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1.
Invest Ophthalmol Vis Sci ; 65(3): 11, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38466290

RESUMO

Purpose: The purpose of this study was to investigate the genotypic and phenotypic characteristics of CRB1-associated early onset retinal dystrophy (CRB1-eoRD) and retinal architecture by swept-source optical coherence tomography (SS-OCT). Methods: Eleven probands with CRB1-eoRD were recruited. Clinical information, genetic analysis, and comprehensive ophthalmic examinations including SS-OCT and SS-OCT angiography (SS-OCTA) were conducted. Results: A total of 81.8% (9/11) of CRB1-eoRD presented as Leber congenital amaurosis (LCA). Common clinical manifestations included coin-like yellow-white retinal spots (20/22, 90.9%) and para-arteriolar retinal pigment epithelial retention (12/22, 54.5%). Nineteen different CRB1 variants were detected in our case series, including 12 missense, 3 frameshifts, 3 nonsense, and 1 splicing. Of them, 12 variants had been reported, and 7 were novel. SS-OCT showed thinner central macula (the LCA group, P < 0.0001), thicker total retina (P < 0.0001), thinner outer retina (P < 0.05), and thicker inner retina (P < 0.0001) compared with the healthy control. The inner/outer (I/O) retina thickness ratio of CRB1-eoRD was 3.0, higher than the healthy control of 1.2 and other inherited retinal diseases (IRDs) of 2.2 (P < 0.0001 and P = 0.0027, respectively). SS-OCTA revealed an increased vascular density and perfusion area of the superficial vascular complex and deep vascular complex in CRB1-eoRD. Conclusions: LCA emerges as a frequently occurring phenotype in CRB1-eoRD. The unique features of SS-OCT and SS-OCTA are illustrated, and the novel biomarker, I/O ratio, may facilitate early diagnosis. The insights gained from this study hold significant value in determining the treatment window for potential forthcoming CRB1 gene therapy.


Assuntos
Amaurose Congênita de Leber , Distrofias Retinianas , Humanos , Retina/diagnóstico por imagem , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Amaurose Congênita de Leber/diagnóstico , Amaurose Congênita de Leber/genética , Genótipo , Fenótipo , Proteínas do Olho/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 131-138, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38436309

RESUMO

OBJECTIVES: To investigate the clinical characteristics and prognosis of pneumococcal meningitis (PM), and drug sensitivity of Streptococcus pneumoniae (SP) isolates in Chinese children. METHODS: A retrospective analysis was conducted on clinical information, laboratory data, and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country. RESULTS: Among the 160 children with PM, there were 103 males and 57 females. The age ranged from 15 days to 15 years, with 109 cases (68.1%) aged 3 months to under 3 years. SP strains were isolated from 95 cases (59.4%) in cerebrospinal fluid cultures and from 57 cases (35.6%) in blood cultures. The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87) and 27% (21/78), respectively. Fifty-five cases (34.4%) had one or more risk factors for purulent meningitis, 113 cases (70.6%) had one or more extra-cranial infectious foci, and 18 cases (11.3%) had underlying diseases. The most common clinical symptoms were fever (147 cases, 91.9%), followed by lethargy (98 cases, 61.3%) and vomiting (61 cases, 38.1%). Sixty-nine cases (43.1%) experienced intracranial complications during hospitalization, with subdural effusion and/or empyema being the most common complication [43 cases (26.9%)], followed by hydrocephalus in 24 cases (15.0%), brain abscess in 23 cases (14.4%), and cerebral hemorrhage in 8 cases (5.0%). Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old, with rates of 91% (39/43) and 83% (20/24), respectively. SP strains exhibited complete sensitivity to vancomycin (100%, 75/75), linezolid (100%, 56/56), and meropenem (100%, 6/6). High sensitivity rates were also observed for levofloxacin (81%, 22/27), moxifloxacin (82%, 14/17), rifampicin (96%, 25/26), and chloramphenicol (91%, 21/23). However, low sensitivity rates were found for penicillin (16%, 11/68) and clindamycin (6%, 1/17), and SP strains were completely resistant to erythromycin (100%, 31/31). The rates of discharge with cure and improvement were 22.5% (36/160) and 66.2% (106/160), respectively, while 18 cases (11.3%) had adverse outcomes. CONCLUSIONS: Pediatric PM is more common in children aged 3 months to under 3 years. Intracranial complications are more frequently observed in children under 1 year old. Fever is the most common clinical manifestation of PM, and subdural effusion/emphysema and hydrocephalus are the most frequent complications. Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates. Adverse outcomes can be noted in more than 10% of PM cases. SP strains are high sensitivity to vancomycin, linezolid, meropenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.


