Allograft Versus Bioactive Glass (BG-S53P4) in Pediatric Benign Bone Lesions: A Randomized Clinical Trial.

BACKGROUND: Benign bone cysts in children have a high risk of recurrence after bone grafting. The optimal treatment and filling material for these lesions are currently unknown. METHODS: We compared cyst recurrence after intralesional curettage and filling with allograft versus bioactive glass (BG-S53P4; Bonalive) in a randomized clinical trial. The volume of recurrent cyst at 2-year follow-up was the primary outcome. RESULTS: Of 64 eligible children, 51 (mean age, 11.1 years) were randomized to undergo filling of the cyst using morselized allograft (26) or bioactive glass (25). Twelve (46%) of the children in the allograft group and 10 (40%) in the bioactive glass group developed a recurrence (odds ratio [OR] for bioactive glass = 0.79, 95% confidence interval [CI] = 0.25 to 2.56, p = 0.77). The size of the recurrent cyst did not differ between the allograft group (mean, 3.3 mL; range, 0 to 13.2 mL) and the bioactive glass group (mean, 2.2 mL; range, 0 to 16.6 mL, p = 0.43). After adjusting for the type of lesion (aneurysmal bone cyst versus other), bioactive glass also did not prevent larger (>1 mL) recurrent cysts (adjusted OR = 0.42, 95% CI = 0.13 to 1.40, p = 0.16). The Musculoskeletal Tumor Society score improved significantly (p ≤ 0.013) from preoperatively to the 2-year follow-up in both groups (to 28.7 for bioactive glass and 29.1 for bone graft). Four (15%) of the children in the allograft group and 6 (24%) in the bioactive glass group required a reoperation during the follow-up (OR for bioactive glass = 1.74, 95% CI = 0.43 to 7.09, p = 0.50). CONCLUSIONS: Filling with bioactive glass and with allograft in the treatment of benign bone lesions provided comparable results in terms of recurrence and complications. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Postoperative outcomes of pedicle screw instrumentation for adolescent idiopathic scoliosis with and without a subfascial wound drain: a multicentre randomized controlled trial.

AIMS: The aim of this study was to evaluate whether, after correction of an adolescent idiopathic scoliosis (AIS), leaving out the subfascial drain gives results that are no worse than using a drain in terms of total blood loss, drop in haemoglobin level, and opioid consumption. METHODS: Adolescents (aged between 10 and 21 years) with an idiopathic scoliosis (major curve ≥ 45°) were eligible for inclusion in this randomized controlled noninferiority trial (n = 125). A total of 90 adolescents who had undergone segmental pedicle screw instrumentation were randomized into no-drain or drain groups at the time of wound closure using the sealed envelope technique (1:1). The primary outcome was a drop in the haemoglobin level during first three postoperative days. Secondary outcomes were 48-hour postoperative oxycodone consumption and surgical complications. RESULTS: All 90 patients were included in the primary outcome analysis (no drain = 43; drain = 47). The mean total postoperative blood loss (intraoperative and drain output) was significantly higher in the group with a subfascial drain than in the no-drain group (1,008 ml (SD 520) vs 631 ml (SD 518); p < 0.001). The drop in haemoglobin level did not differ between the study groups over the postoperative timepoints (p = 0.290). The 48-hour opioid consumption was significantly higher in the no-drain group (2.0 mg/kg (SD 0.9) vs 1.4 (SD 0.6); p = 0.005). Two patients in the no-drain and one patient in the drain group developed a surgical site infection. CONCLUSION: Leaving the subfascial drain out after pedicle screw instrumentation for AIS is not associated with higher postoperative haemoglobin levels. Patients treated without a subfascial drain needed 30% more opioids during the first 48 hours than those who had a drain.Cite this article: Bone Joint J 2022;104-B(9):1067-1072.

Cast immobilisation in situ versus open reduction and internal fixation of displaced medial epicondyle fractures in children between 7 and 16 years old. A study protocol for a randomised controlled trial.

