Sacral neuromodulation in children and adolescents with defecation disorders.

BACKGROUND: Even if understanding of neuronal enteropathies, such as Hirschsprung's disease and functional constipation, has been improved, specialized therapies are still missing. Sacral neuromodulation (SNM) has been established in the treatment of defecation disorders in adults. The aim of the study was to investigate effects of SNM in children and adolescents with refractory symptoms of chronic constipation. METHODS: A two-centered, prospective trial has been conducted between 2019 and 2022. SNM was applied continuously at individually set stimulation intensity. Evaluation of clinical outcomes was conducted at 3, 6, and 12 months after surgery based on the developed questionnaires and quality of life analysis (KINDLR). Primary outcome was assessed based on predefined variables of fecal incontinence and defecation frequency. KEY RESULTS: Fifteen patients enrolled in the study and underwent SNM (median age 8.0 years (range 4-17 years)): eight patients were diagnosed with Hirschsprung's disease (53%). Improvement of defecation frequency was seen in 8/15 participants (53%) and an improvement of fecal incontinence in 9/12 patients (75%). We observed stable outcome after 1 year of treatment. Surgical revision was necessary in one patient after electrode breakage. Urinary incontinence was observed as singular side effect of treatment in two patients (13%), which was manageable with the reduction of stimulation intensity. CONCLUSIONS: SNM shows promising clinical results in children and adolescents presenting with chronic constipation refractory to conservative therapy. Indications for patients with enteral neuropathies deserve further confirmation.

Suspected Simple Appendicitis in Children: Should We Use a Nonoperative, Antibiotic-Free Approach? An Observational Study.

BACKGROUND: Simple appendicitis may be self-limiting or require antibiotic treatment or appendectomy. The aim of this study was to assess the feasibility and safety of a nonoperative, antibiotic-free approach for suspected simple appendicitis in children. METHODS: This single-center, retrospective study included patients (0-17 years old) who were hospitalized at the pediatric surgery department due to suspected appendicitis between 2011 and 2012. Data from patients who primarily underwent appendectomy were used as controls. The follow-up of nonoperatively managed patients was conducted in 2014. The main outcome of interest was appendicitis recurrence. RESULTS: A total of 365 patients were included: 226 were treated conservatively and 139 underwent appendectomy. Fourteen (6.2% of 226) of the primarily nonoperatively treated patients required secondary appendectomy during follow-up, and histology confirmed simple, uncomplicated appendicitis in 10 (4.4% of 226) patients. Among a subset of 53 patients managed nonoperatively with available Alvarado and/or Pediatric Appendicitis Scores and sonographic appendix diameters in clinical reports, 29 met the criteria for a high probability of appendicitis. Three of these patients (10.3% of 29) underwent secondary appendectomy. No complications were reported during follow-up. CONCLUSIONS: A conservative, antibiotic-free approach may be considered for pediatric patients with suspected uncomplicated appendicitis in a hospital setting. Only between 6 and 10% of these patients required secondary appendectomy. Nevertheless, the cohort of patients treated nonoperatively was likely to have also included individuals with further abdominal conditions other than appendicitis. Active observation and clinical support during the disease course may help patients avoid unnecessary procedures and contribute to spontaneous resolution of appendicitis or other pediatric conditions as the cause of abdominal pain. However, further studies are needed to define validated diagnostic and management criteria.

Interpretable and intervenable ultrasonography-based machine learning models for pediatric appendicitis.

Appendicitis is among the most frequent reasons for pediatric abdominal surgeries. Previous decision support systems for appendicitis have focused on clinical, laboratory, scoring, and computed tomography data and have ignored abdominal ultrasound, despite its noninvasive nature and widespread availability. In this work, we present interpretable machine learning models for predicting the diagnosis, management and severity of suspected appendicitis using ultrasound images. Our approach utilizes concept bottleneck models (CBM) that facilitate interpretation and interaction with high-level concepts understandable to clinicians. Furthermore, we extend CBMs to prediction problems with multiple views and incomplete concept sets. Our models were trained on a dataset comprising 579 pediatric patients with 1709 ultrasound images accompanied by clinical and laboratory data. Results show that our proposed method enables clinicians to utilize a human-understandable and intervenable predictive model without compromising performance or requiring time-consuming image annotation when deployed. For predicting the diagnosis, the extended multiview CBM attained an AUROC of 0.80 and an AUPR of 0.92, performing comparably to similar black-box neural networks trained and tested on the same dataset.

Bado III Monteggia in children - treatment options and outcome: an ultrasound control study.

