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1.
bioRxiv ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38712126

ABSTRACT

The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.61, showed remarkable neutralization breadth against both SARS-CoV-2 variants and viruses from different sarbecovirus clades. C68.61, which targets a conserved RBD class 5 epitope, did not select for escape variants of SARS-CoV-2 or SARS-CoV-1 in culture nor have predicted escape variants among circulating SARS-CoV-2 strains, suggesting this epitope is functionally constrained. We identified 11 additional SARS-CoV-2/SARS-CoV-1 cross-reactive antibodies that target the more sequence conserved class 4 and class 5 epitopes within RBD that show activity against a subset of diverse sarbecoviruses with one antibody binding every single sarbecovirus RBD tested. A subset of these antibodies exhibited Fc-mediated effector functions as potent as antibodies that impact infection outcome in animal models. Thus, our study identified antibodies targeting conserved regions across SARS-CoV-2 variants and sarbecoviruses that may serve as therapeutics for pandemic preparedness as well as blueprints for the design of immunogens capable of eliciting cross-neutralizing responses.

2.
bioRxiv ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38617231

ABSTRACT

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.

3.
Hosp Pharm ; 59(2): 228-233, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38450349

ABSTRACT

Purpose: Critical care pharmacists are considered essential members of the healthcare team; however, justification and recruitment of new positions, especially in the evening or weekend shifts, remains a significant challenge. The purpose of this study was to investigate the number of interventions, type of interventions, and associated cost savings with the addition of 1 board certified critical care clinical pharmacist to evening shift. Methods: This was a prospective collection and characterization of 1 evening shift critical care pharmacist's clinical interventions over a 12-week period. Interventions were collected and categorized daily from 13:00 to 22:00 Monday through Friday. After collection was complete, cost savings estimates were calculated using pharmacy wholesaler acquisition cost. Results: Interventions were collected on 52 of 60 weekdays. A total of 510 interventions were collected with an average of 9.8 interventions accepted per day. The most common interventions included transitions of care, medication dose adjustment, and antibiotic de-escalation and the highest proportion of interventions occurred in the medical intensive care unit. An estimated associated cost avoidance of $66 537.80 was calculated for an average of $1279.57 saved per day. Additionally, 22 (4.1%) of interventions were considered high yield interventions upon independent review by 2 pharmacists. Conclusion: The addition of 1 board-certified critical care pharmacist to evening shift resulted in multiple interventions across several categories and a significant cost avoidance when calculated using conservative measures.

4.
Pediatr Exerc Sci ; 36(2): 66-74, 2024 May 01.
Article in English | MEDLINE | ID: mdl-37758263

ABSTRACT

PURPOSE: Studying physical activity in toddlers using accelerometers is challenging due to noncompliance with wear time (WT) and activity log (AL) instructions. The aims of this study are to examine relationships between WT and AL completion and (1) demographic and socioeconomic variables, (2) parenting style, and (3) whether sedentary time differs by AL completion. METHODS: Secondary analysis was performed using baseline data from a community wellness program randomized controlled trial for parents with toddlers (12-35 mo). Parents had toddlers wear ActiGraph wGT3x accelerometers and completed ALs. Valid days included ≥600-minute WT. Analysis of variance and chi-square analyses were used. RESULTS: The sample (n = 50) comprised racial and ethnically diverse toddlers (mean age = 27 mo, 58% male) and parents (mean age = 31.7 y, 84% female). Twenty-eight families (56%) returned valid accelerometer data with ALs. Participants in relationships were more likely to complete ALs (P < .05). Toddler sedentary time did not differ between those with ALs and those without. CONCLUSIONS: We found varied compliance with WT instructions and AL completion. Returned AL quality was poor, presenting challenges in correctly characterizing low-activity counts to improve internal validity of WT and physical activity measures. Support from marital partners may be important for adherence to study protocols.


Subject(s)
Exercise , Sedentary Behavior , Humans , Male , Female , Child, Preschool , Adult , Parents , Patient Compliance , Accelerometry
5.
Arch Womens Ment Health ; 27(1): 89-97, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37740096

ABSTRACT

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies.


Subject(s)
Maternal Health Services , Veterans , Female , Humans , Pregnancy , Veterans/psychology , Retrospective Studies , Prevalence , Antidepressive Agents/therapeutic use
6.
PLoS Pathog ; 19(12): e1011901, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38157379

ABSTRACT

Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron, but whether such epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated Δ483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including F456L that defines the XBB.1.5-derived EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Angiotensin-Converting Enzyme 2/genetics , Mutation , Amino Acids , Codon , Spike Glycoprotein, Coronavirus/genetics
7.
Cell Host Microbe ; 31(12): 1961-1973.e11, 2023 Dec 13.
Article in English | MEDLINE | ID: mdl-37989312

ABSTRACT

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.


