Vesicoscopic vs. Open Ureteral Reimplantation According to Cohen and Leadbetter-Politano for Vesicoureteral Reflux.

BACKGROUND: The minimally invasive implementations of the established open methods for the correction of primary vesicoureteral reflux have proven to be successful in terms of feasibility and safety. The aim of this study was to investigate to what extent pediatric patients benefit from vesicoscopic operations. METHODS: Between 2010 and 2022, 224 children (359 ureters) underwent ureteral reimplantation for vesicoureteral reflux in our clinic. Children, operated on according to the COHEN technique, underwent an open approach in 39 cases, whereas 151 patients were operated on vesicoscopically. A total of thirty-four children have received a ureteral reimplantation according to the LEADBETTER-POLITANO technique: twenty-nine openly and five vesicoscopically. The open and vesicoscopic groups were compared with regards to perioperative data and postoperative course. RESULTS: The mean operating time was significantly shorter for open than for the vesicoscopic procedures in the COHEN group (99 vs. 149 min, p < 0.001). Similarly, a comparison of ureteral reimplantations, according to LEADBETTER-POLITANO, favored the open procedure, although this was not significant (161 vs. 196 min, p = 0.135). There was no significant difference in the recurrence rate of all the groups. All procedures remained within the accepted range with a success rate of at least 96%. In the postoperative course, a significantly shorter hospital stay (4.1 vs. 7.9 days, p < 0.001 for COHEN-patients; 5.6 vs. 9.2 days for LEADBETTER-POLITANO-patients), as well as a significantly lower need for continuous analgesic administration, was observed for the vesicoscopic approaches of both methods (0.8 days in both vesicoscopic groups vs. 3.7 resp. 3.8 days in open groups, p < 0.001). In addition, the time of bladder drainage was significantly shorter in open techniques (7.2 vs. 1.9 days, p < 0.001 for COHEN-patients; 3 vs. 8.7 days for LEADBETTER-POLITANO-patients). CONCLUSIONS: For almost all underlying causes, the surgical treatment of vesicoureteral reflux can be performed vesicoscopically, even if bilateral, in one session. Patients benefit significantly from the use of minimally invasive surgery in the postoperative course with faster mobilization, less need for analgesics, a shorter bladder drainage and a reduced hospital stay, compared with its open counterparts.

Combined Bentall and Modified Ravitch Procedures: A Case Report and Systematic Review of the Evidence.

Background and Objectives: Marfan syndrome (MS) is a genetic disorder with autosomal dominant inheritance that affects the connective tissue and consequently many organ systems. The cardiovascular manifestations of MS are notorious and include aortic root dilatation or acute aortic dissection, which can cause morbidity and early mortality. However, surgical treatment of aortic pathology may be complicated by musculoskeletal deformity of the chest wall, as in pectus excavatum. In this regard, single-stage combined Bentall and Ravitch surgery is an extreme rarity that has also been scarcely reported in the literature. Patients and Methods: We present the medical history and single-stage Bentall and modified Ravitch surgical treatment of an 18-year-old male MS patient with symptomatic and severe pectus excavatum (PEX) in conjunction with a pear-shaped aortic root aneurysm. To discuss our case in the context of a synopsis of similar published cases, we present a systematic review of combined Bentall surgical aortic aneurysm repair and Ravitch correction of PEX. Results: A total of four studies (one case series and three case reports) and a case from our institution describing a single-stage combined Bentall and Ravitch operation were included. Patients were 22 ± 5.9 years of age (median = 22.5 years) and predominantly male (60%). All cases reported a midline vertical skin incision over the sternum. The most common surgical approach was midsternotomy (80%). In all cases metal struts were used to reinforce the corrected chest wall. Postoperative mortality was zero. Conclusions: Single-stage combined Bentall and Ravitch surgery is an underutilized surgical approach. Its use in MS patients with concomitant PEX and ascending aortic aneurysm that require surgical treatment warrants further investigation. Midsternotomy seems to be a viable access route that provides sufficient exposure in the single-stage surgical setting. Although operative time is long, the intraoperative and postoperative risks appear to be low and manageable.

Semi-occlusive management of fingertip injuries with finger caps: A randomized controlled trial in children and adults.

