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Esophageal atresia is a rare congenital anomaly. Due to increased survival rates, the population of adults born with this malformation is growing. These patients turn out to have an increased risk to develop Barrett's esophagus, esophageal carcinoma or lung abnormalities like bronchiectasis. This is illustrated by three cases: a 42-year-old man with an irresectable esophageal squamous cell carcinoma; a 23-year-old man with a Barrett's esophagus without any reflux complaints; and a 51-year-old women with a reflux esophagitis and extensive bronchiectasis due to a combination of gastroesophageal reflux with chronic aspiration and a reduced sputum clearance because of a history of tracheomalacia. It is important for healthcare providers to be aware of these risks and the possible absence of symptoms, in order to detect abnormalities at an early stage and improve quality of life of these patients.

Aim of the Study Because of the high prevalence of Barrett's esophagus (BE) and esophageal carcinoma, it is internationally recommended to perform routine endoscopies in adult esophageal atresia (EA) patients. This study aimed to evaluate the yield of follow-up after the first screening endoscopy. Methods Prospective cohort study in a tertiary referral center since November 2011 was considered. All patients with EA ≥ 17 years old were invited to participate in the screenings and surveillance program. All patients underwent upper endoscopies with random biopsies of the distal esophagus at the level of the gastroesophageal junction and standard four-quadrant biopsies in case of BE. From the age of 25 years old chromoendoscopy with Lugol's staining was performed for detection of superficial squamous cell carcinoma. Depending on their age and the histologic results patients were recommended follow-up endoscopy every 3–5 years. Ethical approval had been obtained. Results In February 2019, 190 patients (58% male, 83% type C, median age at time of first endoscopy 25.5) (range: 16.8–68.6 years) participated in the screenings and surveillance program. Forty-six patients underwent at least one follow-up endoscopy after median 4.7 (range: 1.0–5.9) years. Most recent surveillance endoscopy revealed a normal esophagus in 62%, esophagitis in 10%, and columnar-lined esophagus in 26% of the patients. Histology revealed inflammatory changes within normal limits in 49%, esophagitis in 22%, gastric metaplasia in 18%, and intestinal metaplasia without dysplasia in 6%. In 8 patients (6 males, median age: 25.9 (range: 22.5–34.4)) columnar-lined mucosa was a new finding at the second endoscopy, after median 5.0 (range: 3.6–5.9) years. In two of them histology revealed intestinal metaplasia without dysplasia. Conclusions In line with previous studies, we found a 4-times increased prevalence (6.3%) of BE in adults with EA. Follow-up endoscopies detected two new cases of BE. Future studies are needed to identify patients at risk and personalize screening and surveillance regimes.

Aim of the Study Patients born with esophageal atresia (EA) appear to have a 30 times higher prevalence of infantile hypertrophic pyloric stenosis (IHPS). This makes sense from a developmental perspective as both the esophagus and the pyloric sphincter are foregut derived structures. We hypothesized that genetic defects, disturbing foregut morphogenesis, are responsible for the specific combination of EA and IHPS. Methods Patients with both EA and IHPS born between 1970 and 2017 and where possible their parents were included. This study was approved by the internal review board of the Erasmus MC. After parental written informed consent, we determined genetic profiles with whole exome sequencing and SNP-array-based copy number variation analysis. We focused on (1) genetic variation in known EA and IHPS disease genes, (2) pathways important for foregut morphogenesis, (3) shared rare genetic variation, and (4) ultrarare variants in variant-intolerant genes, which have a high chance of being de novo. Segregation analysis of possible candidate variants was performed. Results Twenty-seven out of 664 patients (4.1%) born with EA during the study period developed IHPS, of which 15 cases were analyzed. As none of the parents were affected, we considered dominant (de novo) or recessive and X-linked inheritance models. Unfortunately, we could neither identify rare de novo mutations, nor variants fitting a recessive model. We did however identify inherited putative deleterious heterozygous variants in genes either known to be involved in EA or IHPS (e.g., COL7A1, TNXB, WDR11, GDF6) or important in foregut morphogenesis (e.g., GLI3, NKX2.1) in all patients. Moreover, seven genes were affected by rare variation in ≥2 patients (ADAMTSL4, ANKRD26, CNTN2, HSPG2, KCNN3, LDB3, SEC16B) and expressed in the developing foregut, esophagus or pyloric sphincter in mice between E8.25 and E18.5. However, burden analysis did not show a significant difference with unaffected controls. Conclusions Although the presence of genetic variation in likely candidate genes suggests a genetic component, genetic factors alone could not explain the abnormalities seen in these patients. Therefore, we propose a multifactorial model in which the combination of high impact genetic, mechanical, and environmental factors together can shift the balance from normal to abnormal development.

Electrostatic effects play an important role in protein interactions and may alter the biodistribution of antibodies. To study the effect of molecular charge of the biodistribution and infection imaging properties of human polyclonal immunoglobulin G (IgG), its isoelectric point was varied by changing the level of diethylene triamine penta-acetic acid (DTPA) substitution: 0.8, 0.9, 3.7, 5.1 and 5.9 DTPA/IgG. Biodistributions of the different IgG preparations were determined at 10 min, 1, 6, 24, and 48 h post injection in normal rats, and infection imaging properties were determined in rats with Escherichia coli thigh infections. The biodistribution was significantly affected by pI. The immunoglobulin preparations with 0.9 and 3.7 DTPA/IgG showed faster clearance from the circulation and generally lower accumulation in most organs. The images had a target-to-background ratio of approximately 1.3-2.3:1. These results suggest that even though targeting is not affected by the level of DTPA substitutions, preparations with 0.9 and 3.7 DTPA/IgG may be superior imaging agents because of reduced accumulation by background organs.

Personality disorders occur frequently. The presence of one or more personality disorders can influence the severity of the symptoms and can affect coping, treatment indication and drop out.To study the prevalence of personality disorders in an ambulatory health care centre and to investigate the influence of both the severity and the nature of personality disorders on the following: symptomatology, interpersonal behaviour, coping and defence mechanisms, personality traits, treatment indication and drop out.We studied the prevalence of personality disorders in 100 patients using the International Personality Disorder Examination (IPDE), a semi-structured interview. Symptoms, interpersonal behaviour, coping and defence mechanisms and personality traits were assessed by means of self-reports. Patients were assigned to specific types of treatment by their own doctors, who were not aware of the assessment results. results Most of the patients suffered from a personality disorder. Patients with cluster-A-type personality disorders were all assigned to treatment. The majority of patients with cluster- B-type personality disorders were assigned to Axis-ii-type treatment but most patients with cluster-A-and cluster-C personality disorders were assigned to Axis-I-type treatment. The dropout percentage was higher among patients with a personality disorder than among those without. Among patients with personality disorders the drop-out percentage was highest in those from the A and C clusters. Patients with personality pathology from the A cluster were 13 times more likely to drop out than those without A cluster pathology, patients with C cluster pathology were 11 times more likely to drop out than those without C cluster pathology.In ambulatory mental health care more attention needs to be given to the diagnosis of personality disorders. Results suggest that in the treatment of patients with A and C cluster pathology much effort must be directed at fostering therapeutic alliance and compliance to treatment.