Deep learning-based image analysis predicts PD-L1 status from H&E-stained histopathology images in breast cancer.

Programmed death ligand-1 (PD-L1) has been recently adopted for breast cancer as a predictive biomarker for immunotherapies. The cost, time, and variability of PD-L1 quantification by immunohistochemistry (IHC) are a challenge. In contrast, hematoxylin and eosin (H&E) is a robust staining used routinely for cancer diagnosis. Here, we show that PD-L1 expression can be predicted from H&E-stained images by employing state-of-the-art deep learning techniques. With the help of two expert pathologists and a designed annotation software, we construct a dataset to assess the feasibility of PD-L1 prediction from H&E in breast cancer. In a cohort of 3,376 patients, our system predicts the PD-L1 status in a high area under the curve (AUC) of 0.91 - 0.93. Our system is validated on two external datasets, including an independent clinical trial cohort, showing consistent prediction performance. Furthermore, the proposed system predicts which cases are prone to pathologists miss-interpretation, showing it can serve as a decision support and quality assurance system in clinical practice.

The Role of Prematurity in Patients With Hemiplegic Cerebral Palsy.

A multicenter retrospective study was conducted to investigate the perinatal factors, imaging findings and clinical characteristics of hemiplegic cerebral palsy with a particular focus on children born prematurely. Our cohort included 135 patients of whom 42% were born prematurely; 16% were extreme premature infants who were born at 30 weeks or earlier. Nineteen (14%) were twins. Right hemiplegia was slightly more common and accounted for 59% of the patients. Imaging findings of intraventricular hemorrhage and periventricular leukomalacia were more prevalent in premature children whereas stroke, porencephaly, cerebral hemorrhage and cerebral atrophy were more evenly distributed in both term-born and prematurely-born children (p< 0.01). The overall prevalence of epilepsy in the cohort was 26% with no differences in full-term compared to prematurely-born children. Regardless of the gestational birth age, intellectual deficits were more common in the presence of comorbidity of both hemiplegia and epilepsy (p< 0.05).

Iron deficiency in children with attention deficit hyperactivity disorder.

BACKGROUND: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline. OBJECTIVES: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD. METHODS: The study group included 113 newly referred ADHD children aged 5-15 years (mean age 8.8 +/- 2.7). RESULTS: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 46 (41%). There was a very low inverse statistical correlation between scores on Conners' Rating Scale and ferritin levels, probably without clinical significance. CONCLUSIONS: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.

Measles-vaccinated Israeli boy with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a rare neurologic disorder of childhood and adolescence. We describe a 16-year-old boy who manifested the disease despite proper vaccinations. He was hospitalized because of bedwetting, involuntary limb movements, abnormal speech, and balance disturbances. Immunoglobulin G antibodies against measles were strongly positive, with a high relative cerebrospinal fluid/serum ratio. Polymerase chain reaction for measles produced negative results. Electroencephalography registered slow activity with high voltage discharges every few seconds, and with triphasic complex morphology. Magnetic resonance imaging revealed diffuse white matter changes, mostly around the posterior regions and lateral ventricles. Treatment with valproic acid, levetiracetam, carbamazepine, and intravenous immunoglobulin G was ineffective. Inosiplex and interferon-ß-1a were also administrated. The patient became comatose, with generalized myoclonic jerks, and died 1 year later. An autopsy was not performed. This patient illustrates that subacute sclerosing panencephalitis should be suspected among young vaccinated subjects.

l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.

