Incidence and Risk Factors of Neoplastic Progression in Barrett’s Esophagus

Barrett’s esophagus (BE) is a condition in which the normal stratified squamous epithelium lining the distal esophagus is replaced by columnar epithelium with specialized intestinal metaplasia (IM) containing goblet cells. The development of BE is a complication of chronic exposure to the gastric refluxate containing acid and bile.1-3 BE is a premalignant condition which predisposes to the development of esophageal adenocarcinoma (EAC). The development of this malignancy is a gradual stepwise process from no dysplasia (ND) to low-grade dysplasia (LGD), high-grade dysplasia (HGD), and finally EAC. During the past decades, the incidence of both BE5 and EAC has been rising rapidly as demonstrated by a 7-fold increased incidence of EAC between 1973 and 2006.6-8 In general, patients with BE have a 30- to 125-fold increased risk of developing EAC compared to the general population. However, the annual incidence of EAC in BE patients remains unclear, as it shows considerable variation among cohort studies, ranging from 0.2% to almost 3.5% per year. The consensus is however that the incidence of EAC is approximately 0.5% per year.13 EAC usually has a poor prognosis and a high mortality with a 5-year survival rate of less than 20%. As a result of the malignant potential of BE, regular surveillance endoscopies are recommended in patients with BE. The intervals of surveillance depend on the grade of dysplasia present. The goal of surveillance is to detect neoplasia at an early stage, making early treatment with curative intention possible and reducing death from EAC

Low dose aspirin in the prevention of recurrent spontaneous preterm labour - the APRIL study: A multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-)effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) < 37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost-effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth. Trial registration: Clinical trial registration number of the Dutch Trial Register: NTR 5675. EudraCT-registration number: 2015-003220-31

COVID-19 in health-care workers in three hospitals in the south of the Netherlands:A cross-sectional study

Background: 10 days after the first reported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands (on Feb 27, 2020), 55 (4%) of 1497 health-care workers in nine hospitals located in the south of the Netherlands had tested positive for SARS-CoV-2 RNA. We aimed to gain insight in possible sources of infection in health-care workers. Methods: We did a cross-sectional study at three of the nine hospitals located in the south of the Netherlands. We screened health-care workers at the participating hospitals for SARS-CoV-2 infection, based on clinical symptoms (fever or mild respiratory symptoms) in the 10 days before screening. We obtained epidemiological data through structured interviews with health-care workers and combined this information with data from whole-genome sequencing of SARS-CoV-2 in clinical samples taken from health-care workers and patients. We did an in-depth analysis of sources and modes of transmission of SARS-CoV-2 in health-care workers and patients. Findings: Between March 2 and March 12, 2020, 1796 (15%) of 12 022 health-care workers were screened, of whom 96 (5%) tested positive for SARS-CoV-2. We obtained complete and near-complete genome sequences from 50 health-care workers and ten patients. Most sequences were grouped in three clusters, with two clusters showing local circulation within the region. The noted patterns were consistent with multiple introductions into the hospitals through community-acquired infections and local amplification in the community. Interpretation: Although direct transmission in the hospitals cannot be ruled out, our data do not support widespread nosocomial transmission as the source of infection in patients or health-care workers. Funding: EU Horizon 2020 (RECoVer, VEO, and the European Joint Programme One Health METASTAVA), and the National Institute of Allergy and Infectious Diseases, National Institutes of Health

Low dose aspirin in the prevention of recurrent spontaneous preterm labour the APRIL study: a multicenter randomized placebo controlled trial

Background: Preterm birth (birth before 37 weeks of gestation) is a major problem in obstetrics and affects an estimated 15 million pregnancies worldwide annually. A history of previous preterm birth is the strongest risk factor for preterm birth, and recurrent spontaneous preterm birth affects more than 2.5 million pregnancies each year. A recent meta-analysis showed possible benefits of the use of low dose aspirin in the prevention of recurrent spontaneous preterm birth. We will assess the (cost-) effectiveness of low dose aspirin in comparison with placebo in the prevention of recurrent spontaneous preterm birth in a randomized clinical trial. Methods/design: Women with a singleton pregnancy and a history of spontaneous preterm birth in a singleton pregnancy (22-37 weeks of gestation) will be asked to participate in a multicenter, randomized, double blinded, placebo controlled trial. Women will be randomized to low dose aspirin (80 mg once daily) or placebo, initiated from 8 to 16 weeks up to maximal 36 weeks of gestation. The primary outcome measure will be preterm birth, defined as birth at a gestational age (GA) <37 weeks. Secondary outcomes will be a composite of adverse neonatal outcome and maternal outcomes, including subgroups of prematurity, as well as intrauterine growth restriction (IUGR) and costs from a healthcare perspective. Preterm birth will be analyzed as a group, as well as separately for spontaneous or indicated onset. Analysis will be performed by intention to treat. In total, 406 pregnant women have to be randomized to show a reduction of 35% in preterm birth from 36 to 23%. If aspirin is effective in preventing preterm birth, we expect that there will be cost savings, because of the low costs of aspirin. To evaluate this, a cost- effectiveness analysis will be performed comparing preventive treatment with aspirin with placebo. Discussion: This trial will provide evidence as to whether or not low dose aspirin is (cost-) effective in reducing recurrence of spontaneous preterm birth

Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation using whole genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced from humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. Despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission. Sixty-eight percent (68%) of the tested mink farm residents, employees and/or contacts had evidence of SARS-CoV-2 infection. Where whole genomes were available, these persons were infected with strains with an animal sequence signature, providing evidence of animal to human transmission of SARS-CoV-2 within mink farms

Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans

Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation using whole genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced from humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. Despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission. Sixty-eight percent (68%) of the tested mink farm residents, employees and/or contacts had evidence of SARS-CoV-2 infection. Where whole genomes were available, these persons were infected with strains with an animal sequence signature, providing evidence of animal to human transmission of SARS-CoV-2 within mink farms

Identification of ANKRD11 and ZNF778 as candidate genes for autism and variable cognitive impairment in the novel 16q24.3 microdeletion syndrome.

Contains fulltext : 88235.pdf (publisher's version ) (Closed access)The clinical use of array comparative genomic hybridization in the evaluation of patients with multiple congenital anomalies and/or mental retardation has recently led to the discovery of a number of novel microdeletion and microduplication syndromes. We present four male patients with overlapping molecularly defined de novo microdeletions of 16q24.3. The clinical features observed in these patients include facial dysmorphisms comprising prominent forehead, large ears, smooth philtrum, pointed chin and wide mouth, variable cognitive impairment, autism spectrum disorder, structural anomalies of the brain, seizures and neonatal thrombocytopenia. Although deletions vary in size, the common region of overlap is only 90 kb and comprises two known genes, Ankyrin Repeat Domain 11 (ANKRD11) (MIM 611192) and Zinc Finger 778 (ZNF778), and is located approximately 10 kb distally to Cadherin 15 (CDH15) (MIM 114019). This region is not found as a copy number variation in controls. We propose that these patients represent a novel and distinctive microdeletion syndrome, characterized by autism spectrum disorder, variable cognitive impairment, facial dysmorphisms and brain abnormalities. We suggest that haploinsufficiency of ANKRD11 and/or ZNF778 contribute to this phenotype and speculate that further investigation of non-deletion patients who have features suggestive of this 16q24.3 microdeletion syndrome might uncover other mutations in one or both of these genes.1 april 201