Treatment Outcomes of Adolescents Compared to Younger Pediatric Patients with Acute Myeloid Leukemia: Do They Need a Special Approach?

BACKGROUND: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. PATIENTS AND METHODS: We retrospectively analyzed 220 AML patients aged 0-18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1-9.9 years), 59 older children (10-14.9 years), and 39 adolescents (15-18 years). RESULTS: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1-3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/µL [HR, 2.4 (95% CI 1.3-4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. CONCLUSIONS: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.

Anti-PD-1 Therapy in Advanced Pediatric Malignancies in Nationwide Study: Good Outcome in Skin Melanoma and Hodgkin Lymphoma.

BACKGROUND/AIM: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023. RESULTS: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14). At the end of follow-up, complete remission (CR) was observed in 37.7% (15/42) of children and disease stabilization in 9.5% (4/42), with a mean survival 3.6 (95% CI = 2.6-4.6) years. The best survival (OS = 1.0) was observed in the group of patients with Hodgkin lymphoma. For malignant melanoma of the skin, neuroblastoma, and other rare malignancies, the estimated 3-year OS values were, respectively, 0.78, 0.33, and 0.25 (p = 0.002). The best progression-free survival value (0.78) was observed in the group with malignant melanoma. Significantly better effects of immunotherapy were confirmed in patients ≥ 14 years of age and good overall performance ECOG status. Severe adverse events were observed in 30.9% (13/42) patients.

Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia-Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022.

BACKGROUND: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10-15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. METHODS: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). RESULTS: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). CONCLUSIONS: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey.

Venetoclax, the best established BH3-mimetic, is a practice-changing proapoptotic drug in blood cancers in adults. In paediatrics the data are fewer but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the in-terventions could be potentially molecularly guided as vulnerabilities to BH3-mimetics were re-ported. Currently venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated so far with venetoclax in Poland. We set out to gather this experience to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data as available in November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with hematologic complete remission (CR), was reported in 5 patients out of ten, whereas 5 patient did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe BH3-mimetics have clinical activity in children and should be available to pae-diatric haemato-oncology practitioners in well-selected applications.

Pediatric Acute Myeloid Leukemia Post Cytotoxic Therapy-Retrospective Analysis of the Patients Treated in Poland from 2005 to 2022.

Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7-12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015-2022 (two induction cycles followed by stem cell transplantation-SCT in 69% of patients) compared to 2005-2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015-2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.

Characteristics and treatment results of refractory and relapsed acute myeloid leukaemia in paediatric patients treated in Polish Paediatric Leukaemia/Lymphoma Study Group institutions according to the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 and a review of novel treatment possibilities in paediatric acute myeloid leukaemia.

Introduction: This study aimed to present the clinical features and results of treatment of patients diagnosed with refractory or relapsed acute myeloid leukaemia (AML) in Polish Paediatric Leukaemia/Lymphoma Study Group (PPL/LSG) institutions, treated in accordance with the Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012, as their first-line therapy. Material and methods: The outcome data of 10 patients with refractory AML (median age 9.5 years) and 30 with relapsed AML (median age 12 years) were analysed retrospectively. Re-induction was usually based on idarubicin, fludarabine, and cytarabine along with allogeneic haematopoietic stem cell transplant (allo-HSCT) in 5 patients with refractory AML and 7 relapsed AML children. Results: 37.5% (3/8) of refractory AML patients achieved second complete remission second complete remission (CRII). One of ten patients (1/10; 10%) was alive and stayed in complete remission for 34 months after the allo-HSCT. The probability of 3-year event-free survival (pEFS) in this group was 0.125 ±0.11. In the group of relapsed AML patients, the CRII was achieved in 9 patients (34%), and the probability of survival was: pEFS = 0.24 ±0.08; probability overall survival (pOS) = 0.34 ±0.09, with significantly better results achieved in patients who underwent allo-HSCT (pOS = 0.54 ±0.14 vs. 0.08 ±0.08, p < 0.0001). Conclusions: The prognosis of refractory AML and the first AML recurrence in children who were first-line treated in PPL/LSG centres according to Protocol Acute Myeloid Leukaemia Berlin-Frankfurt-Munster 2012 is poor. Failures of re-induction treatment particularly result from difficulties in achieving remission. Allogeneic HSCT improves prognosis in children with refractory and first recurrent AML, under the condition it is performed in complete remission. Novel therapeutic approaches are needed to increase the remission rate and improve the outcomes.

