Spontaneous remission and loss of monosomy 7: a window of opportunity for young children with SAMD9L syndrome.

Monosomy 7 is the most common cytogenetic abnormality in pediatric myelodysplastic syndrome (MDS) and associated with a high risk of disease progression. However, in young children, spontaneous loss of monosomy 7 with concomitant hematologic recovery has been described, especially in the presence of germline mutations in SAMD9 and SAMD9L genes. Here, we report on our experience of close surveillance instead of upfront hematopoietic stem cell transplantation (HSCT) in seven patients diagnosed with SAMD9L syndrome and monosomy 7 at a median age of 0.6 years (range, 0.4-2.9). Within 14 months from diagnosis, three children experienced spontaneous hematological remission accompanied by a decrease in monosomy 7 clone size. Subclones with somatic SAMD9L mutations in cis were identified in five patients, three of whom attained hematological remission. Two patients acquired RUNX1 and EZH2 mutations during the observation period, of whom one progressed to myelodysplastic syndrome with excess of blasts (MDS-EB). Four patients underwent allogeneic HSCT at a median time of 26 months (range, 14-40) from diagnosis for MDSEB, necrotizing granulomatous lymphadenitis, persistent monosomy 7, and severe neutropenia. At last follow-up, six patients were alive, while one passed away due to transplant-related causes. These data confirm previous observations that monosomy 7 can be transient in young children with SAMD9L syndrome. However, they also indicate that delaying HSCT poses a substantial risk of severe infection and disease progression. Finally, surveillance of patients with SAMD9L syndrome and monosomy 7 is critical to define the evolving genetic landscape and to determine the appropriate timing of HSCT (clinicaltrials gov. Identifier: NCT00662090).

High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis.

Linking the genetic background of patients with bleeding diathesis and altered platelet function remains challenging. We aimed to assess how a multiparameter microspot-based measurement of thrombus formation under flow can help identify patients with a platelet bleeding disorder. For this purpose, we studied 16 patients presenting with bleeding and/or albinism and suspected platelet dysfunction and 15 relatives. Genotyping of patients revealed a novel biallelic pathogenic variant in RASGRP2 (splice site c.240-1G>A), abrogating CalDAG-GEFI expression, compound heterozygosity (c.537del, c.571A>T) in P2RY12, affecting P2Y12 signaling, and heterozygous variants of unknown significance in the P2RY12 and HPS3 genes. Other patients were confirmed to have Hermansky-Pudlak syndrome type 1 or 3. In 5 patients, no genetic variant was found. Platelet functions were assessed via routine laboratory measurements. Blood samples from all subjects and day controls were screened for blood cell counts and microfluidic outcomes on 6 surfaces (48 parameters) in comparison with those of a reference cohort of healthy subjects. Differential analysis of the microfluidic data showed that the key parameters of thrombus formation were compromised in the 16 index patients. Principal component analysis revealed separate clusters of patients vs heterozygous family members and control subjects. Clusters were further segregated based on inclusion of hematologic values and laboratory measurements. Subject ranking indicated an overall impairment in thrombus formation in patients carrying a (likely) pathogenic variant of the genes but not in asymptomatic relatives. Taken together, our results indicate the advantages of testing for multiparametric thrombus formation in this patient population.

Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab.

PURPOSE: Real-world data and study data regarding therapy with Emicizumab in pediatric cohorts with haemophilia A is scarce. Especially, data on previously untreated pediatric patients (PUPs) and minimally treated patients (MTPs) are missing. METHODS: Thirteen pediatric patients with haemophilia A and treatment with Emicizumab were retrospectively evaluated for Annual Bleeding Rates (ABR) pre-and post-Emicizumab treatment. Safety data and data on management of minor surgery as well as laboratory results were collected. Additionally, we describe the clinical features of two PUPs and one MTP that are included in our cohort. RESULTS: Median age at initiation of Emicizumab was 5.3 (range: 0.26-17.5) years, three patients were younger than one year at initiation of treatment with Emicizumab. Median follow-up time on Emicizumab was 23.8 (range: 0.7-40) months. Total ABR (p = 0.009) as well as spontaneous (p = 0.018), traumatic (p = 0.018), and joint (p = 0.027) ABR reduced significantly post-Emicizumab transition. Safety profile was favourable as only one local site reaction occurred; no cessation of treatment was necessary. Surgery was successfully performed in three patients receiving rFVlla pre- and post-surgery. Emicizumab trough levels showed a median of 43.2 µg/ml (range: 23.9-56.8) after three doses of 3 mg/kg and 51.9 µg/ml (range: 30.4-75) at first follow-up with 1.5 mg/kg. CONCLUSION: Emicizumab is safe and efficient in pediatric patients with and without inhibitors. More data on larger multicenter cohorts and especially on PUPs/MTPs are still needed.