BACKGROUND: Human fingertips can regenerate functionally and cosmetically excellent skin and soft tissues. Physiological conditions suppress scar formation and are thus a prerequisite for regenerative healing. Self-adhesive film dressings can provide such favorable conditions. The semi-occlusive treatment is superior to surgery. However, standard dressings leak malodorous wound fluid eventually until the wound is dry. Therefore, we developed and tested a silicone finger cap that forms a mechanically protected, wet chamber around the injury. Its puncturable reservoir allows access to the wound fluid for diagnostic and research purposes and the delivery of pro-regenerative drugs in the future. METHODS: Patients >2 years with full-thickness fingertip injuries unsuitable for simple primary closure were randomized to start treatment with either the film dressing or the silicone finger cap. After 2 weeks, we changed to the other treatment. Patients' choice on the preferred treatment after 4 weeks was the primary outcome parameter. Additionally, we monitored adverse events, unplanned visits, tissue gain, functionality, cosmetic outcome, and quality of life. RESULTS: We randomized 11 patients 2 to 72 years to each group. Eighteen to 20 (90%, intention-to-treat) patients preferred the finger cap. All patients were satisfied with the cosmetic outcome, 88.9% had no disturbing sensibility changes, and 73.7% could report no distortion in the finger's daily use. Epithelialization took between 5 weeks for Allen II and up to 9 weeks in Allen IV injuries. There were 19 device-related adverse events under film dressing and 13 under the finger cap. There were neither severe adverse device effects nor unexpected severe adverse device effects. CONCLUSION: Employing the summative or synthetic primary endpoint "patient decision for one or the other procedure," our pseudocross-over-designed RCT succeeded in statistically significantly demonstrating the superiority of the silicone finger cap over conventional film therapy. The finger cap was safe and effective, reaching excellent results on all treated injuries without any need for disinfection, antibiotics, shortening of protruding bones, or treatment of hypergranulations. Distal to the tendon insertions, we did not see any limitations regarding injury mechanism, amputation plane, or patients' age.

Diagnostics and Treatment of Volkmann Ischemic Contracture in a Seven-Year-Old Child.

A 7-year-old boy presented 6 weeks after open reduction and crossed Kirschner wire (K-wire) fixation of a supracondylar humerus fracture. Previous treatments had restored skeletal anatomy without documented complications. However, the patient would not move the entire arm, including his forearm and hand. Any passive movement led to anxious adverse reactions, and there was partial numbness of all fingers. After intensive physio- and occupational therapy supported by nerve stimulation and psychological counseling, anxiety-related functional deficits of the shoulder and elbow resolved to reveal the severe Volkmann contracture of the right hand developed fully. Electroneurography, X-ray, magnetic resonance imaging of the forearm, and ultrasonography showed nonfunctional ulnar and a partially disturbed radial motor nerve distal to the elbow along with damaged flexor muscles of the forearm after compartment syndrome. In addition, damage to the median nerve at the elbow level was diagnosed. After intense conservative therapy, we partially resected fibrotic fascia of the superficial flexor compartment, freed ulnar and median nerves, and performed staircase-like releases of tendons and tenotomies. We achieved a full range of motion of all fingers and markedly improved the range of motion of the wrist. The Disabilities of the Arm, Shoulder and Hand scores for function improved from 80 to 16 at the 2-year follow-up postoperatively, but some impairments of fine motor function persisted. Subtle symptoms of a developing compartment syndrome need to be recognized. Overlooked and untreated, a consecutive Volkmann contracture can turn the extremity nonfunctional. Intensive physical, psychological, and surgical therapy in a specialized center can restore function but requires endurance and perseverance throughout the lengthy recovery.

Vesicoscopic Cross-Trigonal Ureteral Reimplantation for Vesicoureteral Reflux: Intermediate Results.

For the treatment of vesicoureteral reflux, the introduction of vesicoscopic procedures offers new perspectives for improving patient comfort and quality. Our aim was to examine whether minimally invasive vesicoscopic cross-trigonal ureteral reimplantation (VCUR) would meet expectations. Between 2012 and 2021, 99 girls and 35 boys with high-grade vesicoureteral reflux (VUR) underwent VCUR. For two boys, we failed to establish the pneumovesicum, leading to conversion to open surgery. The mean age was 4.5 years, ranging from 10 months to 18 years. VCUR was successfully performed in 132 patients, including 75 patients with bilateral VUR and 12 children with double ureters with unilateral or bilateral VUR, corresponding to a total of 229 operated ureters. The mean time of operation was 151 min for all patients. There were no perioperative complications, with the exception of three cases of pneumoperitoneum without consequences. Postoperatively, we recognized three cases of acute hydronephrosis, two of them required transient drainage. Three patients developed extravasation of urine after the postoperative removal of the transurethral catheter, rapidly resolved by new drainage. In two patients, we combined VCUR with laparoscopic heminephrectomy and opposite laparoscopic nephrectomy, respectively. Overall, mean postoperative hospital stay was 4.2 days. We observed recurrent VUR in seven ureters, resulting in a success rate for VCUR of 96.9%. These results demonstrate the feasibility of VCUR and its potential to displace open surgery with high safety and wide applicability.

