Impact of Left Ventricular Diastolic Dysfunction on Lung Transplantation Outcome in Patients With Pulmonary Arterial Hypertension.

Diastolic dysfunction may influence perioperative outcome, early graft function, and long-term survival. We compared the outcomes of double lung transplantation (DLTx) for patients with pulmonary arterial hypertension (PAH) with preoperative left ventricular (LV) diastolic dysfunction with the outcomes of patients without diastolic dysfunction. Of 116 consecutive patients with PAH (who underwent transplantation between January 1995 and December 2013), 44 met our inclusion and exclusion criteria. Fourteen (31.8%) patients with diastolic dysfunction pretransplantation had a higher body mass index (29 [IQR 21.5-32.6] vs 22.4 [IQR 19.9-25.3] kg/m2 ) and mean pulmonary arterial pressure (54.6 ± 10 mmHg vs 47 ± 11.3 mmHg) and right atrial pressure (16.5 ± 5.2 mmHg vs 10.6 ± 5.2 mmHg). The patients received extracorporeal life support more frequently (33% vs 7% [p = 0.02]), had worse APACHE II scores (21.7 ± 7.4 vs 15.3 ± 5.3 [p = 0.02]), and a trend toward worse ventilator-free days (2.5 [IQR 6.5-32.5] vs 17 [IQR 3-23] [p = 0.08]). There was no effect on development of primary graft dysfunction or intensive care unit/hospital survival. One-year survival was worse (hazard ratio [HR] 4.45, 95% confidence interval [CI] 1.3-22, p = 0.02). Diastolic dysfunction was the only variable that correlated with overall survival (HR 5.4, 95% CI 1.3-22, p = 0.02). Diastolic dysfunction leads to early postoperative morbidity and worse survival in patients with PAH after DLTx.

Beneficial effect of Lactococcus lactis NCC 2287 in a murine model of eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a severe inflammatory disease of the esophagus which is characterized histologically by an eosinophilic infiltration into the esophageal tissue. The efficacy of probiotics in the context of atopic diseases has been well investigated but, to date, there has been no study which has evaluated probiotic effects on EoE inflammation. This study sought to identify a probiotic which improves esophageal inflammation in experimental EoE. METHODS: Two candidate probiotics, Lactococcus lactis NCC 2287 and Bifidobacterium lactis NCC 2818, were tested in a murine model of EoE elicited by epicutaneous sensitization with Aspergillus fumigatus protein extract. Administration of bacterial strains in drinking water was used, respectively, as a preventive or treatment measure, or continuously throughout the study. Inflammatory parameters were assessed in the esophagus, skin, and lungs after allergen challenge. RESULTS: In this EoE model, supplementation with L. lactis NCC 2287 significantly decreased esophageal and bronchoalveolar eosinophilia but only when given as a therapeutic treatment. No significant effect on eosinophilia was observed when NCC 2287 was given as a preventive or a continuous intervention. NCC 2287 supplementation had no significant effect on immunoglobulin levels, skin symptom scores, or on transepidermal water loss. Supplementation with another probiotic, B. lactis NCC 2818, had no significant effect on esophageal eosinophilia. CONCLUSION: We identified a L. lactis strain, able to attenuate esophageal eosinophilic inflammation in a preclinical model of EoE. This effect is strain specific and depends on the timing and duration of bacterial supplementation. Confirmation of these observations in human clinical trials is warranted.

Survival in sensitized lung transplant recipients with perioperative desensitization.

Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients.

Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion.

The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context.

Anatomical correlations of the international 10-20 sensor placement system in infants.

Developmental research, as well as paediatric clinical activity crucially depends on non-invasive and painless brain recording techniques, such as electroencephalography (EEG), and near infrared spectroscopy (NIRS). However, both of these techniques measure cortical activity from the scalp without precise knowledge of the recorded cerebral structures. An accurate and reliable mapping between external anatomical landmarks and internal cerebral structures is therefore fundamental to localise brain sources in a non-invasive way. Here, using MRI, we examined the relations between the 10-20 sensor placement system and cerebral structures in 16 infants (3-17 weeks post-term). We provided an infant template parcelled in 94 regions on which we reported the variability of sensors locations, concurrently with the anatomical variability of six main cortical sulci (superior and inferior frontal sulcus, central sulcus, sylvian fissure, superior temporal sulcus, and intraparietal sulcus) and of the distances between the sensors and important cortical landmarks across these infants. The main difference between infants and adults was observed for the channels O1-O2, T5-T6, which projected over lower structures than in adults. We did not find any asymmetry in the distances between the scalp and the brain envelope. However, because of the Yakovlean torque pushing dorsally and frontally the right sylvian fissure, P3-P4 were not at the same distance from the posterior end of this structure. This study should help to refine hypotheses on functional cognitive development by providing an accurate description of the localization of standardised channels relative to infants' brain structures. Template and atlas are publicly available on our Web site (http://www.unicog.org/pm/pmwiki.php/Site/InfantTemplate).

[Studying dysfunctional personality trends among sex offenders]. / Étude des tendances dysfonctionnelles de la personnalité chez des auteurs d'infractions sexuelles.

OBJECTIVE: A review of the literature reveals a consensus on the high prevalence of personality disorders among sexual offenders. Studies show that there is no unique personality profile for sex offenders. In France, little research has been conducted on this population with standardized assessment tools. The objective of the present study is to identify the distribution of personality disorders among sexual offenders using a new French questionnaire, i.e. the TD12. In view of the literature, we postulate that this tool will identify the diversity of personality disorders observed by various authors, but with a higher proportion of cluster B disorders. METHODOLOGY: This study was conducted among 56 men, including 28 sex offenders aged from 21 to 70 years old, and a control group of 28 men without psychiatric disorders. The sex offenders in this study are men convicted or charged with sex offenses of various kinds: exhibitionism, the recording, distribution and possession of pornography depicting minors, aggravated corruption of a minor, sexual assault of a minor, or rape of a minor. They were examined using an inventory of dysfunctional trends recently developed by Rolland and Pichot with the aim of assessing dysfunctional personality styles. The TD-12 questionnaire is composed of 140 items describing thoughts, feelings and behaviors. It is based on the diagnostic criteria of Axis II of DSM IV-TR and consists of twelve scales that match the personality disorders described in this diagnostic manual (ten officially recognized disorders and two additional disorders). RESULTS: From a categorical viewpoint, results indicate rigid dysfunctional trends with regard to avoidant personality disorder in sex offenders compared to the control group (Chi(2)=9.16; P=0.005). However, there were no significant differences between the two groups regarding the number of rigid dysfunctional trends. Potentially controllable dysfunctional personality trends are identified for the dependent personality (Chi(2)=6.72; P=0.02) and the depressive personality (Chi(2)=9.63; P=0.004). Moreover, the results show differences related to type of crime. The mean score on the Docile-Dependent scale is higher among subjects who had only downloaded images of child pornography (n=8) compared to subjects who had committed at least one sexual offense against a victim (n=20) (58.75±8.43 versus 49.55±11.66, P=0.04). CONCLUSION: These results are somewhat in contradiction with previous studies. The often described cluster B personalities are not significantly observed in this study. These results show the prevalence of avoidant personality disorder, which in fact corresponds to a clinically observed sex offender profile characterized by inhibition, relationship difficulties with adults, fear of being judged or rejected, and social isolation. The study also shows the value of considering the personality profile in relation to the modus operandi. It is important to continue this research on larger groups in order to refine the results.

ABO-incompatible lung transplantation in an infant.

Waitlist mortality continues to be a limiting factor for all solid-organ transplant programs. Strategies that could improve this situation should be considered. We report the first ABO-incompatible lung transplantation in an infant. The recipient infant was ABO blood group A1 and the donor group B. The recipient was diagnosed with surfactant protein B deficiency, which is a fatal condition and lung transplantation is the only definitive therapy. At 32 days of age, a bilateral lung transplantation from a donation after cardiac death (DCD) donor was performed. Intraoperative plasma exchange was the only preparatory procedure performed. No further interventions were required as the recipient isohemagglutinins were negative before transplant and have remained negative to date. At 6 months posttransplant, the recipient is at home, thriving, with normal development. This outcome suggests that ABO-incompatible lung transplantation is feasible in infants, providing another option to offer life-saving lung transplantation in this age range.

Validation of the spontaneous lateral laxity sign for radial collateral ligament sprain of the metacarpophalangeal joint of the fingers: Anatomical study.

Severe collateral ligament sprain of the metacarpophalangeal joint (MCP) of the fingers is rare. Clinical examination is mandatory to diagnose severity. The purpose of our study was to validate a clinical sign for MCP joint laxity: the spontaneous lateral laxity sign (SLLS), recently described by Meyer et al. to diagnose severe MCP radial collateral ligament (RCL) sprain, with a comparison with the already validated rotational laxity test (RLT). SLLS and RLT were assessed before RCL transection, after RCL transection and after RCL repair on 40 long fingers in 10 fresh thawed cadavers. SLLS was performed with the elbow on the table, wrist in 70° flexion, in neutral pronation-supination, hands drooping passively with the dorsal side toward the examiner and the ulnar side toward the table. The MCP joints were at rest, in passive slight extension. Positive results were defined as an overlap of the damaged finger on the next, or as an increased abduction of the little finger. Correlation between the two tests was calculated. SLLS was positive in 0% of cases before RCL transection, 100% after transection and 0% after repair. Mean arcs of pronation and supination on RLT were 16 and 19.5 mm before section, 24 and 33 mm after section (52% and 69% increase compared to preoperative data), and 17 and 21 mm after repair (7% and 8% increase). Correlation between the two tests was 100%. The spontaneous lateral laxity sign is a simple and reliable clinical sign for diagnosing complete long-finger MCP RCL tears requiring surgery. LEVEL OF EVIDENCE: : III, case-control study.

Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation.

Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation. We have recently demonstrated a feasible technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37 degrees C with Steen solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO(2) 531 +/- 43 vs. 244 +/- 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens-1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery.

Neoadjuvant aortic endografting.

The advent and success of endovascular repair of abdominal aneurysms led to the development of catheter-based techniques to treat thoracic aortic pathology. Such diseases, including thoracic aortic aneurysms, acute and chronic type B dissections, penetrating aortic ulcers, and traumatic aortic transection, challenge surgeons to perform complex open operative repairs in high-risk patients. The minimally invasive nature of thoracic endografting provides an attractive alternative therapy. We present two cases of covered stent grafts deployed in the thoracic aorta to perform resection of the aortic wall infiltrated by malignancy in order to avoid a major vascular intervention and a traditional vascular graft interposition. This may become a potential new utility for aortic endografts.

Surgical treatment of celiac artery aneurysm associated with median arcuate ligament.

Celiac artery aneurysms are rare but potentially fatal because of the risk of rupture. Atherosclerosis and fibrous dysplasia are the two most common etiologies. Median arcuate ligament compression of the celiac artery is common but usually asymptomatic. We report three cases of post-stenotic celiac artery aneurysm with median arcuate ligament compression admitted to our hospital over the past two years. Although the incidence is rare with only 8 cases reported in the literature, a median arcuate ligament may have a role in the development of celiac artery aneurysms and its presence can influence the surgical strategy.

Impact of human donor lung gene expression profiles on survival after lung transplantation: a case-control study.

Primary graft dysfunction (PGD) continues to be a major cause of early death after lung transplantation. Moreover, there remains a lack of accurate pretransplant molecular markers for predicting PGD. To identify distinctive donor lung gene expression signatures associated with PGD, we profiled human donor lungs using microarray technology prior to implantation. The genomic profiles of 10 donor lung samples from patients who subsequently developed clinically defined severe PGD were compared with 16 case-matched donor lung samples from those who had a favorable outcome without PGD (development set, n = 26). Selected PCR validated predictive genes were tested by quantitative reverse transcription-polymerase chain reaction in an independent test set (n = 81). Our microarray analyses of the development set identified four significantly upregulated genes (ATP11B, FGFR2, EGLN1 and MCPH1) in the PGD samples. These genes were also significantly upregulated in donor samples of the test set of patients with poor outcomes when compared to those of patients with good outcomes after lung transplantation. This type of biological donor lung assessment shows significant promise for development of a more accurate diagnostic strategy to assess donor lungs prior to implantation.

Nonintegrative transformation in the filamentous fungus Podospora anserina: stabilization of a linear vector by the chromosomal ends of Tetrahymena thermophila.

The effect of the chromosomal ends of Tetrahymena thermophila on the stability of linear transforming molecules in the filamentous fungus Podospora anserina was tested. A derivative of an integrative vector for this fungus has been constructed, so that after linearization, the ends of the plasmid are the telomeric sequences of T. thermophila. After transformation, this linear molecule was maintained as an extrachromosomal plasmid with no integrated copies in about 50% of the transformants. Under selective conditions, there was approximately one linear molecule per 5 to 10 nuclei, and these extrachromosomal molecules were rapidly lost under nonselective conditions. The circular plasmid carrying an inverted repeat of T. thermophila telomeres could be linearized and processed in vivo.

Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. AIMS: To measure lymphatic vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to adenocarcinoma and determine whether LVD can predict the risk of cancer. In addition, to correlate LVD with lymph node metastasis and assess whether LVD could be used as a prognostic indicator for outcome or survival. METHODS: LVD and microvascular density (MVD) were assessed after immunohistochemical staining of vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were correlated with clinicopathological features. RESULTS: LVD was significantly reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical outcome; however, patients who had either lymph node metastasis or invasion of tumour cells into peritumorous lymphatic vessels had a significantly worse overall survival. MVD was also assessed as a prognostic marker; its increase appeared to be linked more with the development of Barrett's metaplasia than adenocarcinoma. CONCLUSIONS: The reduction in lymphatic vessel numbers was not useful for determining disease outcome in the patient group studied. It is the entry of tumour cells into pre-existing peritumorous lymphatic vessels that confers a significantly worse overall survival.

[Instrumental delivery with perineum-fetal head distance >55 MM on ultrasound]. / Extraction instrumentale sur une hauteur de présentation supérieur à 55mm à l'échographie transpérinéale.

OBJECTIVE: Compare the issue of an operative vaginal delivery associated to the fetal presentation diagnosed by transperineal ultrasound. Three groups were formed: ≥55 mm, between 45 and 55 mm, and <45 mm. METHODS: A monocentric prospective study on 108 patients has been conducted between April 2011 and August 2014. The distance between perinea and skull has been analyzed to compare the success of operative vaginal delivery considering the level of the fetal presentation in the pelvic cavity. RESULTS: The failed operative vaginal deliveries are more frequent while the fetal head is above 55 mm (16.7%) or while the fetal head is between 45 and 55 mm (9.1%) than while the fetal skull is under 45 mm (1.8%) (P=0.04). However there is no significant difference for the fetal shoulder dystocia (5.6% vs 3.0% vs 3.5%, P=0.5), nor for the newborn outcomes (16.7 vs 15.2 vs 14; P=0.9). CONCLUSION: Despite the high rate of failed operative vaginal delivery above 55 mm, it should be considered not to prohibit but send free to the obstetrician appreciation.

A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.

OBJECTIVE: Complement activation has been shown to play a significant role in ischemia-reperfusion injury after lung transplantation. TP-10 (soluble complement receptor 1 inhibitor) inhibits the activation of complement by inactivating C3a and C5a convertases. This was a clinical trial of TP-10 to reduce ischemia-reperfusion injury in lung transplantation. METHODS: In a randomized, double-blinded, multicenter, placebo-controlled trial, 59 patients from four lung transplant programs received TP-10 (10 mg/kg, n = 28) or placebo (n = 31) before reperfusion. This dose achieved 90% complement inhibition for 24 hours, and activity had returned toward normal by 72 hours. RESULTS: At 24 hours, 14 of 28 patients in the TP-10 group (50%) were extubated, whereas only 6 of 31 patients in the placebo group (19%) were (P = .01). The total times on the ventilator and in the intensive care unit both tended to be shorter in the TP-10 group, but these differences did not achieve statistical significance. Among patients requiring cardiopulmonary bypass (n = 5 in placebo group and n = 7 in TP-10 group), the mean duration of mechanical ventilation was reduced by 11 days in the TP-10 group (10.6 +/- 5.0 days vs 21.5 +/- 5.9 days in placebo group, P = .2). Operative deaths, incidences of infection and rejection, and length of hospital stay were not significantly different between the two groups. CONCLUSIONS: Short-term complement inhibition with TP-10 led to early extubation in a significantly higher proportion of lung transplant recipients. The effect of TP-10 was greater among patients undergoing cardiopulmonary bypass, with a large reduction in ventilator days. Complement inhibition thus significantly decreases the duration of mechanical ventilation and could be useful in improving the outcome of lung transplant recipients.

In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat.

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 x 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIO2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (PaO2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (PaO2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher PaO2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05) compared with the other groups. rTNF-alpha and INF-gamma were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.

Immunochemical studies of guinea pig progesterone-binding plasma protein.

An antiserum specific for guinea pig progesterone-binding plasma protein (PBP) has been prepared. Using a very sensitive immunoenzymatic assay, PBP could be detected not only in pregnant guinea pig plasma (970 microgram/ml of plasma at day 40--60 of pregnancy), but also in the plasma of fetuses (2.77 micrograms/ml), umbilical arteries (1.79 micrograms/ml), umbilical vein (2.90 micrograms/ml), and in amniotic fluid (0.47 microgram/ml). The protein was also found in low concentration in the plasma of nonpregnant females (2.10 micrograms/ml) and males (1.56 micrograms/ml). The antiserum was used to search for immunological similarities between various steroid-binding proteins. No cross reaction was found with cavian or human corticosteroid-binding globulin and human sex steroid-binding plasma protein. There was no cross reaction between guinea pig PBP and PBP of other pregnant hystricomorphs (viscacha, degu, and coypu). Moreover, no evidence was found of an interaction between guinea pig uterine progesterone receptor and the anti-PBP antiserum.