Arcucci, Silvia; Ramos-Delgado, Fernanda; Cayron, Coralie; Therville, Nicole; Gratacap, Marie-Pierre; Basset, Celine; Thibault, Benoit; Guillermet-Guibert, Julie Organismal roles for the PI3K alpha and beta isoforms: their
specificity, redundancy or cooperation is context-dependent Journal Article In: BIOCHEMICAL JOURNAL, vol. 478, no. 6, pp. 1199-1225, 2021, ISSN: 0264-6021. @article{ISI:000631179600002,
title = {Organismal roles for the PI3K alpha and beta isoforms: their
specificity, redundancy or cooperation is context-dependent},
author = {Silvia Arcucci and Fernanda Ramos-Delgado and Coralie Cayron and Nicole Therville and Marie-Pierre Gratacap and Celine Basset and Benoit Thibault and Julie Guillermet-Guibert},
doi = {10.1042/BCJ20210004},
issn = {0264-6021},
year = {2021},
date = {2021-03-01},
journal = {BIOCHEMICAL JOURNAL},
volume = {478},
number = {6},
pages = {1199-1225},
abstract = {PI3Ks are important lipid kinases that produce phosphoinositides
phosphorylated in position 3 of the inositol ring. There are three
classes of PI3Ks: class I PI3Ks produce PIP3 at plasma membrane level.
Although D. melanogaster and C. elegans have only one form of class I
MK, vertebrates have four class I PI3Ks called isoforms despite being
encoded by four different genes. Hence, duplication of these genes
coincides with the acquisition of coordinated multi-organ development.
Of the class I PI3Ks, PI3K alpha and PI3K beta encoded by PIK3CA and
P/K3CB, are ubiquitously expressed. They present similar putative
protein domains and share PI(4,5)P-2 lipid substrate specificity.
Fifteen years after publication of their first isoform-selective
pharmacological inhibitors and genetically engineered mouse models
(GEMMs) that mimic their complete and specific pharmacological
inhibition, we review the knowledge gathered in relation to the
redundant and selective roles of PI3K alpha and Pl3K beta. Recent data
suggest that, further to their redundancy, they cooperate for the
integration of organ-specific and context-specific signal cues, to
orchestrate organ development, physiology, and disease. This knowledge
reinforces the importance of isoform-selective inhibitors in clinical
settings.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
PI3Ks are important lipid kinases that produce phosphoinositides
phosphorylated in position 3 of the inositol ring. There are three
classes of PI3Ks: class I PI3Ks produce PIP3 at plasma membrane level.
Although D. melanogaster and C. elegans have only one form of class I
MK, vertebrates have four class I PI3Ks called isoforms despite being
encoded by four different genes. Hence, duplication of these genes
coincides with the acquisition of coordinated multi-organ development.
Of the class I PI3Ks, PI3K alpha and PI3K beta encoded by PIK3CA and
P/K3CB, are ubiquitously expressed. They present similar putative
protein domains and share PI(4,5)P-2 lipid substrate specificity.
Fifteen years after publication of their first isoform-selective
pharmacological inhibitors and genetically engineered mouse models
(GEMMs) that mimic their complete and specific pharmacological
inhibition, we review the knowledge gathered in relation to the
redundant and selective roles of PI3K alpha and Pl3K beta. Recent data
suggest that, further to their redundancy, they cooperate for the
integration of organ-specific and context-specific signal cues, to
orchestrate organ development, physiology, and disease. This knowledge
reinforces the importance of isoform-selective inhibitors in clinical
settings. |
Belliere, Julie; Colombat, Magali; Kounde, Clement; Recher, Christian; Ribes, David; Huart, Antoine; Chauveau, Dominique; Demas, Veronique; Luquet, Isabelle; Beyne-Rauzy, Odile; Tavitian, Suzanne; Faguer, Stanislas Kidney Involvement in Patients With Chronic Myelomonocytic Leukemia or
BCR-ABL-Negative Myeloproliferative Neoplasms Journal Article In: KIDNEY INTERNATIONAL REPORTS, vol. 6, no. 3, pp. 737-745, 2021, ISSN: 2468-0249. @article{ISI:000631874200022,
title = {Kidney Involvement in Patients With Chronic Myelomonocytic Leukemia or
BCR-ABL-Negative Myeloproliferative Neoplasms},
author = {Julie Belliere and Magali Colombat and Clement Kounde and Christian Recher and David Ribes and Antoine Huart and Dominique Chauveau and Veronique Demas and Isabelle Luquet and Odile Beyne-Rauzy and Suzanne Tavitian and Stanislas Faguer},
doi = {10.1016/j.ekir.2020.12.005},
issn = {2468-0249},
year = {2021},
date = {2021-03-01},
journal = {KIDNEY INTERNATIONAL REPORTS},
volume = {6},
number = {3},
pages = {737-745},
abstract = {Introduction: The identification of specific molecular signatures and
the development of new targeted drugs have changed the paradigm of
onco-nephrology, now allowing a multiscale approach of kidney
involvement related to hematologic malignancies relying on combined
hematologic and molecular assessments. In this study, we aimed to refine
the spectrum of kidney disorders associated with chronic myelomonocytic
leukemia (CMML) or BCR-ABL-negative myeloproliferative neoplasms (MPNs),
2 very rare conditions scarcely described.
Methods: Case series. Patients with myeloid neoplasms who were referred
to Toulouse University Hospital Nephrology Unit and were diagnosed with
acute kidney injury (AKI), chronic kidney disease (CKD), or urine
abnormalities were retrospectively included. Results: Eighteen patients (males n=13, CMML n=8, essential thrombocytosis [ET] n=7, polycythemia vera [PV] n=1, and myelofibrosis n=2) developed kidney disease 7.7 +/- 2 years after the
diagnosis of the malignancy. Twelve patients had AKI at presentation.
Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy (n=14) showed various patterns, including pauci-immune glomerulosclerosis (n=5), extramedullary hematopoiesis (n=6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation (n=8). Immunostaining of CD61
confirmed the infiltration of megakaryocytes within glomeruli or
interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy n=2, AA amyloidosis n=1).
Massive kidney infiltration by CMML was identified in 1 patient. After a
mean follow-up of 2416 months, malignancy was considered as stable in 11
patients (61%), but 22% of patients had progressed to end-stage renal
failure. The remaining had persistently reduced kidney function. No
correlation between the malignancy and the renal presentation and
outcomes could be identified.
Conclusions: Kidney complications of CMML/MPN are heterogenous, and
kidney biopsy may help to identify new molecular targets to prevent the
development of kidney fibrosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction: The identification of specific molecular signatures and
the development of new targeted drugs have changed the paradigm of
onco-nephrology, now allowing a multiscale approach of kidney
involvement related to hematologic malignancies relying on combined
hematologic and molecular assessments. In this study, we aimed to refine
the spectrum of kidney disorders associated with chronic myelomonocytic
leukemia (CMML) or BCR-ABL-negative myeloproliferative neoplasms (MPNs),
2 very rare conditions scarcely described.
Methods: Case series. Patients with myeloid neoplasms who were referred
to Toulouse University Hospital Nephrology Unit and were diagnosed with
acute kidney injury (AKI), chronic kidney disease (CKD), or urine
abnormalities were retrospectively included. Results: Eighteen patients (males n=13, CMML n=8, essential thrombocytosis [ET] n=7, polycythemia vera [PV] n=1, and myelofibrosis n=2) developed kidney disease 7.7 +/- 2 years after the
diagnosis of the malignancy. Twelve patients had AKI at presentation.
Eight patients had glomerular presentation (high-range proteinuria 33%, microscopic hematuria 56%). Kidney biopsy (n=14) showed various patterns, including pauci-immune glomerulosclerosis (n=5), extramedullary hematopoiesis (n=6), or tubular atrophy and interstitial fibrosis with polymorphic inflammation (n=8). Immunostaining of CD61
confirmed the infiltration of megakaryocytes within glomeruli or
interstitium in 5 of 8 patients. Other pictures of glomerulopathy were identified in 3 patients (IgA nephropathy n=2, AA amyloidosis n=1).
Massive kidney infiltration by CMML was identified in 1 patient. After a
mean follow-up of 2416 months, malignancy was considered as stable in 11
patients (61%), but 22% of patients had progressed to end-stage renal
failure. The remaining had persistently reduced kidney function. No
correlation between the malignancy and the renal presentation and
outcomes could be identified.