Operative Volume of Newborn Surgery in German University Hospitals: High Volume Versus Low Volume Centers.

INTRODUCTION: Adequate patient volume is essential for the maintenance of quality, meaningful research, and training of the next generation of pediatric surgeons. The role of university hospitals is to fulfill these tasks at the highest possible level. Due to decentralization of pediatric surgical care during the last decades, there is a trend toward reduction of operative caseloads. The aim of this study was to assess the operative volume of the most relevant congenital malformations at German academic pediatric surgical institutions over the past years. METHODS: Nineteen chairpersons representing university-chairs in pediatric surgery in Germany submitted data on 10 index procedures regarding congenital malformations or neonatal abdominal emergencies over a 3-year period (2015 through 2017). All institutions were categorized according to the total number of respective cases into "high," "medium," and "low" volume centers by terciles. Some operative numbers were verified using data from health insurance companies, when available. Finally, the ratio of cumulative case load versus prevalence of the particular malformation was calculated for the study period. RESULTS: From 2015 through 2017, a total 2,162 newborns underwent surgery for congenital malformations and neonatal abdominal emergencies at German academic medical centers, representing 51% of all expected newborn cases nationwide. The median of cases per center within the study period was 101 (range 18-258). Four institutions (21%) were classified as "high volume" centers, four (21%) as "medium volume" centers, and 11 (58%) as "low volume" centers. The proportion of patients operated on in high-volume centers varied per disease category: esophageal atresia/tracheoesophageal fistula: 40%, duodenal atresia: 40%, small and large bowel atresia: 39%, anorectal malformations: 40%, congenital diaphragmatic hernia: 56%, gastroschisis: 39%, omphalocele: 41%, Hirschsprung disease: 45%, posterior urethral valves: 39%, and necrotizing enterocolitis (NEC)/focal intestinal perforation (FIP)/gastric perforation (GP): 45%. CONCLUSION: This study provides a national benchmark for neonatal surgery performed in German university hospitals. The rarity of these cases highlights the difficulties for individual pediatric surgeons to gain adequate clinical and surgical experience and research capabilities. Therefore, a discussion on the centralization of care for these rare entities is necessary.

Distribution of RET proto-oncogene variants in children with appendicitis.

BACKGROUND: In addition to patient-related systemic factors directing the immune response, the pathomechanisms of appendicitis (AP) might also include insufficient drainage leading to inflammation caused by decreased peristalsis. Genetic predisposition accounts for 30%-50% of AP. M. Hirschsprung (HSCR), also characterized by disturbed peristalsis, is associated with variants in the RET proto-oncogene. We thus hypothesized that RET variants contribute to the etiology of AP. METHODS: DNA from paraffin-embedded appendices and clinical data of 264 children were analyzed for the RET c.135A>G variant (rs1800858, NC_000010.11:g.43100520A>G). In 46 patients with gangrenous or perforated AP (GAP), peripheral blood DNA was used for RET sequencing. RESULTS: Germline mutations were found in 13% of GAP, whereas no RET mutations were found in controls besides the benign variant p.Tyr791Phe (NC_000010.11:g.43118460A>T). In GAP, the polymorphic G-allele in rs2435352 (NC_000010.11:g.43105241A>G) in intron 4 was underrepresented (p = 0.0317). CONCLUSION: Our results suggest an impact of the RET proto-oncogene in the etiology of AP. Mutations were similar to patients with HSCR but no clinical features of HSCR were observed. The pathological phenotypes in both populations might thus represent a multigenic etiology including RET germline mutations with phenotypic heterogeneity and incomplete penetrance.

A rare PALB2 germline variant causing G2/M cell cycle arrest is associated with isolated myelosarcoma in infancy.