Creatine and creatine phosphate provide storage and transmission of phosphate-bound energy in muscle and brain. Of the three inborn errors of creatine metabolism causing brain creatine depletion, l-arginine:glycine amidinotransferase (AGAT) deficiency has been described in only two families. We describe clinical and biochemical features, magnetic resonance spectroscopy (MRS) findings and response to creatine supplementation in two siblings with a novel mutation in the AGAT-encoding GATM gene. The sister and brother were evaluated at age 12 and 18years, respectively, because of mild mental retardation, muscle weakness and low weight. Extensive work-up had previously yielded negative results. Electron microscopy of the muscle revealed tubular aggregates and the activity of respiratory chain complexes was decreased in the muscle. Urine organic acid concentrations normalized to urine creatinine concentration were all increased, suggesting a creatine metabolism disorder. Brain MRS was remarkable for absence of creatine. Urine guanidinoacetate levels by tandem mass spectrometry were low, suggesting AGAT deficiency. GATM sequencing revealed a homozygous single nucleotide insertion 1111_1112insA, producing a frame-shift at Met-371 and premature termination at codon 376. Eleven months after commencing treatment with oral creatine monohydrate 100mg/kg/day, repeat MRI/MRS showed significantly increased brain creatine in the sister and a slight increase in the older brother. The parents' impression of improved strength and stamina was substantiated by increased post-treatment versus pre-treatment scores in the Vineland Adaptive Behavior Scale, straight-arm raising and timed up-and-go tests. Similarly, there was an apparent improvement in cognitive function, with significantly increased IQ-scores in the sister and marginal improvement in the brother.

Evidence-based review of bone strength in children and youth with cerebral palsy.

Children with cerebral palsy have various risk factors for compromised bone health. Evidence concerning their bone fragility is gathering; however, there is no consensus regarding risk factors, indications for evaluation, follow-up, or treatment. We performed an evidence-based review targeted to address the following questions concerning children with cerebral palsy: Is bone strength impaired and what are the risk factors? Are these children at increased risk for bone fractures? What are the relations between bone mineral density and fracture risk? What methods can be used for bone health assessment? How can bone strength be improved? Currently, the most acceptable method for evaluating bone status in children is dual-energy x-ray absorptiometry. Evidence demonstrates reduced bone mass in children with cerebral palsy; yet, no clear association with fractures. Preventive methods are suggested.

Bach flower remedies used for attention deficit hyperactivity disorder in children--a prospective double blind controlled study.

OBJECTIVE: To evaluate the effectiveness of Bach flower remedies in the treatment of children with attention deficit hyperactivity disorder (ADHD), in a double blind prospective controlled study. METHODS: Fourty Children with ADHD, aged 7-11 years, diagnosed according to the DSM criteria, were randomised to Bach flower remedies or placebo treatments for a period of 3 months. Children's performance was evaluated by the teacher before commencement of treatment and subsequently each month during the study period. RESULTS: Bach flower remedies have no statistically significant effect when compared to placebo in the treatment of children with ADHD. There was a significant correlation between treatment duration's and improvement of performance, with no difference between the treatment group compared to the placebo. CONCLUSIONS: There is no statistically significant difference between the effects of Bach flower remedies compared with placebo in the treatment of children with ADHD.

Childhood macrophagic myofasciitis-consanguinity and clinicopathological features.

Macrophagic myofasciitis has been almost exclusively detected in adults only. We describe six children of Arab Moslem origin with this disorder. Three presented with hypotonia, developmental delay and seizures and were evaluated for a mitochondrial disorder. The other three children had hypotonia and predominantly motor delay. Five of the six families were consanguineous. A massive collection of macrophages was present in the fascia and adjacent epimysium in all biopsies. The macrophages were periodic-acid-Schiff positive and immunoreactive for CD68. One biopsy which was evaluated by electron microscopy and energy-dispersive X-ray microanalysis showed crystalline structures containing aluminum in macrophages. Two children with motor delay and hypotonia were treated with oral prednisone for 3 months with no clinical improvement. Genetic predisposition probably accounts for the variability in the prevalence of macrophagic myofasciitis in different populations. At least in childhood, there seems to be no connection between macrophagic myofasciitis as a pathological entity and the clinical symptoms and signs.

Parkinsonian features after streptococcal pharyngitis.

Bradykinesia and rigidity developed in a 10-year-old girl during an episode of Sydenham chorea. These parkinsonian features improved over 6 months. Serum analysis demonstrated elevated anti-streptolysin-O and anti-basal ganglia antibodies. We suggest that autoimmune antibodies may cause remitting parkinsonian signs subsequent to streptococcal tonsillitis as part of the spectrum of poststreptococcal CNS disease.