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1.
Eur J Health Law ; 27(1): 35-57, 2020 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33652409

RESUMEN

The European General Data Protection Regulation (GDPR) has dotted the i's and crossed the t's in the context of academic medical research. One year into GDPR, it is clear that a change of mind and the uptake of new procedures is required. Research organisations have been looking at the possibility to establish a code-of-conduct, good practices and/or guidelines for researchers that translate GDPR's abstract principles to concrete measures suitable for implementation. We introduce a proposal for the implementation of GDPR in the context of academic research which involves the processing of health related data, as developed by a multidisciplinary team at the University Hospitals Leuven. The proposal is based on three elements, three stages and six specific safeguards. Transparency and pseudonymisation are considered key to find a balance between the need for researchers to collect and analyse personal data and the increasing wish of data subjects for informational control.


Asunto(s)
Investigación Biomédica/legislación & jurisprudencia , Seguridad Computacional/legislación & jurisprudencia , Confidencialidad/legislación & jurisprudencia , Centros Médicos Académicos , Anonimización de la Información/normas , Unión Europea , Hospitales Universitarios , Humanos , Acceso de los Pacientes a los Registros/normas , Investigadores
2.
Br J Surg ; 105(7): 885-892, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29623678

RESUMEN

BACKGROUND: The number of transmen seeking gender-confirming surgery has risen steadily throughout the last decade. Pathologists are increasingly confronted with transmale mastectomy specimens. It is not clear whether routine histopathological examination is useful. This study explored the possible benefit of routine investigation through detailed description of lesions encountered in mastectomy specimens after female-to-male gender-confirming surgery. METHODS: Breast tissue from a cohort of transmen was reviewed. The presence of benign and malignant breast lesions was recorded. The number of terminal duct-lobule units (TDLUs) per ten low-power fields (LPFs) was quantified. Information on hormone therapy and morphometry was retrieved for selected patients. RESULTS: The cohort included 344 subjects with a mean age of 25·8 (range 16-61) years at the time of surgery; the age at surgery decreased significantly over time. Older individuals presented with a significantly higher number of breast lesions. The number of TDLUs per LPF was lower in heavier breasts, but did not correlate with age. Breast lesions, either benign or malignant, were present in 166 individuals (48·3 per cent). Invasive breast cancer was found in two (0·6 per cent); one tumour was an unexpected finding. The number of breast lesions encountered on histopathological examination increased significantly when more tissue blocks were taken. CONCLUSION: The discovery of an unexpected breast cancer in a 31-year-old transman emphasizes the importance of thorough routine histopathological examination of mastectomy specimens. The number of tissue blocks taken should be based on age and breast weight.


Asunto(s)
Mama/patología , Mastectomía , Cirugía de Reasignación de Sexo/métodos , Transexualidad/cirugía , Adolescente , Adulto , Factores de Edad , Mama/cirugía , Neoplasias de la Mama/patología , Femenino , Disforia de Género/cirugía , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Factores de Riesgo , Transexualidad/patología , Adulto Joven
3.
Osteoporos Int ; 27(2): 489-97, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26294291

RESUMEN

UNLABELLED: Bone loss and vascular calcification coincide in patients with end-stage renal disease, similar as to what is observed in the general population. In the present bone biopsy study, we provide further evidence that (micro-)inflammation may represent a common soil for both diseases. INTRODUCTION: Vascular calcification is a common complication of end-stage renal disease (ESRD) and is predictive of subsequent cardiovascular disease and mortality. Mounting evidence linking bone disorders with vascular calcification has contributed to the development of the concept of the bone-vascular axis. Inflammation is involved in the pathogenesis of both disorders. The aim of the present study was to evaluate the relationship between aortic calcification, inflammation, and bone histomorphometry in patients with ESRD. METHODS: Parameters of inflammation and mineral metabolism were assessed in 81 ESRD patients (55 ± 13 year, 68 % male) referred for renal transplantation. Static bone histomorphometry parameters were determined on transiliac bone biopsies performed during the transplant procedure. Aortic calcification was quantified on lateral lumbar X-rays using the Kauppila method. RESULTS: Aortic calcification, low bone turnover, and low bone area were observed in 53, 37, and 21 % of patients respectively. Inflammatory markers were found to be independently associated with aortic calcification (hsIL-6) and low bone area (TNF-α). Low bone area associated with aortic calcification, independent of age, diabetes, and inflammation. CONCLUSIONS: Low bone area and inflammation associates with aortic calcification, independent of each other and traditional risk factors. Our data emphasize the role of (micro-)inflammation in the bone-vascular axis in CKD.