BACKGROUND: Isolated myelosarcoma of infancy is a rare presentation of acute myelogenous leukaemia (AML). Because of its rarity and early onset in infancy underlying genetic predisposition is potentially relevant in disease initiation. METHODS AND RESULTS: We report an oncologic emergency in an infant with thoracic and intraspinal aleukaemic myeloid sarcoma causing acute myelon compression and lower leg palsy. Whole-exome sequencing of the patient's germline DNA identified a rare PALB2 (OMIM 610355) variant (p.A1079S), which is located in a domain critical for the gene's proper function within the homology-directed repair pathway. In line with potential DNA damage repair defects mediated by the PALB2 deregulation, the patient's fibroblasts showed increased sensitivity towards radiation and DNA intercalating agents. CONCLUSION: Therefore, we suggest PALB2 p.A1079S as a pathogenic variant potentially contributing to the here observed patient phenotype.

Dynamics of caspase activation upon UV induced genotoxic injury.

PURPOSE: Caspases are common mediators of cell death. Evasion of cell death including apoptosis are considered to be hallmarks of cancer. A deeper understanding of the apoptotic cascade may aid improving cancer therapies. Our aim was to characterize the progression of cell death following UV-induced genotoxic injury in a defined cell culture model. MATERIALS AND METHODS: Hela cells were UV-irradiated with doses ranging from 0.1 to 60 mJ/cm2. Cells were counted and colony forming assays were performed with caspase inhibitors. RESULTS: In our model of HeLa cells, cells remain >90% viable until 6 hrs after UV radiation (UVR), but more than half of the cells are dead after 12 - 72 hrs after UVR. Within a dose range between 0.1 and 50 mJ/cm2, viability ranges roughly between 20 and 30%. The difference between the lowest dose applied (0.1 mJ/cm2) and the other doses applied is significant, with the exception of the next higher dose of 1 mJ/cm2. The activation of caspases precedes the cell death induction by several hrs. Caspase-9 starts to be activated at 1 hr after UVR followed by caspases 3, 6 and 7 which are fully active at 2 hrs after UVR while caspase-8 is fully active only 3 hrs after UVR. Most caspases are only weakly or not active at 0.1 mJ/cm2 after 3 hrs, but fully active at the same time point with increased radiation doses. PARP-1, a caspase substrate, is cleaved immediately after activation of the caspases. Colony formation activity of the tumor cells decreases exponentially after UVR dropping down to < 0.01% plating efficiency at a dose of 60 mJ/cm2. Interestingly, this drop in plating efficiency cannot be rescued by any of the two caspase inhibitors tested. CONCLUSIONS: UV-induced cell death in this model involves the activation of apoptosis-related caspases, but this activation seems to be dispensable for the execution of cell death. Further experiments should clarify which mechanisms of cell death are really necessary for the execution of this type of cell death.

Prenatal Prediction of Outcome by Fetal Gastroschisis in a Tertiary Referral Center.

: The aim of this study was to find a prenatal parameter to be able to predict possible prenatal complications or postnatal surgical options, thus allowing the fetal medicine specialist, together with pediatric surgeons and neonatologists, to improve the counseling of the parents and to determine the timing of delivery and therapy. This was a retrospective analysis of prenatal diagnosis and outcome of fetuses with 34 cases of gastroschisis between the years 2007 and 2017. A total of 34 fetuses with gastroschisis were examined and 33 outcomes registered: 22 cases of simple gastroschisis (66.7%) and 11 cases of complex gastroschisis (33.3%). A cut-off value of 18 mm for intraabdominal bowel dilatation (IABD) showed a positive predictive value (PPV) of 100% for predicting simple gastroschisis. IABD gives the best prediction for simple versus complex gastroschisis (cut-off of 18 mm). Extra-abdominal bowel dilatation (EABD) cut-off values of 10 mm and 18 mm showed low sensitivity and specificity to predict complex gastroschisis.

Conservative treatment of fingertip injuries in children - first experiences with a novel silicone finger cap that enables woundfluid analysis.