INTRODUCTION: Medial epicondyle fracture of the humerus is a common injury in childhood. There is uniform agreement that minimally displaced fractures (dislocation ≤2 mm) can be treated nonoperatively with immobilisation. Open fractures, fractures with joint incarceration or ulnar nerve dysfunction require surgery. There is no common consensus in treatment of closed medial epicondyle fractures with >2 mm dislocation without joint incarceration or ulnar nerve dysfunction. We hypothesise that there is no difference in treatment outcomes between nonoperative and operative treatment. METHODS AND ANALYSIS: This is a multicentre, controlled, prospective, randomised noninferiority study comparing operative treatment to non-operative treatment of >2 mm dislocated paediatric medial epicondyle fractures without joint incarceration or ulnar nerve dysfunction. A total of 120 patients will be randomised in 1:1 ratio to either operative or nonoperative treatment. The study will have a parallel nonrandomised patient preference arm. Operative treatment will be open reduction and internal fixation. Nonoperative treatment will be upper limb immobilisation in long arm cast for 4 weeks. Data will be collected at baseline and at each follow-up up to 2 years. Quick-DASH is used as primary outcome measure. Secondary outcomes are patient-reported pain, differences in range of motion, Pediatric Quality of Life Inventory, cosmetic visual analogue scale and Mayo Elbow Performance Score. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Helsinki University Hospital (HUS) ethical board HUS/1443/2019. Each study centre has obtained their own permission for the study. A written authorisation from legal guardian will be acquired and the child will be informed about the trial. Results of the trial will be disseminated as published articles in peer-reviewed journals. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov with registration number NCT04531085.

Physeal Fractures of Distal Tibia: A Systematic Review and Meta-analysis.

BACKGROUND: Fractures involving the distal tibia growth plate are common in children. Injury or treatment that damages the growth plate may result in progressive angular deformity or leg length discrepancy. There is no consensus on treatment and follow-up of these injuries. This study aims to describe which factors increase the risk of premature physeal closure (PPC). MATERIAL AND METHODS: A systematic review and meta-analysis were performed. Altogether 395 articles were reviewed, and ultimately 12 of them were found eligible, comprising 1997 patients. The most usual type of fracture was Salter-Harris (SH) II (n=855, 49%) followed by SH III (n=296, 17%) and SH I (n=261, 15%). The risk of PPC according to number of reduction attempts, method of treatment, and residual displacement was the primary outcome. RESULTS: The total rate of PPC was 13% (n=245). The PPC rate varied from 0.2% to 42% across the studies. Patients with SH IV fractures were most likely to develop PPC (20%), followed by those with SH II (12%) (P<0.05) and repeated (>2) reduction maneuvers were associated with a higher risk of PPC (pooled odds ratio, 8.5; 95% confidence interval, 6.3-12.17; P<0.05). Open reduction was associated with a lower risk of PPC when analyzing only displaced fractures (odds ratio, 0.63; 95% confidence interval, 0.38-0.91; P<0.05). INTERPRETATION: This meta-analysis implies that residual displacement after reduction is the most significant factor in predicting PPC. It seems that open reduction might reduce the PPC rate among patients with dislocated fractures. In addition, there is some evidence that a higher number of reduction attempts correlates positively with the risk of PPC.

Risk of premature physeal closure in fractures of distal tibia.

The reported incidence of premature physeal closure (PPC) in fractures of the distal tibia has varied between 5 and 36%, but there is no consensus on the cause. We wanted to determine incidence and predictors of PPC in distal tibia physeal fractures in a population-based patient cohort. Two hundred forty-one patients (195 Peterson type I-V fractures and 46 transitional fractures) treated for a physeal fracture of the distal tibia during a 5-year period in two tertiary-level teaching hospitals. Odds ratios (OR) for developing PPC for different parameters (Peterson fracture type, associated fibula fracture, primary and postreduction displacement, number of reductions and the method of treatment) were calculated by binary logistic regression analysis. In 195 children with Peterson type I-V fractures PPC was diagnosed in 21 children (11%), of which 11 (6%) had surgery at mean 14 months from the fracture to correct either angular deformity or leg length discrepancy. The incidence of distal tibia PPC is at least 0.05/1000 children. More than one reduction attempt was the most significant risk factor (OR 7.0) for PPC. Peterson fracture type, associated fibula fracture, initial or post-reduction displacement or type of treatment did not correlate with PPC. The incidence of distal tibia PPC is at least 0.05/1000 children. The number of reductions correlates positively with the risk of PPC.