Asunto(s)
Enfermedades de la Aorta/etiología , Inflamación/complicaciones , Fallo Renal Crónico/complicaciones , Osteoporosis/etiología , Calcificación Vascular/etiología , Adulto , Anciano , Biopsia , Remodelación Ósea/fisiología , Femenino , Humanos , Ilion/patología , Inflamación/fisiopatología , Mediadores de Inflamación/metabolismo , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Osteoporosis/patología , Osteoporosis/fisiopatología
4.
Transpl Infect Dis ; 18(1): 125-31, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26688125

RESUMEN

Renal transplant recipients are highly susceptible to infections caused by uncommon pathogens because of their immunocompromised state. We report a case of disseminated Mycobacterium genavense infection in a patient with a combined renal and cardiac transplant. Diagnosing M. genavense infections remains a challenge because of the absence of specific clinical symptoms in combination with the difficulties of culturing the organism using standard mycobacterial culture procedures. This clinical case demonstrates the importance of molecular techniques as part of the initial work-up in order to rapidly establish the diagnosis.


Asunto(s)
Trasplante de Corazón/efectos adversos , Trasplante de Riñón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico por imagen , Micobacterias no Tuberculosas/aislamiento & purificación , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/genética
5.
Am J Transplant ; 15(11): 2900-7, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26484837

RESUMEN

Whether warm ischemia during the time to complete the vascular anastomoses determines renal allograft function has not been investigated systematically. We investigated the effect of anastomosis time on allograft outcome in 669 first, single kidney transplantations from brain-dead donors. Anastomosis time independently increased the risk of delayed graft function (odds ratio per minute [OR] 1.05, 95% confidence interval [CI] 1.02-1.07, p < 0.001) and independently impaired allograft function after transplantation (p = 0.009, mixed-models repeated-measures analysis). In a subgroup of transplant recipients, protocol-specified biopsies at 3 months (n = 186), 1 year (n = 189), and 2 years (n = 153) were blindly reviewed. Prolonged anastomosis time independently increased the risk of interstitial fibrosis and tubular atrophy on these protocol-specified biopsies posttransplant (p < 0.001, generalized linear models). In conclusion, prolonged anastomosis time is not only detrimental for renal allograft outcome immediately after transplantation, also longer-term allograft function and histology are affected by the duration of this warm ischemia.


Asunto(s)
Muerte Encefálica , Funcionamiento Retardado del Injerto/patología , Rechazo de Injerto/patología , Trasplante de Riñón/métodos , Tempo Operativo , Adulto , Anastomosis Quirúrgica/métodos , Bélgica , Estudios de Cohortes , Funcionamiento Retardado del Injerto/fisiopatología , Femenino , Fibrosis/etiología , Fibrosis/patología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Necrosis Tubular Aguda/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrectomía/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Donantes de Tejidos , Receptores de Trasplantes/estadística & datos numéricos , Trasplante Homólogo , Resultado del Tratamiento
6.
BMC Cancer ; 15: 912, 2015 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-26577449