Adolescent Athletes at Risk of Exercise-Induced Bronchoconstriction: A Result of Training or Pre-Existing Asthma?

Exercise may trigger bronchoconstriction, especially in a group of athletes in whom bronchospasm during exercise is reported to occur more frequently than in nonathletes. The aim of this study was to determine the prevalence and environmental risk factors contributing to exercise-induced bronchoconstriction (EIB) in adolescent athletes. A prospective study was conducted among a group of 101 adolescent athletes who underwent spirometry, exercise challenge, fractional exhaled nitric oxide (FeNO) measurements, and allergy assessment. The study group was divided into three subgroups of athletes based on the most common sports environments: swimmers, "indoor" athletes, and "outdoor" athletes. The clinical evaluation demonstrated a high frequency of EIB in the study group. Moreover, a large proportion of the athletes in whom EIB was observed reported no pre-existing symptoms suggestive of bronchospasm or asthma. Among patients without a previous diagnosis of asthma, clinical evaluation confirmed 22% with positive exercise challenges, compared with 77% of adolescents with negative test results. Moreover, among the athletes with a history of asthma, 39% had positive exercise challenges. Both EIB and asthma are common conditions that affect adolescent athletes. Physicians should pay particular attention to this group, as the symptoms can lead to under- and overdiagnosis.

One Hundred Consecutive Neutropenic Febrile Episodes Demonstrate That CXCR3 Ligands Have Predictive Value in Discriminating the Severity of Infection in Children with Cancer.

This study assesses the value of the CXCR3 ligands CXCL9/MIG, CXCL10/IP-10 and CXCL11/I-TAC when used to supplement the standard infection markers C-reactive protein (CRP) and procalcitonin (PCT) in the diagnostic algorithm of neutropenic fever in children with cancer. The concentration of CRP, PCT and chemokines was determined during the first hour of fever and 12-24 h afterwards in pediatric oncology patients with neutropenia. Among 100 consecutive febrile episodes in neutropenic patients, 34 cases demonstrated fever of unknown origin (FUO) (group A), 47 demonstrated mild clinically or microbiologically proven infection (Group B) and 19 severe infection (Group C). Significantly higher PCT-1 levels were found in group C (0.24 ng/mL) vs. group A (0.16 ng/mL), and PCT-2 in group C (1.2 ng/mL) vs. A (0.17 ng/mL), and in C vs. B (0.2 ng/mL). Chemokine concentrations (I-TAC-1, IP-10-1, IP-10-2) were significantly lower in Group A vs. B+C; I-TAC 1: 48.64 vs. 70.99 pg/mL, p = 0.03; IP-10 1: 59.95 vs. 96.84 pg/mL, p = 0.04; and IP-10 2: 102.40 vs. 149.39 pg/mL, p = 0.05. The selected pro-inflammatory chemokines I-TAC and IP10 might help to distinguish cancer patients with febrile neutropenia with the highest risk of infection. Although procalcitonin could serve as a marker of a high risk of infection, its delayed response diminishes its usefulness.

Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019.

BACKGROUND: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). METHODS: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983-1993, n = 187), AML-PPGLBC 94 (1994-1997, n = 74), AML-PPGLBC 98 (1998-2004, n = 151), AML-BFM 2004 Interim (2004-2015, n = 356), and AML-BFM 2012 (2015-2019, n = 131). RESULTS: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10;11)(p12;q23) and DEK-NUP214/t(6;9)(p23;q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD. CONCLUSIONS: The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years.

A multistep approach to the genotype-phenotype analysis of Polish patients with tuberous sclerosis complex.

