Incidence, treatment techniques, and results of distal humeral coronal shear fractures in children and adolescents-a multicenter study of the German Section of Pediatric Traumatology (SKT).

PURPOSE: Distal humeral coronal shear fractures (CSF) are uncommon and may be challenging to treat due to their size, location, and intraarticular nature. The purpose of this study was to analyze treatment concepts of this rare entity in the growing age. METHODS: Based on a multi-center data analysis we retrospectively reviewed patients below 16 years of age with CSF treated at 13 high-volume pediatric trauma centers. RESULTS: Data from 51 patients with a CSF treated between 01/2012 and 12/2021 were analyzed. The mean age was 12.9 years (10-15), and there was a trend towards male patients (30: 21). The initial diagnostic approach was conventional X-ray in all cases. In addition, a CT scan (n = 33), MRI scan (n = 9), or both (n = 3) were performed. All fractures except two showed relevant displacement. Consequently, only two cases received conservative treatment consisting of plaster immobilization. Surgical treatment was performed in 49 cases consisting of open or mini-open reduction and metal/resorbable screw osteosynthesis (n = 39), plates (n = 4), K-wire pinning (n = 6), and others (n = 6), as well as combinations. In 1 case open reduction without osteosynthesis was performed. Postoperative additional plaster immobilization was performed in 40 cases (for a mean of 19 days (2-42)), physiotherapy was initiated in 29 cases, and metal removal was performed in 28 cases (after a mean of 18.1 weeks (4-44)). After a mean follow-up of 9.9 months (2-25), elbow axial deviation (5° valgus) was observed in one case and mild loss of elbow ROM in six cases (11.7%). Complications included revision of the osteosynthesis because of insufficient articular reconstruction (n = 4), removal of a free joint body (n = 1), an osteonecrosis (n = 1), and a cartilage defect (n = 1). CONCLUSION: In pediatric patients CSFs start to occur at the age of 10, but are typically observed at the age of 13 and older. Because of their intraarticular nature and predilection toward displacement, these fractures are frequently treated operatively. The surgical strategy requires open reduction and anatomic reconstruction of the articular surface. Stable internal fixation, most often achieved by screws, permits early mobilization and leads to good outcomes in most cases. This is presumably due to the fact that mostly simple fractures occur in children and mostly complex injuries in older adults. LEVEL OF EVIDENCE: III, retrospective analysis.

Design and Synthesis of Novel HIV-1 NNRTIs with Bicyclic Cores and with Improved Physicochemical Properties.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent cornerstones of current regimens for treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, NNRTIs usually suffer from low aqueous solubility and the emergence of resistant viral strains. In the present work, novel bicyclic NNRTIs derived from etravirine (ETV) and rilpivirine (RPV), bearing modified purine, tetrahydropteridine, and pyrimidodiazepine cores, were designed and prepared. Compounds 2, 4, and 6 carrying the acrylonitrile moiety displayed single-digit nanomolar activities against the wild-type (WT) virus (EC50 = 2.5, 2.7, and 3.0 nM, respectively), where the low nanomolar activity was retained against HXB2 (EC50 = 2.2-2.8 nM) and the K103N and Y181C mutated strains (fold change, 1.2-6.7×). Most importantly, compound 2 exhibited significantly improved phosphate-buffered saline solubility (10.4 µM) compared to ETV and RPV (≪1 µM). Additionally, the binding modes of compounds 2, 4, and 6 to the reverse transcriptase were studied by X-ray crystallography.

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.

Synthesis and Evaluation of Novel Acyclic Nucleoside Phosphonates as Inhibitors of Plasmodium falciparum and Human 6-Oxopurine Phosphoribosyltransferases.

Acyclic nucleoside phosphonates (ANPs) are a promising class of antimalarial therapeutic drug leads that exhibit a wide variety of Ki values for Plasmodium falciparum (Pf) and human hypoxanthine-guanine-(xanthine) phosphoribosyltransferases [HG(X)PRTs]. A novel series of ANPs, analogues of previously reported 2-(phosphonoethoxy)ethyl (PEE) and (R,S)-3-hydroxy-2-(phosphonomethoxy)propyl (HPMP) derivatives, were designed and synthesized to evaluate their ability to act as inhibitors of these enzymes and to extend our ongoing antimalarial structure-activity relationship studies. In this series, (S)-3-hydroxy-2-(phosphonoethoxy)propyl (HPEP), (S)-2-(phosphonomethoxy)propanoic acid (CPME), or (S)-2-(phosphonoethoxy)propanoic acid (CPEE) are the acyclic moieties. Of this group, (S)-3-hydroxy-2-(phosphonoethoxy)propylguanine (HPEPG) exhibits the highest potency for PfHGXPRT, with a Ki value of 0.1 µM and a Ki value for human HGPRT of 0.6 µM. The crystal structures of HPEPG and HPEPHx (where Hx=hypoxanthine) in complex with human HGPRT were obtained, showing specific interactions with active site residues. Prodrugs for the HPEP and CPEE analogues were synthesized and tested for in vitro antimalarial activity. The lowest IC50 value (22 µM) in a chloroquine-resistant strain was observed for the bis-amidate prodrug of HPEPG.

Additional Tension Screws Improve Stability in Elastic Stable Intramedullary Nailing: Biomechanical Analysis of a Femur Spiral Fracture Model.

PURPOSE: For pediatric femoral shaft fractures, elastic stable intramedullary nailing (ESIN) is an accepted method of treatment. But problems regarding stability with shortening or axial deviation are well known in complex fracture types and heavier children. Biomechanical in vitro testing was performed to determine whether two modified osteosyntheses with an additional tension screw fixation or screw fixation alone without nails could significantly improve the stability in comparison to classical ESIN. METHODS: A total of 24 synthetic adolescent-sized femoral bone models (Sawbones, 4th generation; Vashon, Washington, United States) with an identical spiral fracture (length 100 mm) were used. All grafts underwent retrograde fixation with two C-shaped steel nails (2C). Of the 24, 8 osteosyntheses were supported by one additional tension screw (2C1S) and another 8 by two screws (2S) in which the intramedullary nails were removed before testing. Each configuration underwent biomechanical testing in 4-point bending, external rotation (ER) and internal rotation (IR). Furthermore, the modifications were tested in axial physiological 9 degrees position for shifting and dynamic compression as well as dynamic load. RESULTS: Both screw configurations (2C1S and 2S) demonstrated a significantly higher stability in comparison to the 2C configuration in 4-point bending (anterior-posterior, 0.95 Nm/mm [2C] < 8.41 Nm/mm [2C1S] and 15.12 Nm/mm [2S]; posterior-anterior, 8.55 Nm/mm [2C] < 12.65 Nm/mm [2C1S] and 17.54 Nm/mm [2S]; latero-medial, 1.17 Nm/mm [2C] < 5.53 Nm/mm [2C1S] and 9.15 Nm/mm [2S]; medio-lateral, 1.74 Nm/mm [2C] < 9.69 Nm/mm [2C1S] and 12.20 Nm [2S]; all p < 0.001) and during torsion (ER, 0.61 Nm/degree [2C] < 4.10 Nm/degree [2C1S] and 9.29 Nm/degree [2S]; IR, 0.18 Nm/degree [2C] < 6.17 Nm/degree [2C1S] and 10.61 Nm/degree [2S]; all p < 0.001]. The shifting in compression in 9 degrees position was only slightly influenced. The comparison of 2S versus 2C1S showed more stability for 2S than 2C1S in all testing, except the axial 9 degrees compression tests for shifting. In contrast to the 2C configuration, both modifications (2C1S and 2S) turned out to be stable in dynamic 9 degrees axial compression with a force of 100 up to 1,000 N at 2.5 Hz in 250,000 load cycles. CONCLUSIONS: In this in vitro adolescence femur spiral fracture model, the stability of ESIN could be significantly improved by two modifications with additional tension screws. If transferred in clinical practice, these modifications might offer earlier weight bearing and less problems of shortening or axial deviation.

Modification of elastic stable intramedullary nailing with a 3rd nail in a femoral spiral fracture model - results of biomechanical testing and a prospective clinical study.

