Since many proteins are O-glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake