Female Pediatric Patients Research Articles

Pediatric Malignant Phyllodes Tumors of the Breast: Characteristics and Outcomes Based on the Surveillance Epidemiology and End Results Database

BackgroundMalignant phyllodes tumors of the breast are uncommon in women and rare in children. This study aimed to assess the differences in survival among five specific pathologic groups of breast malignancies and the differences between pediatric and adult breast phyllodes malignancy. Materials and methodsUsing the Surveillance, Epidemiology, and End Results database, we collected data on 270 pediatric (aged ≤21 y) female breast malignant tumor patients and 2773 female malignant phyllodes tumor patients between 1976 and 2015. We evaluated survival differences among younger patients with breast malignancy and compared the pediatric and adult groups based on characteristics, treatment patterns, and survival months. Finally, we identified the risk and protective factors for breast phyllodes cases using a multivariable Cox analysis. ResultsWe collected and analyzed 270 malignant breast cancer patients aged ≤21 y and 2773 malignant phyllodes tumor patients. Pediatric patients with malignant phyllodes tumors (22.2%, n = 60) exhibited better overall survival (OS; log-rank, P = 0.012) and cancer-specific survival (CSS; log-rank, P = 0.005) among the younger patients with malignant breast tumors. Furthermore, pediatric patients with malignant phyllodes tumors showed better OS (log-rank, P = 0.004), and similar CSS (log-rank, P = 0.105), compared with older patients. After adjustments for potential confounding factors, age >21 y, Black race, tumor size of >100 mm, high grade, wider invasion, positive nodal status, larger scope surgery, and no surgery were found to be associated with worse OS. All these factors, except for race, were found to be independent risk factors for CSS. ConclusionsThe prognosis of malignant phyllodes tumors in children is better than that of adults. Appropriate surgical scope and risk of overtreatment should be considered when treating pediatric malignant phyllodes tumor patients.

Female adolescents demonstrate greater oculomotor and vestibular dysfunction than male adolescents following concussion

ObjectiveTo examine differences between male and female adolescents on measures of balance, vestibular and oculomotor function within 3 weeks of concussion among a group of pediatric patients presenting to a sports medicine clinic. DesignMedical record review. SettingSports medicine clinic. Participants197 female (median age = 15.2 years) and 381 male (median age = 14.6 years) pediatric patients seen for a concussion, evaluated 9.3 ± 5.2 (mean ± SD) days post-concussion. Main outcome measuresPatients completed Balance Error Scoring System (BESS), tandem gait, gaze stability, and near point of convergence (NPC) tests. ResultsA higher proportion of female patients exhibited abnormal NPC (22% vs. 14%; p = 0.017), gaze stability (53% vs. 43%; p = 0.028), and tandem gait tests (20% vs. 13%; p = 0.026) compared to male patients. Multivariable analysis indicated an independent association between female sex and increased odds of abnormal NPC (adjusted odds ratio [aOR] = 1.79, 95% CI = 1.07–3.00), and tandem gait tests (aOR = 1.96, 95% CI = 1.12–3.41) following concussion. ConclusionsOur results indicate that within the first three weeks of a concussion, female pediatric patients demonstrated increased odds of exhibiting abnormal near point of convergence, and tandem gait test performance compared to male patients.

Endotracheal intubation with video laryngoscope at semilateral decubitus position: a case report of a pediatric patient with a back stab wound

Background: Endotracheal intubation is routinely performed in a supine position. However, this position might be difficult for some emergent patients. Although several alternative positions have been suggested for adult patients, such studies on pediatric patients are rare. Case presentation: We present a case of a female pediatric patient with a pencil stab wound to the back requiring an emergent operation under general endotracheal anesthesia. Placing her in supine position would have been inappropriate because of the protruding pencil. The patient was moved to a semilateral decubitus position for intubation. The endotracheal tube was inserted with a video laryngoscope. Her vital signs and oxygen saturation were stable during operation. The patient was discharged without complications. Conclusion: Semilateral intubation in pediatric patients using a video laryngoscope may be feasible under some specific conditions that make it inappropriate to place patients in a supine position.