The Bado III Monteggia lesion is an uncommon fracture in children. Radial head dislocation can occur due to intra- or extra-articular fractures of the olecranon. In extra-articular ulnar fractures, heterogeneous operative methods are proposed in different case reports. The objective of this study is to determine if closed reduction of the ulnar fracture, either without osteosynthesis or by using TEN, is a safe treatment option. In a multicenter study, we retrospectively analyzed 26 children who were treated for an extra-articular proximal metaphyseal ulnar fracture with dislocation of the radial head. These patients underwent a follow-up examination after an average of four years. The investigation included a physical examination, visualization of the elbow anatomy, and specifically, the radial head retention in the joint by ultrasound. Of the 26 patients, 18 were treated by closed reduction and intramedullary osteosynthesis (TEN), 7 were treated by closed reduction and cast immobilization without osteosynthesis, and 1 child was treated by open reduction of the ulna and plate osteosynthesis. In the follow-up examination, 25 children showed an excellent outcome, as well as inapparent sonography. Although this is a retrospective study with different types of treatment, closed reduction of the ulna with or without osteosynthesis appears to be effective. We believe that the correct primary reduction is the key to an excellent long-term outcome. Regarding the invasiveness of the treatment, reduction without or with TEN osteosynthesis should be the preferred approach in extra-articular pediatric Bado III fractures.

Genome-wide identification of disease-causing copy number variations in 450 individuals with anorectal malformations.

Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2, LPP, and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.

Standardized Rehabilitation or Individual Approach?-A Retrospective Analysis of Early Rehabilitation Protocols after Isolated Posterior Cruciate Ligament Reconstruction.

(1) Background: Isolated posterior cruciate ligament (PCL) tears represent a severe type of injury. In hospitals, PCL reconstruction (PCL-R) is less frequently performed than other types of knee surgery. It is unclear whether there is consensus among surgeons on how to perform rehabilitation after PCL-R or if there are different, more individual approaches in daily routines. (2) Methods: Rehabilitation protocols and their main criteria (the progression of weight bearing and range of motion, the use of knee braces, rehabilitation training, and sports-specific training) were retrospectively analyzed after PCL-R. (3) Results: Only 33 of 120 (27.5%) analyzed institutes use rehabilitation protocols after PCL-R. The applied protocols showed vast differences between the individual rehabilitation criteria, especially with regard to the progression of weight bearing and the range of motion. The only standardized recommendations were the obligatory use of knee braces and the general restriction of weight bearing and range of motion immediately post-surgery. Therefore, because of the lack of a consensus about a standardized rehabilitation protocol after PCL-R, no recommendation can be made on one particular protocol. (4) Conclusion: There is no acknowledged standardized rehabilitation protocol after PCL-R. In clinical practice, recommendations are influenced by, i.a., surgeons' opinions and experience. The lack of scientific evidence on a particular standardized rehabilitation protocol after PCL-R suggests that rehabilitation protocols need to be tailored to the individual patient.

Immune-modulating properties of blue light do not influence reepithelization in vitro.

Phototherapy is gaining more attention in the treatment of various diseases. Especially, blue light seems to be a promising approach for wound healing promotion due to its antimicrobial and immune-modulating properties. Despite this, there is only little research focusing on the immune-modulating properties of blue light and its possible effects on wound healing. Therefore, we investigated the effects of blue light irradiation on peripheral blood mononuclear cells (PBMC) and the influence on reepithelization in vitro. PBMCs were irradiated with DermoDyne® (DermoDyne HealthCare, Berlin, Germany) and effects on cell viability, cytokine expression, and scratch wound closure were evaluated afterwards. Irradiated cells showed a higher Interleukin-γ concentration while irradiation reduced resazurin concentration in a time-dependent manner. No differences in reepithelization were detectable when keratinocytes were treated with the supernatant of these blue light irradiated PBMCs. Blue light-mediated ex vivo stimulation of PBMCs does not cause faster reepithelization in an in vitro setting. Further research is needed to investigate the wound healing effects of phototherapy with blue light.

Increased Incidence of Perforated Appendicitis in Children During COVID-19 Pandemic in a Bavarian Multi-Center Study.