BACKGROUND: Elastic stable intramedullary nailing (ESIN) is the standard treatment for displaced diaphyseal femoral fractures in children. However, high complication rates (10-50%) are reported in complex fractures. This biomechanical study compares the stiffness with a 3rd nail implanted to that in the classical 2C-shaped configuration and presents the application into clinical practice. METHODS: For each of the 3 configurations of ESIN-osteosynthesis with titanium nails eight composite femoral grafts (Sawbones®) with an identical spiral fracture were used: 2C configuration (2C-shaped nails, 2 × 3.5 mm), 3CM configuration (3rd nail from medial) and 3CL configuration (3rd nail from lateral). Each group underwent biomechanical testing in 4-point bending, internal/external rotation and axial compression. RESULTS: 2C and 3CM configurations showed no significant differences in this spiroid type fracture model. 3CL had a significantly higher stiffness during anterior-posterior bending, internal rotation and 9° compression than 2C, and was stiffer in the lateral-medial direction than 3CM. The 3CL was less stable during p-a bending and external rotation than both the others. As biomechanical testing showed a higher stability for the 3CL configuration in two (a-p corresponding to recurvation and 9° compression to shortening) of three directions associated with the most important clinical problems, we added a 3rd nail in ESIN-osteosynthesis for femoral fractures. 11 boys and 6 girls (2.5-15 years) were treated with modified ESIN of whom 12 were '3CL'; due to the individual character of the fractures 4 patients were treated with '3CM' (third nail from medial) and as an exception 1 adolescent with 4 nails and one boy with plate osteosynthesis. No additional stabilizations or re-operations were necessary. All patients achieved full points in the Harris-Score at follow-up; no limb length discrepancy occurred. CONCLUSION: The 3CL configuration provided a significantly higher stiffness than 2C and 3CM configurations in this biomechanical model. These results were successfully transmitted into clinical practice. All children, treated by 3CL or 3CM according to the individual character of each fracture, needed no additional stabilization and had no Re-Do operations. As a consequence, at our hospital all children with femoral diaphyseal fractures with open physis are treated with this modified ESIN-technique.

Elastic stable intramedullary nailing for displaced pediatric clavicle midshaft fractures: a prospective study of the results and patient satisfaction in 24 children and adolescents aged 10 to 15 years.

BACKGROUND: Whereas displaced clavicle fractures in young children are treated nonoperatively, older children are more likely to suffer persistent pain and misalignments during a longer period of treatment. This study presents the outcomes of elastic stable intramedullary nailing for displaced clavicle fractures in children over the age of 10. METHODS: Prospectively, this study evaluates elastic stable intramedullary nailing for displaced clavicle midshaft fractures in children and adolescents, aged 10 to 15 years, from July 2004 to June 2010. We analyzed all complications, patient pain and long-term results, measured using the Constant & Murley Shoulder Score, the Client Satisfaction Questionnaire-8, and ultrasound. RESULTS: Eight girls and 16 boys (aged 10 to 15 y), 1 with bilateral fracture, were recruited. Sixteen mini-open reductions were necessary. All adolescents reported full mobilization from the first postoperative day, full activity after 1 week, and sporting activity after 1 month. Self-reported pain was very low. Five complications occurred: 1 implant breakage (kick-boxing); 2 nail deformations (fall during football, collision in ice-hockey); and 2 imminent skin perforations. The mean Constant & Murley Shoulder Score at follow-up after 1 year was 99.5 of 100 points; the mean patient satisfaction in the Client Satisfaction Questionnaire-8 was 30.6 of 32 points. Axial deviation of the clavicle was always <10 degrees; shortening <0.5 cm. CONCLUSIONS: Elastic stable intramedullary nailing can be offered for displaced midshaft clavicle fractures in children older than 10 years. They benefit from little pain, early mobilization, and fast full range of motion. To avoid complications the maximum projection of the ends of the nails must be 5 mm; no sports should be allowed for 4 weeks, contact sports for 8 weeks.

Severe complications in wound healing and fracture treatment in two brothers with congenital insensitivity to pain with anhidrosis.

Congenital insensitivity to pain with anhidrosis is an autosomal recessive disorder caused by mutations in the neurotrophic tyrosine receptor kinase 1 (NTRK1) gene, which encodes the receptor for nerve growth factor. We report the clinical and radiological pitfalls in the diagnosis and treatment of two brothers, aged 5 and 8 years, with congenital insensitivity to pain with anhidrosis, the older brother having a proven NTRK1 mutation. In the neonatal period, both presented with recurrent episodes of fever of unknown origin, but their clinical problems changed later. In addition to severe mental retardation and self-harming behaviour, the older brother developed recurrent nonbacterial destructive infections of both the calcaneus and later the talus. No immunodeficiency was found. The younger brother had three complex fractures with a long history of healing problems: overwhelming production of callus, osteomyelitis and movement restrictions. He has less mental retardation than his older brother and shows no self-mutilation.

Biomechanical analysis of a synthetic femoral spiral fracture model: Do end caps improve retrograde flexible intramedullary nail fixation?

