Importance of support groups to the health and well-being of vulnerable children and young people living with HIV: a case study of the Kids Clubs program in Haiti.

BACKGROUND: Although access to antiretroviral therapy (ART) among children and young people living with HIV has increased in recent years, adherence to medication and viral suppression remain challenges. Evidence of benefits of support groups is growing and reflects a range of models and approaches. Since 2014, hospital-linked psychosocial support groups for children and young people living with HIV, known as Kids Clubs, have been established throughout Haiti. The program provides safe spaces for them to meet with peers, supports medication adherence, delivers health and life skills education, and facilitates linkages with clinic visits and social services. This study describes program enrollment and participant engagement, ART adherence and viral suppression among participants, and other outcomes attributed to the program by participants, caregivers, and program implementers. METHODS: Our mixed methods study included quantitative analysis of program monitoring data on rollout and attendance, and medication adherence and viral load results extracted from medical records. We collected qualitative data from club members, caregivers, and implementers about their experiences with the clubs and the impact of participation. RESULTS: From January 2014-December 2018, 1330 individuals aged 8-29 were enrolled in the program; over three-quarters participated for at least 12 months. In 2018, 1038 members attended at least one club meeting; more than half missed three or fewer monthly meetings. Three-quarters of ever-enrolled members reported consistent medication use at their most recent clinic visit; 64.2% (600/935) of those with a recent viral load test were virally suppressed. Level of club attendance was positively associated with ART adherence (p < 0.01) and viral suppression (p < 0.05). Club members, caregivers, and implementers noted the value of the clubs to participants' retention in care and medication adherence, health knowledge, and capacity to deal with peer pressure, stigma, shyness, and depression. CONCLUSIONS: The Kids Club program has been successful in scaling HIV support services to highly vulnerable children and young people through peer-based groups, and program participation has led to a range of benefits. Efforts to innovate, evaluate, and scale support strategies for vulnerable young populations must be accelerated in order to ensure that they survive, thrive, and reach their full potential.

Which Knots Are Recommended in Laparoscopic Surgery and How to Avoid Insecure Knots.

STUDY OBJECTIVE: To investigate why security of identical knot sequences is variable and how to avoid occasionally insecure knots. DESIGN: A factorial design was used to assess factors affecting the security of half knot (H) and half-hitch (S) knot combinations. The effect of tying forces and the risk factors to transform H knots into S knots were investigated. The risk factors evaluated were as follows: starting with an H1 or H2 instead of an H3 knot, inexperience, short sutures, and monomanual knot tying. Security of transformed knots, S2S1 and S2S2 knots, and their recuperation with 2 additional half hitches, SSb or SbSb, were evaluated. SETTING: Training center for laparoscopic suturing. PATIENTS: Not applicable. INTERVENTIONS: Security of knots was evaluated in vitro. MEASUREMENTS AND MAIN RESULTS: The forces that caused knot combinations to open before breaking of the suture were used to calculate the risk of opening with low forces. Tying more strongly increased the security of half knots (H2H1sH1s) (p <.02) and half hitches (p <.001). The forces needed to transform an H3 into an S3 are higher than those for an H2 (p <.001), and the risk increases when the surgeon is inexperienced (p <.001), when sutures are short (p <.001), and when monomanual knot tying (p <.001) is used. Inadvertently made S2S1 and S2S2 knots are dangerous, with the exception of the symmetric S2S2, which is stable. Unstable knots such as S2S1a and S2S2a knot combinations improve with 2 additional blocking half hitches (SbSb), but S2S2aSbSb remains occasionally insecure. CONCLUSION: To reduce the risk of accidentally transforming a first H into an S knot, it is recommended to start with an H3, tie with force, avoid short sutures, and use bimanual suturing. This permits the recommendation to use preferentially H3H2 knots or 5 half hitches (SSSbSbSb). When in doubt, half knot combinations should be secured with at least 2 blocking half hitches.

What is the Best Surgeon's Knot? Evaluation of the Security of the Different Laparoscopic Knot Combinations.

