Success and complications in lumbar punctures of pediatric patients with leukemia: a study protocol for a randomized clinical crossover trial of a bioimpedance needle system versus conventional procedure.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children. At present, the long-term survival from pediatric ALL is well over 90%. However, the probability of event-free survival is reduced if the lumbar puncture (LP) procedures at the beginning of the patient's intrathecal therapy cause blood leakage into the spinal canal and blast cells contaminate the cerebrospinal fluid. According to the literature, such traumatic LP procedures concern one out of five pediatric patients with ALL. Recently, a novel medical device measuring the tissue bioimpedance at the tip of a spinal needle was found feasible in pediatric patients with ALL. The LP procedure was successful at the first attempt in 80% of procedures, and the incidence of traumatic LPs was then 11%. The purpose of the present study is to compare the bioimpedance spinal needle system with the standard clinical practice resting on a conventional spinal needle and investigate its efficacy in clinical practice. METHODS: The study is a multicenter, randomized, two-arm crossover noninferiority trial of pediatric hemato-oncology patients that will be conducted within the usual clinical workflow. Patients' LP procedures will be performed alternately either with the IQ-Tip system (study arm A) or a conventional Quincke-type 22G spinal needle (study arm B). For each enrolled patient, the order of procedures is randomly assigned either as ABAB or BABA. The total number of LP procedures will be at least 300, and the number of procedures per patient between two and four. After each study LP procedure, the performance will be recorded immediately, and 1-week diary-based and 4-week record-based follow-ups on symptoms, complications, and adverse events will be conducted thereafter. The main outcomes are the incidence of traumatic LP, first puncture success rate, and incidence of post-dural puncture headache. DISCUSSION: The present study will provide sound scientific evidence on the clinical benefit, performance, and safety of the novel bioimpedance spinal needle compared with the standard clinical practice of using conventional spinal needles in the LP procedures of pediatric patients with leukemia. TRIAL REGISTRATION: ISRCTN ISRCTN16161453. Registered on 8 July 2022.

Supportive care in pediatric acute myeloid leukemia:Expert-based recommendations of the NOPHO-DB-SHIP consortium.

INTRODUCTION: Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. AREA COVERED: The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. EXPERT OPINION: Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome.

Traumatic lumbar punctures in diagnostic and intrathecal treatment punctures of pediatric hemato-oncology patients.

Successful first diagnostic lumbar puncture (LP) is crucial because intrathecal chemotherapy has not yet protected the central nervous system against cancer cells. If blood contaminates the cerebrospinal fluid (CSF) with blasts, they may enter the central neural system and compromise the patient's health. We retrospectively determined the incidence of traumatic lumbar punctures (TLP) in 2,507 LPs of 250 pediatric hemato-oncology patients aged from one to 18 years, including both diagnostic and intrathecal treatment procedures, and 2,617 LPs of 1,525 other age-matched pediatric patients. We used ≥10 erythrocytes/µL in the CSF sample as the criterion of TLP. TLPs were less frequent in hemato-oncology patients than in other patients (31.6% vs. 48.5%, p < 0.0001). The incidence of TLP was significantly lower in the first diagnostic LP than in subsequent intrathecal treatment LPs (20.5% vs. 31.6%, p = 0.0046). According to logistic regression analysis, the odds of TLP was 1.6-fold if the LP procedure was not performed in the hemato-oncology department. The odds of the patient's next LP being traumatic were threefold if the previous first LP was traumatic. A week or less time between the first and next LP tripled the odds of TLP as well. The patient's age category was not significantly associated with the incidence of TLP. Given the risks of TLP, hemato-oncology patients' first diagnostic LP should include administration of chemotherapy, as generally recommended, and be performed under general anesthesia or deep sedation by an experienced physician to optimize not only the success of the first LP procedure but also following procedures.

Bioimpedance spinal needle provides high success and low complication rate in lumbar punctures of pediatric patients with acute lymphoblastic leukemia.