Conclusions: Kidney complications of CMML/MPN are heterogenous, and
kidney biopsy may help to identify new molecular targets to prevent the
development of kidney fibrosis. |
Pyra, Pierrick; Darcourt, Jean; Aubert-Mucca, Marion; Brandicourt, Pierre; Patat, Olivier; Cheuret, Emmanuel; Brochard, Karine; Sevely, Annick; Calviere, Lionel; Karsenty, Clement Case Report: Successful Cerebral Revascularization and Cardiac
Transplant in a 16-Year-Old Male With Syndromic BRCC3-Related Moyamoya
Angiopathy Journal Article In: FRONTIERS IN NEUROLOGY, vol. 12, 2021, ISSN: 1664-2295. @article{ISI:000639412900001,
title = {Case Report: Successful Cerebral Revascularization and Cardiac
Transplant in a 16-Year-Old Male With Syndromic BRCC3-Related Moyamoya
Angiopathy},
author = {Pierrick Pyra and Jean Darcourt and Marion Aubert-Mucca and Pierre Brandicourt and Olivier Patat and Emmanuel Cheuret and Karine Brochard and Annick Sevely and Lionel Calviere and Clement Karsenty},
doi = {10.3389/fneur.2021.655303},
issn = {1664-2295},
year = {2021},
date = {2021-03-01},
journal = {FRONTIERS IN NEUROLOGY},
volume = {12},
abstract = {Background: BRCC3/MTCP1 deletions are associated with a rare familial
moyamoya angiopathy with extracranial manifestations.
Case: We report the case of an adolescent male presenting with
progressive and symptomatic moyamoya angiopathy and severe dilated
cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1. He was
treated for renovascular hypertension by left kidney homograft and right
nephrectomy in infancy and had other syndromic features, including
cryptorchidism, growth hormone deficiency, and facial dysmorphism. Due
to worsening of the neurological and cardiac condition, he was treated
by a direct superficial temporal artery to middle cerebral artery bypass
to enable successful cardiac transplant without cerebral damage.
Conclusions: BRCC3-related moyamoya is a devastating disease with severe
heart and brain complications. This case shows that aggressive
management with cerebral revascularization to allow cardiac transplant
is feasible and efficient despite end-stage heart failure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: BRCC3/MTCP1 deletions are associated with a rare familial
moyamoya angiopathy with extracranial manifestations.
Case: We report the case of an adolescent male presenting with
progressive and symptomatic moyamoya angiopathy and severe dilated
cardiomyopathy caused by a hemizygous deletion of BRCC3/MTCP1. He was
treated for renovascular hypertension by left kidney homograft and right
nephrectomy in infancy and had other syndromic features, including
cryptorchidism, growth hormone deficiency, and facial dysmorphism. Due
to worsening of the neurological and cardiac condition, he was treated
by a direct superficial temporal artery to middle cerebral artery bypass
to enable successful cardiac transplant without cerebral damage.
Conclusions: BRCC3-related moyamoya is a devastating disease with severe
heart and brain complications. This case shows that aggressive
management with cerebral revascularization to allow cardiac transplant
is feasible and efficient despite end-stage heart failure. |
Santos-Zas, Icia; Lemarie, Jeremie; Zlatanova, Ivana; Cachanado, Marine; Seghezzi, Jean-Christophe; Benamer, Hakim; Goube, Pascal; Vandestienne, Marie; Cohen, Raphael; Ezzo, Maya; Duval, Vincent; Zhang, Yujiao; Su, Jin-Bo; Bize, Alain; Sambin, Lucien; Bonnin, Philippe; Branchereau, Maxime; Heymes, Christophe; Tanchot, Corinne; Vilar, Jose; Delacroix, Clement; Hulot, Jean-Sebastien; Cochain, Clement; Bruneval, Patrick; Danchin, Nicolas; Tedgui, Alain; Mallat, Ziad; Simon, Tabassome; Ghaleh, Bijan; Silvestre, Jean-Sebastien; Ait-Oufella, Hafid Cytotoxic CD8(+) T cells promote granzyme B-dependent adverse
post-ischemic cardiac remodeling Journal Article In: NATURE COMMUNICATIONS, vol. 12, no. 1, 2021, ISSN: 2041-1723. @article{ISI:000627412900015,
title = {Cytotoxic CD8(+) T cells promote granzyme B-dependent adverse
post-ischemic cardiac remodeling},
author = {Icia Santos-Zas and Jeremie Lemarie and Ivana Zlatanova and Marine Cachanado and Jean-Christophe Seghezzi and Hakim Benamer and Pascal Goube and Marie Vandestienne and Raphael Cohen and Maya Ezzo and Vincent Duval and Yujiao Zhang and Jin-Bo Su and Alain Bize and Lucien Sambin and Philippe Bonnin and Maxime Branchereau and Christophe Heymes and Corinne Tanchot and Jose Vilar and Clement Delacroix and Jean-Sebastien Hulot and Clement Cochain and Patrick Bruneval and Nicolas Danchin and Alain Tedgui and Ziad Mallat and Tabassome Simon and Bijan Ghaleh and Jean-Sebastien Silvestre and Hafid Ait-Oufella},
doi = {10.1038/s41467-021-21737-9},
issn = {2041-1723},
year = {2021},
date = {2021-03-01},
journal = {NATURE COMMUNICATIONS},
volume = {12},
number = {1},
abstract = {Acute myocardial infarction is a common condition responsible for heart
failure and sudden death. Here, we show that following acute myocardial
infarction in mice, CD8(+) T lymphocytes are recruited and activated in
the ischemic heart tissue and release Granzyme B, leading to
cardiomyocyte apoptosis, adverse ventricular remodeling and
deterioration of myocardial function. Depletion of CD8(+) T lymphocytes
decreases apoptosis within the ischemic myocardium, hampers inflammatory
response, limits myocardial injury and improves heart function. These
effects are recapitulated in mice with Granzyme B-deficient CD8(+) T
cells. The protective effect of CD8 depletion on heart function is
confirmed by using a model of ischemia/reperfusion in pigs. Finally, we
reveal that elevated circulating levels of GRANZYME B in patients with
acute myocardial infarction predict increased risk of death at 1-year
follow-up. Our work unravels a deleterious role of CD8(+) T lymphocytes
following acute ischemia, and suggests potential therapeutic strategies
targeting pathogenic CD8(+) T lymphocytes in the setting of acute
myocardial infarction. Immune cells contribute to adverse remodeling
following myocardial infarction. Here the authors show in mice and pigs
that CD8(+) lymphocytes release Granzyme B in the infarcted heart
leading to cardiomyocyte death, enhanced inflammation and deterioration
of cardiac function.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Acute myocardial infarction is a common condition responsible for heart
failure and sudden death. Here, we show that following acute myocardial
infarction in mice, CD8(+) T lymphocytes are recruited and activated in
the ischemic heart tissue and release Granzyme B, leading to
cardiomyocyte apoptosis, adverse ventricular remodeling and
deterioration of myocardial function. Depletion of CD8(+) T lymphocytes
decreases apoptosis within the ischemic myocardium, hampers inflammatory
response, limits myocardial injury and improves heart function. These
effects are recapitulated in mice with Granzyme B-deficient CD8(+) T
cells. The protective effect of CD8 depletion on heart function is
confirmed by using a model of ischemia/reperfusion in pigs. Finally, we
reveal that elevated circulating levels of GRANZYME B in patients with
acute myocardial infarction predict increased risk of death at 1-year
follow-up. Our work unravels a deleterious role of CD8(+) T lymphocytes
following acute ischemia, and suggests potential therapeutic strategies
targeting pathogenic CD8(+) T lymphocytes in the setting of acute
myocardial infarction. Immune cells contribute to adverse remodeling
following myocardial infarction. Here the authors show in mice and pigs
that CD8(+) lymphocytes release Granzyme B in the infarcted heart
leading to cardiomyocyte death, enhanced inflammation and deterioration
of cardiac function. |
Tasta, Oriane; Swiader, Audrey; Grazide, Marie-Helene; Rouahi, Myriam; Parant, Olivier; Vayssiere, Christophe; Bujold, Emmanuel; Salvayre, Robert; Guerby, Paul; Negre-Salvayre, Anne A role for 4-hydroxy-2-nonenal in premature placental senescence in
preeclampsia and intrauterine growth restriction Journal Article In: FREE RADICAL BIOLOGY AND MEDICINE, vol. 164, pp. 303-314, 2021, ISSN: 0891-5849. @article{ISI:000621328400005,
title = {A role for 4-hydroxy-2-nonenal in premature placental senescence in
preeclampsia and intrauterine growth restriction},
author = {Oriane Tasta and Audrey Swiader and Marie-Helene Grazide and Myriam Rouahi and Olivier Parant and Christophe Vayssiere and Emmanuel Bujold and Robert Salvayre and Paul Guerby and Anne Negre-Salvayre},
doi = {10.1016/j.freeradbiomed.2021.01.002},
issn = {0891-5849},
year = {2021},
date = {2021-02-01},
journal = {FREE RADICAL BIOLOGY AND MEDICINE},
volume = {164},
pages = {303-314},
abstract = {Premature placental senescence is a hallmark of pregnancy-related
disorders such as intrauterine growth restriction (IUGR) and
preeclampsia (PE), two major cause of maternal and neonatal morbidity
and mortality. Oxidative stress and lipid peroxidation are involved in
the pathogenesis of PE and IUGR, and may play a role in placental aging.
