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1.
Eur Radiol ; 34(4): 2374-2383, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37812295

RESUMO

OBJECTIVES: To evaluate safety and effectiveness of selective internal radiation therapy (SIRT) using yttrium-90 for localized and locally advanced intrahepatic cholangiocarcinoma (iCCA). METHODS: A retrospective review was performed of patients with localized iCCA treated with SIRT at a single institution. Overall survival (OS), local tumor response, progression-free survival (PFS), and toxicity were collected. Stratified analysis was performed based on surgical resection. Predictor analysis of OS was performed using the Fine-Grey regression analysis model with patients bridged to surgery regarded as competing events. RESULTS: A total of 28 consecutive patients with localized iCCA were treated with a total of 38 sessions of SIRT (17 segmental, 13 lobar, and 8 combined deliveries) and a mean dominant target dose per session of 238.4 ± 130.0 Gy. The cumulative radiologic response rate was 16/28 (57.1%) with a median PFS of 265 days. Median survival time (MST) was 22.9 months for the entire cohort with 1-year and 3-year survival of 78.4% and 45.1%, respectively. Ten patients (34.5%) were downstaged to surgical intervention (7 resection, 3 transplant) and showed longer OS (p = 0.027). The 1-year and 3-year OS for patients who received surgery were 100% and 62.5% (95% CI: 14.2-89.3%), respectively. Age (p = 0.028), Eastern Cooperative Oncology Group performance status (p = 0.030), and objective radiologic response (p=0.014) are associated with OS. Two ≥grade 3 hyperbilirubinemia, anemia, and one pleuro-biliary fistula occurred post-SIRT. CONCLUSIONS: SIRT for localized iCCA is safe and effective in achieving radiological response, downstaging to surgery and transplant, and resulting in pathologic necrosis. CLINICAL RELEVANCE STATEMENT: Selective internal radiation therapy should be considered for patients with localized and locally advanced intrahepatic cholangiocarcinoma. KEY POINTS: • The effectiveness of radioembolization for intrahepatic cholangiocarcinoma (iCCA) can be underestimated given the inclusion of extrahepatic disease. • Radioembolization is safe and effective for local and locally advanced iCCA. Age, Eastern Cooperative Oncology Group performance status, and radiologic response are associated with survival. • Radioembolization should be considered for patients with localized and locally advanced iCCA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Microesferas , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/patologia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Hepáticas/patologia
2.
J Vasc Interv Radiol ; 35(7): 989-997.e2, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38490364

RESUMO

PURPOSE: To assess the safety and effectiveness of using modified radiation lobectomy (mRL) to treat primary hepatic tumors located in the right hepatic lobe (Segments V-VIII) and to determine future liver remnant (FLR) hypertrophy. MATERIALS AND METHODS: A retrospective review was performed at a single institution to include 19 consecutive patients (7 females, 12 males) who underwent single-session mRL for right-sided primary hepatic tumors: 15 received segmentectomy plus lobectomy (segmental dose of >190 Gy and lobar dose of >80 Gy); 4 were treated with the double-segmental approach (dominant segments of >190 Gy and nondominant segments of >80 Gy). Treated tumors included 13 hepatocellular carcinoma (HCC), 4 cholangiocarcinoma (CCA), and 2 mixed-type HCC-CCA with a median dominant tumor size of 5.3 cm (interquartile range [IQR], 3.7-7.3 cm). FLR of the left hepatic lobe was measured at baseline, T1 (4-8 weeks), T2 (2-4 months), T3 (4-6 months), and T4 (9-12 months). RESULTS: Objective tumor response and tumor control were achieved in 17 of the 19 (89.5%) and 18 of the 19 (94.7%) patients, respectively. FLR hypertrophy was observed at T1 (median, 47.8%; P = .025), T2 (median, 48.4%; P = .012), T3 (median, 50.4%; P = .015), and T4 (median, 59.1%; P < .001). Patients without cirrhosis demonstrated greater hypertrophy by 6 months (median, 55.8% vs 47.2%; P = .031). One patient developed a Grade 3 adverse event (ascites requiring paracentesis) at 1-month follow-up. Grade ≥2 serum toxicities were associated with worse baseline Child-Pugh Score, serum albumin, and total bilirubin (P < .05). Among 7 patients who underwent neoadjuvant mRL, 2 underwent resection and 1 received liver transplant. CONCLUSIONS: mRL appears safe and effective for treatment of right-sided primary hepatic tumors with the benefit of promoting FLR hypertrophy.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Humanos , Masculino , Feminino , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Embolização Terapêutica/efeitos adversos , Colangiocarcinoma/radioterapia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Tempo , Carga Tumoral , Neoplasias dos Ductos Biliares/radioterapia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Hipertrofia , Adulto , Regeneração Hepática
3.
J Vasc Interv Radiol ; 35(5): 712-721.e3, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38336031