Diagnosis and surgical management of Herlyn-Werner-Wunderlich syndrome

Abstract Abdominal pain in the adolescent population is rarely attributed to anatomic variance. Minimal consideration placed on this pathology can present a diagnostic dilemma and delay in care if such options are not investigated. Our case report describes the workup, step-by-step imaging and multidisciplinary approach to a twelve-year-old female who presented with abdominal pain at an outside facility, where she was originally diagnosed with a pelvic mass seeming to arise from the left ovary on ultrasound. Subsequent CT at the authors’ institution indicated a hydrometrocolpos and possible uterine and vaginal duplication; exam under anesthesia revealed uterine didelphys with obstructed left hemivagina. MRI confirmed the diagnosis of Herlyn-Werner-Wunderlich Syndrome and return to the operating room resulted in successful evacuation of the obstructed hemivagina by vaginal septum resection. Post-operatively, she is doing well, menstruating without difficulty, and has not had recurrence of symptoms. This case elucidates the need for consideration of Mullerian duct anomalies in female pediatric patients presenting with lower abdominal pain.

Are demographics associated with mucoepidermoid or acinic cell carcinoma parotid malignancies in children?

ObjectiveTo identify possible associations between patient demographics and parotid cancer histological type in pediatric patients.MethodsPediatric patients (ages: birth-18.0 years) in the Surveillance, Epidemiology, and End Results (SEER) database were included from 1973 to 2014 based on a diagnosis of mucoepidermoid carcinoma or acinic cell carcinoma of the parotid gland using the ICD O-3 codes of C07.9 and 8430 or 8550. Patients were classified into the following cohorts: <14 and 14–18 years of age based on the mean age at diagnosis.ResultsThree hundred and three pediatric patients were diagnosed with mucoepidermoid carcinoma or acinic cell carcinoma of the parotid gland within the SEER 18 registries. Female pediatric patients 14–18 years of age were 7.68 times more likely to have an acinic cell carcinoma (adjusted OR: 7.68 [95% CI: 2.01–29.44]). When stratified by histological type, 58.9% of female pediatric patients ≥14 years of age had an acinic cell carcinoma as compared to 37.3% of male pediatric patients ≥14 years of age, 36.5% of female pediatric patients <14 years of age, and 34.0% of male pediatric patients <14 years of age (P = 0.01).ConclusionsBased on this study, pediatric female patients between the ages of 14 and 18 years are the most likely cohort to have acinic cell carcinoma. The results of this study may assist providers during the work up of a pediatric patient with a suspected parotid malignancy.

Ovarian tumors in children: how common are lesion recurrence and metachronous disease? A UK CCLG Surgeons Cancer Group nationwide study

BackgroundOvarian tumors in children are rare, mature teratoma being the most common histological entity. Robust guidelines to aid patient follow-up after resection are distinctly lacking. Although mature teratoma has a very good prognosis following complete resection, small studies have reported the occurrence of metachronous disease and recurrence to a variable degree (2.5–23% of patients). Nevertheless, there are surgeons who recommend no follow-up is required for these children after primary tumor resection. We investigated the incidence of (i) recurrence and (ii) metachronous disease in pediatric patients following ovarian tumor resection. MethodsRetrospective multicenter study amongst UK pediatric surgical oncology centers. Females <16 years with diagnosis of ovarian tumor from 2006 to 2016 were included. Functional/neonatal ovarian cysts were excluded. ResultsThree hundred ten patients with ovarian tumors treated at 12 surgical oncology centers were identified. Mean age at surgery was 11 years [IQR 8–14]. Most common diagnosis were mature teratoma (57%, 177 cases), immature teratoma (10.9%, 34 cases) and serous cystadenoma (7.7%, 24 cases). 8.1% (25 cases) of all females were identified with tumor recurrence/ metachronous disease. 5.1% (9 cases) of patients with mature teratoma had recurrent/ metachronous disease. Most of these patients were diagnosed at routine clinic follow-up. ConclusionOur study clearly shows that ovarian tumor recurrence(s) and metachronous disease occur, even in “benign” ovarian tumors. We recommend female pediatric patients should have robust follow-up care plans after primary diagnosis and resection of ovarian tumor(s). Level of Evidence StatementThis is a level II evidence study. It is a retrospective multicentre collaborative study which summarizes data from a national cohort of children.