STUDY OBJECTIVE: To investigate the security of various knot combinations in laparoscopic surgery. DESIGN: Prospective nonrandomized trial (Canadian Task Force classification II). SETTING: Storz Training Centre, Sao Paulo, Brazil. INTERVENTION: Different knot combinations (n = 2000) were performed in a laparoscopic trainer. Dry or wet 2.0 polyglycolic acid or dry 2-0 poliglecaprone 25 was used. The tails were cut at 10 mm, and the loops were tested in a dynamometer. The primary endpoints were the forces at which the knot combination opened or at which the suture broke. Resulting tail lengths were measured. MEASUREMENTS AND MAIN RESULTS: Surprisingly, the combination of a 2-throw half knot (H2) and a symmetric 1-throw half knot (H1s) (a surgical flat knot) opened at <1 Newton (N) in 2.5% of tests and at <10 N in 5% of tests. This occasional opening at low forces persisted after 1 or 2 additional H1s knots. A sequence of an H2 or a 3-throw half knot (H3) followed by a H2, either symmetric or asymmetric (H2H2 or H3H2), resulted in 100% secure knots that never opened at forces below 30 N. Other safe combinations were H2H1s followed by 2 blocking half hitches, and a sequence of 5 half hitches with 3 blocking sequences. CONCLUSION: A traditional surgical knot (H2H1s) occasionally opens with little force and thus is potentially dangerous. Safe knots are H2H2 and H3H2 combinations, a sequence of 5 half hitches with 3 blocking sequences, and H2H1s together with 2 blocking half hitches.

Predicting formation of adhesions after gynaecological surgery: development of a risk score.

PURPOSE: Risk factors for post-surgical adhesions following gynaecological surgery have been identified, but their relative importance has not been precisely determined. No practical tool exists to help gynaecological surgeons evaluate the risk of adhesions in their patients. The purpose of the study was to develop an Adhesion Risk Score to provide a simple tool that will enable gynaecological surgeons to routinely quantify the risk of post-surgical adhesions in individual patients. METHODS: A group of European gynaecological surgeons searched the literature to identify the risk factors and the surgical operations reported as carrying a risk of post-surgical adhesions. Through consensus process of meetings and communication, a four-point scale was then used by each surgeon to attribute a specific weight to each item and collective agreement reached on identified risk factors and their relative importance to allow construct of a useable risk score. RESULTS: Ten preoperative and 10 intraoperative risk factors were identified and weighed, leading to the creation of two sub-scores to identify women at risk prior to and during surgery. The Preoperative Risk Score can range from 0 to 36, and the Intraoperative Risk Score from 3 to 31. Several thresholds between these limits may be used to identify women with low, medium, and high risk of post-surgical adhesions. CONCLUSIONS: Gynaecological surgeons are encouraged to use this Adhesion Risk Score to identify the risk of adhesions in their patients. This will allow better informed use of available resources to target preventive measures in women at high risk of post-surgical adhesions.

Conditioning of the abdominal cavity reduces tumor implantation in a laparoscopic mouse model.

PURPOSE: The addition of 4 % O2 and 10 % N2O to the CO2 pneumoperitoneum (PP), together with slight cooling and humidification (conditioning), contributes to reducing adhesions by preventing mesothelial damage. We investigated the effect of peritoneal damage during laparoscopy on tumor implantation. METHODS: In Experiment 1, different tumor cell concentrations were injected into control mice without PP and into mice with 60-min dry CO2PP (mesothelial damage). In Experiment 2, tumor cells were injected into control mice (group I) and in mice with mesothelial damage (group II). In groups III to VI, mesothelial damage was decreased by adding humidification, humidification + 10 % N2O, humidification + 10 % N2O + 4 % O2, and conditioning, respectively. RESULTS: In Experiment 1, the tumors increased with the number of cells injected and with mesothelial damage in the abdominal cavity (p = 0.018) and abdominal wall (p < 0.0001). Experiment 2 confirmed that 60 min of dry CO2PP increased the number of tumors in the abdominal cavity and wall (p = 0.026 and p = 0.003, respectively). The number of tumors was decreased in the abdominal cavity by conditioning (p = 0.030) and in the abdominal wall using humidified CO2 (p = 0.032) or conditioning (p = 0.026). CONCLUSIONS: Tumor implantation was enhanced by peritoneal damage (60 min of dry CO2PP and desiccation), but this was prevented by conditioning. If confirmed in humans, conditioning would become important for oncologic surgery.

Segmental Rectum Resection for Deep Endometriosis and Excision Similarly Improve Sexual Function and Pain.

Segmental rectum resections for indications other than endometriosis were reported to result in up to 40% sexual dysfunctions. We, therefore, evaluated sexual function after low bowel resection (n = 33) for deep endometriosis in comparison with conservative excision (n = 23). Sexual function was evaluated with the FSFI-19 (Female Sexuality Functioning Index) and EHP 30 (Endometriosis Health Profile). The pain was evaluated with visual analogue scales. Linear excision and bowel resections improved FSFI, EHP 30, and postoperative pain comparably. By univariate analysis, a decreased sexual function was strongly associated with pain both before (p < 0.0001) and after surgery (p = 0.0012), age (p = 0.05), and duration of surgery (p = 0.023). By multivariate analysis (proc logistic), the FSFI after surgery was predicted only by FSFI before or EHP after surgery. No differences were found between low bowel segmental resection and a more conservative excision. In conclusion, improving pain after surgery can explain the improvement in sexual function. A deleterious effect of a bowel resection on sexual function was not observed for endometriosis. Sexual function in women with endometriosis can be evaluated using a simplified questionnaire such as FSFI-6.

Genetic Predisposition of Postoperative Adhesions Varies in Substrains of BALB/c Mice.

Postoperative adhesions are a major clinical problem because of the associated infertility, chronic pain, bowel obstruction, and the associated costs. Variability in adhesion formation was suggested by clinical observations that apparently similar interventions can cause little to severe adhesions. This is supported by the presence of polymorphisms and genetic predisposition to develop adhesions in animal models and humans. We previously demonstrated differences in postoperative adhesions between different mouse strains. In this study, we aimed to investigate the variability in adhesion formation in inbred substrains of BALB/c mice. Since genetic differences in inbred substrains are minimal, they might be an opportunity to tackle the genetics of adhesion formation.

Laparoscopic ureteral repair in gynaecological surgery.

PURPOSE OF REVIEW: To review laparoscopic surgery in the treatment options for ureteral lesions in gynaecological surgery. RECENT FINDINGS: Laparoscopic treatment of ureteral injuries has been increasingly reported over the past years. Treatment has progressively shifted from ureteroneocystostomy performed by laparotomy to less invasive treatment options such as ureteral stenting or dilatation in case of stricture, stenting under laparoscopic guidance and laparoscopic stitching of lacerations, laparoscopic ureteral reanastomosis or laparoscopic ureteroneocystostomy for transections. Deep endometriosis surgery of an associated hydronephrosis is associated with a high incidence of ureteral lesions making preoperative stenting desirable in order to facilitate the eventual repair, while avoiding the more problematic insertion of a stent after a lesion is made.The available data confirm the excellent outcome of stenting obstructive lesions. When stenting proves difficult or in case of a ureteral leakage, laparoscopic aided stenting is strongly suggested, in order to avoid further damage while permitting simultaneous repair if necessary. Laparoscopic suturing of a laceration over a stent is clearly superior to stenting only. Results of ureteral reanastomosis of a transected ureter vary from 88 to 100%; an occasional subsequent stenosis can be treated with dilatation. Bladder reimplantation has become feasible by laparoscopy and results seem promising. Laparoscopic bladder reimplantation is suggested as the method of choice in case of failure of a previous laparoscopic treatment. SUMMARY: Data strongly support laparoscopy as the method of choice for the management of ureteral lesions.

Pneumoperitoneum induced mesothelial cell changes in a laparoscopic mouse model.

BACKGROUND: CO2 pneumoperitoneum (PP) during laparoscopic surgery, can cause hypoxia and desiccation in the peritoneal mesothelial cell, resulting in a time-dependent retraction and bulging of these cells, an acute inflammatory reaction and enhanced adhesion formation. Since hypoxia is prevented by adding 4% of oxygen (O2) to the CO2 PP, the aim of this study was to evaluate the effect of adding 4% O2 to the CO2 PP on mesothelial cell morphology. METHODS: In a standardized laparoscopic mouse model (n=8 mice per group), a control group with a 30- or 60-min PP with humidified CO2 + 4% of O2 (groups I and II) was compared to a hypoxic group with 30- or 60-min humidified pure CO2 (groups III and IV) and a desiccation group with 60-min of dry CO2 PP (group V). The effect upon the peritoneum morphology was evaluated by scanning electron microscopy (SEM) of abdominal wall peritoneal biopsies. Biopsies, taken immediately (n=4) and 24 hrs (n=4) after surgery, were compared to a group without PP (group VI, n=4). SEM pictures were blindly scored for cell retraction, deletion of microvilli, fibrin deposition, holes in the epithelial layer and visibility of cell borders using a semi-quantitative scoring system. RESULTS: PP Hypoxia (CO2 PP) has a deleterious effect upon mesothelial morphology, immediately (holes: p= 0.04) and 24 hrs later (cell retraction: p=0.005; total score: p=0.03) . Desiccation has also a deleterious effect immediately (microvilli p=0.0090; fibrin deposition p=0.05) and 24 hrs after surgery (cell retraction: p=0.0036; holes: p=0.0004; microvilli: p< 0.0001, fibrin deposition: p=0.0225; borders: p=0.0007). This deleterious effect increases with duration of CO2 PP, affecting cell retraction (p=0.016), holes (p=0.0441), and the total score (p=0.0488). The addition of 4% of O2 to the CO2 PP failed to reach statistical significance. CONCLUSIONS: These data confirm that CO2 PP and dry gas have a deleterious effect on mesothelial cell morphology. Humidification of the insufflation gas reduces this deleterious effect. The hypothesis of a protective effect of adding O2 failed to reach significance.

Effect of Reteplase and PAI-1 antibodies on postoperative adhesion formation in a laparoscopic mouse model.

BACKGROUND: Postoperative adhesions remain an important clinical problem, accounting for infertility, chronic pain and bowel obstruction. Its prevention is still inadequate and overall poorly understood. The aim of this study was to investigate the effect of Reteplase (a recombinant plasminogen activator, r-PA) and of PAI-1 antibodies upon adhesion formation in a laparoscopic model. METHODS: Pneumoperitoneum-enhanced adhesions were induced by performing a bipolar lesion in female BALB/c mice and by using pure and humidified CO(2) as insufflation gas for 60 min. In experiment 1, four doses of 0.125, 0.25, 0.5 and 1 mg/0.5 ml r-PA and one and two doses of 1 mg r-PA were administrated i.p. Two control groups were included, one without any treatment and the second one receiving four times 0.5 ml of saline. In experiment 2, four doses of 0, 1, 10 and 100 microg/0.5 ml r-PA were administrated i.p. In experiment 3, PAI-1 neutralising and non-neutralising antibodies were injected i.p. after performing the lesion on day 0 and days 2 and 4. Adhesions were scored after 7 days. RESULTS: Adhesion formation was less with the administration of four doses of 1 microg r-PA (proportion, p < 0.04, Wilcoxon). An increase in adhesion formation was observed when higher number of doses and amounts of r-PA were used (Proc GLM, eight groups, two variables, p = 0.05 for the amount of r-PA and p < 0.02 for the number of doses administrated). No effect was observed with the PAI-1 antibodies. CONCLUSIONS: Low-dose i.p. administration of rPA is effective in the prevention of adhesions in a laparoscopic mouse model.

ypT0N+: the unusual patient with pathological complete tumor response but with residual lymph node disease after neoadjuvant chemoradiation for esophageal cancer, what's up?