RESUMO

PURPOSE: To identify factors of incomplete treatment after segmental transarterial radioembolization (TARE) for treatment-naive and solitary hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 75 consecutive patients (age, 68.5 years [SD ± 8.0]; 25/75 [33.3%] women) with treatment-naive, solitary HCC underwent segmental or subsegmental TARE with glass microspheres (tumor size, 3.8 cm [SD ± 2.2]; administered dose, 222.6 Gy [SD ± 123.9]) at a single institution from November 2015 to June 2022. Radiologic response and progression-free survival (PFS) were assessed as per modified Response Evaluation Criteria in Solid Tumors. RESULTS: Complete treatment was achieved in 48 of 75 (64.0%) patients (mean follow-up, 33.2 months [SD ± 27.4]). Patients with incomplete treatment (27/75, 36%) presented with larger tumor size (5.0 [SD ± 2.5] vs 3.1 [SD ± 1.6] cm; P = .0001), with more tumors located in the watershed zone (81.5% vs 41.7%; P = .001). These patients were less likely to be bridged to transplant or resection (22.2% vs 52.1%; P = .015). Watershed tumors demonstrated worse target tumor PFS (median PFS, 19 months vs not reached; P = .0104) and overall PFS (9.1 months vs not reached; P = .0077). Watershed location was associated with worse PFS among tumors >3 cm in size (8.4 months vs not reached; P = .035) but not in tumors ≤3 cm in size (52.2 months vs not reached; P = .915). CONCLUSIONS: Tumor size and watershed location were associated with incomplete treatment after segmental TARE for HCC. Watershed tumors were associated with worse PFS, particularly tumors larger than 3 cm. These tumors may require careful treatment planning and repeated treatments to ensure a durable response.


Assuntos
Carcinoma Hepatocelular , Progressão da Doença , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos , Carga Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Fatores de Tempo , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Estudos Retrospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Risco , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos , Resultado do Tratamento
4.
Hum Mol Genet ; 30(22): 2068-2081, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34170319

RESUMO

Primary autosomal recessive microcephaly and Seckel syndrome spectrum disorders (MCPH-SCKS) include a heterogeneous group of autosomal recessive inherited diseases characterized by primary (congenital) microcephaly, the absence of visceral abnormalities, and a variable degree of cognitive impairment, short stature and facial dysmorphism. Recently, biallelic variants in the nuclear pore complex (NPC) component nucleoporin 85 gene (NUP85) were reported to cause steroid-resistant nephrotic syndrome (SRNS). Here, we report biallelic variants in NUP85 in two pedigrees with an MCPH-SCKS phenotype spectrum without SRNS, thereby expanding the phenotypic spectrum of NUP85-linked diseases. Structural analysis predicts the identified NUP85 variants cause conformational changes that could have an effect on NPC architecture or on its interaction with other NUPs. We show that mutant NUP85 is, however, associated with a reduced number of NPCs but unaltered nucleocytoplasmic compartmentalization, abnormal mitotic spindle morphology, and decreased cell viability and proliferation in one patient's cells. Our results also indicate the link of common cellular mechanisms involved in MCPH-SCKS spectrum disorders and NUP85-associated diseases. In addition to the previous studies, our results broaden the phenotypic spectrum of NUP85-linked human disease and propose a role for NUP85 in nervous system development.


