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Cytotherapy May 2024The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other...
BACKGROUND AIMS
The success of chimeric antigen receptor (CAR) T-cell therapy in treating B-cell malignancies has led to the evaluation of CAR T-cells targeting a variety of other malignancies. Although the efficacy of CAR T-cells is enhanced when administered post-lymphodepleting chemotherapy, this can trigger bone marrow suppression and sustained cytopenia after CD19.CAR T-cell therapy. Additionally, systemic inflammation associated with CAR T-cell activity may contribute to myelosuppression. Cytopenias, such as neutropenia and thrombocytopenia, elevate the risk of severe infections and bleeding, respectively. However, data on the incidence of prolonged cytopenias after immune effector therapy in the solid tumor context remain limited.
OBJECTIVE
We compared the incidence of prolonged cytopenias after immune effector therapy including genetically modified T-cells, virus-specific T-cells (VSTs) and NKT-cells, as well non-gene-modified VSTs for leukemia, lymphoma, and solid tumors (ST) to identify associated risk factors.
METHODS
A retrospective analysis was conducted of 112 pediatric and adult patients with relapsed and/or refractory cancers who received lymphodepleting chemotherapy followed by immune effector therapy. Patients treated with 13 distinct immune effector cell therapies through 11 single-center clinical trials and 2 commercial products over a 6-year period were categorized into 3 types of malignancies: leukemia, lymphoma and ST. We obtained baseline patient characteristics and adverse events data for each participant, and tracked neutrophil and platelet counts following lymphodepletion.
RESULTS
Of 112 patients, 104 (92.9%) experienced cytopenias and 88 (79%) experienced severe cytopenias. Patients with leukemia experienced significantly longer durations of severe neutropenia (median duration of 14 days) compared with patients with lymphoma (7 days) or ST (11 days) (P = 0.002). Patients with leukemia also had a higher incidence of severe thrombocytopenia (74.1%), compared with lymphoma (46%, P = 0.03) and ST (14.3%, P < 0.0001). Prolonged cytopenias were significantly associated with disease type (63% of patients with leukemia, 44% of patients with lymphoma, and 22.9% of patients with ST, P = 0.006), prior hematopoietic stem cell transplant (HSCT) (66.7% with prior HSCT versus 38.3% without prior HSCT, P = 0.039), and development of immune effector cell-associated neurotoxicity syndrome (ICANS) (75% with ICANS versus 38% without ICANS, P = 0.027). There was no significant association between prolonged cytopenias and cytokine release syndrome.
CONCLUSIONS
Immune effector recipients often experience significant cytopenias due to marrow suppression following lymphodepletion regardless of disease, but prolonged severe cytopenias are significantly less common after treatment of patients with lymphoma and solid tumors.
PubMed: 38819365
DOI: 10.1016/j.jcyt.2024.04.075 -
Taiwanese Journal of Obstetrics &... May 2024We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf...
Perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II.
OBJECTIVE
We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2).
CASE REPORT
A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene.
CONCLUSION
Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.
Topics: Humans; Female; Acrocephalosyndactylia; Pregnancy; Ultrasonography, Prenatal; Adult; Receptor, Fibroblast Growth Factor, Type 2; Craniosynostoses; Thanatophoric Dysplasia; Mutation; Diagnosis, Differential; Magnetic Resonance Imaging; Heterozygote; Infant, Newborn; Skull
PubMed: 38802203
DOI: 10.1016/j.tjog.2024.03.005 -
Journal of Orthopaedic Science :... May 2024Webplasty can be conducted for complex syndactyly caused by Apert syndrome (also referred to as Apert hand) by extending the soft tissue in the lateral direction using...
BACKGROUND
Webplasty can be conducted for complex syndactyly caused by Apert syndrome (also referred to as Apert hand) by extending the soft tissue in the lateral direction using an external fixator. This study aimed to verify the usefulness of webplasty without skin grafting.
METHODS
Webplasty with lateral extension was conducted at a single institution from 2015 to 2023. The patients were four children with Apert hand aged 1-3 years. A custom-made small external fixator was used for all of the soft tissue extension.
RESULTS
Webplasty without skin grafting was completed by the time all five patients were 5-6 years of age.
CONCLUSION
Webplasty without skin grafting was possible with lateral extension of the soft tissue using a simple external fixator.
PubMed: 38772762
DOI: 10.1016/j.jos.2024.04.007 -
Medical Microbiology and Immunology May 2024To date, there is no licensed vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV). Therefore, MERS-CoV is one of the diseases targeted by the Coalition...