Introduction: Since early 2020 the COVID-19 pandemic and statutory preventive reorganization of treatment capacities with cancellation of elective surgery as well as curfew regulations led to vastly decreased utilization of primary health care. Materials and Methods: To assess whether there are negative effects on pediatric acute care in Bavaria during the spring 2020 lockdown a state-wide retrospective multi-center study was performed to analyze the rate of perforated appendicitis during lockdown. Children who have been operated on during the corresponding period in 2018/19 served as control group. Results: Overall, 514 patients (292 boys, 222 girls) were included (2020: 176 patients; 2019: 181 patients; 2018: 157 patients). Median age was 11.2 years. Four hundred thirty-nine patients (85.4%) underwent laparoscopic surgery, 69 (13.4%) open surgery and 1.2% underwent conversion from laparoscopic to open surgery. In 2020 a perforation rate of 27.8% (49/176 patients) was found, in 2018-2019 perforation rate was 20.7% (70/338 patients, p = 0.0359, Cochran-Mantel-Haenszel-Test). Subgroup analysis showed that in younger patients (≤ 11.2 years), in 2020 perforation rate was significantly higher with 37.6% (32/85 patients), while 22.2% (39/176) in 2018/2019 (p = 0.014, Fisher's exact test).In boys perforation rate was significantly higher in 2020 with 35.0% (35/100 patients) compared to 21.4% in 2018-2019 (p = 0.0165, Fisher's exact test). Conclusion: During the period of curfew regulations in Bavaria the rate of perforated appendicitis in childhood increased significantly, especially in younger children and boys. Potentially this has to be attributed to delayed presentation to pediatric surgery care. Because of potential long-term sequelae of perforated appendicitis these adverse effects during curfew have to be taken into account for future political decision making to ensure reasonable patient care and avoid collateral damage in near-future or on-going pandemic situations.

Using Machine Learning to Predict the Diagnosis, Management and Severity of Pediatric Appendicitis.

Background: Given the absence of consolidated and standardized international guidelines for managing pediatric appendicitis and the few strictly data-driven studies in this specific, we investigated the use of machine learning (ML) classifiers for predicting the diagnosis, management and severity of appendicitis in children. Materials and Methods: Predictive models were developed and validated on a dataset acquired from 430 children and adolescents aged 0-18 years, based on a range of information encompassing history, clinical examination, laboratory parameters, and abdominal ultrasonography. Logistic regression, random forests, and gradient boosting machines were used for predicting the three target variables. Results: A random forest classifier achieved areas under the precision-recall curve of 0.94, 0.92, and 0.70, respectively, for the diagnosis, management, and severity of appendicitis. We identified smaller subsets of 6, 17, and 18 predictors for each of targets that sufficed to achieve the same performance as the model based on the full set of 38 variables. We used these findings to develop the user-friendly online Appendicitis Prediction Tool for children with suspected appendicitis. Discussion: This pilot study considered the most extensive set of predictor and target variables to date and is the first to simultaneously predict all three targets in children: diagnosis, management, and severity. Moreover, this study presents the first ML model for appendicitis that was deployed as an open access easy-to-use online tool. Conclusion: ML algorithms help to overcome the diagnostic and management challenges posed by appendicitis in children and pave the way toward a more personalized approach to medical decision-making. Further validation studies are needed to develop a finished clinical decision support system.

Does Phototherapy Promote Wound Healing? Limitations of Blue Light Irradiation.

INTRODUCTION: Phototherapy is gaining increased attention in the research and treatment of various diseases. In particular, the use of blue light seems to bear promise, owing to its antimicrobial and immune-modulating properties; however, research focused on the effects of blue light on keratinocytes and reepithelization is rare. In addition, few studies to date have evaluated devices that are used in daily hospital routine. OBJECTIVE: This study investigated the effects of phototherapy on keratinocytes with 2 established devices in vitro. MATERIALS AND METHODS: Human adult low calcium high temperature keratinocytes were irradiated with 2 different devices, and the effects on scratch wound closure, proliferation, cell viability, and cytokine expression were evaluated. RESULTS: Blue light irradiation reduced reepithelization at high doses in a scratch wound healing model (wound closure on day 1: control group, 25.57 percentage points [PP] ± 2.36 standard deviation vs Device A for 10 minutes, 1.33 PP ± 1.01) and mitochondrial activity measured with resazurin conversion (Device A for 10 minutes, 33.28% ± 12.34). Irradiated cells demonstrated a lower ratio of proliferating cell nuclear antigen-positive cells and, as a result, lower proliferation. CONCLUSIONS: Blue light reduces keratinocyte proliferation and migration at high doses and therefore could negatively affect wound healing. Available irradiation devices for possible use in wound therapy should be critically scrutinized and evaluated with in vitro methods prior to clinical use.

Safety and performance of biodegradable magnesium-based implants in children and adolescents.