RESUMEN

BACKGROUND: Current knowledge of the aetiology of hereditary breast cancer in the four main South African population groups (black, coloured, Indian and white) is limited. Risk assessments in the black, coloured and Indian population groups are challenging because of restricted information regarding the underlying genetic contributions to inherited breast cancer in these populations. We focused this study on premenopausal patients (diagnosed with breast cancer before the age of 50; n = 78) and triple negative breast cancer (TNBC) patients (n = 30) from the four South African ethnic groups. The aim of this study was to determine the frequency and spectrum of germline mutations in BRCA1, BRCA2 and PALB2 and to evaluate the presence of the CHEK2 c.1100delC allele in these patients. METHODS: In total, 108 South African breast cancer patients underwent mutation screening using a Next-Generation Sequencing (NGS) approach in combination with Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large rearrangements in BRCA1 and BRCA2. RESULTS: In 13 (12 %) patients a deleterious mutation in BRCA1/2 was detected, three of which were novel mutations in black patients. None of the study participants was found to have an unequivocal pathogenic mutation in PALB2. Two (white) patients tested positive for the CHEK2 c.1100delC mutation, however, one of these also carried a deleterious BRCA2 mutation. Additionally, six variants of unknown clinical significance were identified (4 in BRCA2, 2 in PALB2), all in black patients. Within the group of TNBC patients, a higher mutation frequency was obtained (23.3 %; 7/30) than in the group of patients diagnosed before the age of 50 (7.7 %; 6/78). CONCLUSION: This study highlights the importance of evaluating germline mutations in major breast cancer genes in all of the South African population groups. This NGS study shows that mutation analysis is warranted in South African patients with triple negative and/or in premenopausal breast cancer.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Quinasa de Punto de Control 2/genética , Proteínas Nucleares/genética , Neoplasias de la Mama Triple Negativas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Alelos , Etnicidad/genética , Proteína del Grupo de Complementación N de la Anemia de Fanconi , Femenino , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Persona de Mediana Edad , Premenopausia , Eliminación de Secuencia/genética , Sudáfrica , Neoplasias de la Mama Triple Negativas/diagnóstico , Neoplasias de la Mama Triple Negativas/patología
7.
Genet Couns ; 25(2): 203-8, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25059020

RESUMEN

Birt-Hogg Dubé syndrome is an autosomal dominant disease with variable clinical expression. It is characterized by cutaneous manifestations, renal tumors and lung cysts. Other tumors, such as adrenal tumors and tumors originating from the neural crest cells such as meningioma and neurothekeoma have also been described. This syndrome is caused by germline mutations in the folliculin (FLCN) gene located on chromosome 17p. We report, for the first time, a patient with BHDS and a history of a vestibular schwannoma in adolescence. The diagnosis of BHDS was confirmed, by identifying a nonsense mutation in exon 10 of the FLCN gene. A vestibular schwannoma also originates from neural crest cells, just as other neural tumors, previously encountered in patients with BHDS. The reported mutations cause a truncation of the protein, folliculin. The exact role of folliculin is still undetermined. Two different theories suggest the effect of tumorigenesis. One is that folliculin plays an important role in the AMPK-mTOR pathway which leads to proliferation of cells when activated. The other is that the folliculin acts as a possible tumor suppressor gene, since there is a high frequency of second hits in the FLCN-gene. In order to confirm a possible relation of BHDS and neural crest tumors, further research is necessary in the tumorigenesis of the folliculin gene.


Asunto(s)
Síndrome de Birt-Hogg-Dubé/genética , Neuroma Acústico/etiología , Proteínas Proto-Oncogénicas/genética , Proteínas Supresoras de Tumor/genética , Adulto , Síndrome de Birt-Hogg-Dubé/complicaciones , Codón sin Sentido , Exones/genética , Femenino , Humanos , Neuroma Acústico/cirugía
8.
Acta Chir Belg ; 114(5): 324-31, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-26021537

RESUMEN

BACKGROUND: Maximal use of native arteriovenous fistulas (AVFs) for patients on hemodialysis therapy remains a clinical challenge. Primary failure rates remain high with risk factors such as female gender, diabetes mellitus, lower arm AVF and higher age. We wondered if a strategy of careful clinical examination prior to AVF creation and a preference towards an upper arm AVF in case of doubt about the quality of the vein in patients with any of the above mentioned risk factors, would lead to better maturation rates. METHODS: The records of all patients who received an AVF between January 2005 and December 2009 at our University Hospitals Leuven were studied retrospectively. Demographic data, comorbidity, fistula characteristics, fistula maturation and fistula complications were recorded and analyzed. RESULTS: Of 344 patients enrolled, 156 (45.3%) received a lower arm AVF and 188 (54.7%) an upper arm AVF. Two hundred and seventy-six (80.2%) fistulas had a normal maturation. Lower arm AVF was a significant risk factor for non-maturation in this series (73.1% versus 86.2% ; p = 0,0024). Female gender, diabetes and high age were not, but female gender showed a significant difference in distribution in upper arm versus lower arm fistulas (62.40% versus 37.6% ; p = 0,0218). CONCLUSIONS: Careful clinical examination prior to upper or lower arm AVF creation together with the integration of risk assessment in the planning of AVF is worthwhile. A preference towards upper arm fistulas if major risk factors are -present can improve overall maturation rates and lead to the same maturation rates as in the overall dialysis population. Therefore, the presence of risk factors for non-maturation should not lead to the underuse of native AVFs.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Tronco Braquiocefálico/cirugía , Venas Braquiocefálicas/cirugía , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Niño , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento , Adulto Joven
9.
Acta Chir Belg ; 114(3): 203-5, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25102711

RESUMEN

We present a case of visceral ischemia due to an anatomic versus balloon length mismatch. An 80-year-old women underwent elective coronary artery bypass graft surgery. The direct post-operative period was complicated by low cardiac output, not responding to inotropic or vasopressor drugs. An intra-aortic balloon pump (IABP) was inserted during an explorative rethoracotomy. The first 3 days, an improvement of the hemodynamic function was seen. During this period, hepatic dysfunction, renal failure with need for hemodialysis and rising values of serum lactate were seen. A computed tomography (CT) of the chest and abdomen showed splenic infarction, ascites and signs of gastric and intestinal ischemia. The IABP was blocking the celiac trunk, the superior mesenteric artery and the renal arteries and was immediately removed. The patient died shortly after due to multiple organ failure. To prevent ischemic complications in smaller patients, we advise a follow-up CT after placement of the IABP.


Asunto(s)
Puente de Arteria Coronaria , Contrapulsador Intraaórtico/efectos adversos , Isquemia/etiología , Mesenterio/irrigación sanguínea , Estómago/irrigación sanguínea , Lesión Renal Aguda/etiología , Anciano de 80 o más Años , Ascitis/etiología , Fibrilación Atrial/etiología , Resultado Fatal , Femenino , Humanos , Ácido Láctico/sangre , Diálisis Renal , Infarto del Bazo/etiología , Transaminasas/sangre
10.
Acta Gastroenterol Belg ; 87(1): 37-39, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38431789

RESUMEN

Acute colitis is a common feature of infection with Shiga-toxin producing Escherichia coli (STEC) and can mimic acute severe ulcerative colitis. Early recognition is important as there is a risk of developing Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), defined by the triad of microangiopathic haemolytic anemia, thrombocytopenia and organ damage. In severe cases STEC-HUS can cause severe neurological complications and can be fatal. We present a patient with a medical history of refractory ulcerative colitis, where making the diagnosis of STEC-HUS was challenging since the initial clinical presentation was difficult to differentiate from a flare of ulcerative colitis. This case illustrates that STEC induced colitis can mimic acute severe ulcerative colitis. This finding is of utmost clinical importance because of the potential life-threatening complications of STEC-HUS. Therefore it should be excluded promptly in patients with acute severe ulcerative colitis by using multiplex-PCR assay on a faecal sample.