To date, there is no licensed vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV). Therefore, MERS-CoV is one of the diseases targeted by the Coalition for Epidemic Preparedness Innovations (CEPI) vaccine development programs and has been classified as a priority disease by the World Health Organization (WHO). An important measure of vaccine immunogenicity and antibody functionality is the detection of virus-neutralizing antibodies. We have developed and optimized a microneutralization assay (MNA) using authentic MERS-CoV and standardized automatic counting of virus foci. Compared to our standard virus neutralization assay, the MNA showed improved sensitivity when analyzing 30 human sera with good correlation of results (Spearman's correlation coefficient r = 0.8917, p value < 0.0001). It is important to use standardized materials, such as the WHO international standard (IS) for anti-MERS-CoV immunoglobulin G, to compare the results from clinical trials worldwide. Therefore, in addition to the neutralizing titers (NT = 1384, NT = 384), we determined the IC and IC of WHO IS in our MNA to be 0.67 IU/ml and 2.6 IU/ml, respectively. Overall, the established MNA is well suited to reliably quantify vaccine-induced neutralizing antibodies with high sensitivity.
Topics: Middle East Respiratory Syndrome Coronavirus; Humans; Neutralization Tests; Antibodies, Neutralizing; Antibodies, Viral; Coronavirus Infections; Animals; Inhibitory Concentration 50; Sensitivity and Specificity
PubMed: 38722338
DOI: 10.1007/s00430-024-00789-w -
Plastic and Reconstructive Surgery Apr 2024Children with syndromic craniosynostosis require multiple cranial expansion procedures. The purpose of this study was to determine how many expansions are typically...
INTRODUCTION
Children with syndromic craniosynostosis require multiple cranial expansion procedures. The purpose of this study was to determine how many expansions are typically performed through maturity, to assess complication rates, and to identify trends that might reduce the burden of care.
METHODS
A retrospective chart review was performed of all consecutive patients undergoing cranial vault enlargement procedures for syndromic craniosynostosis by a single surgeon.
RESULTS
Of 444 patients treated with Apert or Crouzon/Pfeiffer syndromes, 348 had complete long-term records. The mean age at last follow up was 16.9 years. Initial cranial expansions were performed at a significantly younger age for those beginning care at outside centers: 7.7-months versus 25.7-months in Dallas. 26.4% had ventriculoperitoneal shunts (syndrome-specific incidences: Apert 16%, Crouzon 27%, Pfeiffer 54%). Of 498 procedures, 80% were anterior, 18% posterior, and 2% were mid-vaults. The overall complication rate was 2%, with no differences found between anterior and posterior procedures. Those treated solely in Dallas underwent a mean of 1.9 expansions. Children with Pfeiffer syndrome underwent more expansions (2.7) than those with Apert or Crouzon syndromes. Factors correlationing with more expansions included: earlier surgical interventions, use of distraction, venticuloperitoneal shunts, and treatment begun at outside centers (3.1 procedures).
CONCLUSIONS
Children with syndromic craniosynostosis treated at a single center underwent an average of 2 skull expansion procedures with a 2% complication rate. Calvarial distraction, ventriculoperitoneal shunts, and earlier surgical interventions, were all associated with higher numbers of expansion procedures. Further research is needed to determine if these correlations are causal.
PubMed: 38589995
DOI: 10.1097/PRS.0000000000011460 -
Pediatrics Jun 2024The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules...
BACKGROUND AND OBJECTIVES
The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children.
METHODS
We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5).
RESULTS
Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, which is consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region.
CONCLUSIONS
Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicron subvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.
Topics: Humans; BNT162 Vaccine; Infant; 2019-nCoV Vaccine mRNA-1273; Child, Preschool; Male; Antibodies, Neutralizing; Prospective Studies; Female; Immunogenicity, Vaccine; COVID-19; Antibodies, Viral; SARS-CoV-2; COVID-19 Vaccines; Cohort Studies; Spike Glycoprotein, Coronavirus
PubMed: 38548700
DOI: 10.1542/peds.2024-066190 -
Iranian Journal of Allergy, Asthma, and... Feb 2024Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these...
Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these patients may affect the nature and function of the immune system. Thus, in this study, cell count and phagocytotic function of neutrophils were evaluated which may be influenced by changes in the hormonal rate and growth factors. In this study, the neutrophil count value and the oxidative burst were evaluated in six patients diagnosed with SSS and six healthy individuals. There was a significant reduction in the neutrophil count observed in SSS patients compared to healthy controls (37.41±7.93 percent vs. 66.5±6.8 percent). However, there was no significant difference in neutrophil oxidative index between patients with SSS and control subjects (172.33±55.08 vs. 217.00±77.38). We concluded that in patients with SSS, the phagocytic activity of neutrophils was not affected by hormonal changes, while the number of neutrophils and neutrophil-to-lymphocyte ratio (NLR) index were decreased.
Topics: Humans; Neutrophils; Respiratory Burst; Intellectual Disability; Leukocyte Count; Lymphocyte Count; Abnormalities, Multiple; Growth Disorders; Acrocephalosyndactylia; Osteochondrodysplasias; Hypoparathyroidism; Seizures
PubMed: 38485906
DOI: 10.18502/ijaai.v23i1.14959 -
Plastic and Reconstructive Surgery Jan 2024Perioperative airway management following midface advancements in children with Apert and Crouzon/Pfeiffer syndrome can be challenging, and protocols often differ. This...