Assuntos
Empiema , Hidrocefalia , Meningite Pneumocócica , Derrame Subdural , Lactente , Feminino , Masculino , Humanos , Criança , Recém-Nascido , Adolescente , Meningite Pneumocócica/tratamento farmacológico , Meningite Pneumocócica/epidemiologia , Meropeném , Vancomicina , Levofloxacino , Linezolida , Moxifloxacina , Estudos Retrospectivos , Rifampina , Streptococcus pneumoniae , Cloranfenicol
3.
Turk Neurosurg ; 34(2): 283-288, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38497181

RESUMO

AIM: To analyze the demographic and clinical data of preterm or low birth weight newborns with periventricular hemorrhage. MATERIAL AND METHODS: This retrospective study analyzed patients admitted to the neonatal intensive care unit of a Bahcesehir University School of Medicine-Affiliated Hospital due to preterm birth or low birth weight between June 1, 2012, and April 30, 2021. Categorical values were evaluated by Pearson chi-square or Fisher's exact test. The Mann-Whitney U test compared continuous values between the groups. Logistic regression was used to evaluate the factors that affected permanent cerebrospinal fluid (CSF) diversion. RESULTS: The study finally evaluated 180 newborns. Ninety-one newborns (50.5%) had grade I, 18 (10%) had grade II, 22 (12.2%) had grade III, and 49 (27.2%) had grade IV hemorrhage. One hundred and forty-nine patients (82.8%) were delivered by cesarean section, and 31 (17.2%) were delivered vaginally. All patients with low-grade hemorrhage who needed temporary CSF diversion eventually required permanent CSF diversion. For high-grade hemorrhage, 15 (grade III, 1; grade IV, 14) of 51 (29.4%) patients with ventricular access device (VAD) insertion required permanent CSF diversion. Fifteen (grade III, 6; grade IV, 9) of these 51 (29.4%) patients did not need permanent CSF diversion; thus, their VADs were removed. CONCLUSION: The permanent CSF diversion rate was significantly higher in the high-grade hemorrhage group, which had significantly lower weight and gestational age at birth. Moreover, only weight at VAD insertion had minimal effect on the need for permanent CSF diversion.


Assuntos
Hidrocefalia , Nascimento Prematuro , Humanos , Recém-Nascido , Gravidez , Feminino , Unidades de Terapia Intensiva Neonatal , Estudos Retrospectivos , Cesárea , Hidrocefalia/epidemiologia , Hidrocefalia/cirurgia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/cirurgia , Hospitais Universitários , Demografia
4.
Nagoya J Med Sci ; 86(1): 149-154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38505727

RESUMO

The 22q11.2 deletion syndrome has many complications; one of them is immunodeficiency. However, the time of onset and the degree of immunodeficiency can vary. We report a case of a preterm infant with congenital cytomegalovirus infection complicated with 22q11.2 deletion syndrome and immunological abnormalities. Ultrasonography revealed pulmonary atresia, ventricular septal defect, major aortopulmonary collateral artery, and thymic hypoplasia. His serum chemistry tests on admission revealed immunoglobulin G, A, and M levels of 1,547 mg/dL, 70 mg/dL, and 274 mg/dL, respectively. A surface antigen analysis of the peripheral lymphocytes using flow cytometry revealed the following: relatively low CD4-positive T-cell levels (18.1%; 1,767/µL), very high CD8-positive T-cell levels (58.9%; 5,751/µL), and CD4/CD8 ratio of 0.31. The level of T-cell receptor excision circles was relatively low at 17.5 copies/µL. After birth, the CD8-positive T-cell level began to gradually decrease, whereas the CD4/CD8 ratio began to increase. Thrombocytopenia, neutropenia, and skin petechiae were observed on admission. However, the condition improved. Treatment for congenital cytomegalovirus infection was not provided due to the absence of viremia. Unfortunately, the patient died suddenly on the 158th day of life, and the cause of death was unknown. To the best of our knowledge, no association between 22q11 deletion syndrome and cCMV has been described in the recent medical literature. According to the calculation, around one newborn infant who have both 22q11 deletion syndrome and cCMV infection will be born each year in Japan. Healthcare providers should pay more attention to this medical situation in the future.


Assuntos
Infecções por Citomegalovirus , Síndrome de DiGeorge , Cardiopatias Congênitas , Atresia Pulmonar , Lactente , Humanos , Recém-Nascido , Síndrome de DiGeorge/complicações , Recém-Nascido Prematuro , Infecções por Citomegalovirus/complicações
5.
Int Breastfeed J ; 19(1): 19, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509505