In this prospective single-arm study of 50 pediatric patients with acute lymphoblastic leukemia (ALL), we evaluated the clinical performance of a novel bioimpedance spinal needle system in 152 intrathecal treatment lumbar punctures (LP) of these patients. The system detects in real-time when the needle tip reaches the cerebrospinal fluid (CSF) in the spinal canal. The success was defined as getting a CSF sample and/or administering the intrathecal treatment with one needle insertion. Incidence of traumatic LP (TLP) was defined as ≥ 10 erythrocytes/µL of CSF. Post-procedural complications were monitored with a one-week diary and one-month register follow-up. The success of the first attempt was 79.5%, with the CSF detection sensitivity of 86.1%. The incidence of TLP was 17.3%. A successful first attempt was associated with a significantly lower incidence of TLP (10% vs 40%, p = 0.0015). During the week after the procedure, the incidence of post-dural puncture headache was 6%. During the follow-up, no major complications were observed. In conclusion, the novel bioimpedance spinal needle system achieved a high success rate and low incidence of TLP and other complications in pediatric patients with ALL in a real-world clinical setting, indicating clinical utility for this system in pediatric hemato-oncology.

Asymptomatic Right Atrial Thrombosis After Acute Lymphoblastic Leukemia Treatment.

Right atrial thrombosis is a rare, but potentially serious complication of acute lymphoblastic leukemia treatment. We conducted a retrospective multicenter study to assess the incidence, treatment, and outcome of asymptomatic right atrial thrombosis detected at routine echocardiography of children after acute lymphoblastic leukemia treatment in the Nordic and Baltic countries. Eleven (2.7%, 95% confidence interval, 1.4-4.9) of 406 patients had asymptomatic right atrial thrombosis, ranging from 10 to 25 mm at detection. Three patients were treated with anticoagulation. None of the thromboses affected cardiac function, and they showed neither sign of progress nor spontaneous or treatment-related regress at follow-up.

Impact of COVID-19 in paediatric early-phase cancer clinical trials in Europe: A report from the Innovative Therapies for Children with Cancer (ITCC) consortium.

INTRODUCTION: Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC). METHODS: A survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020. RESULTS: Thirty-one of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared with that in 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. In addition, 26% of sites had restrictions on performing trial assessments because of local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organisational and structural changes. CONCLUSION: The study reveals a profound disruption of paediatric cancer early-phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises.

Randomized controlled and double-blinded study of Caphosol versus saline oral rinses in pediatric patients with cancer.

BACKGROUND: Oral mucositis (OM) is a significant side effect of cancer treatment. The purpose of this study was to compare topically administered Caphosol to saline rinses in the prevention of mucositis in pediatric cancer patients. PROCEDURE: A controlled, double-blinded, and randomized clinical crossover study recruited patients between 2 to 17.99 years of age who were diagnosed with a malignancy and were receiving either high-dose methotrexate (≥1 g/m2 ), anthracycline, or cisplatin chemotherapy (NCT0280733). All patients received two 7-day cycles of the mouth rinses; that is, one cycle of Caphosol and one cycle of saline in a randomized order. Oral changes and symptoms were evaluated using the World Health Organisation (WHO) toxicity scale and the Children's International Mucositis Evaluation Scale (ChIMES). The primary endpoint was the frequency and severity of OM and oral symptoms. RESULTS: A total of 56 patients were recruited to the study, of whom 45 were randomized with a median age of 6.5 years (range 2.1-17.1 years). No cases of severe OM were observed. Grade ≥ 3 oral symptoms were present at least once in six (13%) patients during the Caphosol cycle and 13 (29%) patients during the saline cycle (P = .12). The peak of symptom scores was evident at around day 4-7 after administration of the chemotherapy with no marked differences between the rinse solutions. Multivariable regression analysis did not indicate a benefit of using Caphosol over the saline solution. CONCLUSIONS: No difference in prevention of oral mucositis was observed between the use of Caphosol or saline rinses.

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.

National treatment guidelines decreased the use of racemic adrenaline for bronchiolitis in four Finnish university hospitals.

