Current and Novel Therapeutical Approaches of Classical Homocystinuria in Childhood With Special Focus on Enzyme Replacement Therapy, Liver-Directed Therapy and Gene Therapy.

Classical homocystinuria is a hereditary defect of the enzyme cystathionine beta synthase, which is produced in the liver. If this enzyme fails, the synthesis pathway of cysteine from methionine is interrupted, leading to the accumulation of homocysteine in the blood plasma and homocysteine in the urine. After birth, the children are unremarkable except for the characteristic laboratory findings. Symptoms rarely appear before the second year of life. The most common symptom is a prolapse of the crystalline lens. This finding is seen in 70% of untreated 10-year-old affected individuals. As the earliest symptom, psychomotor retardation occurs in the majority of patients already during the first two years of life. Limiting factors in terms of life expectancy are thromboembolism, peripheral arterial disease, myocardial infarction, and stroke. These symptoms are due to the damage to the vessels caused by the elevated amino acid levels. About 30% suffer a thromboembolic event by the age of 20, about half by the age of 30. This review focus on present and new therapeutical approaches like the role of enzyme replacement with presentation of different novel targets in research like pegtibatinase, pegtarviliase, CDX-6512, erymethionase, chaperones, proteasome inhibitors and probiotic treatment with SYNB 1353. Furthermore, we analyze the role of liver-directed therapy with three dimensional (3D) bioprinting, liver bioengineering of liver organoids in vitro and liver transplantation. The role of different gene therapy options to treat and cure this extremely rare disease in childhood will be discussed.

Medical honey and its role in paediatric patients.

BACKGROUND: The use of complementary medical treatment in wound management has continued to grow throughout the world. There is a large body of evidence that supports the use of honey as a wound dressing for a wide range of wound types. The authors present an update of present knowledge about honey as a form of complementary medicine in paediatric wound management. METHODS: The literature cited was found by searching the PubMed, BIOSIS and ISI Web of Science databases for the phrase 'honey and wound'. Papers where honey was used in a mixture with other therapeutic substances were excluded. Randomised controlled trials as well as case studies were taken into consideration. RESULTS: This paper reviews data on the effectiveness of honey in wound healing; 80 citations or references were found that matched the criteria. Furthermore, the wound-healing properties of honey are described and the mechanism of action discussed. The authors' data show that honey induced enhanced epithelialisation, minimised scar formations and had an anti-microbiotic effect. CONCLUSION: These results should encourage the use of medical honey in the field of paediatrics. It is a safe and natural substance that induces wound healing at a greater rate than conventional methods.

The role of complementary medicine in a pediatric day center in Germany.

BACKGROUND: The role of complementary alternative medicine (CAM) in pediatrics has considerably increased in the last years. The knowledge about potential side effects and possible interactions with conventional drugs is still limited, and often pediatricians do not know whether their patients use CAM. This can be critical, as in order to diagnose and treat illnesses properly physicians need to know about the full extent of the self-administered therapy of their patients. Many studies have been conducted in other countries in order to assess the extent of CAM use and the types of substances that are consumed, but in Germany data in regard to pediatric interventions are lacking. We therefore developed a questionnaire to evaluate the frequency of CAM use among German pediatric patients. PATIENTS AND METHODS: 115 parents visiting the pediatric day center in Epe between September and November 2011 responded to the questionnaire. The survey contains questions concerning the prevalence of CAM use and data about socioeconomic factors. RESULTS: A total of 75.7% of all children enrolled in the study had already been treated with CAM by their parents, while only 43.6% of the parents knew that there can be interactions with CAM and prescribed drugs. In only half of the cases (50.6%) the pediatrician knew about the CAM usage of the child. CONCLUSION: The frequency of CAM usage among children is higher than anticipated. It is essential that pediatricians know about possible interactions with conventional medicine, and it lies in their responsibility to include the question about CAM usage in their standard protocols.

Topical timolol for small infantile hemangioma: a new therapy option.

The main characteristic of infantile hemangioma is that it grows rapidly after birth and mostly regresses spontaneously. It is a common practice for only a small part of the hemangioma to be treated, as they can be extremely disfiguring and destructive to normal tissue as well as possibly being life-threatening. Recent studies have discovered that the use of topical 0.5% timolol maleate gel is a new therapy option for infantile hemangioma. We have treated two children with hemangioma in our pediatric day center with topical timolol gel (Nyogel). We examined the children before the therapy and took photographs of the hemangioma. After a period of two weeks, pictures were re-taken and compared. A significant change in color from dark red to a lighter shade of red and partially even to skin color could be detected. The treatment outcome of our cases indicates that timolol gel is well-tolerated and effective for the therapy for infantile hemangioma. We further want to highlight the necessity to treat even small hemangiomas, as a reliable prediction of the possible extent of the expansion and involution does not exist.