Subject(s)
Chiroptera , Severe acute respiratory syndrome-related coronavirus , Animals , Humans , Angiotensin-Converting Enzyme 2 , SARS-CoV-2/genetics , Tropism , Spike Glycoprotein, Coronavirus , Antibodies, Viral
8.
Article in English | MEDLINE | ID: mdl-37932518

ABSTRACT

The COVID-19 pandemic resulted in increased feelings of emotional distress and disruptions in care across diverse patients subgroups, including those with chronic medical conditions such as inflammatory bowel diseases (IBD). We sought to understand the impact of the pandemic on the physical and emotional well-being of individuals with IBD and concurrent depression and/or anxiety symptoms. We conducted qualitative interviews after the beginning of the pandemic with 46 adults with IBD. Participants reported increased levels of emotional distress, feelings of social isolation, and uncertainty over whether IBD medications put them at increased risk. Young adults discussed feeling as if their lives had been disrupted. In addition, several individuals demonstrated resiliency and emphasized positives about the pandemic, including increased connectivity with family and friends, the convenience of being able to work from home despite their IBD symptoms, and lessened feelings of "missing out." Our findings highlight several opportunities to improve the health and well-being of individuals with IBD and beyond including increased support for combatting social isolation, enhanced counseling about medication risks and benefits, and the incorporation of resiliency skills building.

9.
Children (Basel) ; 10(10)2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37892357

ABSTRACT

Many adolescent health surveys ask if respondents are male or female. Non-response may be due to fear of de-anonymisation or being a gender-nonconforming youth. The present study investigates the frequency of non-response and its potential reasons. To this end, data from 54,833 adolescents aged 11-18 from six countries, participating in the 2018 Health Behaviour in School-aged Children (HBSC) study, were analysed. Respondents were divided into three groups: (1) "Responders" who answered both questions on age and gender, (2) "Age non-responders" who did not answer the question on age, and (3) "Gender non-responders" who answered the question on age but not the one on gender. These groups were compared regarding their non-response to other questions and regarding their health. Overall, 98.0% were responders, 1.6% were age non-responders and 0.4% were gender non-responders. On average, age non-responders skipped more questions (4.2 out or 64) than gender non-responders (3.2) and responders (2.1). Gender non-responders reported more psychosomatic complaints, more frequent substance use and lower family support than responders. This study shows that age and gender non-responders differ in their response styles, suggesting different reasons for skipping the gender question. The health disparities found between the groups suggest that further research should use a more nuanced approach, informed by LGBT+ youth's insights, to measure sex assigned at birth and gender identity.

10.
bioRxiv ; 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37745441

ABSTRACT

Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron variants, but whether such large epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous RBD deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe many tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated Δ483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including mutations like F456L that define the newly emerging EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space.

11.
bioRxiv ; 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37745523

ABSTRACT

Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad ACE2 usage and that RBD mutations further expand receptor promiscuity and enable human ACE2 utilization. We determined a cryoEM structure of the PRD-0038 RBD bound to R. alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryoEM and monoclonal antibody reactivity revealed its distinct antigenicity relative to SARS-CoV-2 and identified PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicited greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared to SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.

12.
LGBT Health ; 10(4): 306-314, 2023 05.
Article in English | MEDLINE | ID: mdl-36787477

ABSTRACT

Purpose: Transgender and nonbinary (TNB) youth face elevated levels of discrimination, stigma, mental health disorders, and suicidality when compared with their cisgender counterparts. Family and school support may mitigate some of the effects of the stressors facing TNB youth. This study aimed to better understand the impact of each of these sources of support on TNB youths' mental health and wellbeing. Methods: We used data collected between 2018 and 2019 as part of the Canadian Trans Youth Health Survey, a bilingual online survey to measure social support, physical health, and mental health in a sample of 220 TNB youth aged 14-25 living in Québec, Canada. We examined the relationships among different sources of support, and mental health and wellbeing outcomes using logistic regression. Analyses were conducted on the full sample and according to linguistic groups (French and English). Results: Participants reported high levels of mental health symptoms, self-harm, and suicidality, and mental health symptoms were higher in the English-speaking group (p = 0.005). In models controlling for age, family connectedness was associated with good/excellent self-reported mental health (odds ratio [OR] = 2.62, p = 0.001) and lower odds of having considered suicide (OR = 0.49, p = 0.003) or attempted suicide (OR = 0.43, p = 0.002), whereas school connectedness was associated with higher odds of good/very good/excellent general (OR = 2.42, p = 0.013) and good/excellent mental (OR = 2.45, p = 0.045) health. Conclusion: Family and school support present consistent associations with TNB youths' health and may constitute key areas for intervention for those supporting them.


