Severe Colitis and Malnutrition in Association with Neonatal Hemophagocytic Lymphohistiocytosis

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome of overwhelming immune activation causing multiorgan dysfunction that may be genetic and/or acquired. Patients with familial HLH often present by one year of age, though most are asymptomatic in the first month of life. We present the case of a neonate with diarrhea and malnutrition who developed signs and symptoms consistent with a clinical diagnosis of HLH. Case: A neonate born at 35 5/7 weeks was transferred to a Level IV neonatal intensive care unit at 39 4/7 weeks for failure to thrive. Though feeding adequately and non-dysmorphic, he had persistent diarrhea on multiple formulas and only gained small amounts of weight via total parental nutrition. He was the first child of consanguineous parents of South Asian descent. Evaluation was inconsistent with milk soy protein intolerance and malabsorption syndromes. Very-early-onset inflammatory bowel disease and congenital diarrheas/enteropathies were considered. Intestinal biopsy was concerning for an underlying primary immunodeficiency. Additional studies showed a mild increase in T cells and low IgM. Lymphocyte proliferation to mitogens and expression of FOXP3, XIAP, and SAP by flow cytometry were unremarkable. At age 44 weeks, he acutely became lethargic, with fevers to 40°C and metabolic acidosis, further developing anemia, thrombocytopenia, lymphocytosis, transaminitis, and hepatosplenomegaly. Hypofibrinogenemia, hyperferritinemia (\u3e10,000), and elevated Soluble IL-2R level led to HLH diagnosis. Per HLH-94 protocol, he began dexamethasone and etoposide; he also received emapalumab. Despite treatment, fulminant liver failure with uncontrollable DIC ensued. Life-sustaining treatments were withdrawn and he died at 46 3/7 weeks. Discussion: Though colitis is not classically a feature of most primary HLH syndromes, it has been described in one subset of familial HLH. However, sequencing of the associated gene (STXBP2) was normal in our patient. Similarly, among EBV-driven HLH, X-linked lymphoproliferative disease and XIAP deficiency are associated with hypogammaglobulinemia and colitis respectively, but expression of these was normal without evidence of EBV. Perforin/granzyme B expression was increased. Whole-exome sequencing (WES) revealed several variants of unknown significance but was ultimately nondiagnostic. While neonates are more likely to have genetic causes for HLH, around 40% of neonates do not have established genetic diagnoses after WES. Conclusion: Timely recognition of HLH maximizes the potential for effective treatment like hematopoietic stem cell transplantation. Recognition of colitis as a presenting symptom may facilitate this challenging diagnosis. Rapid and inclusive genetic evaluation, including WES, may help identify the underlying etiology and guide treatment for neonatal HLH.https://digitalcommons.unmc.edu/chri_forum/1020/thumbnail.jp

Active Learning Pedagogies to Design a New Advanced Genetics Course: Using Students\u27 Feedback to Create a Tailored STEM Class for SSU

The STEM field is constantly evolving where graduate schools, medical schools, and the science job market are becoming more competitive. It is important for the students of Salem State University (SSU) that their curriculum is consistently being adapted to fit these new needs. A large percentage of the SSU biology community aims to enter the medical field, biotechnology field, or go on to pursue post graduate education. These are paths that require students to have an advanced level of knowledge pertaining to genetics and this is an area Salem State is starting to fall behind in compared to options offered at various local universities. We currently only offer two introductory genetics courses, this requires students to learn everything they will need to know about genetics for their future careers in one semester. If we were to offer an advance genetics course students would graduate with advance knowledge in this field and have a better chance getting into post graduate schools or landing job opportunities. Using the feedback of students in the SSU science community we have found a way to both fill this new need and satisfy their interest and concerns via a new Advanced Genetics of Disease course

Efficacy and safety of anticoagulant treatment in patients with cancer-related venous thrombotic disease.