No single reason behind adult lower urinary tract symptoms in patients with posterior urethral valves.

Objective: To analyze which factors in the history of a posterior urethral valve (PUV) patient relate to lower urinary tract symptoms (LUTS) in adulthood. This study also aimed to evaluate whether the patients have developed signs of a myogenic failure of detrusor. Materials and methods: LUTS were evaluated with a DAN-PSS questionnaire in 78 adult patients treated for PUV in childhood. Symptom scores (SS) were compared with patient characteristics and types of treatment. The results of uroflowmetry and post-voiding residual (PVR) measurements were collected from their latest visit to Helsinki University Children's Hospital. Results: The median total symptom score (TSS) was 1 (IQR = 0-5, range = 0-18). The patient age during the investigation and SS were associated (R = 0.220, p = 0.032), but the primary creatinine level and SS were not (R = 0.260, p = 0.081). The median age for achieving continence was 6.3 years. The SS and the age when becoming continent were not associated (p = 0.365 and p = 0.679, respectively). In the age group of 39 years or more, 19 patients with a previous bladder neck incision (BNI) had a higher storage-SS than 15 patients without any previous bladder neck incision (1 (IQR = 0-5) vs 0 (IQR = 0-0), p = 0.030). According to symptoms and post-voiding residual measurements, myogenic failure in adults seems to be rare. Conclusions: LUTS are common, but severe symptoms referring to myogenic failure are rare in men treated for PUV in childhood. The specific reasons for LUTS are difficult to indicate and even the sickest children do not necessarily have LUTS in adulthood.

Treatment of Unstable Pediatric Tibia Shaft Fractures in Finland.

BACKGROUND: Surgical treatment of pediatric tibia shaft fractures has gained popularity despite closed reduction and cast-immobilization providing good long-term results. There is no consensus about optimal methods and satisfactory quality of treatment. MATERIALS AND METHODS: During 2010 to 2014, 226 pediatric patients were treated under anesthesia for tibia shaft fractures in Finland's five university hospitals. A total of 164 (73%) patients had closed fractures of the tibia or both tibia and fibula without other injuries (62 tibia only and 102 both tibia and fibula). Forty-one (18%) had open tibia fractures, 16 had additional fractures, and 5 (2%) had sustained a polytrauma (Injury Severity Score [ISS] > 15). Treatment methods, follow-up protocols, complications, and the outcome were analyzed. RESULTS: A total of 143 (63%) of the tibia fractures were treated surgically: 87 (53%) closed fractures, 36 (88%) open fractures, 15 (94%) with additional fractures, and 5 (2%) polytrauma patients. The rate of surgical treatment of closed tibia fractures was significantly higher in patients older than 10 and in patients with a concomitant fibula fracture. Fasciotomy was done in 33 (15%) patients. Reoperations were performed in 13 (6%) patients because of unsatisfactory treatment (inappropriate primary reduction 6, malunion 6, and non-union 1). There were no differences between the five university hospitals in treatment or follow-up protocols. CONCLUSION: Internal fixation is used for the majority of tibia shaft fractures treated under anesthesia in university hospitals in Finland. Serious fracture or treatment related complications are very rare, but the percentage (6%) of re-operations because of unsatisfactory standard of treatment should be lower and could probably be improved by concentrating internal fixation to fewer hands. A prospective randomized controlled trial comparing non-operative treatment to intramedullary nailing in pediatric tibia fractures should be performed.

Controlled Outcomes for Achievement of Urinary Continence among Boys Treated for Posterior Urethral Valves.