Subject(s)
Transgender Persons , Humans , Adolescent , Mental Health , Quebec/epidemiology , Canada , Social Support
13.
RSC Med Chem ; 14(1): 135-143, 2023 Jan 25.
Article in English | MEDLINE | ID: mdl-36760747

ABSTRACT

Fragment-based drug design relies heavily on structural information for the elaboration and optimisation of hits. The ability to identify neighbouring binding hot spots, energetically favourable interactions and conserved binding motifs in protein structures through X-ray crystallography can inform the evolution of fragments into lead-like compounds through structure-based design. The composition of fragment libraries can be designed and curated to fit this purpose and herein, we describe and compare screening libraries containing compounds comprising between 2 and 18 heavy atoms. We evaluate the properties of the compounds in these libraries and assess their ability to probe protein surfaces for binding hot spots.

14.
Transplant Cell Ther ; 29(6): 396.e1-396.e5, 2023 06.
Article in English | MEDLINE | ID: mdl-36828177

ABSTRACT

BACKGROUND: Extracorporeal photopheresis (ECP) is frequently utilized in the treatment of steroid-refractory acute and chronic graft-versus-host disease (GVHD). Although the mechanism of action is not fully understood, it has been postulated that its therapeutic effect is immunologic tolerance linked to the associated apoptosis of the treated cells. Despite significant advances in allogeneic hematopoietic stem cell transplantation (HSCT), prophylaxis and treatment of GVHD remain a challenge and major limitation associated with this therapy. Use of ECP is a valuable strategy; however, it is time, cost, resource intensive, and not readily accessible. OBJECTIVE: In an effort to expand access to this therapy, we are investigating the use of cryopreserved ECP-treated cells. This will provide the ability to administer a significant proportion of the treatment at a facility closer to the patient's residence, thereby decreasing the number of visits to the primary treatment center with the goal of improving and expanding access to this therapy. Here we report the effects of cryopreservation on ECP-treated leukocytes. STUDY DESIGN: Mononuclear cells were pheresed from human patients, ECP-treated, and collected for viability and apoptotic analysis. Cells were then cryopreserved at -80°C or -150°C for 1 week, 1 month, and 3 months. Following thaw, repeat viability and apoptosis studies were performed on the leukocytes. RESULTS: WBC viability for freshly ECP-treated leukocytes was 84.5% ± 3.5 at 1 week, 87.3% ± 5.2 at 1 month, and 79.1% ± 1.1 at 3 months post thaw. Similar results were seen for cells frozen in cryovials. Leukocytes frozen the day after ECP treatment had 1 week and 1 month WBC viabilities of 84.0 ± 4.1 and 83.1 ± 2.1, respectively. Apoptotic potential was well preserved at 3 months, with cryopreserved ECP-treated lymphocytes being 19.2%, 44.5%, 75.5%, and 94.0% apoptotic after thaw on days 0, 1, 2, and 3 in culture, respectively. CONCLUSIONS: ECP-treated leukocytes cryopreserved at -80°C or -150°C for 3 months remain viable and as capable of apoptosis as freshly treated cells. Cryopreservation of an ECP-product warrants further in vivo investigation as a strategy to facilitate access to this needed therapy.


Subject(s)
Graft vs Host Disease , Photopheresis , Humans , Cryopreservation , Graft vs Host Disease/prevention & control , Leukocytes , Lymphocytes
15.
Neurol Clin ; 41(1): 161-176, 2023 02.
Article in English | MEDLINE | ID: mdl-36400553

ABSTRACT

Diagnosis and treatment of postconcussional syndrome (PCS) is challenging because symptoms are vague, difficult to confirm, and attributable to other conditions. There are no uniformly accepted diagnostic PCS criteria. Clinical care largely focuses on symptom reduction and management. Moreover, the coronavirus disease 2019 (COVID-19) pandemic has increased the challenge because post-acute COVID-19 syndrome symptoms overlap with PCS. Future research should center on base rates of PCS-type symptoms in nonneurological samples and the identification and improved understanding of moderating variables contributing to the frequency, intensity, and duration of PCS symptoms.


Subject(s)
COVID-19 , Post-Concussion Syndrome , Humans , Neuropsychological Tests , Post-Concussion Syndrome/diagnosis , Post-Concussion Syndrome/etiology , Post-Acute COVID-19 Syndrome
16.
Hosp Pharm ; 58(6): 569-574, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38560536

ABSTRACT

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r2 = .13, P = .11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P = .27) and higher harm scores (15 vs 7, P = .33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors.