Asunto(s)
Colitis Ulcerosa , Colitis , Infecciones por Escherichia coli , Síndrome Hemolítico-Urémico , Escherichia coli Shiga-Toxigénica , Humanos , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/diagnóstico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/complicaciones , Colitis/diagnóstico
11.
Burns ; 50(4): 1003-1010, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38383170

RESUMEN

INTRODUCTION: Autologous split thickness skin grafting using meshing technique remains the preferred option for the management of deep dermal and full thickness burns. The limited donor site availability seen in patients with extensive burns, however, restricts use of the mesh grafting technique for skin expansion. Meek micrografting was developed to allow for greater expansion, and, therefore, more reliable treatment of extensive burns. This study aimed to present our outcomes using the Meek micrografting technique and identify risk factors for graft failure. METHODS: A retrospective review of patients admitted to our large academic hospital who were treated with the Meek micrografting technique from 2013 to 2022 was conducted. Patient demographics, surgical characteristics and outcomes were reported. Regression analyses were performed to identify factors that influence graft take and reoperation rate. RESULTS: A total of 73 patients with a mean age of 45.7 ± 19.9 years and mean burn size of 60.0 ± 17.8%TBSA, with 45.3 ± 14.9% TBSA being third degree burns, received Meek transplantation. The mean graft take after removal of the pre-folded polyamide gauze at the tenth post-operative day was 75.8 ± 14.7%. Pre-treatment with use of an allograft, longer waiting time between admission and Meek grafting and transplantation over a dermal matrix were identified as positive predictors for graft take, while age was established as a negative predictor. CONCLUSION: By examining the outcomes of the Meek micrografting technique in extensive burn wounds we identified that preconditioning of the wound bed, through allograft or negative pressure wound therapy application, positively correlates with improved outcomes, including higher graft take. At the same time, older age was seen to negatively correlate with graft take. Overall, Meek transplantation displays a favorable safety profile with promising outcomes. Future prospective studies and clinical trials can optimize the procedure and help establish it as the golden standard for extensive and complex burns.


Asunto(s)
Quemaduras , Trasplante de Piel , Humanos , Quemaduras/cirugía , Quemaduras/terapia , Trasplante de Piel/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Supervivencia de Injerto , Superficie Corporal , Adulto Joven , Expansión de Tejido/métodos , Reoperación/estadística & datos numéricos , Reoperación/métodos , Adolescente , Mallas Quirúrgicas
12.
Am J Transplant ; 13(1): 86-99, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23136888

RESUMEN

The impact of early histological lesions of renal allografts on long-term graft survival remains unclear. We included all renal allograft recipients transplanted at a single center from 1991 to 2001 (N = 1197). All indication biopsies performed within the first year after transplantation were rescored according to the current Banff classification. Mean follow-up time was 14.8 ± 2.80 years. In multivariate Cox proportional hazards analysis, arteriolar hyalinosis and transplant glomerulopathy were independently associated with death-censored graft survival, adjusted for baseline demographic covariates. Arteriolar hyalinosis correlated with interstitial fibrosis, tubular atrophy, mesangial matrix increase, vascular intimal thickening and glomerulosclerosis. Clustering of the patients according to these chronic lesions, reflecting the global burden of chronic injury, associated better with long-term graft survival than each of the chronic lesions separately. Early chronic histological damage was an independent risk factor for late graft loss, irrespective whether a specific, progressive disease was diagnosed or not, while T cell-mediated rejection did not. We conclude that individual chronic lesions like arteriolar hyalinosis, tubular atrophy, interstitial fibrosis, glomerulosclerosis, mesangial matrix increase and vascular intimal thickening cannot be seen as individual entities. The global burden of early chronic histological damage within the first year after transplantation importantly affects the fate of the allografts.


Asunto(s)
Rechazo de Injerto , Enfermedades Renales/patología , Trasplante de Riñón , Adulto , Biopsia , Femenino , Humanos , Enfermedades Renales/clasificación , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
13.
Am J Transplant ; 13(7): 1910-4, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23730777

RESUMEN

Kidney transplantation is the treatment of choice for end-stage renal disease whereas indications for intestinal transplantation are currently restricted to patients with irreversible small bowel failure and severe complications of total parenteral nutrition (mostly shortage and infection of venous accesses, major electrolyte disturbances and liver failure). Enteric hyperoxaluria is secondary to certain intestinal diseases like intestinal resections, chronic inflammatory bowel disease and other malabsorption syndromes and can lead to end-stage renal disease requiring kidney transplantation. We report two patients suffering from renal failure due to enteric hyperoxaluria (secondary to extensive intestinal resection) in whom we elected to replace not only the kidney but also the intestine to prevent recurrence of hyperoxaluria in the transplanted kidney.