AIM: Inhaled racemic adrenaline was used for bronchiolitis in many hospitals in Finland prior to new national current care guidelines for bronchiolitis in 2014, which limited its recommendations to on-demand rescue therapy. We studied the drug's use before and after the new guidelines to gauge changes in prescribing habits. METHODS: This 2012-2016 study analysed how many 0.5 mL doses of racemic adrenaline were used for children by emergency rooms, paediatric wards and paediatric intensive care units at four university hospitals and estimated drug and staff costs. RESULTS: There were substantial differences in the yearly consumption of racemic adrenaline between the hospitals before and after the bronchiolitis guidelines were published, with reductions in drug costs and staff time. The overall use more than halved during the study period, particularly in two hospitals where baseline consumptions were highest, but not in a third where baseline consumption was already low. In the fourth, the baseline consumption was modest and there was a constant decrease during the study years. CONCLUSION: The current care guidelines for bronchiolitis had some impact on clinical practice, as the overall use of racemic adrenaline more than halved, but considerable differences remained in the four study hospitals after their publication.

National allergy programme had little impact on parent-reported food allergies in children aged 6-7 years.

AIM: The ten-year Finnish national allergy programme was launched in 2008 to lessen the disease and psychological burden of allergy. This study assessed the prevalence of parent-reported food allergies requiring avoidance diets at primary school in children aged six and seven years. METHODS: The cohort comprised 1937 children (51% boys) who started primary school in Tampere, Finland, in August 2016. School health nurses charted parent-reported, doctor-diagnosed food allergies requiring avoidance diets as part of the routine health examination. RESULTS: We found that 127 (6.6%) children had parent-reported, doctor-diagnosed allergies to at least one food and 37 (1.9%) were allergic to basic foods, namely cows' milk, wheat and one other grain. All required an avoidance diet. The figure did not differ significantly from the 2.7% and 2.5% found by studies of this age group in 2009 and 2013, respectively. Allergies to fresh fruit and vegetables decreased from 5.8% in 2009 to 3.6% in 2016. CONCLUSION: We studied the national allergy programme that started in 2008 and found that there was a nonsignificant overall decrease in the number of children aged six to seven years on avoidance diets for allergies between 2009 and 2016. The only allergies that showed significant decreases were fresh fruit and vegetables.

Treatment injuries are rare in children's femoral fractures.

BACKGROUND AND PURPOSE: The current treatment for femoral fractures in children is mostly operative, which contrasts with treatment of other long bone fractures in children. We analyzed treatment injuries in such patients in Finland in order to identify avoidable injuries. Our other aims were to calculate the incidence of these fractures and to describe the treatment method used. METHODS: The Patient Insurance Centre (PIC) provides financial compensation of patients who have sustained an injury in connection with medical care. We retrospectively analyzed incidence, treatment methods, and all compensation claims concerning treatment of femoral fractures in children who were 0-16 years of age during the 8-year period 1997-2004. RESULTS: The incidence of childhood femoral fractures in Finland was 0.27 per 1,000 children aged < 17 years, and two-thirds of the patients were treated operatively during the study period. 30 compensation claims were submitted to PIC during the 8-year study period. The compensation claims mainly concerned pain, insufficient diagnosis or treatment, extra expenses, permanent disability, or inappropriate behavior of medical personnel. Of the claims, 16 of 30 were granted compensation. Compensation was granted for delay in treatment, unnecessary surgery, and for inappropriate surgical technique. The mean amount of compensation was 2,300 euros. Of the injuries that led to compensation, 11 of 16 were regarded as being avoidable in retrospect. INTERPRETATION: The calculated risk of a treatment injury in childhood femoral fracture treatment in Finland is approximately 2%, and most of these injuries can be avoided with proper treatment.

Injuries as a result of treatment of tibial fractures in children: Claims for compensation submitted to the Patient Insurance Center in Finland.