RESUMO

BACKGROUND: The number of pregnant women with congenital heart disease (CHD) is rising, and the disease poses increased risks of cardiovascular and obstetric complications during pregnancy, potentially impacting breastfeeding success. This study aimed to investigate breastfeeding in primiparous women with CHD compared to primiparous women without CHD, and to examine potential hindering factors for breastfeeding in women with CHD. METHODS: The data were gathered between 2014 and 2019 and obtained by merging the Swedish Congenital Heart Disease Register (SWEDCON) with the Swedish Pregnancy Register. Primiparous women ≥ 18 years of age with CHD (n = 578) were matched by age and municipality to 3049 women without CHD, giving birth after 22 gestational weeks. Multivariable logistic regression analysis was used to identify factors associated with non-breastfeeding in women with CHD. RESULTS: Fewer women with CHD breastfed than women without CHD two days (94% vs. 97%, p = 0.001) and four weeks after birth (84% vs. 89%, p = 0.006). When all women were analysed, having CHD was associated with non-breastfeeding at both two days and four weeks after birth. For women with CHD, body mass index (BMI) ≥ 30 (OR 3.1; 95% CI 1.4, 7.3), preterm birth (OR 6.4; 95% CI 2.1, 19.0), self-reported history of psychiatric illness (OR 2.4; 95% CI 1.2, 5.1), small for gestational age (OR 4.2; 95% CI 1.4, 12.2), and New York Heart Association Stages of Heart Failure class II - III (OR 6.0; 95% CI 1.4, 26.7) were associated with non-breastfeeding two days after birth. Four weeks after birth, factors associated with non-breastfeeding were BMI ≥ 30 (OR 4.3; 95% CI 2.1, 9.0), self-reported history of psychiatric illness (OR 2.2; 95% CI 1.2, 4.2), and preterm birth (OR 8.9; 95% CI 2.8, 27.9). CONCLUSIONS: The study shows that most women with CHD breastfeed, however, at a slightly lower proportion compared to women without CHD. In addition, factors related to the heart disease were not associated with non-breastfeeding four weeks after birth. Since preterm birth, BMI ≥ 30, and psychiatric illness are associated with non-breastfeeding, healthcare professionals should provide greater support to women with CHD having these conditions.


Assuntos
Cardiopatias Congênitas , Nascimento Prematuro , Gravidez , Recém-Nascido , Humanos , Feminino , Aleitamento Materno , Cardiopatias Congênitas/complicações , Paridade , Recém-Nascido Pequeno para a Idade Gestacional
6.
J Gastrointest Surg ; 28(1): 77-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38353080

RESUMO

BACKGROUND: The approach to patients with choledochal cysts (CCs) remains varied and subject to institutional practices. Owing to the rarity of the disease, the optimal treatment remains poorly defined, particularly in the adult population. This study aimed to review the literature on adult patients with CCs to evaluate trends of diagnosis and management in Western countries. METHODS: A literature search of 3 electronic databases was performed on adult patients diagnosed with CCs in Western institutions. A review of published literature was completed with comprehensive screening by 2 independent reviewers. Studies were analyzed, and data on surgical approach, malignancies, and follow-up were collected. Findings are presented in concordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: Of the 3488 articles retrieved, 21 studies evaluated Western adults with CCs for a combined population of 1337 patients. The most common Todani subtypes included types I (64%) and IV (22%). Symptoms at presentation included abdominal pain and jaundice, although many were asymptomatic. Ultrasound was used most frequently for diagnosis, followed by computed tomography and endoscopic cholangiopancreatography. The combined malignancy rate was 10.9%, with cholangiocarcinoma being the most prevalent. Complete extrahepatic cyst resection was standard for type I and IV CCs. Among malignancies, 18.5% and 16.4% were observed in patients with prior resection and internal drainage, respectively. CONCLUSIONS: A significant proportion of patients who undergo resection of CC disease harbor malignancy. Cancer risk seems reduced but not eliminated with complete resection, which remains the standard treatment. Additional studies are needed to standardize guidelines for the diagnosis and postoperative care of patients in Western countries.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Cisto do Colédoco , Adulto , Humanos , Cisto do Colédoco/diagnóstico , Cisto do Colédoco/cirurgia , Dor Abdominal , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/epidemiologia , Neoplasias dos Ductos Biliares/cirurgia , Estudos Retrospectivos
7.
EMBO Mol Med ; 16(3): 616-640, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38383802

RESUMO

Haplo-insufficiency of the gene encoding the myelin protein PMP22 leads to focal myelin overgrowth in the peripheral nervous system and hereditary neuropathy with liability to pressure palsies (HNPP). Conversely, duplication of PMP22 causes Charcot-Marie-Tooth disease type 1A (CMT1A), characterized by hypomyelination of medium to large caliber axons. The molecular mechanisms of abnormal myelin growth regulation by PMP22 have remained obscure. Here, we show in rodent models of HNPP and CMT1A that the PI3K/Akt/mTOR-pathway inhibiting phosphatase PTEN is correlated in abundance with PMP22 in peripheral nerves, without evidence for direct protein interactions. Indeed, treating DRG neuron/Schwann cell co-cultures from HNPP mice with PI3K/Akt/mTOR pathway inhibitors reduced focal hypermyelination. When we treated HNPP mice in vivo with the mTOR inhibitor Rapamycin, motor functions were improved, compound muscle amplitudes were increased and pathological tomacula in sciatic nerves were reduced. In contrast, we found Schwann cell dedifferentiation in CMT1A uncoupled from PI3K/Akt/mTOR, leaving partial PTEN ablation insufficient for disease amelioration. For HNPP, the development of PI3K/Akt/mTOR pathway inhibitors may be considered as the first treatment option for pressure palsies.


Assuntos
Artrogripose , Doença de Charcot-Marie-Tooth , Neuropatia Hereditária Motora e Sensorial , Fosfatidilinositol 3-Quinases , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt , Roedores/metabolismo , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Proteínas da Mielina/genética , Proteínas da Mielina/metabolismo , Serina-Treonina Quinases TOR
8.
Nat Commun ; 15(1): 1696, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402207

RESUMO

The yellow fever 17D vaccine (YF17D) is highly effective but is frequently administered to individuals with pre-existing cross-reactive immunity, potentially impacting their immune responses. Here, we investigate the impact of pre-existing flavivirus immunity induced by the tick-borne encephalitis virus (TBEV) vaccine on the response to YF17D vaccination in 250 individuals up to 28 days post-vaccination (pv) and 22 individuals sampled one-year pv. Our findings indicate that previous TBEV vaccination does not affect the early IgM-driven neutralizing response to YF17D. However, pre-vaccination sera enhance YF17D virus infection in vitro via antibody-dependent enhancement (ADE). Following YF17D vaccination, TBEV-pre-vaccinated individuals develop high amounts of cross-reactive IgG antibodies with poor neutralizing capacity. In contrast, TBEV-unvaccinated individuals elicit a non-cross-reacting neutralizing response. Using YF17D envelope protein mutants displaying different epitopes, we identify quaternary dimeric epitopes as the primary target of neutralizing antibodies. Additionally, TBEV-pre-vaccination skews the IgG response towards the pan-flavivirus fusion loop epitope (FLE), capable of mediating ADE of dengue and Zika virus infections in vitro. Together, we propose that YF17D vaccination conceals the FLE in individuals without prior flavivirus exposure but favors a cross-reactive IgG response in TBEV-pre-vaccinated recipients directed to the FLE with potential to enhance dengue virus infection.


Assuntos
Dengue , Vírus da Encefalite Transmitidos por Carrapatos , Vacina contra Febre Amarela , Infecção por Zika virus , Zika virus , Humanos , Anticorpos Antivirais , Anticorpos Neutralizantes , Infecção por Zika virus/prevenção & controle , Epitopos , Imunoglobulina G , Dengue/prevenção & controle
9.
J Am Coll Cardiol ; 83(7): 726-738, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38355242

RESUMO

BACKGROUND: The molecular mechanisms underlying Fontan-associated liver disease (FALD) remain largely unknown. OBJECTIVES: This study aimed to assess intrahepatic transcriptomic differences among patients with FALD according to the degree of liver fibrosis and clinical outcomes. METHODS: This retrospective cohort study included adults with the Fontan circulation. Baseline clinical, laboratory, imaging, and hemodynamic data as well as a composite clinical outcome (CCO) were extracted from medical records. Patients were classified into early or advanced fibrosis. RNA was isolated from formalin-fixed paraffin-embedded liver biopsy samples; RNA libraries were constructed with the use of an rRNA depletion method and sequenced on an Illumina Novaseq 6000. Differential gene expression and gene ontology analyses were performed with the use of DESeq2 and Metascape. RESULTS: A total of 106 patients (48% male, median age 31 years [IQR: 11.3 years]) were included. Those with advanced fibrosis had higher B-type natriuretic peptide levels and Fontan, mean pulmonary artery, and capillary wedge pressures. The CCO was present in 23 patients (22%) and was not predicted by advanced liver fibrosis, right ventricular morphology, presence of aortopulmonary collaterals, or Fontan pressures on multivariable analysis. Samples with advanced fibrosis had 228 upregulated genes compared with early fibrosis. Samples with the CCO had 894 upregulated genes compared with those without the CCO. A total of 136 upregulated genes were identified in both comparisons and were enriched in cellular response to cytokine stimulus or oxidative stress, VEGFA-VEGFR2 signaling pathway, TGF-ß signaling pathway, and vasculature development. CONCLUSIONS: Patients with FALD and advanced fibrosis or the CCO exhibited upregulated genes related to inflammation, congestion, and angiogenesis.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Hepatopatias , Adulto , Humanos , Masculino , Feminino , Estudos Retrospectivos , Cirrose Hepática/genética , Cirrose Hepática/patologia , Hepatopatias/genética , Hepatopatias/cirurgia , Fibrose , Perfilação da Expressão Gênica , RNA , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/cirurgia
10.
J Am Heart Assoc ; 13(4): e028957, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38348778

RESUMO

BACKGROUND: Congenital heart disease (CHD) is common in children and associated with greater risk of thrombotic complications. Management of these complications with standard-of-care treatment is suboptimal for these children. METHODS AND RESULTS: The effectiveness and safety of dabigatran were demonstrated in pivotal pediatric studies for the treatment of acute venous thromboembolism (VTE; NCT01895777) and secondary VTE prevention (NCT02197416). We report safety and efficacy outcomes from subgroup analyses of these studies for children with CHD (diagnosed according to local practice) and those without. In NCT01895777, 17/21 (81.0%) and 16/27 (59.3%) patients with CHD (including cyanotic) treated with dabigatran and standard of care, respectively, met the primary end point (complete thrombus resolution, freedom from recurrent VTE, and freedom from VTE-related death; odds ratio [OR], 0.34 [95% CI, 0.08-1.23]). In patients without CHD, 41.0% (n=64) versus 34.9% (n=22) achieved this end point with the respective treatments (OR, 0.77 [95% CI, 0.42-1.41]). Although numerical differences were observed, no heterogeneity in treatment effect of dabigatran on the composite primary end point was detected in patients with and without CHD (interaction P =0.2674). In NCT02197416, recurrent VTE at 12 months occurred in 0/17 patients with CHD versus 3/194 (1.5%) without. No patient with CHD experienced major or clinically relevant nonmajor bleeding events. CONCLUSIONS: Data on favorable anticoagulant alternatives for the unmet needs of children with CHD are emerging, and our exploratory results suggest that dabigatran could be an appropriate treatment choice, although challenging sample size limitations in pediatric studies require cautious interpretation of findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01895777, NCT02197416.


Assuntos
Dabigatrana , Cardiopatias Congênitas , Tromboembolia Venosa , Criança , Humanos , Anticoagulantes/efeitos adversos , Dabigatrana/efeitos adversos , Cardiopatias Congênitas/complicações , Prevenção Secundária , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Ensaios Clínicos como Assunto
11.
J Med Case Rep ; 18(1): 53, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38347580

RESUMO

BACKGROUND: Neurosarcoidosis occurs symptomatically in 5-10% of patients with sarcoidosis, and hydrocephalus is a rare complication of neurosarcoidosis, with either acute or subacute onset and presenting symptoms related to increased intracranial pressure. It represents a potentially fatal manifestation with a mortality rate of 22% (increased to 75% in case of coexistence of seizures) that requires a prompt initiation of treatment. High-dose intravenous corticosteroid treatment and neurosurgical treatment must be considered in all cases of neurosarcoidosis hydrocephalus. CASE PRESENTATION: Here we present a case of hydrocephalus in neurosarcoidosis, complicated by generalized seizures, in a 29-year-old Caucasian male patient treated with medical treatment only, with optimal response. CONCLUSION: Since neurosurgery treatment can lead to severe complications, this case report underlines the possibility to undergo only medical treatment in selected cases. Further studies are needed to stratify patients and better identify those eligible for only medical approach.


Assuntos
Doenças do Sistema Nervoso Central , Hidrocefalia , Sarcoidose , Humanos , Masculino , Adulto , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/diagnóstico , Hidrocefalia/complicações , Hidrocefalia/tratamento farmacológico , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Sarcoidose/diagnóstico , Corticosteroides/uso terapêutico , Convulsões/complicações
12.
Int Orthop ; 48(3): 657-666, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38195946

RESUMO

PURPOSE: The aim of this review is to appraise the current evidence on the epidemiology, pathophysiology, diagnosis and management of os acetabuli. METHODS: A scoping review was conducted according to the Joanna Briggs Institute guidelines. A systematic search was performed on Medline (PubMed), Embase and Cochrane Library. Inclusion criteria comprised observational and interventional studies and review articles published in the English language that focused on patients with os acetabuli according to the PRISMA extension of scoping reviews checklist using the terms 'Os Acetabuli' or 'os acetabula' or 'acetabular ossicles'. A narrative synthesis of results was undertaken, and the included articles were divided into (i) definition, (ii) aetiology, (iii) diagnosis and imaging and (iv) management of os acetabuli. RESULTS: 107 articles were screened, with 22 meeting the eligibility criteria. A total of 8836 patients were considered, of which 604 had os acetabuli. The mean age was 32.8 years. The prevalence of os acetabuli ranged from 3.4 to 7.7%, with a higher prevalence in males compared to females. True os acetabuli was defined as an unfused secondary ossification centre along the acetabular rim. The aetiology of os acetabuli is thought to be secondary to acetabular dysplasia and/or femoroacetabular impingement. Standard of care for management of symptomatic os acetabuli is considered to be arthroscopic excision unless the excision results in acetabular undercoverage and/or instability, in which case, fixation is recommended. CONCLUSIONS: Successful management of os acetabuli depends on understanding the pathology and treating the underlying cause rather than treating the os acetabuli in isolation. Future work needs to focus on establishing clear diagnostic criteria, consensus on definition and an evidence-based treatment algorithm.


Assuntos
Impacto Femoroacetabular , Luxação Congênita de Quadril , Luxação do Quadril , Masculino , Feminino , Humanos , Adulto , Articulação do Quadril/cirurgia , Acetábulo/diagnóstico por imagem , Acetábulo/cirurgia , Impacto Femoroacetabular/cirurgia , Luxação do Quadril/cirurgia , Luxação Congênita de Quadril/complicações , Artroscopia/métodos
13.
BMC Biol ; 22(1): 12, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273307

RESUMO

BACKGROUND: Many viruses enter host cells by hijacking endosomal trafficking. CapZ, a canonical actin capping protein, participates in endosomal trafficking, yet its precise role in endocytosis and virus infection remains elusive. RESULTS: Here, we showed that CapZ was transiently associated with early endosomes (EEs) and was subsequently released from the matured EEs after the fusion of two EEs, which was facilitated by PI(3)P to PI(3,5)P2 conversion. Vacuolin-1 (a triazine compound) stabilized CapZ at EEs and thus blocked the transition of EEs to late endosomes (LEs). Likewise, artificially tethering CapZ to EEs via a rapamycin-induced protein-protein interaction system blocked the early-to-late endosome transition. Remarkably, CapZ knockout or artificially tethering CapZ to EEs via rapamycin significantly inhibited flaviviruses, e.g., Zika virus (ZIKV) and dengue virus (DENV), or beta-coronavirus, e.g., murine hepatitis virus (MHV), infection by preventing the escape of RNA genome from endocytic vesicles. CONCLUSIONS: These results indicate that the temporal association of CapZ with EEs facilitates early-to-late endosome transition (physiologically) and the release of the viral genome from endocytic vesicles (pathologically).


Assuntos
Fosfatos de Fosfatidilinositol , Infecção por Zika virus , Zika virus , Animais , Humanos , Camundongos , Endocitose/fisiologia , Endossomos/metabolismo , Sirolimo/farmacologia , Sirolimo/metabolismo , Vesículas Transportadoras , Internalização do Vírus , Infecção por Zika virus/metabolismo
14.
J Am Heart Assoc ; 13(3): e029427, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38293915

RESUMO

BACKGROUND: The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early in the pressure-loaded RV. Here we test the hypothesis that microRNA (miR)-34a, which is induced in RV hypertrophy and RV failure (RVF), blocks the hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to the attenuated angiogenic response and increased susceptibility to RV failure. METHODS AND RESULTS: Mice underwent pulmonary artery banding to induce RV hypertrophy and RVF. Capillary rarefaction occurred immediately. Although hypoxia-inducible factor-1α expression increased (0.12±0.01 versus 0.22±0.03, P=0.05), VEGF expression decreased (0.61±0.03 versus 0.22±0.05, P=0.01). miR-34a expression was most upregulated in fibroblasts (4-fold), but also in cardiomyocytes and endothelial cells (2-fold). Overexpression of miR-34a in endothelial cells increased cell senescence (10±3% versus 22±2%, P<0.05) by suppressing sirtulin 1 expression, and decreased tube formation by 50% via suppression of hypoxia-inducible factor-1α, VEGF A, VEGF B, and VEGF receptor 2. miR-34a was induced by stretch, transforming growth factor-ß1, adrenergic stimulation, and hypoxia in cardiac fibroblasts and cardiomyocytes. In mice with RVF, locked nucleic acid-antimiR-34a improved RV shortening fraction and survival half-time and restored capillarity and VEGF expression. In children with congenital heart disease-related RVF, RV capillarity was decreased and miR-34a increased 5-fold. CONCLUSIONS: In summary, miR-34a from fibroblasts, cardiomyocytes, and endothelial cells mediates capillary rarefaction by suppressing the hypoxia-inducible factor-1α-VEGF axis in RV hypertrophy/RVF, raising the potential for anti-miR-34a therapeutics in patients with at-risk RVs.


Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , MicroRNAs , Rarefação Microvascular , Criança , Humanos , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rarefação Microvascular/metabolismo , Insuficiência Cardíaca/metabolismo , Hipertrofia Ventricular Direita , Miócitos Cardíacos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Cardiopatias Congênitas/metabolismo
15.
Pediatr Cardiol ; 45(3): 632-639, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38182891

RESUMO

In individuals with a single ventricle undergoing evaluation before Fontan surgery, the presence of excessive pulmonary blood flow can contribute to increased pulmonary artery pressure, notably in those who had a Glenn procedure with antegrade pulmonary flow. 28 patients who had previously undergone Glenn anastomosis with antegrade pulmonary blood flow (APBF) and with elevated mean pulmonary artery (mPAP) pressure > 15 mmHg in diagnostic catheter angiography were included in the study. After addressing other anatomical factors that could affect pulmonary artery pressure, APBF was occluded with semi-compliant, Wedge or sizing balloons to measure pulmonary artery pressure accurately. 23 patients (82% of the cohort) advanced to Fontan completion. In this group, median mPAP dropped from 20.5 (IQR 19-22) mmHg to 13 (IQR 12-14) mmHg post-test (p < 0.001). Median PVR post-test was 1.8 (IQR 1.5-2.1) WU m2. SpO2 levels decreased from a median of 88% (IQR 86%-93%) pre-test to 80% (IQR 75%-84%) post-test (p < 0.001). In five patients, elevated mPAP post-test occlusion on diagnostic catheter angiography led to non-completion of Fontan circulation. In this group, median pre- and post-test mPAP were 23 mmHg (IQR 21.5-23.5) and 19 mmHg (IQR 18.5-20), respectively (p = 0.038). Median post-test PVR was 3.8 (IQR 3.6-4.5) WU m2. SpO2 levels decreased from a median of 79% (IQR 76%-81%) pre-test to 77% (IQR 73.5%-80%) post-test (p = 0.039). Our study presents a specialized approach for patients initially deemed unsuitable for Fontan due to elevated pulmonary artery pressures. We were able to successfully complete the Fontan procedure in the majority of these high-risk cases after temporary balloon occlusion test.