Assuntos
Nanismo/diagnóstico , Nanismo/genética , Microcefalia/diagnóstico , Microcefalia/genética , Mutação , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fenótipo , Encéfalo/anormalidades , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Fibroblastos/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Complexo de Proteínas Formadoras de Poros Nucleares/química , Linhagem , Síndrome
5.
J Vasc Interv Radiol ; 34(11): 1970-1976.e1, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37532096

RESUMO

Radiation segmentectomy with a dose of >190 Gy using yttrium-90 (90Y) glass microspheres for intrahepatic cholangiocarcinoma (iCCA) has been shown to be safe and effective. The present study further increased the dose to >400 Gy for treatment of iCCA as complete pathologic necrosis has been shown in hepatocellular carcinoma using this ablative approach. A total of 10 patients with 13 tumors (median size, 5.3 cm; range, 1.5-13.6 cm) at a single institution underwent >400-Gy segmental radioembolization. Objective response was achieved in all tumors (13 of 13, 100%). One patient developed a Grade 3 or greater major adverse event (stroke and hepatic decompensation). One patient was bridged to transplant (>95% pathologic necrosis), whereas another underwent resection (>99% necrosis). Contralateral hypertrophy was observed in 6 out of 6 patients treated with modified lobectomy dosing, with a functional liver reserve increase from a median of 31.5% to 57.1%. The present report suggests that segmental transarterial radioembolization with >400 Gy is feasible in terms of safety and effectiveness for treating iCCA.


Assuntos
Neoplasias dos Ductos Biliares , Carcinoma Hepatocelular , Colangiocarcinoma , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/tratamento farmacológico , Microesferas , Carcinoma Hepatocelular/patologia , Radioisótopos de Ítrio/efeitos adversos , Embolização Terapêutica/efeitos adversos , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/radioterapia , Necrose/induzido quimicamente , Necrose/tratamento farmacológico , Ductos Biliares Intra-Hepáticos , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/radioterapia , Resultado do Tratamento , Estudos Retrospectivos
6.
Vascular ; 31(3): 579-584, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35034526

RESUMO

OBJECTIVES: The objective of this study is to document the combined use of catheter-based thrombectomy/thrombolysis with endovascular repair of high-risk segments of the inferior vena cava in the setting of iatrogenic and traumatic injuries. While the use of endovascular techniques to treat caval thrombosis is well documented and often preferred due to its minimally invasive nature, there is still little literature that focuses on the nuances related to injury of high mortality areas of the IVC as a result of major trauma, transplant, and other surgical interventions. METHODS: An IRB-approved retrospective review of all patients undergoing IVC thrombectomy was performed at a single tertiary care academic center between January 2018 and July 2021. Cases were subsequently selected based on those who underwent primary mechanical thrombectomy followed by endovascular stenting (or angioplasty). Among this cohort, four patients who underwent this procedure in the context of iatrogenic and traumatic injuries were included. RESULTS: All four patients undergoing primary mechanical thrombectomy followed by endovascular stenting (or angioplasty) due to IVC thrombus and/or stenosis were technically successful with immediate positive clinical outcomes. CONCLUSIONS: Mechanical thrombectomy in conjunction with IVC recanalization via stenting may be a useful intervention with promising technical success and positive clinical outcomes for occlusive thrombosis and IVC stenosis.


Assuntos
Procedimentos Endovasculares , Trombose Venosa , Humanos , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Constrição Patológica , Resultado do Tratamento , Grau de Desobstrução Vascular , Trombectomia/efeitos adversos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/cirurgia , Procedimentos Endovasculares/efeitos adversos , Estudos Retrospectivos , Doença Iatrogênica
7.
J Vasc Interv Radiol ; 33(12): 1570-1577.e1, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36100064

RESUMO

PURPOSE: To compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm. MATERIALS AND METHODS: Twenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM). RESULTS: Before PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28-1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21-1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20-1.32; P = .167). CONCLUSIONS: The present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
8.
Med J Aust ; 216(11): 578-582, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35578795