Opioid Prescribing Patterns for Low Back Pain Among Commercially Insured Children

Abstract INTRODUCTION Low back pain (LBP) may affect up to 20% of the pediatric population. No specific guidelines exist regarding pharmacotherapy for acute LBP in the pediatric population. Given this observation and the lack of data available regarding pharmacotherapy for pediatric LBP, we sought to characterize patterns of opioid prescribing in the pediatric population. METHODS We used a national database to identify pediatric patients (age 5-17) with newly diagnosed with LBP between 2008 and 2015 who did not have a red flag diagnosis, had not received an opioid prescription in the 6 mo prior to diagnosis, and had 12-mo of continuous enrollment after diagnosis. We used logistic regression to model the association between sex, geographic region, categorical age, and our primary outcome, receipt of an opioid prescription in the year following diagnosis. RESULTS Our sample included 268 228 opioid-naïve pediatric patients diagnosed with LBP between 2008 and 2015. We observed that 47 631 (17.8%) patients received physical therapy, 29 903 (11.2%) patients received chiropractic manipulative therapy, 658 (0.25%) patients received epidural steroid injection, and 281 (0.10%) patients received surgery. A total of 35 274 (13.2%) pediatric LBP patients were prescribed opioids within 12 mo from their diagnosis. Opioid prescribing decreased in all age groups over the study period age group 5 to 9 decreased from 4.2% to 2.7%, age group 10 to 14 decreased from 10.3% to 7.7%, and age group 15 to 18 yr decreased from 20.9% to 17.1%. Female pediatric patients were more likely than male patients to receive an opioid prescription (OR, 1.12, P &lt; .0001). Patients ages 10 to 14 (OR, 2.89, P &lt; .0001) and 15 to 18 (OR, 6.98, P &lt; .0001) were significantly more likely to be prescribed opioids compared to patients in the youngest age group. CONCLUSION To our knowledge, we report the first observational cohort study of opioids and LBP in the pediatric population. Our findings indicate that opioids are being used for newly diagnosed LBP and receipt of opioids are associated with patient demographic factors.

The incidence of paediatric ACL injury is increasing in Finland

PurposeAnterior cruciate ligament (ACL) injury is a common knee injury in paediatric and adolescent patients. The population-based incidence of paediatric ACL injury is, however, unknown. Recent studies suggest increased ACL injury rates among adolescents, especially in active, sports-participating population. The purpose of this study was to investigate the population-based incidence rates of ACL injuries and trends in paediatric ACL reconstruction surgery.MethodAll ACL injuries were identified (ICD-10 diagnosis code S83.5) leading to hospitalisation or surgery using validated Finnish National Hospital Discharge Register (NHDR) data from 1997 to 2014. The sample comprised 19,961,205 Finnish residents aged less than 18 years at the time of injury. Hospital admissions with the diagnosis code S83.5 were analysed more thoroughly including, sex, age and the need for surgical interventions.ResultsDuring the 18-year study period, 4725 subjects of the study population had sustained an ACL injury. The total ACL injury incidence in study population was 23.3 per 100,000 person-years. The median age of the patients at the time of injury was 16 years (range 4–17). The incidence of ACL injury increased with age, and the highest incidence was observed among 17-year old (113.5 per 100,000 person-years). Incidence rate did not differ between genders. From the total ACL injury population of 4725 hospitalisations, 3168 (67.0%) underwent ACL reconstruction, of which 2988 (94.3%) were treated with arthroscopic reconstruction and 180 (5.6%) with open surgery. In addition, 1557 (33.0%) were treated non-operatively without ACL reconstruction. The annual incidence of ACL injuries in the Finnish paediatric population has increased during the past 15 years. The lowest incidence rate was seen in 1999 (incidence of 17.7 per 100,000 person-years, 195 ACL injuries) and the highest in 2011 (incidence of 31.5 per 100,000 person-years, 346 ACL injuries). The highest increase in ACL injuries was seen in girls aged 13–15 years, with an increase of 143%.ConclusionACL injury is not a negligible knee injury in the paediatric population. The incidence of paediatric ACL injury has increased during the past 15 years. Moreover, a twofold increase in incidence of paediatric ACL injury was noted during the last 10 years of the study period. Incidence rates among male and female paediatric patients were comparable.Level of evidenceIII.