Assuntos
Técnica de Fontan , Cardiopatias Congênitas , Humanos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Circulação Pulmonar/fisiologia , Cardiopatias Congênitas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Técnica de Fontan/métodos
16.
Parasit Vectors ; 17(1): 18, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216956

RESUMO

BACKGROUND: The unplanned and intensified use of insecticides to control mosquito-borne diseases has led to an upsurge of resistance to commonly used insecticides. Aedes aegypti, the main vector of dengue, chikungunya, and Zika virus, is primarily controlled through the application of adulticides (pyrethroid insecticides) and larvicides (temephos). Fine spatial-scale analysis of resistance may reveal important resistance-related patterns, and the application of mathematical models to determine the phenotypic resistance status lessens the cost and usage of resources, thus resulting in an enhanced and successful control program. METHODS: The phenotypic resistance for permethrin, deltamethrin, and malathion was monitored in the Ae. aegypti populations using the World Health Organization (WHO) adult bioassay method. Mosquitoes' resistance to permethrin and deltamethrin was evaluated for the commonly occurring base substitutions in the voltage-gated sodium channel (vgsc) gene. Rational functions were used to determine the relationship between the kdr alleles and the phenotypic resistant percentage of Ae. aegypti in Sri Lanka. RESULTS: The results of the bioassays revealed highly resistant Ae. aegypti populations for the two pyrethroid insecticides (permethrin and deltamethrin) tested. All populations were susceptible to 5% malathion insecticide. The study also revealed high frequencies of C1534 and G1016 in all the populations studied. The highest haplotype frequency was detected for the haplotype CC/VV, followed by FC/VV and CC/VG. Of the seven models obtained, this study suggests the prediction models using rational approximation considering the C allele frequencies and the total of C, G, and P allele frequencies and phenotypic resistance as the best fits for the area concerned. CONCLUSIONS: This is the first study to our knowledge to provide a model to predict phenotypic resistance using rational functions considering kdr alleles. The flexible nature of the rational functions has revealed the most suitable association among them. Thus, a general evaluation of kdr alleles prior to insecticide applications would unveil the phenotypic resistance percentage of the wild mosquito population. A site-specific strategy is recommended for monitoring resistance with a mathematical approach and management of insecticide applications for the vector population.


Assuntos
Aedes , Inseticidas , Nitrilas , Piretrinas , Infecção por Zika virus , Zika virus , Animais , Inseticidas/farmacologia , Resistência a Inseticidas/genética , Aedes/genética , Malation/farmacologia , Permetrina , Sri Lanka , Mosquitos Vetores/genética , Piretrinas/farmacologia , Mutação
17.
BMJ Open ; 14(1): e077743, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216203

RESUMO

PURPOSE: The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the pregnancies, fetuses, babies, children and adults with congenital anomalies and rare diseases across England. The congenital anomaly (CA) register provides a resource for patients and their families, clinicians, researchers and public health professionals in furthering the understanding of CAs. PARTICIPANTS: NCARDRS registers CAs occurring in babies born alive and stillborn, fetal losses and terminations in England. NCARDRS collects data from secondary and tertiary healthcare providers, private providers and laboratories covering fetal medicine, maternity or paediatric services. Data describe the pregnancy, mother, baby and anomaly. Established in 2015, NCARDRS expanded CA registration coverage from 22% of total births in England in 2015 to national coverage, which was achieved in 2018. Prior to 2015, data collection was performed independently by regional registers in England; these data are also held by NCARDRS. FINDINGS TO DATE: NCARDRS registers approximately 21 000 babies with CAs per year with surveillance covering around 600 000 total births, the largest birth coverage for a CA register globally. Data on prevalence, risk factors and survival for children with CAs are available. Data have been used in several peer-reviewed publications. Birth prevalence statistics, including public health indicators such as the association with maternal age, infant and perinatal mortality, are published annually. NCARDRS supports clinical audit for screening programmes and service evaluation. FUTURE PLANS: NCARDRS provides a valuable resource for the understanding of the epidemiology, surveillance, prevention and treatment of CAs. Currently, approximately 21 000 new registrations of babies or fetuses with suspected or confirmed CAs are added each year. Identifiers are collected, enabling linkage to routinely collected healthcare and population statistics, further enhancing the value of the data.


Assuntos
Anormalidades Congênitas , Medicina Estatal , Lactente , Adulto , Criança , Humanos , Gravidez , Feminino , Coleta de Dados , Natimorto , Idade Materna , Inglaterra/epidemiologia , Anormalidades Congênitas/epidemiologia
18.
J Clin Periodontol ; 51(4): 464-473, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185798

RESUMO

AIM: WHIM (warts, hypogammaglobulinaemia, infections and myelokathexis) syndrome is a rare combined primary immunodeficiency disease caused by gain-of-function (GOF) mutations in the chemokine receptor CXCR4 and includes severe neutropenia as a common feature. Neutropenia is a known risk factor for periodontitis; however, a detailed periodontal evaluation of a WHIM syndrome cohort is lacking. This study aimed to establish the evidence base for the periodontal status of patients with WHIM syndrome. MATERIALS AND METHODS: Twenty-two adult WHIM syndrome patients and 22 age- and gender-matched healthy volunteers (HVs) were evaluated through a comprehensive medical and periodontal examination. A mouse model of WHIM syndrome was assessed for susceptibility to naturally progressing or inducible periodontitis. RESULTS: Fourteen patients with WHIM syndrome (63.6%) and one HV (4.5%) were diagnosed with Stage III/IV periodontitis. No WHIM patient presented with the early onset, dramatic clinical phenotypes typically associated with genetic forms of neutropenia. Age, but not the specific CXCR4 mutation or absolute neutrophil count, was associated with periodontitis severity in the WHIM cohort. Mice with a Cxcr4 GOF mutation did not exhibit increased alveolar bone loss in spontaneous or ligature-induced periodontitis. CONCLUSIONS: Overall, WHIM syndrome patients presented with an increased severity of periodontitis despite past and ongoing neutrophil mobilization treatments. GOF mutations in CXCR4 may be a risk factor for periodontitis in humans.