Parent satisfaction with a pediatric practice in Germany: a questionnaire-based study.

BACKGROUND: Parental satisfaction with a pediatric day center is essential for the medical treatment of children, since it is closely related to compliance. In order to ascertain factors which predict parental satisfaction as well as to discover possible weak points, we developed a questionnaire. METHODS: 127 parents visiting the pediatric day center from October to November 2010 were asked to respond to a questionnaire. The survey was given to them directly by the doctor after their visit and it provided the opportunity to determine subjective and soft factors in quality management, which is essential for a pediatric practice. The questionnaire consisted of 27 items divided into three scales. The scales were as follows: satisfaction concerning the infrastructure and organization, satisfaction concerning the communicative and empathic competence of the doctor as well as the other staff, and finally the results and the overall impression. Moreover, the survey asked the respondents for their comments on the pediatric day center and sociodemographic data were queried. RESULTS: A total of 67 parents (52,7%) responded to the survey. The mean parental satisfaction concerning infrastructure and organization achieved 3,61 (scale 1-very unsatisfied--through 4-very satisfied). The mean satisfaction with the expertise of the doctor and the staff was 3,56 and the overall satisfaction was 3,65. Ninety-one percent of the parents would visit the pediatric practice again and 84,2% would definitely recommend the practice to others. CONCLUSION: Surveys on parental satisfaction are essential for the success of a pediatric day center. Apart from the doctors abilities to interact with the parents, other factors, such as a short waiting period, a friendly and helpful staff, as well as appealing premises are essential for a high overall level of satisfaction.

Benzocaine-induced methaemoglobinaemia: a case study.

Benzocaine is a widely used topical anaesthetic and has been reported to cause toxic methaemoglobinaemia in otherwise healthy individuals with no predisposing risk factors. This article reports on a rare case of benzocaine-induced methaemoglobinaemia following adenotonsillectomy in a 5-year-old girl. Topical benzocaine was applied orally for the relief of postoperative wound pain on the eighth postoperative day. Two hours after application, generalized cyanosis, mild dyspnoea and some degree of agitation developed. The methaemoglobin level was 38.5%. Treatment with methylene blue was initiated immediately. Symptoms completely disappeared 4 hours after initiation of methylene blue therapy. The further course was uneventful. Therefore, all health professionals should be aware that topical anaesthetics after surgery can induce methaemoglobinaemia in children, even after a prolonged interval, and especially when applied on wound surfaces.

Does honey have a role in paediatric wound management?

Topical honey treatment has been shown to possess antimicrobial properties, promote autolytic debridement, stimulate growth of wound tissues to hasten healing, and to start the healing process in dormant wounds, stimulating anti-inflammatory activity that rapidly reduces pain, oedema and exudate production. This article provides an overview of the use of honey as a medicinal substance, particularly its use in wound treatment, and reviews the published data concerning honey as a form of complementary and alternative medicine in paediatric wound management. The literature reviewed was found by searching the PubMed, BIOSIS, and ISI Web of Science databases for the term honey. Exclusion criteria were articles where honey was used in a mixture with other therapeutic substances.

Surgical experience and cosmetic outcomes in children with sacrococcygeal teratoma.

To determine the extent of progress in the treatment of sacrococcygeal teratomas (SCTs), the experience of 25 patients over a period of 30 years between 1972 and 2002 was evaluated. The medical records of the children were reviewed for demographics, histology, clinical course, bladder, anorectal and sexual function, and outcome. In particular, analysis of long-term cosmetic results after surgery for SCT was performed. The follow-up period ranged from 1 day to 396 months (median, 212 months). In more than half of the cases, unsatisfactory cosmetic long-term results after surgery for SCT were found. This study demonstrates that poor cosmetic results in the buttock region were the most common long-term complication after surgery for SCT, possibly leading to further corrective operations in later life. A better surgical procedure for closing the buttock region in the treatment of SCT should be discussed. Early assessment of bladder, anorectal, and sexual function along with long-term cosmetic results should be integrated into the well-established long-term oncology follow-up program. Moreover one has to keep in mind that cesarean section could become necessary as the primary delivery technique in female patients who have had surgery for SCT. More evaluations concerning this aspect are necessary.