Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis

PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS). Our aim was to conduct a systematic review of the evidence of whether post-natal erythromycin exposure is associated with subsequent development of IHPS. METHODS: A systematic review of postnatal erythromycin administration and IHPS was performed. Papers were included if data were available on development (yes/no) of IHPS in infants exposed/unexposed to erythromycin. Data were meta-analysed using Review Manager 5.3. A random effects model was decided on a priori due to heterogeneity of study design; data are odds ratio (OR) with 95 % CI. RESULTS: Nine papers reported data suitable for analysis; two randomised controlled trials and seven retrospective studies. Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p = 0.02]. However, significant heterogeneity existed between the studies (I (2) = 84 %, p < 0.0001). Data on erythromycin exposure in the first 14 days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p < 0.00001]. CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2 weeks of life

Congenital diaphragmatic hernia subtypes: Comparing birth prevalence, occurrence by maternal age, and mortality in a national birth cohort

BACKGROUND: Population-based administrative data have rarely been used to compare the birth prevalence, risk factors for occurrence, and mortality of congenital diaphragmatic hernia (CDH) subtypes. OBJECTIVES: We used a national birth cohort to identify CDH subtypes and compared their birth prevalence, relationship with maternal age after accounting for sociodemographic factors, and 1-year mortality rates. METHODS: Linked hospital admission and death records were used to identify isolated and complex CDH cases (involving additional anomalies) among singleton livebirths in England between 2002 and 2018. The prevalence of each CDH subtype per 10,000 livebirths was estimated overall and by infant, birth and maternal characteristics. The relationship between maternal age and each subtype relative to no CDH was examined using multivariable log-binomial regression to estimate risk ratios (RRs). One-year mortality rates were examined using Kaplan-Meier curves and the hazard ratio (HR) of complex versus isolated CDH was calculated using Cox regression. RESULTS: Among 9.5 million livebirths, we identified 1285 with isolated CDH and 1150 with complex CDH. The overall prevalence of isolated and complex CDH was 1.4 (95% confidence interval [CI] 1.3, 1.4) and 1.2 (95% CI 1.1, 1.3) per 10,000 livebirths, respectively. Only complex CDH was associated with maternal age. Compared with maternal age 25-34 years, complex CDH risk was elevated for maternal age < 20 years (RR 1.31, 95% CI 1.00, 1.72). Risk was highest for maternal age ≥ 40 years (RR 1.61, 95% CI 1.21, 2.15) although accounting for chromosomal anomalies attenuated the risk (RR 1.39, 95% CI 1.00, 1.92). The 1-year mortality rate for complex CDH (33.1%, 95% CI 30.5, 35.9) was slightly higher than for isolated CDH (29.7%, 95% CI 27.3, 32.3) (HR 1.10, 95% CI 0.96, 1.27). CONCLUSIONS: Mechanisms of occurrence differed between and within CDH subtypes and 1-year mortality of complex CDH was slightly higher than for isolated CDH

Isolation and Expansion of Muscle Precursor Cells from Human Skeletal Muscle Biopsies

One of the major issues concerning human skeletal muscle progenitor cells is represented by the efficient isolation and in vitro expansion of cells retaining the ability to proliferate, migrate and differentiate once transplanted. Here we describe a method (1) effective in obtaining human muscle precursor cells both from fresh and frozen biopsies coming from different muscles, (2) selective to yield cells uniformly positive for CD56 and negative for CD34 without FACS sorting, (3) reliable in maintaining proliferative and in vitro differentiative capacity up to passage 10

Robust phase retrieval for high resolution edge illumination x-ray phase-contrast computed tomography in non-ideal environments