The aim of this study was to evaluate a cost-effective diagnostic strategy for identification of casual variants for tuberous sclerosis complex (TSC) in the Polish population and to correlate the genetic results with selected phenotypic features. Fifty-five patients, aged 3-44 years, with a clinical diagnosis of TSC were enrolled into the study. All patients received a three-step analysis: next generation sequencing screening (NGS), multiplex ligation-dependent probe amplification (MLPA) and deep sequencing. This multistep approach obtained positive results in 51/55 (93%) patients: of the 51 positives TSC1 variants were observed in 16 (31%) and TSC2 variants in 35 (69%); these included 13 novel variants and two patients with mosaicism. Four patients (7%) had no mutation identified (NMI). Among the TSC1 gene variants, there were five nonsense, four frameshift, three large deletions, two missense and two splicing variants. For the TSC2 gene, 11 were missense, eight splicing, six frameshift, four large deletions, two in-frame deletions and four nonsense variants. The patients with TSC2 changes had their clinical diagnosis of TSC at a younger age than those with TSC1 changes (one year vs three years, p = 0.041). The TSC2 group demonstrated a higher number of major symptoms per patient (p = 0.04). Subependymal giant cell astrocytoma with concomitance of other brain lesions was more common in patients with missense mutations in either gene (23% vs 0%, p = 0.02). Such a multistep molecular diagnostic strategy could increase the possibility of detecting causal variants for TSC and may allow detection of mosaicism at low levels. Missense pathogenic variants in TSC1 or TSC2 gene might be associated with a higher risk of brain lesions.

Maintenance Therapy With Everolimus for Subependymal Giant Cell Astrocytoma in Patients With Tuberous Sclerosis - Final Results From the EMINENTS Study.

The aim of this EMINENTS prospective, single-center, open-label, single-arm study was to evaluate the cumulative efficacy and safety of reduced doses of everolimus (maintenance therapy) in patients with tuberous sclerosis and subependymal giant cell astrocytoma (SEGA). Methods: The trial included 15 patients who had undergone at least 12 months of treatment with a standard everolimus dose. The dose of everolimus was reduced to three times a week, with a daily dose as in standard regimen. Data of 14 patients were analyzed. SEGA volume (SV) was evaluated at study entry and subsequent time points by an experienced radiologist. Adverse events (AEs) noted during maintenance therapy were compared to the AEs of standard dose period. Results: Patients were followed over a mean duration 58.37 months (95%CI: 45.95-70.78). The differences in SEGA volume between subsequent time points (0, 3, 6,12, 18, 24, 36, 48, and 60 months) were not statistically significant (p = 0.16). At the end of the study, 7 out of 10 patients had stable SEGA volume. No clinical symptoms of progression were observed in any patients. No patient or tumor-related risk factors of progression were identified. Regarding AEs, infections (stomatitis, bronchitis, diarrhea) and laboratory abnormalities (neutropenia, anemia, hyperglycemia) occurred less frequently during maintenance therapy compared to the standard dose regimen. Conclusions: Final results from EMINENTS study confirm that maintenance therapy with everolimus might represent a rational therapeutic option for patients TSC and SEGA after effective full dose treatment. It could be an option for patients who experienced everolimus-related AEs, instead of discontinuation of therapy. Careful evaluation of possible progression, especially concerning first six months of maintenance therapy should be advised. Clinical Trial Registration: www.drks.de, identifier DRKS00005584.

Nivolumab for the Treatment of Advanced Pediatric Malignancies.

BACKGROUND/AIM: Nivolumab is an immune checkpoint inhibitor with high antitumor activity in selected neoplasms. The aim of the study was to evaluate the efficacy and safety of nivolumab in pediatric patients with various types of highly malignant advanced tumors. PATIENTS AND METHODS: Ten patients with a median age of 15.1 years were included in the study. The indications for treatment were: malignant skin melanoma (n=5), brain tumor (n=2), malignant melanoma of the brain (n=1), Hodgkin lymphoma (n=1) and soft tissue sarcoma (n=1). RESULTS: Complete disease remission was observed in 4 patients. Overall survival at 24 months from diagnosis for the entire group was 0.36. Two patients receiving combination therapy of nivolumab and ipilimumab did not achieve a remission. Adverse events of immunotherapy were observed in 4/10 patients. CONCLUSION: Nivolumab is a promising option in pediatric advanced malignancies. Treatment with immunotherapy was relatively well tolerated, and emerging side-effects were manageable.

Fetuin-A and Interleukine-8 in Children with the Clinical Remission of Type 1 Diabetes.

