Causes of poor eye contact in infants: a population-based study.

Background: Establishing eye contact between infants and parents is important for early parent-child bonding and lack of eye contact may be a sign of severe underlying disease. The aim of the study was to evaluate the causes of poor or lacking eye contact in infants.

Methods: Cross-sectional study reviewing all referrals of infants ≤1 year of age from January 1rst, 2016 to December 31rst, 2018.

Medical and surgical treatment of rhino-orbital-cerebral mucormycosis in a child with leukemia.

Purpose: Rhino-orbital-cerebral mucormycosis (ROCM) is a rare opportunistic infection with a high mortality despite relevant treatment.

Observations: A 3-year-old girl under treatment for acute lymphoblastic leukemia developed periorbital swelling, ophthalmoplegia and a necrotic palatal lesion during a period of neutropenia. Imaging revealed sinusitis, pre- and postseptal cellulitis.

Correction: Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Presenting features and imaging in childhood acute myeloid leukemia with central nervous system involvement.

Central nervous system (CNS) involvement in childhood acute myeloid leukemia (AML) can manifest as leukemic cells in the cerebrospinal fluid, a solid CNS tumor, or as neurological symptoms. We evaluated the presenting symptoms and neuroimaging findings in 33 of 34 children with AML and CNS involvement at diagnosis in the period 2000-2012 in Sweden, Finland, and Denmark. Imaging was performed in 22 patients, of whom 16 had CNS-related symptoms.

Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia.

We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate.

The effect of central nervous system involvement and irradiation in childhood acute lymphoblastic leukemia: Lessons from the NOPHO ALL-92 and ALL-2000 protocols.

Background: Central nervous system irradiation (CNS-RT) has played a central role in the cure of acute lymphoblastic leukemia (ALL), but due to the risk of long-term toxicity, it is now considered a less-favorable method of CNS-directed therapy.

Procedures: Retrospectively, we estimated the effect of CNS involvement and CNS-RT on events and overall survival (OS) in 835 children treated for high-risk ALL in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000 trials.

Results: We did not observe a statistically significant difference in the OS or event-free survival (EFS) in patients with CNS involvement at diagnosis, but the risk of isolated CNS relapse was higher (hazard ratio [HR] 7.

Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis.

Background: Each year approximately 200 children and adolescents are diagnosed with acute lymphoblastic leukemia (ALL) in the five Nordic countries, and 3% of these have central nervous system (CNS) involvement confirmed by leukemic cells in the cerebrospinal fluid (CSF) or neurological symptoms. We sought to determine the significance of neuraxis imaging in such patients.

Procedure: Magnetic resonance images of children aged 1-17.

Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases.

Background: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge.

Procedure: In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF) samples versus local conventional cytospin-based cytology (CC) for detecting leukemic cells and evaluating kinetics of elimination of leukemic cells in CSF.

Results: Among 300 patients with newly diagnosed ALL, 87 (29%) had CSF involvement by FCM, while CC was positive in 30 (10%) of 299 patients with available CC data (P < 0.

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity.

Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine methyltransferase (TPMT(IA)) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT.

Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia.

Background: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge.

Procedure: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744 patients on Nordic-Baltic trials. CNS status was classified as CNS1 (no CSF blasts), CNS2 (<5 leukocytes/µl CSF with blasts), CNS3 (≥5 leukocytes/µl with blasts or signs of CNS involvement), TLP+ (traumatic lumbar puncture with blasts), and TLP- (TLP with no blasts).

Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia: influence on cure rates and risk of second cancer.

Background: Previous studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMT(LA)) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMT(WT)) when treated with 6 MP maintenance therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol.

Procedure: We explored the pattern of SMN and relapse in the NOPHO ALL2000 protocol (n = 674) and NOPHO ALL92 protocol (n = 601) in relation to TPMT pheno- and/or genotype.

Second malignant neoplasms after treatment of childhood acute lymphoblastic leukemia.

Purpose: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events.

Patients And Methods: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007.

Results: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.

Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia.

Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during maintenance therapy. Of 447 study patients treated by the NOPHO ALL92 protocol, 120 patients received TMP/SMX continuously for 2-7 d/wk (TMP/SMX(2-7) ) and 287 patients never received TMP/SMX (TMP/SMX(never) ).

[Treatment-resistant depression is treatable].

Depression is considered resistant when two treatment attempts with antidepressants from different classes fail to produce significant clinical improvement. In cases of treatment-resistant depression, it is recommended to reevaluate the diagnosis, clarify comorbidity, substance abuse and lack of compliance. Regarding treatment, evidence is sparse, but switching to a different antidepressant, and combination or augmentation with another agent, admission and treatment with ECT are the options.