RESUMO

OBJECTIVE: To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia. DESIGN, SETTING, PARTICIPANTS: Cross-sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 - 30 June 2021. MAIN OUTCOME MEASURES: Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis. RESULTS: We identified 44 people from ten families who received molecular diagnoses of hereditary pancreatitis during 2006-21 (including 25 Indigenous people [57%] and 27 women [61%]): 36 with PRSS1, five with SPINK1, and three with PRSS1 and SPINK1 mutations (determined by whole exome sequencing). Symptom onset before the age of ten years was reported by 37 people (84%). Pancreatitis-related pain during the preceding four weeks was described as moderate or high by 35 people (79%); 38 people regularly used opioids (86%). Fifteen patients had diabetes mellitus (34%), and eight had undergone pancreatic surgery (18%). The estimated prevalence of hereditary pancreatitis was 1.1 (95% CI, 0.72-1.4) cases per 100 000 population for non-Indigenous and 71 (95% CI, 66-77) cases per 100 000 population for Indigenous South Australians. Among people with adult-onset chronic pancreatitis admitted to South Australian public hospitals during 2001-2019, the proportions of Indigenous people (12%) and women (38%) were smaller than we report for hereditary pancreatitis. CONCLUSION: The estimated prevalence of hereditary pancreatitis in South Australia is higher than in Europe. PRSS1 gene mutations are important causes, particularly among Indigenous young people.


Assuntos
Predisposição Genética para Doença , Pancreatite Crônica , Inibidor da Tripsina Pancreática de Kazal , Tripsina , Austrália , Estudos Transversais , Feminino , Humanos , Masculino , Mutação , Dor , Pancreatite Crônica/genética , Austrália do Sul/epidemiologia , Tripsina/genética , Inibidor da Tripsina Pancreática de Kazal/genética
9.
Hum Mutat ; 42(7): 835-847, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33847015

RESUMO

The pioneering discovery research of X-linked intellectual disability (XLID) genes has benefitted thousands of individuals worldwide; however, approximately 30% of XLID families still remain unresolved. We postulated that noncoding variants that affect gene regulation or splicing may account for the lack of a genetic diagnosis in some cases. Detecting pathogenic, gene-regulatory variants with the same sensitivity and specificity as structural and coding variants is a major challenge for Mendelian disorders. Here, we describe three pedigrees with suggestive XLID where distinctive phenotypes associated with known genes guided the identification of three different noncoding variants. We used comprehensive structural, single-nucleotide, and repeat expansion analyses of genome sequencing. RNA-Seq from patient-derived cell lines, reverse-transcription polymerase chain reactions, Western blots, and reporter gene assays were used to confirm the functional effect of three fundamentally different classes of pathogenic noncoding variants: a retrotransposon insertion, a novel intronic splice donor, and a canonical splice variant of an untranslated exon. In one family, we excluded a rare coding variant in ARX, a known XLID gene, in favor of a regulatory noncoding variant in OFD1 that correlated with the clinical phenotype. Our results underscore the value of genomic research on unresolved XLID families to aid novel, pathogenic noncoding variant discovery.


Assuntos
Deficiência Intelectual , Expressão Gênica , Genes Ligados ao Cromossomo X , Genômica , Humanos , Deficiência Intelectual/diagnóstico , Linhagem
10.
Vascular ; 29(4): 624-629, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32998667

RESUMO

OBJECTIVES: To investigate the incidence and clinical significance of caval pseudoaneurysm and extravasation post-complex inferior vena cava filter retrieval. METHODS: A total of 83 patients (70% female, average age 56) underwent complex inferior vena cava filter retrieval between January 2015 and December 2019 utilizing either rigid endobronchial forceps (n = 69, 83%) and/or excimer laser (n = 20, 24%). Procedural variables were recorded. The incidence and size of caval pseudoaneurysms and extravasation along with treatment type and clinical outcomes were analyzed. RESULTS: Technical success in all cases was 96% (n = 80). Average fluoroscopy time was 23 min (median: 20.2, range: 0.9-129.5). Average filter dwell time was 85 months (range: 2-316 months). Caval pseudoaneurysm was detected on post-retrieval venography in 10 patients (12%) and frank extravasation occurred in 1 case (1%). Average pseudoaneurysm length and width was 20.4 mm (range: 5-45 mm) and 12.9 mm (range: 4-24 mm), respectively. Pseudoaneurysms occurred most frequently during the removal of Optease (n = 5) and Celect (n = 2) filters. The pseudoaneurysms completely resolved with prolonged (>5 min) balloon angioplasty in all but one instance where a small portion of the pseudoaneurysm persisted. This patient was admitted and observed overnight before being discharged without complication. The solitary case of significant extravasation was effectively managed with immediate stent placement and the patient remained hemodynamically stable. CONCLUSIONS: Radiographically detectable caval pseudoaneurysm and extravasation is not uncommon in complex inferior vena cava filter retrieval and, despite being considered a major complication by Society of Interventional Radiology guidelines, can often be managed without stenting or other invasive treatment.