In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a
lipid peroxidation-derived aldehyde present in preeclamptic placentas,
may contribute to premature senescence in placenta-related
complications.
Placentas from PE-affected women, exhibited several senescence patterns,
such as an increased expression of phosphorylated (serine-139) histone
gamma H2AX, a sensitive marker of double-stranded DNA breaks, the
presence of lipofuscin granules, and an accumulation of high molecular
weight cross-linked and ubiquitinated proteins. PE placentas showed an
accumulation of acetylated proteins consistent with the presence of
HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and
senescence markers together with SIRT1 modification by HNE, were
observed in murine placentas from mice treated with lipopolysaccharide
during gestation and used as models of IUGR. The addition of HNE and ONE
(4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated
the senescence-associated- beta-galactosidase, and generated an
accumulation of acetylated proteins, consistent with a modification of
SIRT1 by HNE.
Altogether, these data emphasize the role of HNE and lipid
peroxidation-derived aldehydes in premature placental senescence in PE
and IUGR, and more generally in pathological pregnancies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Premature placental senescence is a hallmark of pregnancy-related
disorders such as intrauterine growth restriction (IUGR) and
preeclampsia (PE), two major cause of maternal and neonatal morbidity
and mortality. Oxidative stress and lipid peroxidation are involved in
the pathogenesis of PE and IUGR, and may play a role in placental aging.
In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a
lipid peroxidation-derived aldehyde present in preeclamptic placentas,
may contribute to premature senescence in placenta-related
complications.
Placentas from PE-affected women, exhibited several senescence patterns,
such as an increased expression of phosphorylated (serine-139) histone
gamma H2AX, a sensitive marker of double-stranded DNA breaks, the
presence of lipofuscin granules, and an accumulation of high molecular
weight cross-linked and ubiquitinated proteins. PE placentas showed an
accumulation of acetylated proteins consistent with the presence of
HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and
senescence markers together with SIRT1 modification by HNE, were
observed in murine placentas from mice treated with lipopolysaccharide
during gestation and used as models of IUGR. The addition of HNE and ONE
(4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated
the senescence-associated- beta-galactosidase, and generated an
accumulation of acetylated proteins, consistent with a modification of
SIRT1 by HNE.
Altogether, these data emphasize the role of HNE and lipid
peroxidation-derived aldehydes in premature placental senescence in PE
and IUGR, and more generally in pathological pregnancies. |
Raimondi, Laura; Parini, Angelo Editorial: Inflammatory Cells in the Sick Heart and Adipose Tissue:
Novel Targets for Old and New Drugs Journal Article In: FRONTIERS IN PHYSIOLOGY, vol. 11, 2021, ISSN: 1664-042X. @article{ISI:000618208900001,
title = {Editorial: Inflammatory Cells in the Sick Heart and Adipose Tissue:
Novel Targets for Old and New Drugs},
author = {Laura Raimondi and Angelo Parini},
doi = {10.3389/fphys.2020.612228},
issn = {1664-042X},
year = {2021},
date = {2021-02-01},
journal = {FRONTIERS IN PHYSIOLOGY},
volume = {11},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Buscail, Etienne; Canivet, Cindy; Shourick, Jason; Chantalat, Elodie; Carrere, Nicolas; Duffas, Jean-Pierre; Philis, Antoine; Berard, Emilie; Buscail, Louis; Ghouti, Laurent; Chaput, Benoit Perineal Wound Closure Following Abdominoperineal Resection and Pelvic
Exenteration for Cancer: A Systematic Review and Meta-Analysis Journal Article In: CANCERS, vol. 13, no. 4, 2021. @article{ISI:000623337600001,
title = {Perineal Wound Closure Following Abdominoperineal Resection and Pelvic
Exenteration for Cancer: A Systematic Review and Meta-Analysis},
author = {Etienne Buscail and Cindy Canivet and Jason Shourick and Elodie Chantalat and Nicolas Carrere and Jean-Pierre Duffas and Antoine Philis and Emilie Berard and Louis Buscail and Laurent Ghouti and Benoit Chaput},
doi = {10.3390/cancers13040721},
year = {2021},
date = {2021-02-01},
journal = {CANCERS},
volume = {13},
number = {4},
abstract = {Simple Summary: Abdominoperineal resection (APR) and pelvic exenteration
(PE) for the treatment of cancer (mainly anal and rectal cancers)
require extensive pelvic resection with a high rate of postoperative
complications. The objective of this work was to systematically review
and meta-analyze the effects of vertical rectus abdominis myocutaneous
flap (VRAMf) and mesh closure on perineal morbidity following APR and
PE. The studies were distributed as follows: Group A comparing primary
closure (PC) and VRAMf, Group B comparing PC and mesh closure, Group C
comparing PC and VRAMf in PE. The meta-analysis of Groups A and B showed
PC to be associated with an increase in the rate of total and major
perineal wound complications. PC was associated with a decrease in total
and major perineal complications in Group C.
Background. Abdominoperineal resection (APR) and pelvic exenteration
(PE) for the treatment of cancer require extensive pelvic resection with
a high rate of postoperative complications. The objective of this work
was to systematically review and meta-analyze the effects of vertical
rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal
morbidity following APR and PE (mainly for anal and rectal cancers).
Methods. We searched PubMed, Cochrane, and EMBASE for eligible studies
as of the year 2000. After data extraction, a meta-analysis was
performed to compare perineal wound morbidity. The studies were
distributed as follows: Group A comparing primary closure (PC) and
VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC
and VRAMf in PE. Results. Our systematic review yielded 18 eligible
studies involving 2180 patients (1206 primary closures, 647 flap
closures, 327 mesh closures). The meta-analysis of Groups A and B showed
PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43-0.71; p < 0.01/Group B: OR 0.54, CI 0.17-1.68; p =
0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI
0.35-0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12-1.17; p < 0.01). PC
was associated with a decrease in total (OR 2.46, 95% CI 1.39-4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90-3.08; p = 0.1) perineal
complications in Group C. Conclusions. Our results confirm the
contribution of the VRAMf in reducing major complications in APR.
Similarly, biological prostheses offer an interesting alternative in
pelvic reconstruction. For PE, an adapted reconstruction must be
proposed with specialized expertise.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Simple Summary: Abdominoperineal resection (APR) and pelvic exenteration
(PE) for the treatment of cancer (mainly anal and rectal cancers)
require extensive pelvic resection with a high rate of postoperative
complications. The objective of this work was to systematically review
and meta-analyze the effects of vertical rectus abdominis myocutaneous
flap (VRAMf) and mesh closure on perineal morbidity following APR and
PE. The studies were distributed as follows: Group A comparing primary
closure (PC) and VRAMf, Group B comparing PC and mesh closure, Group C
comparing PC and VRAMf in PE. The meta-analysis of Groups A and B showed
PC to be associated with an increase in the rate of total and major
perineal wound complications. PC was associated with a decrease in total
and major perineal complications in Group C.
Background. Abdominoperineal resection (APR) and pelvic exenteration
(PE) for the treatment of cancer require extensive pelvic resection with
a high rate of postoperative complications. The objective of this work
was to systematically review and meta-analyze the effects of vertical
rectus abdominis myocutaneous flap (VRAMf) and mesh closure on perineal
morbidity following APR and PE (mainly for anal and rectal cancers).
Methods. We searched PubMed, Cochrane, and EMBASE for eligible studies
as of the year 2000. After data extraction, a meta-analysis was
performed to compare perineal wound morbidity. The studies were
distributed as follows: Group A comparing primary closure (PC) and
VRAMf, Group B comparing PC and mesh closure, and Group C comparing PC
and VRAMf in PE. Results. Our systematic review yielded 18 eligible
studies involving 2180 patients (1206 primary closures, 647 flap
closures, 327 mesh closures). The meta-analysis of Groups A and B showed
PC to be associated with an increase in the rate of total (Group A: OR 0.55, 95% CI 0.43-0.71; p < 0.01/Group B: OR 0.54, CI 0.17-1.68; p =
0.18) and major perineal wound complications (Group A: OR 0.49, 95% CI
0.35-0.68; p < 0.001/Group B: OR 0.38, 95% CI 0.12-1.17; p < 0.01). PC
was associated with a decrease in total (OR 2.46, 95% CI 1.39-4.35; p < 0.01) and major (OR 1.67, 95% CI 0.90-3.08; p = 0.1) perineal
complications in Group C. Conclusions. Our results confirm the
contribution of the VRAMf in reducing major complications in APR.
Similarly, biological prostheses offer an interesting alternative in
pelvic reconstruction. For PE, an adapted reconstruction must be
proposed with specialized expertise. |
Guerard, Adrien; Laurent, Victor; Fromont, Gaelle; Esteve, David; Gilhodes, Julia; Bonnelye, Edith; Gonidec, Sophie Le; Valet, Philippe; Malavaud, Bernard; Reina, Nicolas; Attane, Camille; Muller, Catherine The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of
Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes Journal Article In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 22, no. 4, 2021. @article{ISI:000623822200001,
title = {The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of
Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes},
author = {Adrien Guerard and Victor Laurent and Gaelle Fromont and David Esteve and Julia Gilhodes and Edith Bonnelye and Sophie Le Gonidec and Philippe Valet and Bernard Malavaud and Nicolas Reina and Camille Attane and Catherine Muller},
doi = {10.3390/ijms22041994},
year = {2021},
date = {2021-02-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
volume = {22},
number = {4},
abstract = {Bone metastasis remains the most frequent and the deadliest complication
of prostate cancer (PCa). Mechanisms leading to the homing of tumor
cells to bone remain poorly characterized. Role of chemokines in
providing navigational cues to migrating cancer cells bearing specific
receptors is well established. Bone is an adipocyte-rich organ since 50
to 70% of the adult bone marrow (BM) volume comprise bone marrow
adipocytes (BM-Ads), which are likely to produce chemokines within the
bone microenvironment. Using in vitro migration assays, we demonstrated
that soluble factors released by human primary BM-Ads are able to
support the directed migration of PCa cells in a CCR3-dependent manner.
In addition, we showed that CCL7, a chemokine previously involved in the
CCR3-dependent migration of PCa cells outside of the prostate gland, is
released by human BM-Ads. These effects are amplified by obesity and
ageing, two clinical conditions known to promote aggressive and
metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone
metastasis vs. primary tumors at mRNA levels using Oncomine microarray
database. In addition, immunohistochemistry experiments demonstrated
overexpression of CCR3 in bone versus visceral metastases. These results
underline the potential importance of BM-Ads in the bone metastatic
process and imply a CCR3/CCL7 axis whose pharmacological interest needs
to be evaluated.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bone metastasis remains the most frequent and the deadliest complication
of prostate cancer (PCa). Mechanisms leading to the homing of tumor
cells to bone remain poorly characterized. Role of chemokines in
providing navigational cues to migrating cancer cells bearing specific
receptors is well established. Bone is an adipocyte-rich organ since 50
to 70% of the adult bone marrow (BM) volume comprise bone marrow
adipocytes (BM-Ads), which are likely to produce chemokines within the
bone microenvironment. Using in vitro migration assays, we demonstrated
that soluble factors released by human primary BM-Ads are able to
support the directed migration of PCa cells in a CCR3-dependent manner.
In addition, we showed that CCL7, a chemokine previously involved in the
CCR3-dependent migration of PCa cells outside of the prostate gland, is
released by human BM-Ads. These effects are amplified by obesity and
ageing, two clinical conditions known to promote aggressive and
metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone
metastasis vs. primary tumors at mRNA levels using Oncomine microarray
database. In addition, immunohistochemistry experiments demonstrated
overexpression of CCR3 in bone versus visceral metastases. These results
underline the potential importance of BM-Ads in the bone metastatic
process and imply a CCR3/CCL7 axis whose pharmacological interest needs
to be evaluated. |
Noirrit-Esclassan, Emmanuelle; Valera, Marie-Cecile; Tremollieres, Florence; Arnal, Jean-Francois; Lenfant, Francoise; Fontaine, Coralie; Vinel, Alexia Critical Role of Estrogens on Bone Homeostasis in Both Male and Female:
From Physiology to Medical Implications Journal Article In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 22, no. 4, 2021. @article{ISI:000623848700001,
title = {Critical Role of Estrogens on Bone Homeostasis in Both Male and Female:
From Physiology to Medical Implications},
author = {Emmanuelle Noirrit-Esclassan and Marie-Cecile Valera and Florence Tremollieres and Jean-Francois Arnal and Francoise Lenfant and Coralie Fontaine and Alexia Vinel},
doi = {10.3390/ijms22041568},
year = {2021},
date = {2021-02-01},
journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
volume = {22},
number = {4},
abstract = {Bone is a multi-skilled tissue, protecting major organs, regulating
calcium phosphate balance and producing hormones. Its development during
childhood determines height and stature as well as resistance against
fracture in advanced age. Estrogens are key regulators of bone turnover
in both females and males. These hormones play a major role in
longitudinal and width growth throughout puberty as well as in the
regulation of bone turnover. In women, estrogen deficiency is one of the
major causes of postmenopausal osteoporosis. In this review, we will
summarize the main clinical and experimental studies reporting the
effects of estrogens not only in females but also in males, during
different life stages. Effects of estrogens on bone involve either
Estrogen Receptor (ER)alpha or ER beta depending on the type of bone
(femur, vertebrae, tibia, mandible), the compartment (trabecular or
cortical), cell types involved (osteoclasts, osteoblasts and osteocytes)
and sex. Finally, we will discuss new ongoing strategies to increase the
benefit/risk ratio of the hormonal treatment of menopause.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Bone is a multi-skilled tissue, protecting major organs, regulating
calcium phosphate balance and producing hormones. Its development during
childhood determines height and stature as well as resistance against
fracture in advanced age. Estrogens are key regulators of bone turnover
in both females and males. These hormones play a major role in
longitudinal and width growth throughout puberty as well as in the
regulation of bone turnover. In women, estrogen deficiency is one of the
major causes of postmenopausal osteoporosis. In this review, we will
summarize the main clinical and experimental studies reporting the
effects of estrogens not only in females but also in males, during
different life stages. Effects of estrogens on bone involve either
Estrogen Receptor (ER)alpha or ER beta depending on the type of bone
(femur, vertebrae, tibia, mandible), the compartment (trabecular or
cortical), cell types involved (osteoclasts, osteoblasts and osteocytes)
and sex. Finally, we will discuss new ongoing strategies to increase the
benefit/risk ratio of the hormonal treatment of menopause. |
Pouilles, Jean-Michel; Gosset, Anna; Breteau, Alice; Tremollieres, Florence Anne TBS in early postmenopausal women with severe vertebral osteoporosis Journal Article In: BONE, vol. 142, 2021, ISSN: 8756-3282. @article{ISI:000601336400013,
title = {TBS in early postmenopausal women with severe vertebral osteoporosis},
author = {Jean-Michel Pouilles and Anna Gosset and Alice Breteau and Florence Anne Tremollieres},
doi = {10.1016/j.bone.2020.115698},
issn = {8756-3282},
year = {2021},
date = {2021-01-01},
journal = {BONE},
volume = {142},
abstract = {Introduction/background: Severe vertebral osteoporosis is a rare
condition in early postmenopausal women. We seek to determine whether
Trabecular Bone Score (TBS), which is a new bone texture measurement,
could be of additional value in evaluating trabecular bone properties in
this population.
Methodology: Lumbar spine (LS) and femoral neck (FN) bone mineral
densities (BMDs) and TBS were measured in 105 early postmenopausal women
(group 1: ``cases'', mean age: 53.1 +/- 2.6 yrs.) with severe vertebral osteoporosis defined as a vertebral BMD T-score <= 3, as well
as in 105 healthy postmenopausal women matched for age (group 2) and 105
older osteoporotic women matched for vertebral BMD (group 3, mean age:
63.9 +/- 4 yrs.). None of the women had a secondary cause for
osteoporosis. Correlations between TBS values and BMD were calculated
after controlling for clinical characteristics.
