Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.     

Aus alt mach neu

Background

Fracture healing is a complex biological process with specific temporal expression patterns. During this process new bone tissue is formed, which is similar to the original bone in quality and structure. This occurs in four phases: inflammation, formation of a soft tissue callus, formation of a bony callus and remodelling of the bony callus. This needs the precise orchestration of each cell type involved.

Objectives

This article presents details of the fracture healing phases and the relevant factors. During the aging process there is an increase of reactive oxygen species and a change in expression pattern of growth factors that have a negative effect on the fracture healing process.

Methods

A selective review of the literature was carried out in PubMed concerning the influence of aging on fracture healing.

Conclusion

The healing process is regulated by systemic and local factors. An understanding of these processes and the changes during aging is necessary in order to improve the knowledge of delayed or lack of fracture healing during aging to decide when an intervention is needed.     

Desmosterolosis presenting with multiple congenital anomalies

Desmosterolosis is a rare multiple congenital anomaly syndrome caused by a defect in the enzyme 3-beta-hydroxysterol delta-24-reductase (DHCR24) in the cholesterol biosynthesis pathway. Defects in this enzyme cause increased level of the cholesterol precursor desmosterol while disrupting development of cholesterol, impacting embryogenesis. A total of 9 cases of desmosterolosis have been reported to date. We report a 20-month-old male from consanguineous parents with multiple congenital anomalies including corpus callosum hypoplasia, facial dysmorphism, cleft palate, pectus deformity, short and wide neck and distal contractures. On analysis of the regions of homozygosity found by microarray, we identified DHCR24 as a candidate gene. Sterol quantitation showed a desmosterol level of 162 μg/mL (nl: 0.82 ± 0.48). Genetic testing confirmed the diagnosis with a homozygous likely pathogenic mutation (p.Glu191Lys) in the DHCR24 gene. Our case expands the known diagnostic spectrum for Desmosterolosis. We suggest considering Desmosterolosis in the differential diagnosis of patients who present with concurrent agenesis of the corpus callosum with white matter atrophy and ventriculomegaly, retromicrognathia with or without cleft palate, hand contractures, and delay of growth and development. Children of consanguineous mattings may be at higher risk for rare recessive disorders and testing for cholesterol synthesis defect should be a consideration for affected children. Initial evaluation can be performed using sterol quantitation, followed by genetic testing.     

Platelets display potent antimicrobial activity and release human beta-defensin 2

Platelet-rich plasma (PRP) is a potent agent that improves soft tissue and bone healing. By the release of growth factors and cytokines, PRP is believed to locally boost physiologic healing processes. Recently, antimicrobial activity of PRP has been demonstrated against S. aureus strains. Major scientific effort is being put into the understanding and prevention of infections i.e. by delivery of antimicrobial substances. In previous studies we showed the ideal antibacterial activity-profile of the human beta-defensin 2 (hBD-2) for orthopaedic infections and therefore hypothesized that hBD-2 may be the effector of antimicrobial platelet action. Platelet concentrates were produced from human platelet phresis obtained from a hospital blood bank. They were screened by immunohistochemistry, Western Blot and ELISA for the human beta defensin-2. In?vitro susceptibility to PRP was investigated by a standard disc diffusion test with or without pre-incubation of PRP with anti-hBD-2 antibody. SPSS statistical software was used for statistical analysis. PRP contains hBD-2 470?pg/10(9) platelets or 1786?pg/ml, respectively, (ELISA), which was confirmed by immunohistochemistry and Western Blot. In antimicrobial testing, PRP demonstrates effective inhibition of E. coli, B. megaterium, P. aeruginosa, E. faecalis and P. mirabilis. With this study we confirm the previously reported antimicrobial action of platelet concentrates i.e. PRP. In opposition to previously reported effects against gram positive bacteria our study focuses on gram negative and less common gram positive bacteria that do frequently cause clinical complications. We provide a possible molecular mechanism at least for E. coli and P. mirabilis for this effect by the detection of an antimicrobial peptide (hBD-2). This study may advocate the clinical use of PRP by highlighting a new aspect of platelet action.     

Current incidence of peripheral arterial embolism and role of echocardiography

We reviewed the incidence and outcome of all cases of upper and lower limb embolism surgically treated in our vascular unit, from January 2001 to June 2006, to assess the role of transthoracic and transesophageal echocardiography in defining the source of the embolus. Transthoracic echocardiography was carried out postoperatively, and patients in whom the embolic source was not found underwent transesophageal echocardiography. There were 85 patients (mean age, 69 years) who underwent embolectomy: 58 for lower and 27 for upper limb ischemia. The source or potential source of thrombus was demonstrated in 17 (20%) patients after transthoracic echocardiography. Fifty-three patients had transesophageal echocardiography, the source of embolism was found in 85%, and the subsequent management was changed in 47% of them. Arterial limb emboli are still prevalent in developing countries. Transthoracic echocardiography is a good screening tool for detecting a potential cardiac source of peripheral embolism, with transesophageal echocardiography being reserved for specific indications.     

Cilastatin as a protective agent against drug-induced nephrotoxicity: a literature review

ABSTRACT

Introduction

Cilastatin, a dehydropeptidase I inhibitor, has been used alongside imipenem, a broad spectrum antibiotic, in order to reduce its renal metabolism, consequently increasing its urinary recovery and effectiveness for many years. However, this measure could be useful in preventing imipenem-induced renal damage and decreasing the number of nephrotoxicity reports with imipenem. In this review, the authors gathered all available studies focusing on cilastatin use as a nephroprotective agent, beside well-known nephrotoxic medications like vancomycin, cisplatin, cyclosporine, or tacrolimus.