Asunto(s)
Hiperoxaluria/cirugía , Intestino Delgado/trasplante , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Síndrome del Intestino Corto/cirugía , Adulto , Femenino , Estudios de Seguimiento , Humanos , Hiperoxaluria/complicaciones , Fallo Renal Crónico/etiología , Persona de Mediana Edad , Síndrome del Intestino Corto/complicaciones
14.
Ann Burns Fire Disasters ; 36(4): 347-354, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38680243

RESUMEN

In contrast to tangential excision, enzymatic debridement with NexoBrid® selectively removes non-viable tissue, allowing some deep dermal burn wounds to still heal conservatively. In this retrospective study, we investigated the reduction in surgery and associated scarring following enzymatic debridement in definitely deep burns as proven by laser Doppler imaging. One hundred two exclusively laser Doppler imaging-blue regions of interest where there was no doubt at all about the surgical indication, were selected for analysis in 32 patients treated with NexoBrid®. The total surface area of the 102 exclusively blue regions of interest was 5,086.4cm2. NexoBrid® resulted in a substantial reduction in the need for autografts as 1,986.9cm2 (39%) healed with conservative treatment. This corresponded with a significant reduction in patients (56.3%) requiring surgery. Exclusively laser Doppler imaging-blue regions of interest treated surgically with split thickness skin grafts required significantly more time to heal compared to conservative treatment (37.8±17.5 vs. 27.0±10.5 days). A very limited rate of hypertrophic scarring (16.7%) was observed. This is the first paper demonstrating a proven and significant reduction in the extent of autografting as well as in the number of surgical procedures after selective enzymatic debridement in objectively laser Doppler imaging-defined and therefore proven deep burns. Even after extended conservative treatment with prolonged healing times following NexoBrid®, hypertrophic scar formation was limited (5/54 regions of interest, 9.3%). Also in operated patients, the incidence of hypertrophic scarring following a strict regimen of aftercare was low (12/48 regions of interest, 25%).


À la différence de l'excision chirurgicale tangentielle, le débridement enzymatique au Nexobrid® ne s'intéresse qu'au tissu nécrosé ce qui permet la cicatrisation spontanée de certaines brûlures intermédiaires. Dans cette étude rétrospective, nous avons évalué la diminution des interventions chirurgicales (et des séquelles y afférant) en cas d'utilisation de l'excision enzymatique sur des brûlures affirmées comme profondes par Imagerie Laser- Doppler (ILD). Nous avons analysé 102 régions d'intérêt, apparaissant bleues à l'ILD chez 32 patients traités par Nexobrid®, représentant une surface totale de 5 086,4 cm2. Ceci a permis une cicatrisation spontanée de 1 986,9 cm2 (39% de l'ensemble et 56,3% chez les patients ayant dû être opérés). Les patients traités par excision- greffe sont restés significativement plus longtemps que ceux ayant cicatrisé spontanément (37,8 +/- 17,5 j VS 27 +/- 10,5). L'incidence globale des cicatrices hypertrophiques était basse (16,7%). Ceci est la première publication montrant une diminution significative de la surface greffée et du nombre d'interventions chirurgicales après l'utilisation d'une excision enzymatique chez des patients souffrant de brûlures définies comme profondes par ILD. Même après une cicatrisation spontanée longue après Nexobrid®, l'incidence des cicatrices hypertrophiques reste faible (5/54 régions d'intérêt - 9,3%) quand elle s'élève à 25% après excision- greffe (12/48).