Assuntos
Falso Aneurisma/etiologia , Remoção de Dispositivo/efeitos adversos , Implantação de Prótese/instrumentação , Lesões do Sistema Vascular/etiologia , Filtros de Veia Cava , Veia Cava Inferior/cirurgia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Angioplastia com Balão/instrumentação , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Fatores de Tempo , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/terapia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/lesões
11.
Am J Med Genet A ; 182(5): 1273-1277, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141698

RESUMO

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra-renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one-day-old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post-zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow-up studies for presumed de novo and low-level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.


Assuntos
Anormalidades Congênitas/genética , Rim/anormalidades , Morte Perinatal , Fator de Transcrição 1 de Leucemia de Células Pré-B/genética , Anormalidades Urogenitais/genética , Anormalidades Congênitas/sangue , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/patologia , Exoma , Pai , Feminino , Frequência do Gene , Humanos , Recém-Nascido , Rim/patologia , Masculino , Mosaicismo , Mutação/genética , Fator de Transcrição 1 de Leucemia de Células Pré-B/sangue , Gravidez , Sistema Urinário/patologia , Anormalidades Urogenitais/sangue , Anormalidades Urogenitais/mortalidade , Anormalidades Urogenitais/patologia , Sequenciamento do Exoma
12.
J Vasc Interv Radiol ; 31(1): 53-60.e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734075

RESUMO

PURPOSE: To investigate differences in procedure time, radiation exposure, and periprocedural complications associated with advanced inferior vena cava (IVC) filter retrieval compared with standard snare retrieval. MATERIALS AND METHODS: A total of 378 patients underwent standard or advanced IVC filter retrieval over a 5-year period. Technical success, retrieval techniques, fluoroscopy time, radiation dose, and complications were analyzed. All retrieval procedures with techniques other than a "snare-and-sheath" method were categorized as advanced, including failed standard attempts requiring intraprocedural conversion to advanced techniques. RESULTS: A total of 462 filter retrieval attempts were made in 378 patients (57% female). Success rates for standard and advanced retrieval attempts were 86.8% (317 of 365) and 91.8% (89 of 97), respectively. The rate of periprocedural complications was significantly higher in the advanced retrieval group (P = .006). Complication rates for standard and advanced retrievals were 0.6% (2 of 318; all minor) and 5.2% (5 of 97; 3 minor [3.1%] and 2 major [2.1%]), respectively. The 2 major complications during advanced retrievals included filter fracture and embolization. Average fluoroscopy time for advanced retrievals was significantly higher than for standard retrievals (23.1 min vs 4.3 min; P < .001). Average radiation dose for advanced retrievals was also significantly higher than for standard retrievals (557.2 mGy vs 156.9 mGy; P < .001). Use of general anesthesia was also significantly more common in advanced retrievals compared with standard retrievals (6.2% vs 0.9%; P = .002). CONCLUSIONS: Advanced filter retrieval results in a similarly high rate of technical success compared with standard snare retrieval but is associated with greater fluoroscopy time, anesthesia requirements, and radiation exposure.