Assuntos
Síndromes de Imunodeficiência , Neutropenia , Doenças Periodontais , Periodontite , Doenças da Imunodeficiência Primária , Verrugas , Adulto , Humanos , Animais , Camundongos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/diagnóstico , Doenças da Imunodeficiência Primária/complicações , Doenças da Imunodeficiência Primária/genética , Verrugas/genética , Verrugas/terapia , Neutropenia/complicações , Neutropenia/genética , Doenças Periodontais/complicações , Doenças Periodontais/genética , Periodontite/complicações , Periodontite/genética
19.
Can J Neurol Sci ; 51(1): 137-139, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36927489

RESUMO

The objective was to characterize the progression of sleep complaints in 115 dystrophy type 1 (DM1) patients who filled out a sleep questionnaire twice at a 9-year interval. Daytime napping (22.1% vs. 34.5%, p < 0.05), early awakenings (11.4% vs 21.1%, p < 0.05), nonrestorative sleep (39.5% vs 51.8%, p < 0.05), stimulant use (7.0% vs 19.3%, p < 0.01), breathing cessation (10.7% vs 23.2%, p < 0.01), and nighttime urination (42.5% vs 54.9%, p < 0.05) increased between Time 1 and Time 2. Sleep-related complaints are prominent and augment rapidly in DM1 patients. Physicians need to better identify and treat them to help alleviate the burden they impose on patients and their caregivers.


Évolution des troubles du sommeil dans la dystrophie myotonique de type 1 : une étude longitudinale de 9 ans.L'objectif était de caractériser l'évolution des plaintes liées au sommeil chez 115 patients atteints de dystrophie myotonique de type 1 (DM1) ayant rempli un questionnaire sur le sommeil à deux reprises à 9 ans d'intervalle. La prévalence des siestes (22,1 % vs 34,5 %, p < 0,05), des réveils matinaux précoces (11,4 % vs 21,1 %, p < 0,05), du sommeil non réparateur (39,5 % vs 51,8 %, p < 0,05), de la consommation de stimulants (7,0 % vs 19,3 %, p < 0,01), des arrêts respiratoires (10,7 % vs 23,2 %, p < 0,01) et des mictions nocturnes (42,5 % vs 54,9 %, p < 0,05) a augmenté entre le temps 1 et le temps 2. Les plaintes liées au sommeil sont fréquentes et augmentent rapidement dans la DM1. Les médecins doivent mieux les identifier et les traiter pour aider à alléger le fardeau qu'ils imposent aux patients et à leurs aidants.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Distrofia Miotônica , Humanos , Distrofia Miotônica/complicações , Estudos Longitudinais , Sono
20.
Cell Tissue Bank ; 25(1): 55-66, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36917328

RESUMO

For decades, bovine jugular vein conduits (BJV) and classic cryopreserved homografts have been the two most widely used options for pulmonary valve replacement (PVR) in congenital heart disease. More recently, decellularized pulmonary homografts (DPH) have provided an alternative avenue for PVR. Matched comparison of patients who received DPH for PVR with patients who received bovine jugular vein conduits (BJV) considering patient age group, type of heart defect, and previous procedures. 319 DPH patients were matched to 319 BJV patients; the mean age of BJV patients was 15.3 (SD 9.5) years versus 19.1 (12.4) years in DPH patients (p = 0.001). The mean conduit diameter was 24.5 (3.5) mm for DPH and 20.3 (2.5) mm for BJV (p < 0.001). There was no difference in survival rates between the two groups after 10 years (97.0 vs. 98.1%, p = 0.45). The rate of freedom from endocarditis was significantly lower for BJV patients (87.1 vs. 96.5%, p = 0.006). Freedom from explantation was significantly lower for BJV at 10 years (81.7 vs. 95.5%, p = 0.001) as well as freedom from any significant degeneration at 10 years (39.6 vs. 65.4%, p < 0.001). 140 Patients, matched for age, heart defect type, prior procedures, and conduit sizes of 20-22 mm (± 2 mm), were compared separately; mean age BJV 8.7 (4.9) and DPH 9.5 (7.3) years (p = n.s.). DPH showed 20% higher freedom from explantation and degeneration in this subgroup (p = 0.232). Decellularized pulmonary homografts exhibit superior 10-year results to bovine jugular vein conduits in PVR.


Assuntos
Cardiopatias Congênitas , Valva Pulmonar , Humanos , Bovinos , Animais , Lactente , Adolescente , Criança , Valva Pulmonar/transplante , Veias Jugulares/transplante , Resultado do Tratamento , Cardiopatias Congênitas/cirurgia , Aloenxertos , Estudos Retrospectivos
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