The blast wounded of Raqqa, Syria: observational results from an MSF-supported district hospital

BackgroundIn June 2017, the U.S.-backed Syrian Democratic Forces (SDF) launched a military operation to retake the city of Raqqa, Syria, from the so-called Islamic State. The city population incurred mass numbers of wounded. In the post-offensive period, the population returned to a city (Raqqa) contaminated with improvised explosive devices (IEDs) and explosive remnants of war (ERWs), resulting in a second wave of wounded patients. Médecins Sans Frontières (MSF) supported a hospital in Tal-Abyad (north of Raqqa) and scaled up operations in response to this crisis. We describe the cohort of blast-wounded cases admitted to this hospital in order help prepare future humanitarian responses.MethodsWe retrospectively extracted data from clinical charts in the MSF-supported hospital. We included all new admissions for blast-wounded patients with key data elements documented. We performed comparative analyses from the offensive period (June 6, 2017 to October 17, 2017) and the post-offensive period (October 18, 2017 to March 17, 2018).ResultsWe included 322 blast related injuries. There were more than twice the number of cases with blast injuries in the post-offensive period as the offensive period (225 vs. 97, p = <.001). The offensive period saw a significantly higher proportion of female patients (32.0%, n = 31 vs. 11.1%, n = 25, p < 0.001) and paediatric patients (42.3%, n = 41 vs 24.9%, n = 56, p = 0.002). Blast-injured patients in the post-offensive period included more cases with multiple traumatic injuries (65.8%, n = 148 vs. 39.2%, n = 38, p < 0.001). The treatment of the blast-injured cases in the post-offensive period was more labor intensive with those patients having a higher median number of interventions (2 vs 1, p = <0.001) and higher median number of days in hospital (7 vs 4, p = < 0.001).ConclusionsIn the wake of the Raqqa offensive, the MSF-supported district hospital received an unpredicted second, larger and more complex wave of blast-wounded cases as the population returned to a city strewn with IEDs and ERWs. These findings indicate the high risk of traumatic injury to the population even after warring factions have vacated conflict zones. Medical humanitarian actors should be prepared for a continued and scaled up response in areas known to be highly contaminated with explosive ordnance.

Imperforate hymen: Retrospective review from a single tertiary centre of presenting symptoms and diagnostic process.

To review presentations, diagnostic processes and time to diagnosis of presentations of imperforate hymen at one tertiary paediatric hospital over a 10-year period. The aim was to improve knowledge, enable targeted education and reduce unnecessary tests and diagnostic delay for this congenital obstructive disorder of the female reproductive tract. A pragmatic, retrospective, observational study was conducted of all female patients, aged younger than or equal to 18 years of age, presenting to the Royal Children's Hospital, Melbourne, over an 18-year period. Presenting symptom(s), time to diagnosis, investigations ordered and number of health-care professionals consulted prior to diagnosis were recorded. A total of 27 patients met eligibility criteria, and 85% presented with pain (23/27). Pain was frequently associated with other symptoms (15/23). Over three quarters of patients consulted more than one health-care professional prior to diagnosis (22/27). Of the 27 patients, 19 had imaging undertaken prior to diagnosis. Paediatric and adolescent females managed at our tertiary paediatric hospital are experiencing diagnostic uncertainty and the unnecessary ordering of imaging prior to a diagnosis of imperforate hymen. Targeted education is recommended to health professionals managing female paediatric and adolescent patients.

Obesity prevention in corticosteroid-treated patients: Use and effectiveness of strategies for weight management.

We conducted a systematic review to identify the use and effectiveness of clinical interventions to prevent or mitigate weight gain in patients using systemic corticosteroids. We independently searched nine bibliometric databases for reviews and longitudinal studies published up to 26 October 2018, and assessed the quality of studies meeting inclusion criteria. We identified 3893 records and screened 3037 eligible studies, read four full-texts and extracted data from three randomized control trials. Two studies examined a diet-only intervention for weight management, while one study examined a mixed intervention for diet and exercise. Overall, existing evidence is of poor quality and based on small feasibility studies of either paediatric leukaemia or female lupus patients, which suggested divergent effects of lifestyle interventions on weight, body mass index or waist circumference. Current evidence suggests a state of clinical equipoise that deserves greater research attention given the prevalent use of corticosteroids for treating a variety of chronic conditions. Robust high-quality longitudinal studies to decipher preventive strategies of steroid-induced weight gain must be prioritized in research and policy to improve patient care and prevent further obesity-related disease burden.

