The refusal to permit organ sampling is of around 30% and is one of the principle causes for the lack of sampling. This study was aimed at establishing the frequency of decisions taken with regard to ...donations and the factors associated with refusal.
A prospective study was conducted between April 2, 2000 and March 31, 2001 in hospitals authorised to perform organ sampling in the Western area of France. For each potential donor identified, a questionnaire was filled in after each interview. A logistical model was used in order to identify the independent and statistical factors associated with the refusal to allow sampling of an organ or tissue.
Among the potentials donors, 265 brain dead donors, and 868 donors with ceased heart beats for tissue sampling, were included. The refusal rate was of respectively 32.8 and 45 %. Only 2.4% of potential donors carried cards identifying them as such. While living, the rate of refusal expressed by the two types of potential donors was similar (9%). The brain dead potential donors had more frequently expressed their consent for donation (20.7 vs. 9%). In the organ donors, the interviews were conducted by two persons in only 37.9% of cases, and in 2.4% of cases of potential tissue donors. In the potential organ donors, only those with a card identifying them as such and the hesitations of the family at the start of the interview were significantly associated with a lesser frequency of refusal. In potential tissue donors, the hesitations of the family reduced the refusal rate but age, religious beliefs, death etiology and the person conducting the interview increased it.
The encouraging efforts made for the awareness of donation during a person's lifetime must continue and the use of a donor card extended. The development of co-ordination posters in the hospitals would enhance the development of binomial interviews with the families.
Dandin Philippe, Fleuter Gérard, Javelle Jean-Pierre, Jourdain Sylvie, Roucaute Emeline, Schneider Michel. Recherche et sauvetage d’informations météorologiques anciennes : un apport et un regard ...nécessaires sur le climat. In: La Gazette des archives, n°230, 2013-2. Les sources d’archives pour l’étude du climat et de l’environnement. pp. 45-65.
Abstract
LMX1B
haploinsufficiency causes Nail-patella syndrome (NPS; MIM 161200), characterized by nail dysplasia, absent/hypoplastic patellae, chronic kidney disease, and glaucoma. Accordingly in ...mice,
Lmx1b
has been shown to play crucial roles in the development of the limb, kidney and eye. Although one functional allele of
Lmx1b
appears adequate for development,
Lmx1b
null mice display ventral-ventral distal limbs with abnormal kidney, eye and cerebellar development, more disruptive, but fully concordant with NPS. In
Lmx1b
functional knockouts (KOs),
Lmx1b
transcription in the limb is decreased nearly 6-fold, indicating autoregulation. Herein, we report on two conserved
L
mx1b
-
a
ssociated
cis
-
r
egulatory
m
odules (
LARM1
and
LARM2)
that are bound by Lmx1b, amplify
Lmx1b
expression with unique spatial modularity in the limb, and are necessary for Lmx1b-mediated limb dorsalization. These enhancers, being conserved across vertebrates (including coelacanth, but not other fish species), and required for normal locomotion, provide a unique opportunity to study the role of dorsalization in the fin to limb transition. We also report on two NPS patient families with normal
LMX1B
coding sequence, but with loss-of-function variations in the
LARM1/2
region, stressing the role of regulatory modules in disease pathogenesis.
PURPOSE Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in ...these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.
Congenital limb malformations (CLM) comprise many conditions affecting limbs and more than 150 associated genes have been reported. Due to this large heterogeneity, a high proportion of patients ...remains without a molecular diagnosis. In the last two decades, advances in high throughput sequencing have allowed new methodological strategies in clinical practice. Herein, we report the screening of 52 genes/regulatory sequences by multiplex high‐throughput targeted sequencing, in a series of 352 patients affected with various CLM, over a 3‐year period of time. Patients underwent a clinical triage by expert geneticists in CLM. A definitive diagnosis was achieved in 35.2% of patients, the yield varying considerably, depending on the phenotype. We identified 112 single nucleotide variants and 26 copy‐number variations, of which 52 are novel pathogenic or likely pathogenic variants. In 6% of patients, variants of uncertain significance have been found in good candidate genes. We showed that multiplex targeted high‐throughput sequencing works as an efficient and cost‐effective tool in clinical practice for molecular diagnosis of congenital limb malformations. Careful clinical evaluation of patients may maximize the yield of CLM panel testing.
Thrombocytopenia‐absent radius (TAR) syndrome is characterized by radial defect and neonatal thrombocytopenia. It is caused by biallelic variants of RBM8A gene (1q21.1) with the association of a null ...allele and a hypomorphic noncoding variant. RBM8A encodes Y14, a core protein of the exon junction complex involved in messenger RNA maturation. To date, only two hypomorphic variants have been identified. We report on a cohort of 26 patients affected with TAR syndrome and carrying biallelic variants in RBM8A. Half patients carried a 1q21.1 deletion and one of the two known hypomorphic variants. Four novel noncoding variants of RBM8A were identified in the remaining patients. We developed experimental models enabling their functional characterization in vitro. Two variants, located respectively in the 5′‐untranslated region (5′‐UTR) and 3′‐UTR regions, are responsible for a diminished expression whereas two intronic variants alter splicing. Our results bring new insights into the molecular knowledge of TAR syndrome and enabled us to propose genetic counseling for patients' families.
Split‐hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb malformation typically limited to a defect of the central rays of the autopod, presenting as a median cleft of hands ...and feet. It can be associated with long bone deficiency or included in more complex syndromes. Among the numerous genetic causes, WNT10B homozygous variants have been recently identified in consanguineous families, but remain still rarely described (SHFM6; MIM225300). We report on three novel SHFM families harboring WNT10B variants and review the literature, allowing us to highlight some clinical findings. The feet are more severely affected than the hands and there is a frequent asymmetry without obvious side‐bias. Syndactyly of third–fourth fingers was a frequent finding (62%). Polydactyly, which was classically described in SHFM6, was only present in 27% of patients. No genotype–phenotype correlation is delineated but heterozygous individuals might have mild features of SHFM, suggesting a dose‐effect of the WNT10B loss‐of‐function.
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