Novel GNE Gene Variants Associated with Severe Congenital Thrombocytopenia and Platelet Sialylation Defect.

The GNE gene encodes an enzyme that initiates and regulates the biosynthesis of N-acetylneuraminic acid, a precursor of sialic acids. GNE mutations are classically associated with Nonaka myopathy and sialuria, following an autosomal recessive and autosomal dominant inheritance pattern. Reports show that single GNE variants cause severe thrombocytopenia without muscle weakness. Using panel sequencing, we identified two novel compound heterozygous variants in GNE in a young girl with life-threatening bleedings, severe congenital thrombocytopenia, and a platelet secretion defect. Both variants are located in the nucleotide-binding site of the N-acetylmannosamin kinase domain of GNE. Lectin array showed decreased α-2,3-sialylation on platelets, consistent with loss of sialic acid synthesis and indicative of rapid platelet clearance. Hematopoietic stem cell transplantation (HSCT) normalized platelet counts. This is the first report of an HSCT in a patient with an inherited GNE defect leading to normal platelet counts.

[The Neonatal Subgaleal Hematoma - A Neonatal Emergency]. / Das subgaleale Hämatom beim Neugeborenen ­ ein neonatologischer Notfall.

Subgaleal hematoma (SGH) is a rare complication in neonates that may lead to hemorrhagic shock due to significant blood loss into the subgaleal space. We report of two neonates who developed subgaleal hematoma with severe hemorrhagic shock and encephalopathy. In the first case of a mature female neonate, the development of the subgaleal hematoma was promoted by early-onset sepsis and delivery by vacuum extraction. The second case, of a male preterm neonate, was a complicated fetal development followed by secondary cesarean section. Both cases highlight that a subgaleal hematoma is a severe neonatal emergency. In addition to prompt treatment of the shock, therapy of the coagulopathy is essential.

The Use of Stimulus Preference Assessments for Persons with Neurocognitive Disorder: A Literature Review.

Objectives: Stimulus preference assessments are a systematic, observation-based approach for identifying preferences among individuals with impaired communication skills. The purpose of this paper is to provide a review of the existing empirical literature that has utilized these methods with persons who have neurocognitive disorder (NCD).Methods: Studies were identified by searching online databases using a variety of search terms. Articles were included in the review if they were peer-reviewed, in English, were empirical in nature, and conducted a stimulus preference assessment with older adults diagnosed with NCD.Results: Eleven articles met the search criteria. Results revealed that data from stimulus preference assessments could increase activity engagement, increase requests for preferred items, identify reinforcers, and reduce behavioral and psychological symptoms.Conclusions: A small body of empirical literature suggests that data derived from stimulus preference assessments can be used to improve the lives of persons with NCD and their caregivers. Additional research is needed, however, to determine how effectively these procedures can be implemented into everyday practice in long-term care facilities.Clinical Implications: Stimulus preference assessments may provide a clinically useful means for efficiently identifying preferences in persons with severe NCD who cannot verbalize their needs.

Couple-based interventions for PTSD among military veterans: An empirical review.