BACKGROUND: Little is known about the prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) after neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). The purpose is to analyze the long-term outcomes of EC patients with ypT0N+ following nCRT and esophagectomy. METHODS: From a single institution database, 466 consecutive EC patients undergoing esophagectomy after nCRT were collected (1996-2016). ypT0N+ responders were compared to pathological complete responders (ypT0N0) and to pathological non-complete responders (ypT+N0 and ypT+N+). RESULTS: There were 149 ypT0N0, 31 ypT0N+, 141 ypT+N0 and 145 ypT+N+. Median overall survival (OS) was worse in ypT0N+ (21.7 months) and ypT+N+ (16.8 months) compared to ypT0N0 (55.2 months) and ypT+N0 (42.0 months). Stratification by histology revealed a significant difference in prevalence of ypT0: 62.5% in 184 squamous cell carcinomas (SCC) compared to 23.0% in 282 adenocarcinomas (ADC) (P<0.0001) but not in ypT0N+ (15% vs. 22% respectively, P=0.25). In ADC, locoregional recurrence in ypT0N+ (43%) was comparable to ypT+N+ (31%) and more common compared to ypT0N0 (7%) and ypT+N0 (10%), reflected in median OS rates of 20.6, 17.5, 53.0 and 36.6 months respectively. Median OS in ADC is significantly determined by number of positive lymph nodes, being 21.7 months for pN1 and 2.7 months for pN2/3 (P=0.005) in ypT0N+ and 33.7 months for pN1 and 16.2 months for pN2/3 (P=0.031) in ypT+N+. In SCC, locoregional recurrences were found in 17% of ypT0N+, 33% of ypT+N+, 11% of ypT0N0 and 22% in ypT+N0 and median OS was 26.6, 15.6, 55.2 and 43.8 months respectively. In SCC ypN+ number of affected lymph nodes showed no difference on OS. CONCLUSIONS: ypT0N+ in EC patients following nCRT has a poor prognosis and behaves similar to ypT+N+. However, stratification by histology shows that this is especially true in ADC but seems determined by the number of involved lymph nodes.

JLK inhibitors: isocoumarin compounds as putative probes to selectively target the gamma-secretase pathway.

Alzheimer's disease is characterized by the extracellular deposition of the amyloid beta-peptide that derives from its precursor betaAPP by sequential actions of beta- and gamma- secretases, respectively. Recent studies aimed at identifying these enzymes have been reported as it is thougth that their inhibition should hopefully lead to reduce Abeta load in the AD brains. beta-secretase seems to be due to BACE1, a novel membrane-bound aspartyl protease. gamma-secretase identification is still a matter of controversy. Invalidation of presenilin genes was reported to impair both gamma-secretase-mediated Abeta production and Notch cleavage leading to NICD production. This observation together with another biochemical and pharmacological evidences led to suggest that presenilins could be the genuine long-searched gamma-secretase that would be responsible for both APP and Notch cleavages. We have designed novel non peptidic potential inhibitors of gamma-secretase (referred to as JLK inhibitors) and examined their ability to prevent Abeta40 and Abeta42 secretions as well as NICD production. Three out of a series of these agents drastically lower the recoveries of both Abeta40 and Abeta42 produced by betaAPP-expressing cell lines and concomitantly protect intracellular C99 and C83 recoveries. These inhibitors also prevent Abeta40/42 productions by C99-expressing cells. Interestingly, these inhibitors were totally unable to affect the DeltaENotch cleavage leading to NICD generation. Here, we also further characterize the pharmacological properties and specificity of these JLK inhibitors.

Role of vascular endothelial growth factor receptor 1 in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in mice.