15.
Br J Cancer ; 106(8): 1460-3, 2012 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-22415235

RESUMEN

BACKGROUND: Recent data show that mutations in RAD51D have an aetiological role in ovarian carcinoma, yet mutations do not appear to be associated with an increased risk for breast cancer. We studied ovarian and breast cancer families having at least one woman affected by ovarian carcinoma, to assess the importance of RAD51D mutations in such families. METHODS: The coding region of the RAD51D gene was analysed in 175 BRCA1/2-negative families with family histories of both ovarian and breast cancer ascertained from two Canadian and two Belgian institutions. RESULTS: We identified one previously reported deleterious mutation, p.Arg186(*) (c.556C>T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186(*) segregated with the disease in the family and two ovarian carcinomas available for analysis showed loss of the wild-type allele, but the novel variants are likely neutral. CONCLUSION: RAD51D should be included in genetic screening of ovarian cancer families that do not have BRCA1/BRCA2 mutations. We show that mutations are more likely to be found in families with two or more ovarian cancers, or in probands with first-degree relatives with ovarian cancer, and we feel testing should be preferentially offered to affected women from such families.


Asunto(s)
Neoplasias de la Mama/genética , Proteínas de Unión al ADN/genética , Mutación/genética , Neoplasias Ováricas/genética , Proteína BRCA1 , Proteína BRCA2 , Análisis Mutacional de ADN , Femenino , Pruebas Genéticas , Humanos , Linaje , Sensibilidad y Especificidad
16.
Breast Cancer Res Treat ; 133(1): 393-8, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22370629

RESUMEN

Despite extensive analysis of the BRCA1 and BRCA2 genes, germline mutations are detected in <20% of families with a presumed genetic predisposition for breast and ovarian cancer. Recent literature reported RAD51C as a new breast cancer susceptibility gene. In this study, we report the analysis of 410 patients from 351 unrelated pedigrees. All were referred for genetic testing and we selected families with at least one reported case of ovarian cancer in which BRCA1&2 mutations were previously ruled out. We analyzed the coding exons, intron-exons boundaries, and UTRs of RAD51C. Our mutation analysis did not reveal any unequivocal deleterious mutation. In total 12 unique sequence variations were identified of which two were novel. Our study and others suggest a low prevalence of RAD51C mutations with an exception for some founder populations. This observation is in favor of the rare allele hypothesis in the debate over the nature of the genetic contribution to individual susceptibility to breast and ovarian cancer and further genome-wide studies in high risk families are warranted.


Asunto(s)
Proteínas de Unión al ADN/genética , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Masculino , Mutación Missense , Linaje , Polimorfismo de Nucleótido Simple
17.
ESMO Open ; 7(4): 100524, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35970014

RESUMEN

PRECISION is an initiative from the Belgian Society of Medical Oncology (BSMO) in collaboration with several stakeholders, encompassing four programs that aim to boost genomic and clinical knowledge with the ultimate goal to offer patients with metastatic solid tumors molecularly guided treatments. The PRECISION 1 study has led to the creation of a clinico-genomic database. The Belgian Approach for Local Laboratory Extensive Tumor Testing (BALLETT) and GeNeo studies will increase the number of patients with advanced cancer that have comprehensive genotyping of their cancer. The PRECISION 2 project consists of investigator-initiated phase II studies aiming to provide access to a targeted drug for patients whose tumors harbor actionable mutations in case the matched drug is not available through reimbursement or clinical trials in Belgium.


Asunto(s)
Neoplasias , Medicina de Precisión , Bélgica , Genómica , Humanos , Oncología Médica
18.
Acta Clin Belg ; 76(1): 65-69, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31401947

RESUMEN

A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Kidney biopsy confirmed this diagnosis with histological changes including intimal edema, arteriolar thrombi, and severe tubulointerstitial damage. Fundoscopy showed hypertensive retinopathy stage IV. Subsequent biochemical screening revealed normal complement testing and a marked elevation in homocysteine concentration (161 µmol/L; normal value 7-15 µmol/L). Other secondary causes of TMA were excluded. Further genetic testing for cobalamin C (cblC) deficiency showed no pathogenic mutations in the MMACHC gene. However, a homozygous c.665C>T polymorphism (NM_005957.4) in the methylenetetrahydrofolate reductase (MTHFR) gene was found explaining the severe hyperhomocysteinemia due to reduced activity of MTHFR. Additional genetic testing for alternative complement pathway proteins showed mutations in the genes encoding factor H and factor B, both categorized as possibly pathogenic using mutation prediction software. This is the first described case of TMA in a patient with severe hyperhomocysteinemia caused by a genetic defect other than cblC. We postulate that endothelial damage due to hyperhomocysteinemia and hypertension could have triggered the TMA episode in this patient with two possible predisposing pathogenic mutations in the alternative complement pathway. Furthermore, our case demonstrates the need for complete full diagnostic testing in patients with TMA.