Results: The women in group 1 (cases) were significantly smaller and
thinner and had a history of more fractures than the age-matched
controls (p < 0.05). Mean LS and FN BMD values were significantly lower
in the cases than in the age-matched controls (0.770 +/- 0.05 vs 1.106
+/- 0.11 g/cm(2) and 0.700 +/- 0.07 vs 0.872 +/- 0.12 g/cm(2), for LS
and FN, respectively; p < 0.001). The mean TBS value was also
significantly lower in the cases than in the age matched controls (1.24
+/- 0.08 vs 1.37 +/- 0.07, p < 0.001) but significantly higher than in
the older osteoporotic controls (1.20 +/- 0.07, p < 0.05). After
adjustment for vertebral BMD, the difference in TBS values between the
cases and the age-matched controls was no longer significant although it
remained significantly higher than in the older osteoporotic controls.
This would suggest that in group 1, osteoporosis is rather the
consequence of a low peak bone mass than of further bone degradation
while the greater decrease in TBS value in elderly osteoporotic controls
is more likely to reflect additional damage in bone microarchitecture
associated with aging. In a multivariate analysis including age, vertebral and femoral neck BMD, height and weight (R-2 = 0.60, p <
0.0001), TBS was found to be negatively and independently associated with age (r =-0.31 p < 0.0001) and height (r =-0.20 p < 0.001). The FRAX
score was significantly higher in group 1 and group 3 women than in the
healthy control women (group 2). There were no changes in the results
after adjustment for TBS.
Conclusions: Women presenting with severe vertebral osteoporosis at the
beginning of menopause have TBS values that are, first and foremost,
proportional to their BMD. Whether this indicates that osteoporosis in
this population is the consequence of a low peak bone mass remains to be
determined and further studies are required. Nevertheless, the value of
measuring TBS in addition to BMD appears to be relatively negligible in
early postmenopausal women with severe vertebral osteoporosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction/background: Severe vertebral osteoporosis is a rare
condition in early postmenopausal women. We seek to determine whether
Trabecular Bone Score (TBS), which is a new bone texture measurement,
could be of additional value in evaluating trabecular bone properties in
this population.
Methodology: Lumbar spine (LS) and femoral neck (FN) bone mineral
densities (BMDs) and TBS were measured in 105 early postmenopausal women
(group 1: ``cases'', mean age: 53.1 +/- 2.6 yrs.) with severe vertebral osteoporosis defined as a vertebral BMD T-score <= 3, as well
as in 105 healthy postmenopausal women matched for age (group 2) and 105
older osteoporotic women matched for vertebral BMD (group 3, mean age:
63.9 +/- 4 yrs.). None of the women had a secondary cause for
osteoporosis. Correlations between TBS values and BMD were calculated
after controlling for clinical characteristics.
Results: The women in group 1 (cases) were significantly smaller and
thinner and had a history of more fractures than the age-matched
controls (p < 0.05). Mean LS and FN BMD values were significantly lower
in the cases than in the age-matched controls (0.770 +/- 0.05 vs 1.106
+/- 0.11 g/cm(2) and 0.700 +/- 0.07 vs 0.872 +/- 0.12 g/cm(2), for LS
and FN, respectively; p < 0.001). The mean TBS value was also
significantly lower in the cases than in the age matched controls (1.24
+/- 0.08 vs 1.37 +/- 0.07, p < 0.001) but significantly higher than in
the older osteoporotic controls (1.20 +/- 0.07, p < 0.05). After
adjustment for vertebral BMD, the difference in TBS values between the
cases and the age-matched controls was no longer significant although it
remained significantly higher than in the older osteoporotic controls.
This would suggest that in group 1, osteoporosis is rather the
consequence of a low peak bone mass than of further bone degradation
while the greater decrease in TBS value in elderly osteoporotic controls
is more likely to reflect additional damage in bone microarchitecture
associated with aging. In a multivariate analysis including age, vertebral and femoral neck BMD, height and weight (R-2 = 0.60, p <
0.0001), TBS was found to be negatively and independently associated with age (r =-0.31 p < 0.0001) and height (r =-0.20 p < 0.001). The FRAX
score was significantly higher in group 1 and group 3 women than in the
healthy control women (group 2). There were no changes in the results
after adjustment for TBS.
Conclusions: Women presenting with severe vertebral osteoporosis at the
beginning of menopause have TBS values that are, first and foremost,
proportional to their BMD. Whether this indicates that osteoporosis in
this population is the consequence of a low peak bone mass remains to be
determined and further studies are required. Nevertheless, the value of
measuring TBS in addition to BMD appears to be relatively negligible in
early postmenopausal women with severe vertebral osteoporosis. |
Buscato, Melissa; Davezac, Morgane; Zahreddine, Rana; Adlanmerini, Marine; Metivier, Raphael; Fillet, Marianne; Cobraiville, Gael; Moro, Cedric; Foidart, Jean-Michel; Lenfant, Francoise; Gourdy, Pierre; Arnal, Jean-Francois; Fontaine, Coralie Estetrol prevents Western diet-induced obesity and atheroma
independently of hepatic estrogen receptor alpha Journal Article In: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, vol. 320, no. 1, pp. E19-E29, 2021, ISSN: 0193-1849. @article{ISI:000613698700004,
title = {Estetrol prevents Western diet-induced obesity and atheroma
independently of hepatic estrogen receptor alpha},
author = {Melissa Buscato and Morgane Davezac and Rana Zahreddine and Marine Adlanmerini and Raphael Metivier and Marianne Fillet and Gael Cobraiville and Cedric Moro and Jean-Michel Foidart and Francoise Lenfant and Pierre Gourdy and Jean-Francois Arnal and Coralie Fontaine},
doi = {10.1152/ajpendo.00211.2020},
issn = {0193-1849},
year = {2021},
date = {2021-01-01},
journal = {AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM},
volume = {320},
number = {1},
pages = {E19-E29},
abstract = {Estetrol (E4), a natural estrogen synthesized by the human fetal liver,
is currently evaluated in phase III clinical studies as a new menopause
hormone therapy. Indeed, E4 significantly improves vasomotor and
genito-urinary menopausal symptoms and prevents bone demineralization.
Compared with other estrogens, E4 was found to have limited effects on
coagulation factors in the liver of women allowing to expect less
thrombotic events. To fully delineate its clinical potential, the aim of
this study was to assess the effect of E4 on metabolic disorders. Here,
we studied the pathophysiological consequences of a Western diet (42%
kcal fat, 0.2% cholesterol) in ovariectomized female mice under chronic
E4 treatment. We showed that E4 reduces body weight gain and improves
glucose tolerance in both C57Bl/6 and LDLR-/- mice. To evaluate the role
of hepatic estrogen receptor (ER) alpha in the preventive effect of E4
against obesity and associated disorders such as atherosclerosis and
steatosis, mice har boring a hepatocyte-specific ER alpha deletion
(LERKO) were crossed with LDLR-/- mice. Our results demonstrated that,
whereas liver ER alpha is dispensable for the E4 beneficial actions on
obesity and atheroma, it is necessary to prevent steatosis in mice.
Overall, these findings suggest that E4 could prevent metabolic,
hepatic, and vascular disorders occurring at menopause, extending the
potential medical interest of this natural estrogen as a new hormonal
treatment.
NEW & NOTEWORTHY Estetrol prevents obesity, steatosis, and
atherosclerosis in mice fed a Western diet. Hepatic ERa is necessary for
the prevention of steatosis, but not of obesity and atherosclerosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Estetrol (E4), a natural estrogen synthesized by the human fetal liver,
is currently evaluated in phase III clinical studies as a new menopause
hormone therapy. Indeed, E4 significantly improves vasomotor and
genito-urinary menopausal symptoms and prevents bone demineralization.
Compared with other estrogens, E4 was found to have limited effects on
coagulation factors in the liver of women allowing to expect less
thrombotic events. To fully delineate its clinical potential, the aim of
this study was to assess the effect of E4 on metabolic disorders. Here,
we studied the pathophysiological consequences of a Western diet (42%
kcal fat, 0.2% cholesterol) in ovariectomized female mice under chronic
E4 treatment. We showed that E4 reduces body weight gain and improves
glucose tolerance in both C57Bl/6 and LDLR-/- mice. To evaluate the role
of hepatic estrogen receptor (ER) alpha in the preventive effect of E4
against obesity and associated disorders such as atherosclerosis and
steatosis, mice har boring a hepatocyte-specific ER alpha deletion
(LERKO) were crossed with LDLR-/- mice. Our results demonstrated that,
whereas liver ER alpha is dispensable for the E4 beneficial actions on
obesity and atheroma, it is necessary to prevent steatosis in mice.
Overall, these findings suggest that E4 could prevent metabolic,
hepatic, and vascular disorders occurring at menopause, extending the
potential medical interest of this natural estrogen as a new hormonal
treatment.