SUN-266 Anti-Mullerian Hormone as a Marker of Ovarian Reserve in Female Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Background/Methods: Gonadal dysfunction leading to infertility is a common complication after hematopoietic stem cell transplant (HSCT). Previous work by our group has shown that there is a significantly higher risk of delayed puberty and premature ovarian insufficiency among girls who receive high intensity, myeloablative conditioning (MAC) regimens compared to reduced intensity conditioning (RIC) regimens. Anti-Müllerian Hormone (AMH) is not regulated by gonadotropins and has minimal inter-cycle variations; therefore, it can be used as a marker of follicular ovarian reserve and aid in fertility counseling. We sought to assess ovarian reserve utilizing AMH levels in a retrospective study of female pediatric patients undergoing HSCT from 2013-2017 who received either MAC or RIC regimens. Results: In total, 100 female patients with a median age of 7 years had AMH levels pre-HSCT, of whom 33 (33%) also had post-HSCT levels. A wide variety of diagnoses were included: 32% had malignancy; 19% had immunodeficiency; 17% had Fanconi anemia (FA), 17% had hemoglobinopathy; 12% had non-FA marrow failure, and 3% had a metabolic disorder. Among those with pre-HSCT AMH levels, 71 (71%) had normal AMH for age, and 29 (29%) had low AMH for age. Of the 33 patients who also had post-HSCT AMH, 24 (72%) had low levels following transplantation. Twenty-five patients had both a normal pre-HSCT AMH and subsequent post-HSCT levels performed, 13 of whom (52%) received a MAC regimen and 12 of whom (48%) received RIC regimen. All (13/13) of the patients who received a MAC regimen had low AMH post-HSCT, while only 25% (3/12) of the patients who received a RIC regimen had low AMH post-HSCT (p=0.0002). Eight patients had both a low pre-HSCT AMH and subsequent post-HSCT AMH levels performed, 5 of whom received a MAC regimen and 3 of whom received a RIC regimen. All subject with low pre-HSCT AMH levels additionally had low post-HSCT AMH regardless of conditioning regimen used. Conclusions: AMH levels can be a useful marker for detection of low ovarian reserve and fertility counseling, especially if trends are followed before and after exposure to alkylating agents used for HSCT preparation. Our data show a significantly higher risk of low, downtrending AMH after exposure to high intensity MAC regimens compared to RIC regimens during childhood HSCT, which likely indicates a greater potential for infertility in patients receiving MAC regimens. These data correlate with a previous analysis demonstrating a significantly higher incidence of premature ovarian insufficiency and delayed puberty among girls receiving MAC regimens vs RIC regimens. Long-term follow up of this cohort will provide more information to understand the effects of HSCT on ovarian function and the utility of AMH as a predictor of future fertility potential.

11. Addressing Fertility Preservation in Female Pediatric Oncology Patients: A Quality Improvement Study in Calgary AB Canada

11. Addressing Fertility Preservation in Female Pediatric Oncology Patients: A Quality Improvement Study in Calgary AB Canada

P3BEP (ANZUP 1302): An international randomized phase III trial of accelerated versus standard BEP chemotherapy for adult and pediatric male and female patients with intermediate and poor-risk metastatic germ cell tumors (GCTs).

TPS539 Background: Bleomycin, etoposide, cisplatin (BEP) given 3-weekly x 4 remains standard 1st line chemotherapy for metastatic GCTs. Acceleration of standard regimen with shorter cycle lengths has improved cure rates in other cancers. This is the first international randomised clinical trial for intermediate and poor-risk metastatic extracranial GCTs involving both adult and paediatric age group males and females. We aim to determine if accelerated BEP is superior to standard BEP. Methods: DESIGN: Open label, randomised, stratified multicentre, 2 stage, phase 3 trial. Primary endpoint for stage I (n = 150) is the achievement of a complete response (CR), and for entire trial (n = 500) is progression free survival (PFS). SAMPLE SIZE: 150 and 500 patients gives &gt; 80% power to detect a 20% improvement in achieving a CR and 7% absolute improvement in 2yr PFS, respectively. POPULATION: Males and females aged 11-45 years with intermediate or poor-risk metastatic GCTs of the testis, ovary, retroperitoneum or mediastinum for 1st line chemotherapy. TREATMENT: Randomisation 1:1 to 4 cycles of “standard BEP” or “accelerated BEP”: cisplatin 20mg/m2 IV D1-5; etoposide 100mg/m2 IV D1-5; bleomycin 30000 IU IV weekly; and pegylated G-CSF SC D6 or Filgrastim daily; given every 3 weeks or every 2 weeks respectively. Accelerated BEP arm receives 4 additional weekly doses of bleomycin. ASSESSMENTS: Response assessments at 30 day safety assessment, and 6 months from randomisation or after all post-chemotherapy intervention is completed. Regular follow-up up to 5 years, then annually. Archival tumour tissue and baseline blood collected for translational substudies. STATUS: 25 sites open in ANZ, 11 sites open in UK (led by Cambridge Clinical Trials Unit), 19 sites open in the USA (led by Children’s Oncology Group). As of 23rd October 2018, 59 patients have been recruited. Clinical trial information: NCT02582697.