openBackground: Fin dalla metà dell’Ottocento, grazie alle osservazioni di Armand Trousseau, è nota la presenza di un’importante associazione tra cancro e malattia tromboembolica venosa. La trombosi cancro associata si distingue da altre forme di trombosi per specifiche peculiarità in termini di fattori di rischio, patogenesi, diagnosi e, in particolar modo, per la difficile gestione della terapia anticoagulante, soprattutto in relazione all’elevato rischio di trombosi ricorrenti e complicanze emorragiche. Scopo dello studio: Lo scopo del nostro studio è stato quello di confrontare efficacia e sicurezza di tre diversi trattamenti anticoagulanti, quali l’eparina, la warfarina e i NAO, in un gruppo di soggetti con trombosi cancro-correlata. In particolare, l’efficacia è stata valutata attraverso l’analisi del numero di recidive tromboemboliche registrate sia durante l’assunzione della terapia anticoagulante, sia durante un periodo di follow-up di 18 mesi dalla sospensione del trattamento anticoagulante. La sicurezza è stata valutata in base al numero di eventi emorragici occorsi durante l’assunzione del trattamento anticoagulante. Materiali e metodi: Abbiamo condotto uno studio retrospettivo di coorte monocentrico che ha considerato 245 pazienti con cancro attivo, valutati consecutivamente dal Gennaio 2009 al Dicembre 2019 presso l’Unità Operativa di Malattie Trombotiche ed Emorragiche del Dipartimento di Medicina Interna dell’Azienda Ospedaliera Universitaria di Padova, per episodio di tromboembolismo venoso. I pazienti sono stati suddivisi in tre differenti gruppi sulla base del trattamento anticoagulante somministratogli. Nello specifico abbiamo arruolato n. 135 pazienti nel gruppo eparina, n. 38 nel gruppo warfarina e n. 72 nel gruppo NAO. Tutti i pazienti sono stati sottoposti ad un follow-up di 18 mesi dopo la sospensione del trattamento anticoagulante. Risultati: Abbiamo considerato il gruppo di pazienti trattati con eparina come gruppo di riferimento. Nei soggetti trattati con NAO abbiamo osservato una riduzione significativa del numero di episodi di recidiva di tromboembolismo venoso rispetto ai soggetti trattati con eparina. Per quanto riguarda il profilo di sicurezza i tre diversi farmaci anticoagulanti hanno evidenziato un rischio emorragico simile, senza che si evidenziassero differenze statisticamente significative anche all’analisi multivariata. In particolare, il trattamento con i NAO ha dimostrato un aumento significativo dell’efficacia senza un concomitante aumento del rischio emorragico. Conclusioni: I risultati del nostro studio supportano la scelta dell’utilizzo dei NAO nei pazienti con trombosi cancro associata rispetto al trattamento anticoagulante con eparina o warfarina. A fronte, infatti, di un rischio emorragico simile, i NAO hanno dimostrato una maggiore efficacia. Si rendono necessari studi prospettici su casistiche più numerose per confermare i dati del nostro studio

Features of aura in paediatric migraine diagnosed using the ICHD 3 beta criteria

Background In children and adolescents, the prevalence rate of migraine with aura is 1.6%. Few studies concerning migraine with aura features in paediatric population have been reported. Aim The aim of our study was to investigate clinical features of aura in a retrospective cohort of children with migraine with aura. Furthermore, we studied whether the International Classification of Headache Disorder (ICHD) 3 beta version criteria could efficiently detect migraine with aura in a paediatric population. Results We included 164 patients who experienced aura associated with headache (mean age 9.922.64 years). When the ICHD-II criteria were used, a final diagnosis of migraine with typical aura was obtained in 15.3% of patients, probable migraine with typical aura in 13.4%, and typical aura with headache in 61.8%, while in in 9.5% of patients the diagnosis was undetermined. According to ICHD-3 beta, we diagnosed migraine with typical aura in 77.7% of patients, probable migraine with typical aura in 13.4%, and an undetermined diagnosis in 9.5% (less than two attacks). Conclusion Aura features did not depend on age and were similar to those of adults. However, the headache could be difficult to classify if headache duration was considered. In this view, the ICHD-3 beta offers the advantage of not considering headache features, including pain duration, for the diagnosis of migraine with typical aura, thus making this diagnosis easier in children and adolescents

Diagnosis of primary headache in children younger than 6 years: A clinical challenge

Background: Criteria defined by the International headache Society are commonly used for the diagnosis of the different headache types in both adults and children. However, some authors have stressed some limits of these criteria when applied to preschool age. Objective: Our study aimed to describe the characteristics of primary headaches in children younger than 6 years and investigate how often the International Classification of Headache Disorders (ICHD) criteria allow a definitive diagnosis. Methods: This retrospective study analysed the clinical feature of 368 children younger than 6 years with primary headache. Results: We found that in our patients the percentage of undefined diagnosis was high when either the ICHD-II or the ICHD-III criteria were used. More than 70% of our children showed a duration of their attacks shorter than 1 hour. The absence of photophobia/phonophobia and nausea/vomiting significantly correlate with tension-type headache (TTH) and probable TTH. The number of first-degree relatives with migraine was positively correlated to the diagnosis of migraine in the patients (p<0.001). Conclusions: Our study showed that the ICHD-III criteria are difficult to use in children younger than 6 years. The problem is not solved by the reduction of the lowest duration limit for the diagnosis of migraine to 1 hour, as was done in the ICHD-II

Clinical Features of Pediatric Idiopathic Intracranial Hypertension and Applicability of New ICHD-3 Criteria