Assuntos
Remoção de Dispositivo/métodos , Implantação de Prótese/instrumentação , Filtros de Veia Cava , Veia Cava Inferior , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia Geral , Chicago , Remoção de Dispositivo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/efeitos adversos , Doses de Radiação , Exposição à Radiação , Radiografia Intervencionista , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Adulto Jovem
13.
Hum Mutat ; 40(11): 2021-2032, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31184401

RESUMO

The X-linked NLGN3 gene, encoding a postsynaptic cell adhesion molecule, was involved in a nonsyndromic monogenic form of autism spectrum disorder (ASD) by the description of one unique missense variant, p.Arg451Cys (Jamain et al. 2003). We investigated here the pathogenicity of additional missense variants identified in two multiplex families with intellectual disability (ID) and ASD: c.1789C>T, p.Arg597Trp, previously reported by our group (Redin et al. 2014) and present in three affected cousins and c.1540C>T, p.Pro514Ser, identified in two affected brothers. Overexpression experiments in HEK293 and HeLa cell lines revealed that both variants affect the level of the mature NLGN3 protein, its localization at the plasma membrane and its presence as a cleaved form in the extracellular environment, even more drastically than what was reported for the initial p.Arg451Cys mutation. The variants also induced an unfolded protein response, probably due to the retention of immature NLGN3 proteins in the endoplasmic reticulum. In comparison, the c.1894A>G, p.Ala632Thr and c.1022T>C, p.Val341Ala variants, present in males from the general population, have no effect. Our report of two missense variants affecting the normal localization of NLGN3 in a total of five affected individuals reinforces the involvement of the NLGN3 gene in a neurodevelopmental disorder characterized by ID and ASD.


Assuntos
Transtorno do Espectro Autista/genética , Moléculas de Adesão Celular Neuronais/genética , Disfunção Cognitiva/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Mutação , Proteínas do Tecido Nervoso/genética , Transtorno do Espectro Autista/diagnóstico , Moléculas de Adesão Celular Neuronais/metabolismo , Disfunção Cognitiva/diagnóstico , Feminino , Estudos de Associação Genética , Humanos , Masculino , Proteínas de Membrana/metabolismo , Modelos Moleculares , Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/metabolismo , Linhagem , Fenótipo , Conformação Proteica , Transporte Proteico , Inativação do Cromossomo X
14.
Can Assoc Radiol J ; 70(4): 367-382, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31570169

RESUMO

Inferior vena cava filters are commonly encountered devices on diagnostic imaging that were highlighted in a 2010 Food and Drug Administration safety advisory regarding their complications from long-term implantation. The Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE) trial is an ongoing after-market study investigating the safety and utility of commonly utilized filters in practice today. While most of these filters are safe, prompt recognition and management of any filter-associated complication is imperative to prevent or reduce the morbidity and mortality associated with them. This review is aimed at discussing the appropriate utilization and placement of inferior vena cava filters in addition to the recognition of filter-associated complications on cross-sectional imaging. An overview of the PRESRVE trial filters is also provided to understand each filter's propensity for specific complications.


Assuntos
Diagnóstico por Imagem , Hemorragia/etiologia , Filtros de Veia Cava , Veia Cava Inferior , Remoção de Dispositivo , Humanos , Vigilância de Produtos Comercializados , Desenho de Prótese , Filtros de Veia Cava/efeitos adversos
16.
Am J Med Genet A ; 170A(4): 1059-63, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26708157

RESUMO

Mutations in COL4A1 are well described and result in brain abnormalities manifesting with severe neurological deficits including cerebral palsy, intellectual disability, and focal epilepsy. Families with mutations in COL4A2 are now emerging with a similar phenotype. We describe a family with an autosomal dominant disorder comprising porencephaly, focal epilepsy, and lens opacities, which was negative for mutations in COL4A1. Using whole exome sequencing of three affected individuals from three generations, we identified a rare variant in COL4A2. This COL4A2 (c.2399G>A, p.G800E, CCDS41907.1) variant was predicted to be damaging by multiple bioinformatics tools and affects an invariable glycine residue that is essential for the formation of collagen IV heterotrimers. The cataracts identified in this family expand the phenotypic spectrum associated with mutations in COL4A2 and highlight the increasing overlap with phenotypes associated with COL4A1 mutations.