PURPOSE: We evaluated the age at which boys with a history of posterior urethral valves after no or minimal anticholinergic medication achieve urinary continence and the factors contributing to continence. MATERIALS AND METHODS: We reviewed the hospital records of all males treated for posterior urethral valves at a single institution between 1990 and 2008. Continence was considered to have been attained if no weekly wetting episodes occurred. We evaluated the influence of patient characteristics, including reduced kidney function and primary ring type ureteral stoma, on age at which continence was achieved. RESULTS: A total of 76 patients were assessed. Achievement of daytime and nighttime urinary continence was markedly delayed in patients (mean ± SD age 5.5 ± 3.3 years and 5.4 ± 3.0 years, respectively) compared to the reference population (2.3 ± 0.5 and 2.9 ± 1.2, p <0.001). Increased serum creatinine levels at age 5 years were associated with later daytime and nighttime continence (mean ± SD 6.0 ± 3.2 and 5.5 ± 2.6 years, respectively, vs 4.1 ± 2.3 and 3.7 ± 1.4 years, respectively, in patients with normal serum creatinine, p ≤0.05). Prenatal or neonatal diagnosis of posterior urethral valves was associated with significantly delayed achievement of daytime continence compared to cases diagnosed later (mean ± SD 5.9 ± 3.6 vs 4.1 ± 1.8 years, p = 0.02). Patients with high nadir serum creatinine and vesicoureteral reflux initially also were at increased risk for urinary tract infections (p = 0.003 and p <0.001, respectively). CONCLUSIONS: Patients with posterior urethral valves achieve daytime and nighttime urinary continence significantly later than their healthy peers. Prenatal or neonatal diagnosis and high serum creatinine are associated with later attainment of continence.

The impact of posterior urethral valves on adult quality of life.

OBJECTIVE: To investigate the quality of life of men who had been treated for posterior urethral valves (PUV) in childhood. PATIENTS AND METHODS: Questionnaires were mailed to 108 patients with PUV treated at the Children's Hospital, University of Helsinki, and 67 (62%) of them responded. Three different questionnaires (15D, LSS, and RAND) were used to evaluate the quality of life. RESULTS: The total quality of life in PUV patients was reported as good compared to the general population in the RAND and LSS surveys. However, in the 15D analysis the PUV patients reported lower scores in sleeping, eating, and sexual activity. Those PUV patients who had been treated for renal insufficiency reported lower scores in several dimensions in all three surveys. Patients with urinary incontinence reported more sleeping problems and regarded themselves physically more disabled. CONCLUSIONS: The PUV patients with renal insufficiency or urinary incontinence had impaired quality of life in several dimensions.

Bfk, a novel member of the bcl2 gene family, is highly expressed in principal cells of the mouse epididymis and demonstrates a predominant nuclear localization.

B-cell lymphoma 2 (BCL2) family kin (BFK) is a recently identified novel protein that is similar to proteins of the BCL2 family. In the present study, we discovered that the mouse Bfk transcript is expressed at the highest level in the epididymis. Two transcripts of 0.9 and 2.6 kb in size were identified, with alternative exon 4 structures, resulting in a difference in the last three to five amino acids of the variants. However, the 0.9-kb transcript was found to be the predominant form in the epididymis and mammary gland, another tissue with strong Bfk expression. Epididymal Bfk expression was regulated both by androgens and other testicular factors. It is thus one of the few initial-segment enriched genes under androgen control, the majority of them being regulated by other testicular factors. BFK protein was expressed specifically in the principal cells of the epididymis. Its nuclear localization was evident in the initial segment and caput epididymis and in the epithelium of pregnant female mammary gland. The expression of BFK-enhanced green fluorescent protein recombinant protein in epididymal cells further confirmed the predominant nuclear localization of BFK with nucleo-cytoplasmic shuttling. Overexpressing BFK in epididymal cells did not induce apoptosis. However, enhanced caspase 3 activation was observed in the presence of BFK upon staurosporine-induced apoptosis. This suggests that BFK may have a proapoptotic role only after the process has been initiated by other mechanisms. Being exceptionally highly expressed in the initial segment, Bfk is suggested to have a role in the differentiation of this segment of the epididymis.

Novel epididymal protease inhibitors with Kazal or WAP family domain.