Edge illumination x-ray phase contrast tomography is a recently developed imaging technique which enables three-dimensional visualisation of low-absorbing materials. Dedicated phase retrieval algorithms can provide separate computed tomography (CT) maps of sample absorption, refraction and scattering properties. In this paper we propose a novel “modified local retrieval” method which is capable of accurately retrieving sample properties in a range of realistic, non-ideal imaging environments. These include system misalignment, defects in the used optical elements and system geometry variations over time due to vibrations or temperature fluctuations. System instabilities were analysed, modelled and incorporated into a simulation study. As a result, an additional modification was introduced to the retrieval procedure to account for changes in the imaging system over time, as well as local variations over the field of view. The performance of the proposed method was evaluated in comparison to a previously used "global retrieval" method by applying both approaches to experimental CT data of a rat’s heart acquired in a non-ideal environment. The use of the proposed method resulted in the removal of major artefacts, leading to a significant improvement in image quality. This method will therefore enable acquiring high-resolution, reliable CT data of large samples in realistic settings

Isolation and Expansion of Muscle Precursor Cells from Human Skeletal Muscle Biopsies

One of the major issues concerning human skeletal muscle progenitor cells is represented by the efficient isolation and in vitro expansion of cells retaining the ability to proliferate, migrate and differentiate once transplanted. Here we describe a method (1) effective in obtaining human muscle precursor cells both from fresh and frozen biopsies coming from different muscles, (2) selective to yield cells uniformly positive for CD56 and negative for CD34 without FACS sorting, (3) reliable in maintaining proliferative and in vitro differentiative capacity up to passage 10

Regression Models to Study the Total LOS Related to Valvuloplasty

Background: Valvular heart diseases are diseases that affect the valves by altering the normal circulation of blood within the heart. In recent years, the use of valvuloplasty has become recurrent due to the increase in calcific valve disease, which usually occurs in the elderly, and mitral valve regurgitation. For this reason, it is critical to be able to best manage the patient undergoing this surgery. To accomplish this, the length of stay (LOS) is used as a quality indicator. Methods: A multiple linear regression model and four other regression algorithms were used to study the total LOS function of a set of independent variables related to the clinical and demographic characteristics of patients. The study was conducted at the University Hospital “San Giovanni di Dio e Ruggi d’Aragona” of Salerno (Italy) in the years 2010–2020. Results: Overall, the MLR model proved to be the best, with an R2 value of 0.720. Among the independent variables, age, pre-operative LOS, congestive heart failure, and peripheral vascular disease were those that mainly influenced the output value. Conclusions: LOS proves, once again, to be a strategic indicator for hospital resource management, and simple linear regression models have shown excellent results to analyze it

TGFβ-induced osteogenic potential of human amniotic fluid stem cells via CD73-generated adenosine production

The human amniotic fluid stem cell (hAFSC) population consists of two morphologically distinct subtypes, spindle-shaped and round-shaped cells (SS-hAFSCs and RS-hAFSCs). Whilst SS-hAFSCs are routinely expanded in mesenchymal-type (MT) conditions, we previously showed that they acquire broader differentiation potential when cultured under embryonic-type (ET) conditions. However, the effects of culture conditions on RS-hAFSCs have not been determined. Here, we show that culturing RS-hAFSCs under ET conditions confers faster proliferation and enhances the efficiency of osteogenic differentiation of the cells. We show that this occurs via TGFβ-induced activation of CD73 and the associated increase in the generation of extracellular adenosine. Our data demonstrate that culture conditions are decisive for the expansion of hAFSCs and that TGFβ present in ET conditions causes the phenotype of RS-hAFSCs to revert to an earlier state of stemness. Cultivating RS-hAFSCs in ET conditions with TGFβ may therefore increase their therapeutic potential for clinical applications

Increased robustness and speed in low-dose phase-contrast tomography with laboratory sources

In this article we discuss three different developments in Edge Illumination (EI) X-ray phase contrast imaging (XPCi), all ultimately aimed at optimising EI computed tomography (CT) for use in different environments, and for different applications. For the purpose of reducing scan times, two approaches are presented; the reverse projection" acquisition scheme which allows a continuous rotation of the sample, and the single image" retrieval algorithm, which requires only one frame for retrieval of the projected phase map. These are expected to lead to a substantial reduction of EI CT scan times, a prospect which is likely to promote the translation of EI into several applications, including clinical. The last development presented is the "modified local" phase retrieval. This retrieval algorithm is specifically designed to accurately retrieve sample properties (absorption, refraction, scattering) in cases where high-resolution scans are required in non-ideal environments. Experimental results, using both synchrotron radiation and laboratory sources, are shown for the various approaches

Complex gastroschisis: a new indication for fetal surgery?