BACKGROUND: Clinical partial remission (CPR) in most patients with type 1 diabetes (T1D) is observed shortly after clinical diagnosis. Increasing body weight and impaired insulin sensitivity may play a role in the pathogenesis of CPR. Several cytokines can also participate in the development of insulin resistance. OBJECTIVE: To evaluate the relationship between birth weight, body mass index, and the concentrations of IL-8 and Fetuin-A, and the presence of clinical partial remission in children at the T1D onset. METHODS: The study group consisted of 134 children with a newly diagnosed T1D in whom the presence of CPR was evaluated in a further 2-year course of diabetes. The control group included 47 children without glucose tolerance disorders. The concentrations of IL-8 and Fetuin-A were determined by the ELISA method. RESULTS: CPR occurred in 75.34% of T1D patients. At T1D onset, higher values of BMI SDS in the remitters as compared to the patients without remission were observed. At the T1D onset, the concentrations of Fetuin-A (p=0.031) and IL-8 (p=0.042) were significantly higher in patients compared to those without CPR. CONCLUSION: Evaluation of Fetuin-A and IL-8 levels in patients with a newly diagnosed T1D can differentiate between patients with or without CPR.

Retrospective Analysis of the Treatment Outcome in Myeloid Leukemia of Down Syndrome in Polish Pediatric Leukemia and Lymphoma Study Group From 2005 to 2019.

Background: Children with Down syndrome (DS) have increased risk of myeloid leukemia (ML), but specific treatment protocols ensure excellent outcome. This study was a retrospective analysis of the treatment results and genetic characteristics of ML of DS (ML-DS) in Poland from 2005 to 2019. Methods: All 54 patients with ML-DS registered in the Polish Pediatric Leukemia and Lymphoma Study Group in analyzed period were enrolled to the study. There were 34 children treated with Acute Myeloid Leukemia-Berlin-Frankfurt-Munster 2004 Interim Protocol (group I) and 20 patients treated with ML-DS 2006 Protocol (group II). In the first protocol, there was reduction of the antracyclines doses and intrathecal treatment for ML-DS compared to non-DS patients. In the second protocol, further reduction of the treatment was introduced (omission of etoposide in the last cycle, no maintenance therapy). Results: Probabilities of 5-year overall survival (OS), event-free survival (EFS), and relapse-free survival in the whole analyzed group were 0.85 ± 0.05, 0.83 ± 0.05, and 0.97 ± 0.03, respectively. No significant differences were found between two protocols in the terms of OS and EFS (0.79 ± 0.07 vs. 0.95 ± 0.05, p = 0.14, and 0.76 ± 0.07 vs. 0.95 ± 0.05, p = 0.12, respectively). All deaths were caused by the treatment-related toxicities. Reduction of the treatment-related mortality was noticed (20% in group I and 5% in group II). The only one relapse in the whole cohort occurred in the patient from group I, older than 4 years, without GATA1 gene mutation. He was treated successfully with IdaFLA cycle followed by hematopoietic stem cell transplantation from matched sibling donor. No significant prognostic factor was found in the study group probably due to low number of patients in the subgroups. Conclusions: The study confirms that the reduced intensity protocols are very effective in ML-DS patients. The only cause of deaths was toxicities; however, systematic decrease of the treatment-related mortality was noticed.

Evaluation of skin autofluorescence as a surrogate of advanced glycation end products accumulation in children and adolescents with normal haemoglobin A1c values.