A European multicenter outcome study on the different perioperative airway management policies following midface surgery in syndromic craniosynostosis: a proposal for a Standard Operating Procedure.
BACKGROUND
Perioperative airway management following midface advancements in children with Apert and Crouzon/Pfeiffer syndrome can be challenging, and protocols often differ. This study examined airway management following midface advancements and postoperative respiratory complications.
METHODS
A multicenter, retrospective cohort study was performed to obtain information about the timing of extubation, perioperative airway management, and respiratory complications after monobloc / le Fort III procedures.
RESULTS
Ultimately, 275 patients (129 monobloc and 146 Le Fort III) were included; 62 received immediate extubation and 162 delayed extubation; 42 had long-term tracheostomies and nine perioperative short-term tracheostomies. Short-term tracheostomies were in most centers reserved for selected cases. Patients with delayed extubation remained intubated for three days (IQR 2 - 5). The rate of no or only oxygen support after extubation was comparable between patients with immediate and delayed extubation, 58/62 (94%) and 137/162 (85%) patients, respectively. However, patients with immediate extubation developed less postoperative pneumonia than those with delayed, 0/62 (0%) versus 24/161 (15%) (P = 0.001), respectively. Immediate extubation also appeared safe in moderate/severe OSA since 19/20 (95%) required either no or only oxygen support after extubation. The odds of developing intubation-related complications increased by 21% with every extra day of intubation.
CONCLUSIONS
Immediate extubation following midface advancements was found to be a safe option, as it was not associated with respiratory insufficiency but did lead to fewer complications. Immediate extubation should be considered routine management in patients with no/mild OSA and should be the aim in moderate/severe OSA after careful assessment.
PubMed: 38289904
DOI: 10.1097/PRS.0000000000011317 -
Frontiers in Neurology 2023Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis, broad thumbs and big toes, and partial syndactyly of the hands and feet. This case report...
INTRODUCTION
Pfeiffer syndrome is a rare genetic disorder characterized by craniosynostosis, broad thumbs and big toes, and partial syndactyly of the hands and feet. This case report presents the case of a girl diagnosed with type 2 Pfeiffer syndrome who experienced severe obstructive sleep apnea (OSA).
CASE REPORT
The patient had been using an oropharyngeal airway since the age of 4 months due to snoring and witnessed apnea during sleep. At 11 months old, she was referred to our sleep clinic because of growth limitation and gross motor ability issues. Polysomnography (PSG) showed severe obstructive hypopnea before any treatment, and revealed severe central sleep apnea with the oropharyngeal airway in place. Positive airway pressure (PAP) therapy was initiated, which improved both her sleep and gross motor ability.
CONCLUSION
This case report emphasizes the importance of thorough sleep studies for diagnosing sleep and breathing disorders in Pfeiffer syndrome patients and highlights the effectiveness of PAP therapy in managing these conditions.
PubMed: 38274866
DOI: 10.3389/fneur.2023.1337236 -
Journal of Oral Biosciences Mar 2024The purpose of this study was to perform morphological and immunohistochemical (IHC) analysis of the submandibular glands (SMGs) in early development in Apert syndrome...
OBJECTIVES
The purpose of this study was to perform morphological and immunohistochemical (IHC) analysis of the submandibular glands (SMGs) in early development in Apert syndrome model mice (Ap mice).
METHODS
ACTB-Cre homozygous mice were mated with fibroblast growth factor receptor 2 (Fgfr2) mice; ACTB-Cre heterozygous mice (ACTB-Cre mice) at embryonic day (E) 13.5 served as the control group, and Fgfr2 mice (Ap mice) served as the experimental group. Hematoxylin and eosin (H&E) staining was performed on SMGs; Total SMG area and epithelial area were determined, and the epithelial occupancy ratio was calculated. Immunostaining was performed to assess the localization of FGF signaling-related proteins. Next, bromodeoxyuridine (BrdU)-positive cells were evaluated to assess cell proliferation. Finally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess apoptosis in SMGs.
RESULTS
The epithelial occupancy ratio was significantly higher in SMGs of Ap mice compared with that in SMGs of controls. FGF7 and bone morphogenetic protein 4 (BMP4) exhibited different localizations in SMGs of Ap mice compared with SMGs of controls. Cell proliferation was higher in SMGs of Ap mice compared with that of controls; however, apoptosis did not different significantly between the two groups.
CONCLUSION
Our results suggest that enhanced FGF signaling conferred by missense mutations in FGFR2 promotes branching morphogenesis in SMGs of Ap mice.
Topics: Animals; Mice; Acrocephalosyndactylia; Morphogenesis; Mutation; Receptor, Fibroblast Growth Factor, Type 2; Submandibular Gland
PubMed: 38246420
DOI: 10.1016/j.job.2024.01.001