17.
Neurosurg Focus ; 52(5): E2, 2022 05.
Article in English | MEDLINE | ID: mdl-35535824

ABSTRACT

OBJECTIVE: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. The objectives of this study were to 1) perform a systematic review, thoroughly assessing different multidisciplinary clinic layouts utilized in centers worldwide; and 2) characterize an institutional experience with the management of these conditions, focusing on the patient demographics, clinical presentation, complications, and therapeutic strategies seen in a patient population. METHODS: A systematic review of studies involving multidisciplinary clinics and their reported structure was performed according to PRISMA guidelines using the PubMed database. Then a retrospective chart review of patients enrolled in the Oklahoma Children's Hospital Neurocutaneous Syndromes Clinic was conducted. RESULTS: A search of the PubMed database yielded 251 unique results. Of these, 15 papers were included in the analysis, which identified 16 clinics that treated more than 2000 patients worldwide. The majority of these clinics treated patients with neurofibromatosis (13/16). The remaining clinics treated patients with von Hippel-Lindau syndrome (n = 1), tuberous sclerosis complex (n = 1), and multiple neurocutaneous syndromes (n = 1). The most commonly represented subspecialties in these clinics were genetics (15/16) and neurology (13/16). Five clinics (31%) solely saw pediatric patients, 10 clinics saw a combination of children and adults, and the final clinic had separate pediatric and adult clinics. The retrospective chart review of the Neurocutaneous Syndromes Clinic demonstrated that 164 patients were enrolled and seen in the clinic from April 2013 to December 2021. Diagnoses were made based on clinical findings or results of genetic testing; 115 (70%) had neurofibromatosis type 1, 9 (5.5%) had neurofibromatosis type 2, 35 (21%) had tuberous sclerosis complex, 2 (1%) had von Hippel-Lindau syndrome, 2 (1%) had Gorlin syndrome, and the remaining patient (0.6%) had Aarskog-Scott syndrome. Patient demographics, clinical presentation, complications, and therapeutic strategies are also discussed. CONCLUSIONS: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for neurocutaneous syndromes.


Subject(s)
Neurocutaneous Syndromes , Neurofibromatosis 1 , Tuberous Sclerosis , von Hippel-Lindau Disease , Adult , Child , Humans , Neurocutaneous Syndromes/diagnosis , Neurocutaneous Syndromes/genetics , Neurocutaneous Syndromes/therapy , Neurofibromatosis 1/complications , Neurofibromatosis 1/genetics , Retrospective Studies , Tuberous Sclerosis/complications , von Hippel-Lindau Disease/complications , von Hippel-Lindau Disease/genetics
18.
Mol Cytogenet ; 15(1): 17, 2022 Apr 19.
Article in English | MEDLINE | ID: mdl-35440058

ABSTRACT

BACKGROUND: Partial trisomy of the long arm of chromosome 11 is a rare cytogenetic abnormality. It has been characterized by variable sized duplications that lead to a range of phenotypes including growth retardation, developmental delay/intellectual disability, and distinctive craniofacial abnormalities. Congenital heart defects, skeletal abnormalities, urogenital anomalies, and hypotonia are found in some affected individuals. METHODS: We describe a 16-year-old patient presented with most of the hallmark phenotypes of trisomy 11q syndrome as well as exhibiting symptoms of hearing loss, seizures, and abnormal endocrinological and ophthalmological findings. Routine chromosome analysis and subsequent chromosomal microarray analysis (CMA) were performed to detect genetic abnormalities in this patient. RESULTS: We identified an abnormal male karyotype with a derivative chromosome 4 due to an unbalanced translocation between chromosomes 4 and chromosome 11. The CMA results revealed a 56 Mb duplication of chromosome 11q14.1-qter and a 874 Kb terminal deletion of the short arm of chromosome 4. CONCLUSION: A genomic imbalance resulting in partial trisomy 11q was found in a patient with multiple congenital anomalies. We compared the phenotypes of all known "pure" trisomy 11q cases in the literature and find that trisomy 11q23-qter is both recurrent and the most common cytogenetic abnormality found in the reported cases. It is associated with the core features of trisomy 11q syndrome.

20.
Am J Surg ; 223(1): 146-150, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34340862

ABSTRACT

BACKGROUND: Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. METHODS: A retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. RESULTS: Two patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. CONCLUSIONS: Use of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies. Level of Evidence and Study Type: Level IV, Therapeutic.


Subject(s)
Anticoagulants/administration & dosage , Brain Injuries, Traumatic/complications , Enoxaparin/administration & dosage , Intracranial Hemorrhages/epidemiology , Venous Thrombosis/prevention & control , Adult , Aged , Anticoagulants/adverse effects , Body Weight , Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/drug therapy , Drug Dosage Calculations , Enoxaparin/adverse effects , Female , Humans , Incidence , Intracranial Hemorrhages/chemically induced , Male , Middle Aged , Retrospective Studies , Venous Thrombosis/epidemiology , Venous Thrombosis/etiology
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