Pediatric melanoma: Characterizing 256 cases from the Colorado Central Cancer Registry.

Melanoma is a rare diagnosis in the pediatric population. Differences in incidence, presentation, and survival distinguish pediatric melanoma from adult melanoma. In order to improve our understanding of pediatric melanoma, our case series investigates differences in incidence, age of onset, and anatomic site between male and female pediatric melanoma patients in Colorado between 1988 and 2015. All data were gathered from the Colorado Central Cancer Registry. A request for de-identified data on pediatric melanoma patients between 1988 and 2015 was made by the University of Colorado Department of Dermatology. Chi-square tests were used to compare the differences reported in melanoma between sex, age-groups, and site of lesion. A total of 256 cases of melanoma were reported in Colorado in patients <20years of age between 1988 and 2015. Overall incidence of pediatric melanoma in Colorado increased from 1988 to 1999 but declined from 2001 to 2011. There was a significant predominance of female cases in the 10-14 age-group (P=0.0477) and 15-19 age-group (P=0.0472). Both groups had increased incidence of melanoma with increasing age. The mean age of onset for both sexes was 16years old. Boys were more likely to have melanoma of the scalp and neck (P=0.0523) and less likely to have melanoma of the leg (P=0.0049). Among the pediatric population, girls 10-14 and 15-19years old are at a significantly increased risk of melanoma compared to boys in these age-groups. Our study found sex-specific differences in anatomic site consistent with prior literature. Further investigations should aim to identify causes for these sex-specific differences in order to better guide public health initiatives.

Large gastric trichobezoar causing failure to thrive and iron deficiency anaemia in an adolescent girl: a case report emphasising the imaging findings and review of the literature.

Failure to thrive, iron deficiency anaemia and abdominal pain are common paediatric presentations to general practitioners, outpatient clinics and are often referred to emergency departments. When young female patients suffering from psychiatric disorders, such as trichotillomania and trichophagia present to medical practitioners, the rare diagnosis of a trichobezoar, which is an accumulation of indigestible human hair in the gastrointestinal tract (90 % occurring in the stomach) needs to be suspected. Imaging is the mainstay of trichobezoar diagnosis and requires accurate interpretation to prevent complications. A case of a 14-year-old girl is presented, who was referred from paediatric outpatient clinics for an elective admission to the emergency department. She presented with abdominal pain, iron deficiency anaemia, failure to thrive and an epigastric/left upper quadrant mass felt on examination. A large trichobezoar was found on CT images, confirmed on endoscopy and removed with an open laparotomy. However, on the work-up imaging modalities, the radiologists missed the subtle findings of a trichobezoar. Although uncommon, trichobezoars should be considered as a differential diagnosis in female paediatric patients with a psychiatric history, who present with abdominal pain and epigastric mass. Imaging is the mainstay for trichobezoar diagnosis. As such, radiologists need to be familiar with the apparent, and subtler, pathological findings of this diagnosis and possible differential diagnoses across all imaging modalities. After successful treatment, psychiatric consultation and treatment is imperative in order to prevent reoccurrence.