AIMS: Biodegradable magnesium-based alloy implants represent a promising option in orthopedic surgery, as the clinical outcomes have been reported to be comparable to those of titanium implants and no surgical interventions are required for removal. To date, little is known about the results of the use of these implants in children and adolescents. Therefore, the aim of the present study was to analyze the safety and performance of these implants in children and adolescents. PATIENTS AND METHODS: Eighty-nine patients treated with magnesium-based implants for fracture stabilization, osteotomy and osteochondral refixation were analyzed; 38 were treated by osteosynthesis; 18, osteotomy; and 33, osteochondral refixation. The mean follow-up duration was 8.2 months (range, 1.5-30 months). Clinical and radiographical follow-up examinations were performed at 4-8 weeks and 3-6 months, respectively, to evaluate implant performance and osseous consolidation. RESULTS: Clinical outcomes were rated as good to very good in all patients. Radiolucent zones were apparent after surgery in all patients but were noted to decrease in size during the follow-up period. Revision surgery was necessary in 1 of 89 patients who had a highly unstable osteochondritis dissecans lesion of the knee. None of the magnesium-based implants required surgical removal. CONCLUSION: Magnesium-based implants in children and adolescents results in good clinical outcomes when used for fracture stabilization, osteotomy and osteochondral defect refixation. Future studies are needed to further analyze the significance of the transient appearance and temporal development of radiolucent zones in the growing skeleton as well as the long-term performance of these implants.

The safety and satisfaction of ovarian tissue cryopreservation in prepubertal and adolescent girls.

RESEARCH QUESTION: Is ovarian tissue cryopreservation (OTC) for fertility preservation in prepubertal and adolescent girls safe, and who would benefit most from the procedure? DESIGN: Survey and retrospective study including patients who had OTC under the age of 18 years in a single centre for fertility preservation. Serum anti-Müllerian hormone levels were measured as a marker for detection of diminished ovarian reserve. RESULTS: Fifty-three from 102 women participated in the survey (12 deceased, 19 declined, 17 unreachable, 1 palliative). The average age at OTC was 14.8 ± 2.3 (range: 6-17) years and at survey 21.9 ± 4.3 (range: 16-33) years. Ovarian tissue retrieval (laparoscopy: n = 45, laparotomy: n = 8) was without complications in 52 cases. In 23 (53.5%) of the 43 women who were post-menarchal at OTC, transient amenorrhoea occurred. At survey, 15 women reported a regular menstrual cycle, 25 used oral contraceptives, 9 women reported hormone replacement therapy due to primary ovary insufficiency and 4 had amenorrhoea. Two patients reported the birth of a healthy child after IVF, while 51 patients are still childless, mostly due to their young age (mean: 21.2 years). To date, one patient has had transplantation of the ovarian tissue (17 years at cryopreservation). Forty-nine of the interviewees would again decide on OTC, while three argued against it on the basis of the previous financial cost; one woman was unsure. CONCLUSIONS: Children with cancer may be at risk for gonadal insufficiency. OTC is practically the only technique that can be offered to young girls. The procedure is safe and well accepted.

A retropharyngeal-mediastinal hematoma with supraglottic and tracheal obstruction: The role of multidisciplinary airway management.

A 77-year-old man suffered hypoxemic cardiac arrest by supraglottic and tracheal airway obstruction in the emergency department. A previously unknown cervical fracture had caused a traumatic retropharyngeal-mediastinal hematoma. A lifesaving surgical emergency tracheostomy succeeded. Supraglottic and tracheal obstruction by a retropharyngeal-mediastinal hematoma with successful resuscitation via emergency tracheostomy after hypoxemic cardiac arrest has never been reported in a context of trauma. This clinically demanding case outlines the need for multidisciplinary airway management systems with continuous training and well-implemented guidelines. Only multidisciplinary staff preparedness and readily available equipments for the unanticipated difficult airway solved the catastrophic clinical situation.

Long-term outcome of hyperthermic isolated limb perfusion (HILP) in the treatment of locoregionally metastasised malignant melanoma of the extremities.

OBJECTIVE: The aim is to analyse a modified standardised HILP procedure regarding the response rates, local recurrences and complication rates. PATIENTS AND METHODS: 152 patients (101 females, 51 males) with an average age of 62 years and locoregionally metastasised malignant melanoma underwent HILP using melphalan and dactinomycin between 1992 and 2007. Using M.D. Anderson's classification at the time of the perfusion 51 patients presented in stage IIIA, 43 patients in stage IIIAB and 58 patients in stage IV. If indicated, lymph node dissection was performed simultaneously just before perfusion of the extremity. RESULTS: Complete remission was observed in 91 (62.7%) of 145 patients, partial remission in 26 (17.9%) patients. 28 (19.3%) patients showed no response. The overall response rate was 80.7% (117 of 145 patients). Severe complications (Wieberdink IV/V) were seen in eight cases. The average recurrence-free survival was 17 months. The median survival was 39 months; the five-year overall survival rate was 38%. The overall survival rate was significantly influenced by the stage of the disease. CONCLUSION: HILP is an efficient therapy for multiple or recurrent in-transit metastases of malignant melanoma of the lower extremities. The efficiency increased by improving the technique of the perfusion. Long-term survival can be observed in patients without regional lymph node metastases or distant metastases.