Introduction: Human fingertips are able to regenerate soft tissue and skin after amputation injuries with excellent cosmetic and functional results when treated with semiocclusive dressings. Despite bacterial colonizations, proceeding infections are not reported with this management. The underlying mechanisms for this form of regenerative healing as well as for the resilience to infections are not known. Due to the lack of mechanical protection, the leakage of maloderous woundfluid and the sometimes challenging application, conventional film dressings have their problems, especially in treating young children. We therefore treated selected patients with a novel silicone finger cap with an integrated wound fluid reservoir that enables atraumatic routine wound fluid aspiration. Methods: We report on 34 patients in between 1 and 13 years with traumatic fingertip amputations primarily treated with occlusive dressings. 12 patients were treated with a novel silicone finger cap. We summarized clinical data for each patient. This included photographs and microbiological results from wound fluid analyses, whenever available. Results: The results of both, conventional film dressing and silicone finger cap treatment, were excellent with no hypersensitivity and no restrictions in sensibility and motility. Even larger pulp defects were rearranged in a round shape and good soft tissue coverage of the distal phalanx was achieved. Nail deformities were not observed. We detected a wide spectrum of both aerobic and anaerobic bacteria in the wound fluids but infections were not observed. Epithelialization times did not differ significantly and no severe complications were seen in all primarily conservatively treated patients. Conclusion: This study provides preliminary data demonstrating that the treatment with the silicone finger cap leads to excellent clinical results in wound healing. Interestingly, the wounds were colonized with a wide range of bacteria including species that may cause wound infections. However, we saw no proceeding inflammation and the regeneration was undisturbed. In the future, the efficacy of this new management should be evaluated in randomized, controlled clinical trials to confirm the results under standard conditions and get more insight into the role of the wound microbiome as well as other factors that may promote regeneration. The aspirable Reservoir of the finger cap will enable easy atraumatic sampling of wound fluids both for diagnostic and for research purposes as well as possibly allowing direct administration of pro-regenerative drugs in the future.

Elbow arthroscopy in children and adolescents: analysis of outcome and complications.

BACKGROUND: Chondral or osteochondral lesions, post-traumatic contracture and loose bodies of the elbow are often associated with chronic pain, stiffness, repetitive swelling and joint blockages. Therefore, arthroscopy of the elbow is often used in the elderly for the treatment of osteochondral defects or arthrolysis. There are only a few reports and studies about arthroscopic therapy of the elbow in children and adolescents. This study assesses the clinical outcome of arthroscopic therapy in this age group. METHODS: In a retrospective study, children and adolescents who underwent an elbow arthroscopy in the period from 2010 to 2014 were included. The children were evaluated using the validated outcome measures Mayo Elbow Performance Score (MEPS), range of motion, pain on visual analog scale (VAS), Oxford Elbow Score (OES), quick dash and postoperative satisfaction. Furthermore, all complications were analyzed. RESULTS: In total, 27 patients were included. The mean (range) age was 14 (11-17) years, with a follow-up of 45 months. Fourteen (52%) were female and thirteen children (48%) were male. Twenty children had an arthroscopy due to osteochondritis dissecans and seven children for post-traumatic pain and stiffness. The mean (standard deviation) MEPS improved from 65 (15) to 96 (8; p = .005). The OES and quick dash were 93 and 5.4. The mean extension improved from - 15° (± 13.8) to 3° (± 10.2; p < .001). The mean flexion improved from 131° (± 13.4) to 137° (± 9.5; p = .003). Average pain on VAS was postoperative .2 (± .5), and 81.5% of all children had excellent or good results. There were no complications such as damage of nerves or blood vessels observed. CONCLUSION: Elbow arthroscopy is an appropriate and safe treatment option in children and adolescents with good and excellent postoperative results.

GT-repeat extension in the IL11 promoter is associated with Hirschsprung's disease (HSCR).

Hirschsprung's disease (HSCR) is a congenital disease characterized by intestinal obstruction due to a defective intestinal neural system. Frequently, the disease is associated with an intestinal inflammation. The most common known underlying genetic alterations are in the RET gene but HSCR can also be caused by mutations in other genes that are responsible for the maturation and migration of intestinal neural cells. Recently, a study in an Asian population reported a significant association of several single nucleotide polymorphisms (SNPs) in the IL11 (interleukin 11) gene with HSCR. We further explored the possible association of genetic alterations in the IL11 gene with HSCR and HSCR subtypes in an unrelated Caucasian population. We used a targeted sequencing approach to identify a total of 32 SNPs covering the coding region of the IL11 gene including the proximal part of the promoter and relevant SNPs described in the previous study. Genotype frequencies were compared using additive genetic models in 103 HSCR patients and 128 healthy controls. We failed to observe any significant association of SNPs with HSCR. However, there was a suggestive evidence for an association of the length of a dinucleotide repeat in the IL11 promoter region with HSCR with an over-representation of >7 GT repeat subtypes (OR = 4.982 (1.448-17.040), p-value = 0.0111) in HSCR patients. A similar trend was further observed in a subgroup of patients with long-segment HSCR (L-HSCR). These findings need to be replicated in a well-powered study. Changes in IL11 expression may be a link to the intestinal inflammation frequently observed in patients with HSCR.