INTRODUCTION: Skin autofluorescence (sAF) represents tissue accumulation of advanced glycation end products (AGEs) and correlates with cardiovas-cular morbidity and diabetes risk. THE AIM: To assess sAF in Polish children without diabetes and to investigate whether sAF values in children with chronic diseases (but without glucose metabolism disorders) differ from sAF in healthy children. MATERIAL AND METHODS: Children without diseases known to influence sAF results (diabetes, renal failure) and with HbA1c < 5.7% (39 mmol/mol) were includ-ed, and the total study group was divided into two subgroups: with and without chronic conditions. Skin autofluorescence was meas-ured with an AGE Reader (Diagnoptics BV, Groningen, Netherlands). Data were presented as medians; Mann-Whitney U-test, Kruskall Wallis test, and Spearman's correlation coefficients were used in statistical analyses. RESULTS: The study group included 86 children (41 girls; mean age 10.1 ±4.2 years). Median sAF was 1.20 AU (25th-75th centile: 1.06-1.30). There was a positive correlation between sAF and age (R = 0.37, p = 0.0005). Skin autofluorescence values were higher in children with chronic diseases than in healthy children (1.23 AU [25th-75th centile: 1.10-1.40], n = 51 vs. 1.16 AU [1.06-1.26], n = 36, p = 0.0272). CONCLUSIONS: To our knowledge we present the first data on sAF values in Polish children without glucose metabolism disorders. We suggest that larger, homogenous populations of different ages should be studied to determine if and which diseases affect sAF measurements, and to develop pediatric reference values for sAF. This will allow a wider use of sAF measurement in the assessment of cardiovascular risk in the paediatric population.

Predicting Outcome and Conservative Treatment Failure in Patients with Skull Fracture after Traumatic Brain Injury: A Retrospective Cohort Study.

OBJECTIVE: Traumatic brain injury (TBI) remains a major cause of morbidity and mortality worldwide. The prognostic value of skull fracture (SF) remains to be clearly defined. To evaluate the need for neurosurgical intervention and determine the risk factors of conservative treatment failure (CTF), we retrieved from the hospital database the records of patients with SF after TBI. METHODS: We analyzed 146 consecutive patients (mean age: 49.8 ± 17.5 years) treated at the department of neurosurgery in a 5-year period. Clinical data, radiologic reports, and laboratory results were evaluated retrospectively. RESULTS: A total of 63% of patients were treated conservatively, 21.9% were operated on immediately, and 15.1% experienced CTF. Overall, 73.3% had a favorable outcome; the mortality rate was 13%. Intracranial bleeding occurred in 96.6% of cases, basilar SF in 61%, and cerebrospinal fluid (CSF) leak in 2.8%. The independent risk factors for outcome were Glasgow Coma Scale (GCS) score, age, and platelet count (PCT). The independent risk factors for CTF were epidural hematoma, subdural hematoma, mass effect, edema, international normalized ratio, PCT, mean platelet volume, and CSF leakage. The consensus decision tree algorithm used at the accident and emergency department indicated patients with no need for neurosurgical intervention with an accuracy of 91.7%, sensitivity of 88.9%, and featured the importance of mass effect, GCS, and epidural hematoma. CONCLUSIONS: Tests included in the complete blood count appeared useful for predicting the course in patients with SF, although the most important factors were age and neurologic status, as well as radiologic findings. Our decision tree requires further validation before it can be used in everyday practice.

Diagnostic value of lateral ventricle ratio: a retrospective case-control study of 112 acute subdural hematomas after non-severe traumatic brain injury.

PRIMARY OBJECTIVE: To evaluate correlation between the lateral ventricle ratio (LVR) and the risk of conservative treatment failure (CTF) among patients with acute subdural hematoma (ASDH) after non-severe traumatic brain injury (TBI), we retrieved from the hospital database and performed a retrospective analysis of 1339 cases with TBI treated during the 2008-2016 period. METHODS AND PROCEDURES: 112 patients with ASDH, GCS≥ 9 and initial conservative treatment were enrolled. They were divided according to the final treatment method applied (surgical or conservative). Clinical and radiological data was evaluated. We used ROC curve analysis and multivariate logistic regression model to identify risk factors of CTF. MAIN OUTCOMES AND RESULTS: LVR higher than 1.48 calculated on admission CT scans was the strongest predictor of CTF, with sensitivity of 78.9% and specificity of 93.5% (AUC: 0.774-0.994). LVR, prolonged prothrombin time and coexisting traumatic subarachnoid hemorrhage were independent risk factors. CONCLUSIONS: Despite limitations, study results support the view that patients after non-severe TBI with ASDH and with lateral ventricle asymmetry, defined as LVR> 1.48, require surgical treatment. LVR seems to be indirect, but still the closest method to quantify intracranial compliance. Thus, in the selected group of patients without clinical symptoms of critically diminished compensatory reserve, LVR could indicate those who need a surgical decompression.

Markers influencing the presence of partial clinical remission in patients with newly diagnosed type 1 diabetes.