Assuntos
Catarata/diagnóstico , Catarata/genética , Colágeno Tipo IV/genética , Genes Dominantes , Mutação , Porencefalia/diagnóstico , Porencefalia/genética , Adolescente , Adulto , Idoso , Encéfalo/patologia , Exoma , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imageamento por Ressonância Magnética , Masculino , Linhagem
18.
J Vasc Interv Radiol ; 27(7): 1021-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27212120

RESUMO

PURPOSE: To compare indwelling and retrieval complications of Denali and Celect filters placed in the infrarenal inferior vena cava (IVC). MATERIALS AND METHODS: A retrospective study was conducted over 2 years at a single institution in which 171 Denali and 162 Celect filters were placed in 333 patients with a mean age of 62.3 years ± 15.7 (161 men; 48.3%). Filter indications included venous thromboembolic disease (n = 320; 96.1%) and surgical prophylaxis (n = 13; 3.9%). A jugular approach was used to place 303 filters (91.0%). Computed tomography (CT) follow-up, complications, and retrieval data were obtained. RESULTS: Follow-up CT imaging was performed on 58 filters from each group with lower incidences of caval strut penetration (one vs 12) and filter tilt (one vs 15) in the Denali filter group (P = .002 and P < .001, respectively). There was no difference in incidences of breakthrough pulmonary embolism (P = .68). Retrieval attempts were performed on 43 Denali and 53 Celect filters with mean indwelling times at retrieval of 128.2 and 144.1 days, respectively (P = .40). Mean fluoroscopy time at retrieval was lower in the Denali group (3.1 min vs 6.0 min; P = .01). There were fewer cases of complex retrieval in the Denali group (n = 2 vs 10; P = .06). Tilt, fluoroscopy time, and air kerma were associated with complex retrieval (P = .04, P < .001, and P < .001, respectively). There was one Denali filter deployment complication that led to retrieval failure. CONCLUSIONS: This study suggests that Denali filters are associated with lower incidences of strut penetration and filter tilt as well as shorter fluoroscopy time at retrieval compared with Celect filters when placed in the infrarenal IVC.


Assuntos
Remoção de Dispositivo/efeitos adversos , Implantação de Prótese/efeitos adversos , Implantação de Prótese/instrumentação , Filtros de Veia Cava/efeitos adversos , Veia Cava Inferior , Idoso , Chicago , Angiografia por Tomografia Computadorizada , Remoção de Dispositivo/métodos , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Desenho de Prótese , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem
20.
J Vasc Interv Radiol ; 26(1): 101-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25446424

RESUMO

PURPOSE: To investigate strut penetration in patients with Celect filters, specifically local complications and association with breakthrough pulmonary embolism (PE) or retrieval failure. MATERIALS AND METHODS: A retrospective single-center study was conducted to evaluate patients who received Celect filters between January 2007 and May 2013. A total of 595 filters were placed during the study period. Primary indications included thromboembolic disease (93%) and primary surgical prophylaxis (7%). Complications and retrieval data were assessed by computed tomography (CT) and electronic medical records. RESULTS: A total of 193 patients underwent follow-up abdominal CT at a mean follow-up interval of 176.2 days (range, 0-1,739 d). The rate of strut penetration more than 3 mm outside the caval wall was 28.5% (n = 55). One patient had CT evidence of clinically major strut penetration (1.8%) with strut compression of the right ureter causing hydronephrosis. Indwelling filter time longer than 100 days was associated with strut penetration (P < .001). Age, sex, and history of thromboembolic disease were not associated with strut penetration (P = .51, P = .81, and P = .89). Sixty-three patients presented for follow-up CT pulmonary angiography at a mean of 128.1 days (range, 1-895 d). The rate of breakthrough PE was 12.7%. The overall retrieval success rate was 96.7% (n = 150). Strut penetration was not associated with breakthrough PE or retrieval failure (P = .49 and P = .22). CONCLUSIONS: Although strut penetration is a common complication with Celect filters, there is no association with breakthrough PE or retrieval failure. CT evidence of local complications associated with strut penetration is rare.


Assuntos
Remoção de Dispositivo/estatística & dados numéricos , Falha de Prótese , Embolia Pulmonar/diagnóstico por imagem , Filtros de Veia Cava/efeitos adversos , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
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