Idiopathic intracranial hypertension (IIH) is characterized by intracranial pressure >28 cmH2O in the absence of identifiable causes. Aim of this paper is to describe the clinical phenotype of pediatric IIH and to analyze the applicability of ICHD-3 criteria in comparison to the ICHD-2. We conducted a retrospective analysis of full clinical data of pediatric patients diagnosed with IIH between January 2007 and June 2018. Diagnostic evaluation included neuroimaging (all patients) and ultrasound-based optic nerve sheath diameter measurement (9 patients). Diagnosis of IIH was verified according to both ICHD-2 and ICHD-3 criteria for headache attributed to IIH, to verify the degree of concordance. We identified 41 subjects with suspected IIH; 14 were excluded due a diagnosis of secondary IH or lack of data. We therefore selected 27 subjects (age 4-15 years, mean 11). All patients presented with headache and bilateral papilloedema. Headache was daily in 22% cases, with diffuse gravative pain in 41%. In 4%, pain was exacerbated by cough, stress or tension. The most common presentation symptoms, in addition to headache, were blurred vision or diplopia (70%), vomiting (33%), and dizziness (15%). Twenty patients (74%) were obese. In 6 patients (22%) neuroimaging showed empty sella. Optic nerve sheath distension was detected in 6 out of 9 patients. Regarding the applicability of the ICHD-2 criteria, 18/27 (71%) patients have criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; 27/27 (100%) criterion D. When the ICHD-3 criteria were used, 27/27 (100%) fitted criterion A; 24/27 (89%) criterion B; 27/27 (100%) criterion C; and 27/27 (100%) criterion D. Our study suggests that, as compared with the ICHD-2, the new ICHD-3 criteria for headache attributed to IIH are better satisfied by pediatric patients with IIH. This is mainly due to the fact that qualitative headache characteristics are no longer considered in ICHD-3. Although the risk of under-rating the symptom of headache in IIH should not be disregarded, in pediatric population headache characteristics are usually less defined than in adults and obtaining a precise description of them is often very difficult

Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

<p>Abstract</p> <p>Background</p> <p>The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors.</p> <p>Methods</p> <p>C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine.</p> <p>Results</p> <p>Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice.</p> <p>Conclusions</p> <p>Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine.</p

Maternal alexithymia and attachment style: Which relationship with their children's headache features and psychological profile?

Introduction: A growing body of literature has shown an association between somatic symptoms and insecure "attachment style." In a recent study, we found a relationship between migraine severity, ambivalent attachment style, and psychological symptoms in children/adolescents. There is evidence that caregivers' attachment styles and their way of management/expression of emotions can influence children's psychological profile and pain expression. To date, data dealing with headache are scarce. Our aim was to study the role of maternal alexithymia and attachment style on their children's migraine severity, attachment style, and psychological profile. Materials and methods: We enrolled 84 consecutive patients suffering from migraine without aura (female: 45, male: 39; mean age 11.8 ± 2.4 years). According to headache frequency, children/adolescents were divided into two groups: (1) high frequency (patients reporting from weekly to daily attacks), and (2) low frequency (patients having ≤3 episodes per month). We divided headache attacks intensity into two groups (mild and severe pain). SAFA "Anxiety," "Depression," and "Somatization" scales were used to explore children's psychological profile. To evaluate attachment style, the semi-projective test SAT for patients and ASQ Questionnaire for mothers were employed. Maternal alexithymia traits were assessed by TAS-20. Results: We found a significant higher score in maternal alexithymia levels in children classified as "ambivalent," compared to those classified as "avoiding" (Total scale: p = 0.011). A positive correlation has been identified between mother's TAS-20 Total score and the children's SAFA-A Total score (p = 0.026). In particular, positive correlations were found between maternal alexithymia and children's "Separation anxiety" (p = 0.009) and "School anxiety" (p = 0.015) subscales. Maternal "Externally-oriented thinking" subscale correlated with children's school anxiety (p = 0.050). Moreover, we found a correlation between TAS-20 Total score and SAFA-D "Feeling of guilt" subscale (p = 0.014). Our data showed no relationship between TAS-20 and ASQ questionnaires and children's migraine intensity and frequency. Conclusion: Maternal alexithymia and attachment style have no impact on children's migraine severity. However, our results suggest that, although maternal alexithymic traits have no causative roles on children's migraine severity, they show a relationship with patients' attachment style and psychological symptoms, which in turn may impact on migraine severity

Digital interaction: where are we going?

In the framework of the AVI 2018 Conference, the interuniversity center ECONA has organized a thematic workshop on "Digital Interaction: where are we going?". Six contributions from the ECONA members investigate different perspectives around this thematic