BACKGROUND: Elastic Stable intramedullary Nailing (ESIN) of dislocated diaphyseal femur fractures has become an accepted method for the treatment in children and adolescents with open physis. Studies focused on complications of this technique showed problems regarding stability, usually in complex fracture types such as spiral fractures and in older children weighing > 40 kg. Biomechanical in vitro testing was performed to evaluate the stability of simulated spiral femoral fractures after retrograde flexible titanium intramedullary nail fixation with and without End caps. METHODS: Eight synthetic adolescent-size femoral bone models (Sawbones® with a medullar canal of 10 mm and a spiral fracture of 100 mm length identically sawn by the manufacturer) were used for each group. Both groups underwent retrograde fixation with two 3.5 mm Titanium C-shaped nails inserted from medial and lateral entry portals. In the End Cap group the ends of the nails of the eight specimens were covered with End Caps (Synthes Company, Oberdorf, Switzerland) at the distal entry. RESULTS: Beside posterior-anterior stress (4.11 Nm/mm vs. 1.78 Nm/mm, p < 0.001), the use of End Caps demonstrated no higher stability in 4-point bending compared to the group without End Caps (anterior-posterior bending 0.27 Nm/mm vs. 0.77 Nm/mm, p < 0.001; medial-lateral bending 0.8 Nm/mm vs. 1.10 Nm/mm, p < 0.01; lateral-medial bending 0.53 Nm/mm vs. 0.86 Nm/mm, p < 0.001) as well as during internal rotation (0.11 Nm/° vs. 0.14 Nm/°, p < 0.05). During compression in 9°- position and external rotation there was no statistical significant difference (0.37 Nm/° vs. 0.32 Nm/°, p = 0.13 and 1.29 mm vs. 2.18 mm, p = 0.20, respectively) compared to the "classic" 2-C-shaped osteosynthesis without End Caps. CONCLUSION: In this biomechanical study the use of End Caps did not improve the stability of the intramedullary flexible nail osteosynthesis.

Elastic Stable Intramedullary Nailing (ESIN), Orthoss® and Gravitational Platelet Separation--System (GPS®): an effective method of treatment for pathologic fractures of bone cysts in children.

BACKGROUND: The different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated. METHODS: From 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS®)--System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration. RESULTS: A cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS® and Orthoss® to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary. CONCLUSIONS: The combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS®) enhances the treatment of bone cysts in children, with no resulting complications.

Intramedullary nailing for metacarpal 2-5 fractures.

Twenty-eight patients with 31 closed fractures (27 acute fractures and four with malalignment after conservative treatment) of the metacarpal bones 2-5 were treated with only one elastic stable intramedullary nail and followed prospectively. Treatment protocol was without immobilization or physiotherapy. These patients were reviewed at a mean follow-up time of 15 months for ultrasound results as well as functional outcome concerning complications, pain, range of motion, and grip strength measured with a Vernier-Dynamometer. Satisfaction of the patients was investigated by Clients Satisfaction Questionnaire. Radiographs before nail removal, ultrasound, and clinical examination always showed complete union of the fracture without deviation of axis. All patients gained full range of motion without any limits in daily activity and sports. There was no loss of grip strength compared with the other hand. Patients' satisfaction was very high, especially because of almost no postoperative pain and lack of immobilization. This method can be offered as an effective and safe alternative in the treatment of closed displaced fractures of the 2-5 metacarpus without significant complications.

[Percutaneous closed pin fixation of supracondylar fractures of the distal humerus in children]. / Gekreuzte Kirschner-Draht-Osteosynthese der suprakondylären Humerusfraktur bei Kindern.

OBJECTIVE: Prevention of long-term angular and extension deformity of the elbow and restoration of full range of motion. INDICATIONS: Malalignment of > 20 degrees in the sagittal plane in children > 6 years. Rotatory displacement as well as displacement in the frontal plane. CONTRAINDICATIONS: Severe cardiorespiratory diseases. SURGICAL TECHNIQUE: In most cases, a closed reduction is possible. Fixation of the fracture with two percutaneous Kirschner wires from lateral and medial; the pins cross beyond the fracture line and penetrate the metaphyseal cortex. POSTOPERATIVE MANAGEMENT: Elbow cast in 90 degrees flexion; the cast has to be split. Removal of cast and pins after 3-4 weeks. Occasionally physiotherapy required. RESULTS: Between October 2005 and September 2006, 77 supracondylar fractures were treated. According to the classification of von Laer 31 were type I (no displacement), 14 type II, nine type III, and 23 type IV (wide displacement). 34 of them required operative treatment due to nine type III and 23 type IV displacements, as well as two cases with (unstable) type II. In all patients treated surgically, the elbow angle was successfully restored. At follow-up after 8-14 months, 32 had regained full range of motion. In two children, extension/flexion was 0-10-120 degrees and 0-10-140 degrees , respectively. Two deficits of the ulnar nerve due to the operation as well as one deficit of the median nerve and the radial nerve due to the initial trauma recovered completely. According to the Flynn Score 32 patients had an excellent outcome; one result was classified as good and one as satisfactory. On the Mayo Performance Score all patients reached 100 of 100 points.