Procalcitonin and C-Reactive Protein during Transplant-Related Adverse Events after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients

BackgroundEarly diagnosis and treatment interventions of transplant-related adverse events (TRAE) such as sepsis, fungal, bacterial and viral infection, graft-versus-host disease (GvHD), veno-occlusive disease (VOD), and graft rejection is crucial for the patient outcome. The predictive value of a multitude of serum biomarkers their specific patterns in occurring TRAE have been widely investigated. Procalcitonin (PCT) is a precursor molecule of the hormone calcitonin that regulates calcium homeostasis and is elevated for example during systemic infection, thermal injury or septic shock. A discriminative value of PCT during adverse events after HSCT has been described for adult patients. There is currently no data available concerning PCT in the context of TRAE in children.Material and MethodsIn this single-center retrospective analysis, serum PCT and CRP levels of pediatric patients who underwent allogeneic HSCT for the treatment of hemato-oncological malignancies and non-malignancies were analyzed and correlated to TRAE (graft rejection, VOD, GvHD, sepsis, and viral or fungal infection). Primary objective of this work was to evaluate a predictive and discriminative value of serum PCT and CRP in the early identification of transplant-related complications in these patients. The observation period included the time of measurement directly before start of conditioning, until the day of clinical discharge. Serum PCT and CRP values were analyzed daily during the occurrence of fever or at least 3 times per week.ResultsThe patient group consisted of 124 male and 87 female pediatric patients (n=211) with a median age of 9.0 years (range 0.5-17.8 years) undergoing HSCT for hemato-oncological malignancies and inborn errors of metabolism. Patients received grafts from mismatched unrelated donors (n=66), matched unrelated donors (n=118) or matched family donors (n=27). The patients underwent HSCT for the treatment of acute leukemia (AML, ALL, AML relapse and ALL relapse; 50.7% of the patients), myelodysplastic syndromes (5.2%), anemia (severe aplastic anemia, beta thalassemia, sickle cell anemia; 16.1%), or solid tumors (28.0%). The median observation period was 76 days (range 31-245 days). Graft rejection occurred in 9 patients (4.3%), VOD in 4 patients (1.9%), acute skin GvHD grade II-IV in 31 patients (14.7%), acute intestinal GvHD grade II-IV in 10 patients (4.7%), sepsis in 24 patients (11.4%), viremia in 22 patients (10.4%), and fungemia in 7 patients (3.3%).PCT values were significantly and relevantly elevated (>0.5 ng/mL) during graft rejection (median 1.43 ng/mL, range 1.04-5.46 ng/mL), skin GvHD (median 0.90 ng/mL, range 0.02-4.34 ng/mL), intestinal GvHD (median 1.01 ng/mL, range 0.30-3.05 ng/mL), and sepsis (median 3.09 ng/mL, range 0.57-37.32 ng/mL). CRP values were significantly and relevantly elevated (>0.5 mg/dL) during graft rejection (median 10.34 mg/dL, range 5.45-30.19 mg/dL), skin GvHD (median 1.85 mg/dL, range 0.04-21.63 mg/dL), intestinal GvHD (median 8.73 mg/dL, range 1.05-24.2 mg/dL), sepsis (median 10.26 mg/dL, range 2.67-49.47 mg/dL), viremia (median 1.80 mg/dL, range 0.06-14.04 mg/dL), and fungemia (median 5.10 mg/dL, range 2.30-11.60 mg/dL). A simultaneous significant and relevant elevation of both PCT and CRP values was observed during graft rejection, skin and intestinal GvHD, and sepsis (Fig. 1).ConclusionsEspecially during acute skin and intestinal GvHD, PCT and CRP values strongly and significantly increased beyond the upper normal limits. Simultaneous elevations of PCT and CRP occurred during graft rejection, skin and intestinal GvHD, and sepsis. Taken together, laboratory-chemical analyses of serum PCT in combination with CRP could be a useful discriminative biomarker in the detection of TRAE. Larger, prospective trials are needed, to evaluate these findings.FigureFig. 1. PCT and CRP serum concentrations during acute GvHD, graft rejection, VOD, sepsis, viremia and fungemia. Dotted horizontal lines indicate normal PCT and CRP values (PCT: 0.5 ng/mL | CRP: 0.5 mg/dL). Symbols indicate *: p<0.05; **:p<0.01; ***: p<0.001; ****: p<0.0001; tested by Wilcoxon matched-pairs signed rank test.AcknowledgmentsThis work was supported by the Stefan-Morsch-Stiftung, Birkenfeld, Germany and the Bettina-Bräu-Stiftung, Fürstenfeldbruck, Germany. [Display omitted] DisclosuresLang:Miltenyi Biotec: Patents & Royalties, Research Funding. Handgretinger:Miltenyi Biotec: Patents & Royalties: Co-patent holder of TcR alpha/beta depletion technologies, Research Funding.