BACKGROUND AND PURPOSE: Tibial fractures comprise 10% of all fractures in children. To our knowledge there have been no previous reports of treatment injuries in these fractures. We analyzed compensation claims concerning treatment of these fractures in Finland. We used this information to determine preventable causes of treatment injuries. MATERIAL AND METHODS: In Finland, the Patient Insurance Center (PIC) provides financial compensation for patients who have sustained an injury in connection with medical treatment or operation. We retrospectively analyzed all claims for compensation arising from treatment of tibial fractures in children that had been received by the PIC between 1997 and 2004. The mode of treatment, complications, and permanent sequelae were assessed. We also estimated the number of avoidable treatment injuries. RESULTS AND INTERPRETATION: The PIC received 50 claims for compensation during the 8-year study period. The claims were based on the following issues: pain, incorrect diagnosis and treatment, permanent disability, extra treatment expenses, inappropriate behavior of the medical personnel, and loss of income of the parents. 35/50 claims had received compensation, of which 32 were related to the treatment and 3 to infections. The treatment injuries that had led to compensation comprised a delay in diagnosis and treatment in 15 patients, inappropriate casting in 9, inappropriate operative treatment in 5, and other causes in 3 patients. An unsatisfactory standard of treatment and missed diagnosis were the most common reasons for compensation. In restrospect, all but 1 of the 35 injuries that had led to compensation were considered to be avoidable.

Acute patellar dislocation in children and adolescents. Surgical technique.

BACKGROUND: The treatment of acute patellar dislocation in children is controversial. Some investigators have advocated early repair of the medial structures, whereas others have treated this injury nonoperatively. The present report describes the long-term subjective and functional results of a randomized controlled trial of nonoperative and operative treatment of primary acute patellar dislocation in children less than sixteen years of age. METHODS: The data were gathered prospectively on a cohort of seventy-four acute patellar dislocations in seventy-one patients (fifty-one girls and twenty boys) younger than sixteen years of age. Sixty-two patients (sixty-four knees) without large (>15 mm) intra-articular fragments were randomized to nonoperative treatment (twenty-eight knees) or operative treatment (thirty-six knees). Operative treatment consisted of direct repair of the damaged medial structures if the patella was dislocatable with the patient under anesthesia (twenty-nine knees) or lateral release alone if the patella was not dislocatable with the patient under anesthesia (seven knees). All but four patients who underwent operative treatment had a concomitant lateral release. The rehabilitation protocol was the same for both groups. The patients were seen at two years, and a telephone interview was conducted at a mean of six years and again at a mean of fourteen years. Fifty-eight patients (sixty-four knees; 94%) were reviewed at the time of the most recent follow-up. RESULTS: At the time of the most recent follow-up, the subjective result was either good or excellent for 75% (twenty-one) of twenty-eight nonoperatively treated knees and 66% (twenty-one) of thirty-two operatively treated knees. The rates of recurrent dislocation in the two treatment groups were 71% (twenty of twenty-eight) and 67% (twenty-four of thirty-six), respectively. The first redislocation occurred within two years after the primary injury in twenty-three (52%) of the forty-four knees with recurrent dislocation. Instability of the contralateral patella was noted in thirty (48%) of the sixty-two patients. The only significant predictor for recurrence was a positive family history of patellar instability. The mode of treatment and the existence of osteochondral fractures had no clinical or significant influence on the subjective outcome, recurrent patellofemoral instability, function, or activity scores. CONCLUSIONS: The long-term subjective and functional results after acute patellar dislocation are satisfactory in most patients. Initial operative repair of the medial structures combined with lateral release did not improve the long-term outcome, despite the very high rate of recurrent instability. A positive family history is a risk factor for recurrence and for contralateral patellofemoral instability. Routine repair of the torn medial stabilizing soft tissues is not advocated for the treatment of acute patellar dislocation in children and adolescents.

Acute patellar dislocation in children and adolescents: a randomized clinical trial.