Asunto(s)
Hiperhomocisteinemia , Microangiopatías Trombóticas , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Adulto , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Riñón/patología , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Oxidorreductasas/genética , Complejo Vitamínico B/uso terapéutico
19.
NPJ Genom Med ; 6(1): 95, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34782607

RESUMEN

Neurofibromatosis type 1 (NF1) is caused by loss-of-function variants in the NF1 gene. Approximately 10% of these variants affect RNA splicing and are either missed by conventional DNA diagnostics or are misinterpreted by in silico splicing predictions. Therefore, a targeted RNAseq-based approach was designed to detect pathogenic RNA splicing and associated pathogenic DNA variants. For this method RNA was extracted from lymphocytes, followed by targeted RNAseq. Next, an in-house developed tool (QURNAs) was used to calculate the enrichment score (ERS) for each splicing event. This method was thoroughly tested using two different patient cohorts with known pathogenic splice-variants in NF1. In both cohorts all 56 normal reference transcript exon splice junctions, 24 previously described and 45 novel non-reference splicing events were detected. Additionally, all expected pathogenic splice-variants were detected. Eleven patients with NF1 symptoms were subsequently tested, three of which have a known NF1 DNA variant with a putative effect on RNA splicing. This effect could be confirmed for all 3. The other eight patients were previously without any molecular confirmation of their NF1-diagnosis. A deep-intronic pathogenic splice variant could now be identified for two of them (25%). These results suggest that targeted RNAseq can be successfully used to detect pathogenic RNA splicing variants in NF1.

20.
Eur J Vasc Endovasc Surg ; 39(3): 340-5, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20080420

RESUMEN

OBJECTIVE: This study aims to evaluate the impact of CO(2) venography on the planning and outcome of native arteriovenous fistula (AVF) creation. METHODS: Records of patients who underwent CO(2) venography prior to access surgery between January 2000 and December 2008 were reviewed. CO(2) venography was performed selectively in chronic kidney disease (CKD) in stage IV-V patients without suitable veins on clinical examination. Findings at surgery were compared to CO(2) venography images. Patency of AVFs was analysed by the Kaplan-Meier method. Differences in outcome of maturation were compared using a chi(2) test. RESULTS: A total of 209 CO(2) venograms were obtained in 116 patients. In 89 patients (77%), 101 AVFs (21 forearm AVF (21%) and 80 elbow AVF (79%) were created. Surgical findings corresponded with CO(2) venography findings in 90% of patients. In 10 cases (10%), access was created at the elbow despite a patent forearm cephalic vein on CO(2) venography (n = 2) or access was attempted with a vein which was thought to be unsuitable on CO(2) venography (n = 8). Maturation rate of the latter was 50% (4/8) vs. 88% (80/91) for AVFs created with veins considered usable (P = 0.004). The overall maturation rate was 84% with 1-year primary, assisted primary and secondary patency rates of 63%, 70% and 71%, respectively. CONCLUSION: CO(2) venography is a useful tool for venous mapping prior to vascular access surgery, resulting in an overall maturation rate of 84% and good patency rates.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Dióxido de Carbono , Medios de Contraste , Enfermedades Renales/terapia , Flebografía/métodos , Diálisis Renal , Extremidad Superior/irrigación sanguínea , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Derivación Arteriovenosa Quirúrgica/efectos adversos , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Cuidados Preoperatorios , Reoperación , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Venas/patología , Venas/cirugía , Adulto Joven
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