Gastroschisis (GS) is a congenital abdominal wall defect, in which the bowel eviscerates from the abdominal cavity. It is a non-lethal isolated anomaly and its pathogenesis is hypothesized to occur as a result of two hits: primary rupture of the ‘physiological’ umbilical hernia (congenital anomaly) followed by progressive damage of the eviscerated bowel (secondary injury). The second hit is thought to be caused by a combination of mesenteric ischemia from constriction in the abdominal wall defect and prolonged amniotic fluid exposure with resultant inflammatory damage, which eventually leads to bowel dysfunction and complications. GS can be classified as either simple or complex, with the latter being complicated by a combination of intestinal atresia, stenosis, perforation, volvulus and/or necrosis. Complex GS requires multiple neonatal surgeries and is associated with significantly greater postnatal morbidity and mortality than is simple GS. The intrauterine reduction of the eviscerated bowel before irreversible damage occurs and subsequent defect closure may diminish or potentially prevent the bowel damage and other fetal and neonatal complications associated with this condition. Serial prenatal amnioexchange has been studied in cases with GS as a potential intervention but never adopted because of its unproven benefit in terms of survival and bowel and lung function. We believe that recent advances in prenatal diagnosis and fetoscopic surgery justify reconsideration of the antenatal management of complex GS under the rubric of the criteria for fetal surgery established by the International Fetal Medicine and Surgery Society (IFMSS). Herein, we discuss how conditions for fetoscopic repair of complex GS might be favorable according to the IFMSS criteria, including an established natural history, an accurate prenatal diagnosis, absence of fully effective perinatal treatment due to prolonged need for neonatal intensive care, experimental evidence for fetoscopic repair and maternal and fetal safety of fetoscopy in expert fetal centers. Finally, we propose a research agenda that will help overcome barriers to progress and provide a pathway toward clinical implementation. © 2021 International Society of Ultrasound in Obstetrics and Gynecology

Oesophageal atresia is correctable and survivable in infants less than 1 kg

INTRODUCTION: Management of oesophageal atresia (OA) and trachea-oesophageal fistula (TOF) in babies of low birth weight is challenging especially when associated with other anomalies. Birth weight of <1500 g has previously formed part of a classification system designed to predict outcome, alongside the cardiac status of the patient. Improvements in neonatal care have led to increasing numbers of premature low birth weight infants surviving. The aim of this study was to look at the experience of our institution in the extremely low birth weight (ELBW) patients. METHODS: A retrospective review of our institutions OA database was performed from 1993 to June 2015. Patients of birth weight less than 1000 g were included. A review of our OA/TOF clinical database and notes review established the following; gestation, birth weight, associated anomalies, operative procedures, morbidity and mortality. RESULTS: Of 349 patients with OA across the 22-year period, 9 ELBW patients were identified (<1000 g). Six males and three females. Gestational age ranged from 23 to 34 weeks and median birth weight was 815 g ranging from 630 to 950 g. Overall survival was 56 % (5/9). There were double the numbers of ELBW OA/TOF patients seen in the second half of the study period presumably the result of improving neonatal care. Seven patients had type C OA with TOF and underwent emergency TOF ligation, two had concomitant oesophageal repair. One of these patients died from NEC; the other survived. Of the five who had isolated TOF ligation three died-two from cardiac disease and one from prematurity. Both type A patients survived and after initial gastrostomy placement one had a primary delayed repair, the other a gastric transposition. All three babies under 800 g died-one from cardiac disease the others from conditions indicative of their prematurity-necrotising enterocolitis and intraventricular haemorrhage. CONCLUSIONS: 50 % survival is achievable in OA/TOF under 1 kg and the Spitz classification is still applicable in this group as a whole. However, none of the current classification systems are applicable in infants <800 g who in our study all had poor outcomes. We suggest these should be considered as separate group when predicting outcomes