OBJECTIVE: Treatment for posttraumatic stress disorder (PTSD) is a commonly sought mental health service among military service members and veterans (SM/Vs). Such treatment is typically individually-based, despite many SM/Vs reporting a desire for greater partner involvement in treatment. This review examined couple-based treatments for PTSD among SM/Vs and their romantic partners. METHOD: A database search conducted in July, 2018 yielded 167 studies, of which 16 (10%) met inclusion criteria. Brief intervention summaries, effect sizes, and distress change scores (where applicable) are reported. RESULTS: The 16 studies tested 7 interventions, which showed a reduction in self-rated and clinician-rated PTSD symptoms with large effect sizes observed in most studies. Relationship outcomes also improved for SM/Vs and their partners, with effect sizes ranging from small-to-medium for SM/Vs and small-to-large for partners. CONCLUSIONS: Couple-based interventions show success in reducing PTSD symptoms and improving relationship outcomes, offering several alternatives to individual-based interventions among partnered SM/Vs.

Institutional betrayal following military sexual trauma is associated with more severe depression and specific posttraumatic stress disorder symptom clusters.

OBJECTIVE: Preliminary research suggests that perceptions of institutional betrayal are associated with more severe symptoms of posttraumatic stress disorder (PTSD) and depression, as well as suicide attempts in military sexual trauma (MST) survivors. However, results have not been replicated. Additionally, associations of institutional betrayal with specific PTSD symptom clusters or sexual function are understudied. METHOD: Female service members/veterans who reported experiencing MST (N = 679) completed self-report measures of PTSD and depression symptom severity, suicidal ideation, and sexual function. Institutional betrayal was assessed from free-text descriptions of self-reported index traumas. RESULTS: Institutional betrayal was significantly associated with more severe depression and PTSD symptoms, including avoidance, negative alterations in cognitions and mood, re-experiencing, and dysphoric arousal. CONCLUSIONS: Targeting specific PTSD and depressive symptoms through evidence-based treatment may be important for managing institutional betrayal sequelae. Future research should identify specific strategies to help support survivors in their recovery following institutional betrayal.

Higher self-stigma is related to lower likelihood of disclosing military sexual trauma during screening in female veterans.

OBJECTIVE: Recent prevalence estimates indicate 38% of female service members/veterans (SM/Vs) report military sexual trauma (MST). This estimate is higher than Veterans Affairs estimates, which suggest 28% report MST during screening. The discrepant estimate suggests possible barriers to disclosing MST, which are not well-identified in the literature. The current study examined whether being assaulted by a fellow unit member and stigma for seeking help to treat the sequelae of MST from self, unit leader/command, and romantic partners were correlates of MST nondisclosure among 209 female SM/Vs. METHOD: Participants completed a self-report questionnaire assessing MST nondisclosure, MST assailant characteristics, and stigma from the aforementioned sources as well as demographic, military, and mental health characteristics. Logistic regression analyses adjusting for military rank, MST severity, age, marital status and satisfaction, and probable mental health diagnoses determined whether being assaulted by a fellow unit member (yes/no) or stigma from various sources were associated with MST nondisclosure. RESULTS: Thirty-seven (17.70%) participants did not disclose MST during a previous screening. At the bivariate level, participants who did not disclose MST reported higher self-stigma and anticipated enacted stigma from unit leader/command and romantic partner. After adjusting for covariates, only higher self-stigma was associated with MST nondisclosure. CONCLUSIONS: Female veterans who report higher self-stigma were less likely to disclose their MST during screening. Such findings are consistent with previous literature demonstrating that self-stigma, relative to other forms of stigma, relates to lower help-seeking behaviors. Efforts to increase the disclosure of MST during screening should focus on reducing self-stigma. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Bullying in Senior Living Facilities: Perspectives of Long-Term Care Staff.

Resident-to-resident bullying has attracted attention in the media, but little empirical literature exists related to the topic of senior bullying. The aim of the current study was to better understand resident-to-resident bullying from the perspective of staff who work with older adults. Forty-five long-term care staff members were interviewed regarding their observations of bullying. Results indicate that most staff members have observed bullying. Verbal bullying was the most observed type of bullying, but social bullying was also prevalent. Victims and perpetrators were reported to commonly have cognitive and physical disabilities. More than one half of participants had not received formal training and only 21% reported their facility had a formal policy to address bullying. The implications of these results support the need for detailed policies and training programs for staff to effectively intervene when bullying occurs. [Journal of Gerontological Nursing, 43(7), 34-41.].