NEW & NOTEWORTHY Estetrol prevents obesity, steatosis, and
atherosclerosis in mice fed a Western diet. Hepatic ERa is necessary for
the prevention of steatosis, but not of obesity and atherosclerosis. |
Payrastre, Bernard; Ribes, Agnes Low-dose Btk inhibitors: an `aspirin' of tomorrow? Journal Article In: HAEMATOLOGICA, vol. 106, no. 1, pp. 2-4, 2021, ISSN: 0390-6078. @article{ISI:000623251500002,
title = {Low-dose Btk inhibitors: an `aspirin' of tomorrow?},
author = {Bernard Payrastre and Agnes Ribes},
doi = {10.3324/haematol.2020.265173},
issn = {0390-6078},
year = {2021},
date = {2021-01-01},
journal = {HAEMATOLOGICA},
volume = {106},
number = {1},
pages = {2-4},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Vardon-Bounes, Fanny; Gracia, Romain; Abaziou, Timothee; Crognier, Laure; Seguin, Thierry; Labaste, Francois; Geeraerts, Thomas; Georges, Bernard; Conil, Jean-Marie; Minville, Vincent A study of patients' quality of life more than 5 years after trauma: a
prospective follow-up Journal Article In: HEALTH AND QUALITY OF LIFE OUTCOMES, vol. 19, no. 1, 2021. @article{ISI:000608211500002,
title = {A study of patients' quality of life more than 5 years after trauma: a
prospective follow-up},
author = {Fanny Vardon-Bounes and Romain Gracia and Timothee Abaziou and Laure Crognier and Thierry Seguin and Francois Labaste and Thomas Geeraerts and Bernard Georges and Jean-Marie Conil and Vincent Minville},
doi = {10.1186/s12955-020-01652-1},
year = {2021},
date = {2021-01-01},
journal = {HEALTH AND QUALITY OF LIFE OUTCOMES},
volume = {19},
number = {1},
abstract = {Background: The long-term fate of severely injured patients in terms of
their quality of life is not well known. Our aim was to assess the
quality of life of patients who have suffered moderate to severe trauma
and to identify primary factors of long-term quality of life impairment.
Methods: A prospective monocentric study conducted on a number of
patients who were victims of moderate to severe injuries during the year
2012. Patients were selected based on an Injury Severity Score (ISS)
more than or equal to 9. Quality of life was assessed by the MOS SF-36
and NHP scores as a primary evaluation criterion. The secondary
evaluation criteria were the determination of the socio-economic impact
on quality of life and the identification of factors associated with
disability.
Results: Two hundred and eight patients were contacted by e-mail or
telephone. Fifty-five patients participated in this study (with a
participation level of 26.4%), including 78.2% men, with a median age
of 46. Significant alterations in quality of life were observed with the
NHP and MOS SF-36 scale, including physical and psychological
components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10),
20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores <= 85 on the physical
functioning variable of the MOS SF 36 scale was associated with
disability.
Conclusion: More than five years after a moderate to severe injury,
patients' quality of life was significantly impacted, resulting in
significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score <= 85 on the physical
functioning dimension of the MOS SF-36 scale. This study raises the
question of whether or not early rehabilitation programs should be
implemented in order to limit the long-term impact of major trauma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: The long-term fate of severely injured patients in terms of
their quality of life is not well known. Our aim was to assess the
quality of life of patients who have suffered moderate to severe trauma
and to identify primary factors of long-term quality of life impairment.
Methods: A prospective monocentric study conducted on a number of
patients who were victims of moderate to severe injuries during the year
2012. Patients were selected based on an Injury Severity Score (ISS)
more than or equal to 9. Quality of life was assessed by the MOS SF-36
and NHP scores as a primary evaluation criterion. The secondary
evaluation criteria were the determination of the socio-economic impact
on quality of life and the identification of factors associated with
disability.
Results: Two hundred and eight patients were contacted by e-mail or
telephone. Fifty-five patients participated in this study (with a
participation level of 26.4%), including 78.2% men, with a median age
of 46. Significant alterations in quality of life were observed with the
NHP and MOS SF-36 scale, including physical and psychological
components. This resulted in a major socio-economic impact as 26% of the patients could not resume their professional activities (n = 10),
20% required retraining in other lines of work, and 36.4% had a disability status. The study showed that scores <= 85 on the physical
functioning variable of the MOS SF 36 scale was associated with
disability.
Conclusion: More than five years after a moderate to severe injury,
patients' quality of life was significantly impacted, resulting in
significant socio-economic consequences. Disability secondary to major trauma seems to be associated with a score <= 85 on the physical
functioning dimension of the MOS SF-36 scale. This study raises the
question of whether or not early rehabilitation programs should be
implemented in order to limit the long-term impact of major trauma. |
Larrue, Clement; Guiraud, Nathan; Mouchel, Pierre-Luc; Dubois, Marine; Farge, Thomas; Gotanegre, Mathilde; Bosc, Claudie; Saland, Estelle; Nicolau-Travers, Marie-Laure; Sabatier, Marie; Serhan, Nizar; Sahal, Ambrine; Boet, Emeline; Mouche, Sarah; Heydt, Quentin; Aroua, Nesrine; Stuani, Lucille; Kaoma, Tony; Angenendt, Linus; Mikesch, Jan-Henrik; Schliemann, Christoph; Vergez, Francois; Tamburini, Jerome; Recher, Christian; Sarry, Jean-Emmanuel Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant
acute myeloid leukemia cells Journal Article In: NATURE COMMUNICATIONS, vol. 12, no. 1, 2021, ISSN: 2041-1723. @article{ISI:000611511500003,
title = {Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant
acute myeloid leukemia cells},
author = {Clement Larrue and Nathan Guiraud and Pierre-Luc Mouchel and Marine Dubois and Thomas Farge and Mathilde Gotanegre and Claudie Bosc and Estelle Saland and Marie-Laure Nicolau-Travers and Marie Sabatier and Nizar Serhan and Ambrine Sahal and Emeline Boet and Sarah Mouche and Quentin Heydt and Nesrine Aroua and Lucille Stuani and Tony Kaoma and Linus Angenendt and Jan-Henrik Mikesch and Christoph Schliemann and Francois Vergez and Jerome Tamburini and Christian Recher and Jean-Emmanuel Sarry},
doi = {10.1038/s41467-020-20717-9},
issn = {2041-1723},
year = {2021},
date = {2021-01-01},
journal = {NATURE COMMUNICATIONS},
volume = {12},
number = {1},
abstract = {Drug tolerant/resistant leukemic stem cell (LSC) subpopulations may
explain frequent relapses in acute myeloid leukemia (AML), suggesting
that these relapse-initiating cells (RICs) persistent after chemotherapy
represent bona fide targets to prevent drug resistance and relapse. We
uncover that calcitonin receptor-like receptor (CALCRL) is expressed in
RICs, and that the overexpression of CALCRL and/or of its ligand
adrenomedullin (ADM), and not CGRP, correlates to adverse outcome in
AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency,
and sensitizes to cytarabine in patient-derived xenograft models.
Mechanistically, the ADM-CALCRL axis drives cell cycle, DNA repair, and
mitochondrial OxPHOS function of AML blasts dependent on E2F1 and BCL2.
Finally, CALCRL depletion reduces LSC frequency of RICs
post-chemotherapy in vivo. In summary, our data highlight a critical
role of ADM-CALCRL in post-chemotherapy persistence of these cells, and
disclose a promising therapeutic target to prevent relapse in AML.
Leukemic stem cells which are resistant to chemotherapy are proposed as
relapse-initiating cells (RICs). Here, the authors show that targeting
the adrenomedullin-calcitonin receptor-like receptor decreases RICs
frequency improving chemotherapy response in AML preclinical models.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Drug tolerant/resistant leukemic stem cell (LSC) subpopulations may
explain frequent relapses in acute myeloid leukemia (AML), suggesting
that these relapse-initiating cells (RICs) persistent after chemotherapy
represent bona fide targets to prevent drug resistance and relapse. We
uncover that calcitonin receptor-like receptor (CALCRL) is expressed in
RICs, and that the overexpression of CALCRL and/or of its ligand
adrenomedullin (ADM), and not CGRP, correlates to adverse outcome in
AML. CALCRL knockdown impairs leukemic growth, decreases LSC frequency,
and sensitizes to cytarabine in patient-derived xenograft models.
Mechanistically, the ADM-CALCRL axis drives cell cycle, DNA repair, and
mitochondrial OxPHOS function of AML blasts dependent on E2F1 and BCL2.