Omalizumab et immunothérapie allergénique : cas clinique et revue de la littérature

Several authors have proposed combined omalizumab and allergen immunotherapy (AIT) in patients suffering from severe allergic asthma to both increase disease control and decrease the severity through targeting the main allergen responsible for the respiratory symptoms. In a female pediatric patient suffering from severe asthma, followed-up at the University Hospital of Montpellier (France), we prescribed an AIT to Alternaria after obtaining symptom control with omalizumab. The patient showed an overall improvement in symptoms after AIT was administered and the disease remained controlled long after cessation of omalizumab. There are only a few publications evaluating the efficacy of the association of these two biotherapies in the management of severe allergic asthma. In addition there is, as yet, no common protocol for the administration of the two prescriptions. This approach to treatment would benefit from standardization in order to optimize the management of severe allergic asthma.

Vertical patellar dislocation: A pediatric case report and review of the literature.

Vertical patellar dislocations (VPDs) are a rare event, and even more so among pediatric female patients. There have been less than 30 vertical patellar dislocations reported in the literature since the first in 1844. In this type of dislocation, the patella rotates about its vertical axis with the articular surface facing either medially or laterally. The mechanism of injury for a VPD can be broadly divided into two themes: a twisting injury or direct impact to the medial or lateral edge of the patella. We present a 10-year-old girl with a VPD after experiencing a twisting injury when descending a playground slide. The purpose of this study is to present a case report and review of the literature on vertical patella dislocations, including mechanisms of injury and suggested methods of treatment. We aim to provide a comprehensive understanding of the various categories of patella dislocations to alleviate confusion when classifying patellar dislocations. Furthermore, we provide clear suggestions for reduction methods and techniques with regards to vertical patellar dislocations, including a suggested protocol for an irreducible patella.

Protocol for the P3BEP trial (ANZUP 1302): an international randomised phase 3 trial of accelerated versus standard BEP chemotherapy for adult and paediatric male and female patients with intermediate and poor-risk metastatic germ cell tumours

BackgroundBleomycin, etoposide, and cisplatin (BEP) chemotherapy administered every 3 weeks for 4 cycles remains the standard first line treatment for patients with intermediate- and poor-risk metastatic germ cell tumours (GCTs). Administering standard chemotherapy 2-weekly rather than 3-weekly, so-called ‘accelerating chemotherapy’, has improved cure rates in other cancers. An Australian multicentre phase 2 trial demonstrated this regimen is feasible and tolerable with efficacy data that appears promising. The aim of this trial is to determine if accelerated BEP is superior to standard BEP as first line chemotherapy for adult and paediatric male and female participants with intermediate and poor risk metastatic GCTs.MethodsThis is an open label, randomised, stratified, 2-arm, international multicentre, 2 stage, phase 3 clinical trial. Participants are randomised 1:1 to receive accelerated BEP or standard BEP chemotherapy. Eligible male or female participants, aged between 11 and 45 years with intermediate or poor-risk metastatic GCTs for first line chemotherapy will be enrolled from Australia, the United Kingdom and the United States. Participants will have regular follow up for at least 5 years. The primary endpoint for stage 1 of the trial (n = 150) is complete response rate and for the entire trial (n = 500) is progression free survival. Secondary endpoints include response following treatment completion (by a protocol-specific response criteria), adverse events, health-related quality of life, treatment preference, delivered dose-intensity of chemotherapy (relative to standard BEP), overall survival and associations between biomarkers (to be specified) and their correlations with clinical outcomes.DiscussionThis is the first international randomised clinical trial for intermediate and poor-risk metastatic extra-cranial GCTs involving both adult and pediatric age groups open to both males and females. It is also the largest, current randomised trial for germ cell tumours in the world. Positive results for this affordable intervention could change the global standard of care for intermediate and poor risk germ cell tumours, improve cure rates, avoid the need for toxic and costly salvage treatment, and return young adults to long, healthy and productive lives.Trial registrationACTRN 12613000496718 on 3rd May 2013 and Clinicaltrials.gov NCT02582697 on 21st October 2015.