BACKGROUND: The treatment of acute patellar dislocation in children is controversial. Some investigators have advocated early repair of the medial structures, whereas others have treated this injury nonoperatively. The present report describes the long-term subjective and functional results of a randomized controlled trial of nonoperative and operative treatment of primary acute patellar dislocation in children less than sixteen years of age. METHODS: The data were gathered prospectively on a cohort of seventy-four acute patellar dislocations in seventy-one patients (fifty-one girls and twenty boys) younger than sixteen years of age. Sixty-two patients (sixty-four knees) without large (>15 mm) intra-articular fragments were randomized to nonoperative treatment (twenty-eight knees) or operative treatment (thirty-six knees). Operative treatment consisted of direct repair of the damaged medial structures if the patella was dislocatable with the patient under anesthesia (twenty-nine knees) or lateral release alone if the patella was not dislocatable with the patient under anesthesia (seven knees). All but four patients who underwent operative treatment had a concomitant lateral release. The rehabilitation protocol was the same for both groups. The patients were seen at two years, and a telephone interview was conducted at a mean of six years and again at a mean of fourteen years. Fifty-eight patients (sixty-four knees; 94%) were reviewed at the time of the most recent follow-up. RESULTS: At the time of the most recent follow-up, the subjective result was either good or excellent for 75% (twenty-one) of twenty-eight nonoperatively treated knees and 66% (twenty-one) of thirty-two operatively treated knees. The rates of recurrent dislocation in the two treatment groups were 71% (twenty of twenty-eight) and 67% (twenty-four of thirty-six), respectively. The first redislocation occurred within two years after the primary injury in twenty-three (52%) of the forty-four knees with recurrent dislocation. Instability of the contralateral patella was noted in thirty (48%) of the sixty-two patients. The only significant predictor for recurrence was a positive family history of patellar instability. The mode of treatment and the existence of osteochondral fractures had no clinical or significant influence on the subjective outcome, recurrent patellofemoral instability, function, or activity scores. CONCLUSIONS: The long-term subjective and functional results after acute patellar dislocation are satisfactory in most patients. Initial operative repair of the medial structures combined with lateral release did not improve the long-term outcome, despite the very high rate of recurrent instability. A positive family history is a risk factor for recurrence and for contralateral patellofemoral instability. Routine repair of the torn medial stabilizing soft tissues is not advocated for the treatment of acute patellar dislocation in children and adolescents.

Flexor tendon injuries in pediatric patients.

PURPOSE: The purpose of this research was to study the incidence and outcome of flexor tendon injuries in pediatric patients. METHODS: A survey of flexor tendon repair in children less than 16 years of age was performed in the City of Helsinki during 2000-2005. A retrospective clinical outcome study of all consecutive 28 patients with 45 involved fingers treated in Children's Hospital was also performed at a mean 38 months (range 12-53 months) after surgery. Active motion program after multistrand tendon repair was used in 33 fingers, cast immobilization in 11 fingers, and elastic bands in 1 finger. Functional and cosmetic subjective result was evaluated by a visual analog scale (VAS, 0-100). Range of motion (ROM) of metacarpophalangeal (MCP) and interphalangeal (IP) joints were measured. Grip strength was recorded. Functional outcome methods of Buck-Gramcko, ASSH, Strickland, and distal interphalangeal joint (DIP) ROM methods were applied. RESULTS: The calculated annual incidence of finger flexor injury per child in Helsinki was 0.036 per 1000. There were no ruptures of the multistrand repairs with active motion program, but three 2-strand core sutures failed within 1 month of the repair. Mean functional and cosmetic VAS scores (all 28 patients) were 87 and 84. Mean ROM ratio of the DIP joint in zone 1 and 2 injuries was 60%, compared to 98% in zone 3 and 5 injuries. Ranges of motion of the proximal interphalangeal (PIP) and MCP joints were practically normal in all patients. There was a discrepancy among the functional outcome scores, with good and excellent results in all 45 fingers (Buck-Gramcko), in 39 fingers (ASSH), in 36 fingers (original Strickland), and in 32 fingers (DIP ROM). CONCLUSIONS: Flexor tendon injuries in children are rare. Both subjective and objective outcomes are generally good. Active motion program is an effective technique after multistrand flexor tendon repair at all levels in children. Range of motion of the DIP joint may be a more effective means of evaluating outcome in pediatric flexor tendon injuries. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.