Duodenocolonic Fistula As A Rare Complication of Intestinal Burkitt Lymphoma in a Three-Year-Old Boy.

BACKGROUND: Burkitt lymphoma (BL) in children often presents with abdominal localization. Intestinal perforations have been described mainly during treatment. We report on a three-year-old patient with abdominal BL who was diagnosed with a duodenocolonic fistula. CASE REPORT: A three-year-old boy presented with diarrhea, crampy abdominal pain, and a four-week history of loss of appetite and weight. Ultrasound and MRI detected a colonic tumor forming a duodenocolonic fistula which was verified by gastroduodenoscopy. A surgical biopsy revealed BL. The stage III BL with low LDH was treated with four courses of BFM-type short-pulse chemotherapy. After two courses of chemotherapy the patient developed a mechanic ileus. A segmental resection of a short segment of the colon at the right flexure carrying the residual tumor mass with cicatricial stenosis and fistula followed by colonic end to end anastomosis and covering of the fistula by omentum major were carried out without complication. 15 days after surgery, two additional courses of chemotherapy could be administrated and the boy is in ongoing remission and free of any symptoms with a follow-up interval of 18 months. CONCLUSIONS: Duodeonocolonic fistula at presentation in a child with abdominal BL is extremely rare. Delayed surgery after size of the tumor bulk has been reduced by chemotherapy might represent a risk adapted approach. However, due to limited experience with duodenocolonic fistulas even in larger pediatric lymphoma trials any decision has to be based on the problems to be faced in individual cases.

Study protocol for a randomized controlled pilot-trial on the semiocclusive treatment of fingertip amputation injuries using a novel finger cap.

INTRODUCTION: Fingertip amputation injuries are common in all ages. Conservatively treated fingertips can regenerate skin and soft tissues to form a functionally and cosmetically excellent new fingertip. Little is known about this ability that, in humans, is confined to the fingertips. Even less is known about the role of the bacteria that regularly colonize these wounds without negative impact on regeneration and healing.As an alternative to surgery, self-adhesive film dressings are commonly used to establish a wet chamber around the injury. These dressings leak malodorous wound fluid eventually until the wound is dry. Having that into consideration, we have therefore developed a silicone finger cap that forms a mechanically protected, wet chamber around the injury for optimal regeneration conditions. It contains a puncturable reservoir for excess wound fluid, which can be thus routinely analyzed for diagnostic and research purposes.This study protocol explains the first randomized controlled trial (RCT) on the semiocclusive treatment of fingertip amputations in both children and adults comparing traditional film dressings with the novel silicone finger cap. Being the first RCT using 2 medical devices not yet certified for this indication, it will gather valuable information for the understanding of fingertip regeneration and the design of future definitive studies. METHODS AND ANALYSIS: By employing an innovative pseudo-cross-over-design with a dichotomous primary endpoint based on patients preference, this pilot study will gain statistically significant data with a very limited sample size. Our RCT will investigate acceptance, safety, effectiveness, and efficacy of this novel medical device while gathering information on the clinical course and outcome of conservatively treated fingertip injuries. A total of 22 patients older than 2 years will be randomly assigned to start the conservative treatment with either the traditional film-dressing or the novel finger cap. The treatment will be changed to the other alternative for another 2 weeks before the patient or the guardian is confronted with the decision of which method they would prefer for the rest of the treatment (if required). ETHICS AND DISSEMINATION: Ethical approval (EK 148042015) of the study protocol has been obtained from Institutional Review Board at the TU Dresden. The trial is registered at the European Database on Medical Devices (EUDAMED-No.: CIV-15-03-013246) and at ClinicalTrials.gov (NCT03089060).

