Objectives. Conservative management of patients with flail chest is the treatment of choice. Rib fracture repair is technically challenging; however, with the advent of specially designed molding ...titanium clips, surgical management has been simplified. Surgical stabilization has been used with good outcomes. We are reporting on our institutional matched-case-control study. Methods. Between April 2010 and April 2011, ten polytraumatized patients undergoing rib stabilization for flail chest were matched 1 : 1 to 10 control patients by age ±10 years, sex, neurological or vertebral trauma, abdominal injury, and arm and leg fractures. Surgery was realized in the first 48 hours. Results. There were no significant differences between groups for matched data and prognostic scores: injury severity score, revised trauma score, and trauma injury severity score. Ventilator time (142 ± 224 versus 74 ± 125 hours, P=0.026) and overall hospital stay (142 ± 224 versus 74 ± 125 hours, P=0.026) were significantly lower for the surgical group after adjustment on prognostic scores. There was a trend towards shorter ICU stay for operative patients (12.3 ± 8.5 versus 9.0 ± 4.3 days, P=0.076). Conclusions. Rib fixation with Stracos is feasible and decreases the length of ventilation and hospital stay. A multicenter randomized study is warranted so as to confirm these results and to evaluate impact on pulmonary function status, pain, and quality of life.
Full text
Available for:
DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
This study of the efficiency and the safety of amniotic fluid‐derived mesenchymal stem cell infusion in a preclinical porcine model of renal autotransplantation showed improved glomerular and tubular ...functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The highly translational porcine model used for this study is a powerful tool to assess safety and feasibility of stem cell‐based therapies in the field of solid organ transplantation.
It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid‐derived mesenchymal stem cells (af‐MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti‐inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self‐renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af‐MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af‐MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af‐MSCs in the renal artery 6 days after transplantation. The af‐MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af‐MSC‐based therapies in human kidney transplantation.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
TRPC6 plays important human physiological functions, notably in artery and arterioles constriction, in regulation of vascular volume and in bronchial muscle constriction. It is implicated in ...pulmonary hypertension, cardiovascular disease, and focal segmental glomerulosclerosis and seems to play a role in cancer development. Previously, we identified Guanabenz, an α2-adrenergic agonist used for hypertension treatment (Wytensin®), as an activator of calcium-dependent chloride channels (CaCC) in human Cystic Fibrosis (CF) nasal epithelial cells by transiently increasing Ca2+i via an influx of extracellular Ca2+. In this study, using assays to measure chloride channel activity, we show that guanabenz is an activator of CaCC in freshly dissociated human bronchial epithelial cells from three CF patients with various genotypes (F508del/F508del, F508del/R1066C, F508del/H1085R). We further characterised the effect of guanabenz and show that it is independent of α-adrenergic receptors, is inhibited by the TRPC family inhibitor SKF-96365 but not by the TRPV family inhibitor ruthenium red. Using western-blotting, Ca2+ measurements and iodide efflux assay, we found that TRPC1 siRNA has no effect on guanabenz induced responses whereas TRPC6 siRNA prevented the guanabenz-dependent Ca2+ influx and the CaCC-dependent activity stimulated by guanabenz. In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a α2-adrenergic-independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
Background
Human cardiac stem cells expressing the W8B2 marker (W8B2
+
CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth ...muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported.
Methods
The objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2
+
CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2
+
CSCs into cardiac myocytes.
Results
Our results show an entirely different electrophysiological genomic profile between W8B2
+
CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2
+
CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations.
Conclusions
Taken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.
We developed a glucuronide prodrug of the potent monomethylauristatin E (MMAE). This prodrug is significantly less toxic than the parent drug. However, in the presence of β-glucuronidase the prodrug ...leads to the efficient release of MMAE thereby triggering a subnanomolar cytotoxic activity against several cancer cell lines. Preliminary in vivo experiments conducted in C57BL/6 mice bearing a subcutaneous murine Lewis Lung Carcinoma (LLC) demonstrated the potential of this targeting system for the selective treatment of solid tumors.
The glucuronide prodrug 1 of the potent monomethylauristatin E (MMAE) was synthesized and evaluated as a potential selective antitumor agent for the treatment of solid tumors. Display omitted
•Synthesis of the first glucuronide prodrug of the potent monomethylauristatin E.•Efficient release of the drug upon enzymatic activation.•Subnanomolar cytotoxic activity against several cancer cell lines.•Significant cytotoxic effect on primary cultures of patients with lung cancer.•Significant antitumor effect without overt toxicity in vivo.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still ...lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients.
We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1 s (FEV
) or diffusing capacity of the lung for carbon monoxide (
) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients.
Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV
and
above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV
and/or preoperative
below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%)
1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10%
3.18% respectively).
By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV
or
below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.
We describe the replacement of a single cusp in two patients with severe aortic regurgitation due to endocarditis with a one third stentless bioprosthesis, with excellent results in both.
Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue ...destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Trimetazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241-2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495-504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1alpha) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage.
We describe the case of a 57-year-old woman with noncompaction of the left ventricle and regurgitant bicuspid aortic valve who presented with progressive congestive heart failure and was successfully ...treated with aortic root replacement. The long-term outcome for these patients is poor because of progressive left ventricular impairment, increased rates of life-threatening arrhythmias, and intraventricular thrombi. To our knowledge, only 3 patient with noncompaction of the left ventricle has been reported to have undergone aortic valve replacement for severely regurgitant bicuspid aortic valve. Herein, we describe a patient with noncompaction of the left ventricle who underwent successful mechanical aortic root replacement.
PDF