BACKGROUND: The aim of the study was to compare the selected markers in children with and without partial clinical remission (CR) of newly diagnosed type 1 diabetes (T1D). METHODS: The study group consisted of 186 patients (F/M; 87/99) at onset of T1D and 24 months of follow-up. Partial CR was defined as insulin requirement <0.5 IU/kg and glycated hemoglobin (HbA1c) <7%. RESULTS: Partial CR was observed in 115/186 (61.83%) of patients. At diagnosis body mass index standard deviation (BMI SDS) was higher among remitters than in non-remitters (p=0.0051) and remitters were younger (p=0.0029). In the follow-up a higher triglyceride concentration in non-remitters compared to remitters (p=0.0455) and a lower high density lipoprotein (HDL) cholesterol level (p=0.0119) were noticed. CONCLUSIONS: Younger age and higher BMI at diagnosis of T1D can predispose to partial CR in children. In patients with CR of T1D after 2 years of follow-up a lipid profile improvement is observed.

Alcohol and cigarette use among adolescents with type 1 diabetes.

In this study, we compare the prevalence of alcohol and cigarette use among Polish adolescents with type 1 diabetes mellitus (T1DM) (n = 209), aged 15-18 years, with that of a large cohort of their healthy peers, using standardized questionnaire used in the European School Survey Project on Alcohol and Drugs (ESPAD). The lifetime, previous year, and past 30-day prevalence of alcohol consumption was high among adolescents with T1DM but lower than in the controls (82.8 vs 92.0%, 71.7 vs 85.6%, and 47.5 vs 69.7%, respectively, p < 10-5). The lifetime and 30-day prevalence of cigarette use was also lower among patients than the controls (54.6 vs 65.5%, p = 0.001 and 27.3 vs 35.9%, p = 0.012, respectively). Patients who admitted smoking exhibited worse metabolic control than non-smokers (p < 0.0001) and had a higher chance of developing diabetic ketoacidosis. The incidence of severe hypoglycemia was higher among those who reported getting drunk in the previous 30 days (p = 0.04) and lifetime smoking (p = 0.01). CONCLUSIONS: Although alcohol and cigarette consumption is lower than in controls, it is common among teenagers with type 1 diabetes, effecting metabolic control and causing the risk of acute diabetes complications. Better prevention strategies should be implemented in this group of patients in their early teen years. What is Known: • Substance use remains a significant cause of morbidity and mortality among teenagers with type 1 diabetes. • Current medical literature contains inconsistent data on the prevalence of alcohol and cigarette use among adolescents with type 1 diabetes, mostly due to methodological problems with conducting such surveys. What is New: • Methodological approach: we used a validated questionnaire from the European School Survey Project on Alcohol and Other Drugs (ESPAD) and compared the results to a large national control group of 12,114 healthy students who took part in ESPAD in 2011.

Breaking the Taboo: Illicit Drug Use among Adolescents with Type 1 Diabetes Mellitus.

BACKGROUND: The aim of the study was to explore the prevalence of illicit drug use in a group of Polish adolescents with type 1 diabetes (DM1) in comparison with a national cohort of their healthy peers. METHODS: Two hundred and nine adolescents with DM1, aged 15-18 years, were studied in 2013 with an anonymous questionnaire prepared for the European School Survey Project on Alcohol and Other Drugs (ESPAD). The control group was a representative sample of 12114 students at the same age who took part in ESPAD in 2011. Metabolic control was regarded as good if self-reported HbA1c was <8% or poor if HbA1c was ≥8%. RESULTS: Lifetime prevalence of illicit drug use was lower among adolescents with DM1 than in the control group [58 (28%) versus 5524 (46%), p = 10(-5)]. Cannabis preparations were the most frequently used substances [38 (18.3%) versus 3976 (33.1%), p = 10(-5)], followed by tranquilizers, sedatives, and amphetamine. Lifetime and last 12-month use of cannabis were associated with poorer glycemic control (HbA1c ≥ 8%), p < 0.01 and 0.02, respectively. CONCLUSIONS: Adolescents with DM1 report using illicit drugs to a lesser extent than their healthy peers. The use of cannabis is associated with a poorer metabolic control in teens with DM1.