Foot and ankle fractures during childhood: review of the literature and scientific evidence for appropriate treatment / Fraturas do tornozelo e do pé na infância: revisão da literatura e evidências científicas para o tratamento adequado

ABSTRACT Foot and ankle fractures represent 12% of all pediatric fractures. Malleolar fractures are the most frequent injuries of the lower limbs. Hindfoot and midfoot fractures are rare, but inadequate treatment for these fractures may results in compartment syndrome, three-dimensional deformities, avascular necrosis and early post-traumatic arthritis, which have a significant impact on overall foot and ankle function. Therefore, the challenges in treating these injuries in children are to achieve adequate diagnosis and precise treatment, while avoiding complications. The objective of the treatment is to restore normal anatomy and the correct articular relationship between the bones in this region. Moreover, the treatment needs to be planned according to articular involvement, lower-limb alignment, ligament stability and age. This article provides a review on this topic and presents the scientific evidence for appropriate treatment of these lesions.

RESUMO As fraturas do tornozelo e do pé representam 12% de todas as fraturas pediátricas. Fraturas maleolares são as lesões mais frequentes dos membros inferiores; fraturas do retropé e mediopé são raras, mas o seu tratamento inadequado pode resultar em síndrome de compartimento, deformidades tridimensionais, necrose avascular e osteoartrose pós-traumática precoce, as quais apresentam impacto significativo na função global do tornozelo e pé. Portanto, os desafios no tratamento dessas lesões na criança são o diagnóstico adequado e tratamento preciso para se evitarem as complicações. O objetivo do tratamento é restaurar a anatomia normal e a relação articular correta entre os ossos da região. Além disso, o tratamento deve ser planejado de acordo com acometimento articular, o alinhamento dos membros inferiores, a estabilidade ligamentar e a idade. O algoritmo de tratamento dos traumas complexos do tornozelo e pé na infância é descrito. Este artigo apresenta uma revisão sobre o tema e as evidências científicas para o tratamento adequado dessas lesões.

Genetic mosaicism of a frameshift mutation in the RET gene in a family with Hirschsprung disease.

Mutations and polymorphisms in the RET gene are a major cause of Hirschsprung disease (HSCR). Theoretically, all true heterozygous patients with a new manifestation of a genetically determined disease must have parents with a genetic mosaicism of some extent. However, no genetic mosaicism has been described for the RET gene in HSCR yet. Therefore, we analyzed families with mutations in the RET gene for genetic mosaicism in the parents of the patients. Blood samples were taken from patients with HSCR and their families/parents to sequence the RET coding region. Among 125 families with HSCR, 33 families with RET mutations were analyzed. In one family, we detected a frameshift mutation due to a loss of one in a row of four cytosines in codon 117/118 of the RET gene (c.352delC) leading to a frameshift mutation in the protein (p.Leu118Cysfs*105) that affected two siblings. In the blood sample of the asymptomatic father we found a genetic mosaicism of this mutation which was confirmed in two independent samples of saliva and hair roots. Quantification of peak-heights and comparison with different mixtures of normal and mutated plasmid DNA suggested that the mutation occurred in the early morula stadium of the founder, between the 4- and 8-cell stages. We conclude that the presence of a RET mutation leading to loss of one functional allele in 20 to 25% of the cells is not sufficient to cause HSCR. The possibility of a mosaicism has to be kept in mind during genetic counseling for inherited diseases.

Down-regulation of heat shock protein HSP90ab1 in radiation-damaged lung cells other than mast cells.

Ionizing radiation (IR) leads to fibrosing alveolitis (FA) after a lag period of several weeks to months. In a rat model, FA starts at 8 weeks after IR. Before that, at 5.5 weeks after IR, the transcription factors Sp1 (stimulating protein 1) and AP-1 (activator protein 1) are inactivated. To find genes/proteins that were down-regulated at that time, differentially expressed genes were identified in a subtractive cDNA library and verified by quantitative RT-PCR (reverse transcriptase polymerase chain reaction), western blotting and immunohistochemistry (IH). The mRNA of the molecular chaperone HSP90AB1 (heat shock protein 90 kDa alpha, class B member 1) was down-regulated 5.5 weeks after IR. Later, when FA manifested, HSP90ab1 protein was down-regulated by more than 90% in lung cells with the exception of mast cells. In most mast cells of the normal lung, both HSP90ab1 and HSP70, another major HSP, show a very low level of expression. HSP70 was massively up-regulated in all mast cells three months after irradiation whereas HSP90AB1 was up-regulated only in a portion of mast cells. The strong changes in the expression of central molecular chaperones may contribute to the well-known disturbance of cellular functions in radiation-damaged lung tissue.