Finally, CALCRL depletion reduces LSC frequency of RICs
post-chemotherapy in vivo. In summary, our data highlight a critical
role of ADM-CALCRL in post-chemotherapy persistence of these cells, and
disclose a promising therapeutic target to prevent relapse in AML.
Leukemic stem cells which are resistant to chemotherapy are proposed as
relapse-initiating cells (RICs). Here, the authors show that targeting
the adrenomedullin-calcitonin receptor-like receptor decreases RICs
frequency improving chemotherapy response in AML preclinical models. |
He, Tianlin; Mischak, Michaela; Clark, Andrew L; Campbell, Ross T; Delles, Christian; Diez, Javier; Filippatos, Gerasimos; Mebazaa, Alexandre; McMurray, John J V; Gonzalez, Arantxa; Raad, Julia; Stroggilos, Rafael; Bosselmann, Helle S; Campbell, Archie; Kerr, Shona M; Jackson, Colette E; Cannon, Jane A; Schou, Morten; Girerd, Nicolas; Rossignol, Patrick; McConnachie, Alex; Rossing, Kasper; Schanstra, Joost P; Zannad, Faiez; Vlahou, Antonia; Mullen, William; Jankowski, Vera; Mischak, Harald; Zhang, Zhenyu; Staessen, Jan A; Latosinska, Agnieszka Urinary peptides in heart failure: a link to molecular pathophysiology Journal Article In: EUROPEAN JOURNAL OF HEART FAILURE, 0000, ISSN: 1388-9842. @article{ISI:000648062400001,
title = {Urinary peptides in heart failure: a link to molecular pathophysiology},
author = {Tianlin He and Michaela Mischak and Andrew L Clark and Ross T Campbell and Christian Delles and Javier Diez and Gerasimos Filippatos and Alexandre Mebazaa and John J V McMurray and Arantxa Gonzalez and Julia Raad and Rafael Stroggilos and Helle S Bosselmann and Archie Campbell and Shona M Kerr and Colette E Jackson and Jane A Cannon and Morten Schou and Nicolas Girerd and Patrick Rossignol and Alex McConnachie and Kasper Rossing and Joost P Schanstra and Faiez Zannad and Antonia Vlahou and William Mullen and Vera Jankowski and Harald Mischak and Zhenyu Zhang and Jan A Staessen and Agnieszka Latosinska},
doi = {10.1002/ejhf.2195, Early Access Date = MAY 2021},
issn = {1388-9842},
journal = {EUROPEAN JOURNAL OF HEART FAILURE},
abstract = {Aims Heart failure (HF) is a major public health concern worldwide. The
diversity of HF makes it challenging to decipher the underlying complex
pathological processes using single biomarkers. We examined the
association between urinary peptides and HF with reduced (HFrEF),
mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined
based on the European Society of Cardiology guidelines, and the links
between these peptide biomarkers and molecular pathophysiology.
Methods and results Analysable data from 5608 participants were
available in the Human Urinary Proteome database. The urinary peptide
profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and
controls matched for sex, age, estimated glomerular filtration rate,
systolic and diastolic blood pressure, diabetes and hypertension were
compared applying the Mann-Whitney test, followed by correction for
multiple testing. Unsupervised learning algorithms were applied to
investigate groups of similar urinary profiles. A total of 577 urinary
peptides significantly associated with HF were sequenced, 447 of which
(77%) were collagen fragments. In silico analysis suggested that
urinary biomarker abnormalities in HF principally reflect changes in
collagen turnover and immune response, both associated with fibrosis.
Unsupervised clustering separated study participants into two clusters,
with 83% of non-HF controls allocated to cluster 1, while 65% of
patients with HF were allocated to cluster 2 (P < 0.0001). No separation
based on HF subtype was detectable.
Conclusions Heart failure, irrespective of ejection fraction subtype,
was associated with differences in abundance of urinary peptides
reflecting collagen turnover and inflammation. These peptides should be
studied as tools in early detection, prognostication, and prediction of
therapeutic response.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Aims Heart failure (HF) is a major public health concern worldwide. The
diversity of HF makes it challenging to decipher the underlying complex
pathological processes using single biomarkers. We examined the
association between urinary peptides and HF with reduced (HFrEF),
mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined
based on the European Society of Cardiology guidelines, and the links
between these peptide biomarkers and molecular pathophysiology.
Methods and results Analysable data from 5608 participants were
available in the Human Urinary Proteome database. The urinary peptide
profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and
controls matched for sex, age, estimated glomerular filtration rate,
systolic and diastolic blood pressure, diabetes and hypertension were
compared applying the Mann-Whitney test, followed by correction for
multiple testing. Unsupervised learning algorithms were applied to
investigate groups of similar urinary profiles. A total of 577 urinary
peptides significantly associated with HF were sequenced, 447 of which
(77%) were collagen fragments. In silico analysis suggested that
urinary biomarker abnormalities in HF principally reflect changes in
collagen turnover and immune response, both associated with fibrosis.
Unsupervised clustering separated study participants into two clusters,
with 83% of non-HF controls allocated to cluster 1, while 65% of
patients with HF were allocated to cluster 2 (P < 0.0001). No separation
based on HF subtype was detectable.
Conclusions Heart failure, irrespective of ejection fraction subtype,
was associated with differences in abundance of urinary peptides
reflecting collagen turnover and inflammation. These peptides should be
studied as tools in early detection, prognostication, and prediction of
therapeutic response. |
Mouyen, Thomas; Manigold, Thibaut; Collet, Jean-Philippe; Durand, Eric; Barbey, Christophe; Lhermusier, Thibault; Tchetche, Didier; Chollet, Thomas; Mulliez, Aurelien; Motreff, Pascal; Combaret, Nicolas; Souteyrand, Geraud Transcatheter aortic valve thrombosis: Data from a French multicenter
cohort analysis Journal Article In: CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, 0000, ISSN: 1522-1946. @article{ISI:000620222900001,
title = {Transcatheter aortic valve thrombosis: Data from a French multicenter
cohort analysis},
author = {Thomas Mouyen and Thibaut Manigold and Jean-Philippe Collet and Eric Durand and Christophe Barbey and Thibault Lhermusier and Didier Tchetche and Thomas Chollet and Aurelien Mulliez and Pascal Motreff and Nicolas Combaret and Geraud Souteyrand},
doi = {10.1002/ccd.29555, Early Access Date = FEB 2021},
issn = {1522-1946},
journal = {CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS},
abstract = {Objectives To evaluate the effectiveness of anticoagulant therapies in
patients with clinical transcatheter heart valve (THV) thrombosis, to
describe complications, and to assess their risk profile was the
objectives.
Background Little research has been conducted on clinical THV
thrombosis.
Methods Patients with clinical THV thrombosis were identified based on
greater than 50% increased transvalvular gradient on transthoracic
echocardiogram confirmed by 4-dimensional computed tomography,
transesophageal echocardiogram, or regression with anticoagulant
therapy. A cohort free from thrombosis for more than 1,100 days
postprocedure was used for comparison.
Results Fifty-four patients with clinical THV thrombosis were
identified. Most subjects (98.1%) received anticoagulant therapy which was effective (>= 50% reduction in transvalvular gradient or return to
postprocedure value) in 96%. The rate of serious hemodynamic or embolic
complications in the thrombosis population was 31.5%. A multivariate
analysis of subjects with and without thrombosis indicated a
significantly increased risk of thrombosis from preexisting
thrombocytopenia (odds ratio [OR] 9.96), absence of predilatation (OR = 5.67), renal insufficiency (OR = 4.84), and >10 mmHg mean transvalvular gradient postprocedure (OR = 3.36). No recurrence of
thrombosis was identified during on average 685 days follow-up.
Conclusions These data, from one of the largest cohorts with clinical
THV thrombosis confirm anticoagulants appear effective. The rate of
serious associated complications was high. The findings underline the
importance of recognizing risk factors for thrombosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objectives To evaluate the effectiveness of anticoagulant therapies in
patients with clinical transcatheter heart valve (THV) thrombosis, to
describe complications, and to assess their risk profile was the
objectives.
Background Little research has been conducted on clinical THV
thrombosis.
Methods Patients with clinical THV thrombosis were identified based on
greater than 50% increased transvalvular gradient on transthoracic
echocardiogram confirmed by 4-dimensional computed tomography,
transesophageal echocardiogram, or regression with anticoagulant
therapy. A cohort free from thrombosis for more than 1,100 days
postprocedure was used for comparison.