The epididymal maturation of spermatozoa is regulated by changes in the luminal ion concentration and the processing of the sperm surface membrane by several glycosidases and proteases. In the present study, we identified five novel protease inhibitors that are highly expressed in the mouse epididymis. Four of the proteins were found to belong to the Kazal protease inhibitor family and were named SPINK8, SPINK10, SPINK11, and SPINK12, whereas one of the proteins, WFDC10, contained the WAP four-disulfide core domain structure. The novel genes showed very specific segmental expression patterns. The expression of all the five genes was regulated by testis-derived factors and decreased after gonadectomy. With the exception of Spink11, mRNA levels could be restored by testosterone replacement. We hypothesize that the protease inhibitors discovered represent a group of epididymal genes that contribute to the regulation of sperm maturation by regulating the proteolytic processing of the sperm membrane during epididymal transit.

Identification of novel epididymal genes by expression profiling and in silico gene discovery.

We have used both the UniGene RIKEN epididymal EST library and the Affymetrix microarray profiling for identifying novel epididymal genes in mouse. The use of ESTs is a complementary approach to Affymetrix arrays for identifying novel epididymal genes, while only 32% and 28% of ESTs of unknown genes were present in the U74v.2Set and MG 430 2.0 version Affymetrix arrays, respectively. As expected, the probe set for a notably larger proportion of known genes was present in the Affymetrix arrays, and the coverage was greatly improved by the newer array version. Furthermore, many genes with more than five ESTs in the UniGene library showed variable levels of expression in both versions of the Affymetrix arrays. However, both the Affymetrix and EST data correlated well with that obtained by quantitative RT-PCR, and thus, we conclude that the findings of high EST number but only limited expression in the arrays could be considered as false negatives in the Affymetrix arrays.

Discovery and characterization of new epididymis-specific beta-defensins in mice.

The male urogenital tract epithelium is exposed to several pathogens, but only a few are potent enough to cause infection in a healthy individual. The exact mechanisms that protect the male reproductive tract from ascending pathogenic micro-organisms are still poorly characterized. We recently reported a method to identify novel epididymis-specific genes by analyzing the expressed sequence tags (ESTs) present in the mouse epididymal cDNA library of the UniGene collection at National Center for Biotechnology Information (NCBI). In the present study, we discovered in silico two novel epididymal genes: the beta-defensins Defb41 and Defb42. The full-length cDNAs for the genes were acquired by the RT-PCR and 5'-RACE approaches and were subsequently sequenced. Q-RT-PCR and in situ hybridization revealed Defb41 and Defb42 to be expressed mainly in the proximal caput. The expression of both defensins was found to be regulated by androgens. Based on their structure and expression pattern, Defb41 and Defb42 are suggested to have a role in the antimicrobial protection of sperm and urogenital tract epithelia.

Mouse cysteine-rich secretory protein 4 (CRISP4): a member of the Crisp family exclusively expressed in the epididymis in an androgen-dependent manner.

The final maturation of spermatozoa produced in the testis takes place during their passage through the epididymis. In this process, the proteins secreted into the epididymal lumen along with changes in the pH and salt composition of the epididymal fluid cause several biochemical changes and remodeling of the sperm plasma membrane. The Crisp family is a group of cysteine-rich secretory proteins that previously consisted of three members, one of which-CRISP1-is an epididymal protein shown to attach to the sperm surface in the epididymal lumen and to inhibit gamete membrane fusion. In the present paper, we introduce a new member of the Crisp protein family, CRISP4. The new gene was discovered through in silico analysis of the epididymal expressed sequence tag library deposited in the UniGene database. The peptide sequence of CRISP4 has a signal sequence suggesting that it is secreted into the epididymal lumen and might thus interact with sperm. Unlike the other members of the family, Crisp4 is located on chromosome 1 in a cluster of genes encoding for cysteine-rich proteins. Crisp4 is expressed in the mouse exclusively in epithelial cells of the epididymis in an androgen-dependent manner, and the expression of the gene starts at puberty along with the onset of sperm maturation. The identified murine CRISP4 peptide has high homology with human CRISP1, and the homology is higher than that between murine and human CRISP1, suggesting that CRISP4 represents the mouse counterpart of human CRISP1 and could have similar effects on sperm membrane as mouse and human CRISP1.