Results Fifty-four patients with clinical THV thrombosis were
identified. Most subjects (98.1%) received anticoagulant therapy which was effective (>= 50% reduction in transvalvular gradient or return to
postprocedure value) in 96%. The rate of serious hemodynamic or embolic
complications in the thrombosis population was 31.5%. A multivariate
analysis of subjects with and without thrombosis indicated a
significantly increased risk of thrombosis from preexisting
thrombocytopenia (odds ratio [OR] 9.96), absence of predilatation (OR = 5.67), renal insufficiency (OR = 4.84), and >10 mmHg mean transvalvular gradient postprocedure (OR = 3.36). No recurrence of
thrombosis was identified during on average 685 days follow-up.
Conclusions These data, from one of the largest cohorts with clinical
THV thrombosis confirm anticoagulants appear effective. The rate of
serious associated complications was high. The findings underline the
importance of recognizing risk factors for thrombosis. |
Charles, Pierre-Yves; Vallet, Marion; la Faille, Renaud De; Merville, Pierre; Lagarde, Severine; Grenier, Nicolas; Lebely, Claire; Lepage, Benoit; Allard, Julien; Kamar, Nassim; Tack, Ivan Impact of menopausal status on kidney adaptation after unilateral
nephrectomy for kidney donation in women Journal Article In: JOURNAL OF NEPHROLOGY, 0000, ISSN: 1121-8428. @article{ISI:000656817500001,
title = {Impact of menopausal status on kidney adaptation after unilateral
nephrectomy for kidney donation in women},
author = {Pierre-Yves Charles and Marion Vallet and Renaud De la Faille and Pierre Merville and Severine Lagarde and Nicolas Grenier and Claire Lebely and Benoit Lepage and Julien Allard and Nassim Kamar and Ivan Tack},
doi = {10.1007/s40620-021-01067-1, Early Access Date = JUN 2021},
issn = {1121-8428},
journal = {JOURNAL OF NEPHROLOGY},
abstract = {Introduction Although living kidney donation is not a high-risk surgery,
there is still a need to identify situations at risk of kidney disease
after uninephrectomy. Estrogens exhibit a protective role against
various nephropathies. The aim of this study was to assess renal
adaptation following nephrectomy according to menopausal status in
women.
Methods A prospective bicentric study including living women donors
measured glomerular filtration rate (GFR) (inulin or Cr51--EDTA
clearances) and kidney volume (using CT-scan and 3-dimensional
reconstruction), before and after 1-year post-uninephrectomy. Renal
adaptation was compared according to menopausal status.
Results Sixteen non-menopausal women and 18 menopausal women were
included. One year following uninephrectomy, the mean decrease in GFR
(global population) was - 32 +/- 12 ml/min/1.73 m(2), and the mean
increase in remnant kidney volume was + 32 +/- 13 cm(3)/1.73 m(2). No
significant difference was observed between the two groups for both the
decrease in GFR (-32.9 +/- 13.3 in non-menopausal vs - 31.5 +/- 9.9 in menopausal, ml/min/1.73 m(2)},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction Although living kidney donation is not a high-risk surgery,
there is still a need to identify situations at risk of kidney disease
after uninephrectomy. Estrogens exhibit a protective role against
various nephropathies. The aim of this study was to assess renal
adaptation following nephrectomy according to menopausal status in
women.
Methods A prospective bicentric study including living women donors
measured glomerular filtration rate (GFR) (inulin or Cr51--EDTA
clearances) and kidney volume (using CT-scan and 3-dimensional
reconstruction), before and after 1-year post-uninephrectomy. Renal
adaptation was compared according to menopausal status.
Results Sixteen non-menopausal women and 18 menopausal women were
included. One year following uninephrectomy, the mean decrease in GFR
(global population) was - 32 +/- 12 ml/min/1.73 m(2), and the mean
increase in remnant kidney volume was + 32 +/- 13 cm(3)/1.73 m(2). No
significant difference was observed between the two groups for both the
decrease in GFR (-32.9 +/- 13.3 in non-menopausal vs - 31.5 +/- 9.9 in menopausal, ml/min/1.73 m(2) |
Bello, Arnaud Del; Zakaroff, Alexia G; Meyer, Nicolas; Delas, Audrey; Faguer, Stanislas; Kamar, Nassim; Belliere, Julie Cytokine storm induced by a PD1 inhibitor in a renal transplant patient Journal Article In: AMERICAN JOURNAL OF TRANSPLANTATION, 0000, ISSN: 1600-6135. @article{ISI:000664749300001,
title = {Cytokine storm induced by a PD1 inhibitor in a renal transplant patient},
author = {Arnaud Del Bello and Alexia G Zakaroff and Nicolas Meyer and Audrey Delas and Stanislas Faguer and Nassim Kamar and Julie Belliere},
doi = {10.1111/ajt.16589, Early Access Date = JUN 2021},
issn = {1600-6135},
journal = {AMERICAN JOURNAL OF TRANSPLANTATION},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Teste, M; Broutin, A; Marty, M; Valera, M C; Cunha, F Soares; Noirrit-Esclassan, E Toothbrushing in children with autism spectrum disorders: qualitative
analysis of parental difficulties and solutions in France Journal Article In: EUROPEAN ARCHIVES OF PAEDIATRIC DENTISTRY, 0000, ISSN: 1818-6300. @article{ISI:000657602300001,
title = {Toothbrushing in children with autism spectrum disorders: qualitative
analysis of parental difficulties and solutions in France},
author = {M Teste and A Broutin and M Marty and M C Valera and F Soares Cunha and E Noirrit-Esclassan},
doi = {10.1007/s40368-021-00640-3, Early Access Date = JUN 2021},
issn = {1818-6300},
journal = {EUROPEAN ARCHIVES OF PAEDIATRIC DENTISTRY},
abstract = {Purpose The oral care of a child with autism spectrum disorders (ASD) is
a challenge, not only for dentists, but also for parents. The objective
of this study was to evaluate the difficulties encountered by parents in
maintaining oral hygiene in autistic children and the solutions they
found to facilitate this daily act.
Methods A questionnaire with closed and open questions about
characteristics of the child and oral health at home, conducted via
Google Form, was sent to French families through 301 associations of
parents with autistic children. For the quantitative analysis, logistic
regression was used. The open answers were analysed by theme.
Results This study included 756 offspring aged 14.4 (+/- 8.1) years.
Girls were 1.7 (95% CI: 1.1-2.8) times more likely to have
toothbrushing difficulty than boys. Nonverbal patients (OR:3.2; 95% CI:
2.2-4.9), autistic patients (OR:2.8; 95% CI: 1.4-5.2), patients using
pictograms (OR:1.6; 95% CI: 1.1-2.4), and younger children (OR:0.9;
95% CI: 0.9-0.9) were significantly more likely to encounter
difficulties in tolerating toothbrushing. The qualitative analysis
showed that parents used three main ways to facilitate toothbrushing:
planning, modelling and making it enjoyable. Seventy-nine percent of
parents did not feel sufficiently informed about the different oral
hygiene prevention tools and techniques for their ASD children and would
like to be educated in the daily management of oral hygiene.
Conclusion The role of parents remains essential and professionals
should work in collaboration with them.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose The oral care of a child with autism spectrum disorders (ASD) is
a challenge, not only for dentists, but also for parents. The objective
of this study was to evaluate the difficulties encountered by parents in
maintaining oral hygiene in autistic children and the solutions they
found to facilitate this daily act.
Methods A questionnaire with closed and open questions about
characteristics of the child and oral health at home, conducted via
Google Form, was sent to French families through 301 associations of
parents with autistic children. For the quantitative analysis, logistic
regression was used. The open answers were analysed by theme.
Results This study included 756 offspring aged 14.4 (+/- 8.1) years.
Girls were 1.7 (95% CI: 1.1-2.8) times more likely to have
toothbrushing difficulty than boys. Nonverbal patients (OR:3.2; 95% CI:
2.2-4.9), autistic patients (OR:2.8; 95% CI: 1.4-5.2), patients using
pictograms (OR:1.6; 95% CI: 1.1-2.4), and younger children (OR:0.9;
95% CI: 0.9-0.9) were significantly more likely to encounter
difficulties in tolerating toothbrushing. The qualitative analysis
showed that parents used three main ways to facilitate toothbrushing:
planning, modelling and making it enjoyable. Seventy-nine percent of
parents did not feel sufficiently informed about the different oral
hygiene prevention tools and techniques for their ASD children and would
like to be educated in the daily management of oral hygiene.
Conclusion The role of parents remains essential and professionals
should work in collaboration with them. |