OBJECTIVE: To evaluate the role of vascular endothelial growth factor receptor-1 (VEGFR-1) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Forty female Swiss mice. INTERVENTION(S): Adhesions were induced by standardized lesions during laparoscopy. The CO2 pneumoperitoneum was maintained for the minimum time needed to perform the lesions (10 minutes) or for a longer period (60 minutes) to evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, respectively. Mice were treated either with IgG or with antibodies against VEGFR-1. MAIN OUTCOME MEASUREMENT(S): Adhesions were quantitatively and qualitatively scored after 7 days during laparotomy. RESULT(S): In IgG-treated mice, 60 minutes of CO2 pneumoperitoneum increased basal adhesions. In VEGFR-1 antibody-treated mice, basal adhesions were similar to the control group and 60 minutes of CO2 pneumoperitoneum did not increase adhesions. Therefore, in these mice, pneumoperitoneum-enhanced adhesions were lower than in IgG-treated mice. CONCLUSION(S): The data confirm that CO2 pneumoperitoneum is a cofactor in adhesion formation and demonstrate that VEGFR-1 plays a role in pneumoperitoneum-enhanced adhesions, which is consistent with a role of placental growth factor, VEGF-A, and VEGF-B in pneumoperitoneum-enhanced adhesions. These observations give new insight into the pathogenesis of adhesion formation.

Effect of adding more than 3% oxygen to carbon dioxide pneumoperitoneum on adhesion formation in a laparoscopic mouse model.

OBJECTIVE: To investigate the effect of the addition of 3% or higher oxygen concentrations to the carbon dioxide (CO2) pneumoperitoneum. DESIGN: Prospective, randomized trial. SETTING: Academic research center. ANIMAL(S): Female Naval Medical Research Institute mice (n = 100). INTERVENTION(S): Sixty minutes of CO2 pneumoperitoneum with 0%, 3%, 6%, 9%, or 12% oxygen; induction of adhesions by the creation of standardized peritoneal lesions during laparoscopy. MAIN OUTCOME MEASURE(S): Adhesions were quantitatively and qualitatively scored after 7 days during laparotomy to determine [1] the effect of 60 minutes of CO2 pneumoperitoneum with 0%, 3%, 6%, 9%, or 12% oxygen on adhesion formation, and [2] the effect of duration of CO2 pneumoperitoneum and insufflation pressure on adhesion formation with the addition of 0%, 3%, and 12% oxygen. RESULT(S): Compared with a CO2 pneumoperitoneum with 3% oxygen, adhesion formation is greater when either no oxygen or more than 3% oxygen is added to the CO2 pneumoperitoneum. These effects persisted at higher insufflation pressures and longer duration of pneumoperitoneum, both known to increase adhesion formation with pure CO2. CONCLUSION(S): This study confirms that adhesion formation is decreased with the addition of 3% oxygen to the CO2 pneumoperitoneum. The addition of higher oxygen concentrations, however, is deleterious. Adhesions always increase with time and duration of the pneumoperitoneum.

Role of CO(2) pneumoperitoneum-induced acidosis in CO(2) pneumoperitoneum-enhanced adhesion formation in mice.

The effect of assisted ventilation and CO(2) pneumoperitoneum during laparoscopic surgery upon blood gases and adhesion formation were evaluated in mice. We confirmed that the CO(2) pneumoperitoneum induces acidosis and enhances adhesion formation, and an association between both effects was demonstrated, together with its modulation by the assisted ventilation.

Role of hypoxia inducible factors 1alpha and 2alpha in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.

OBJECTIVE: To evaluate the role of hypoxia inducible factors (HIFs) 1alpha and 2alpha in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Forty Swiss/129SvJ wild-type mice and transgenic mice partially deficient for the genes encoding for HIF-1alpha (HIF-1alpha(+/-)) or HIF-2alpha (HIF-2alpha(+/-)). INTERVENTION(S): Adhesions were induced by standardized lesions during laparoscopy. To evaluate "basal adhesions" and "pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period, respectively. MAIN OUTCOME MEASURE(S): Adhesions were blindly scored after 7 days. RESULT(S): In both HIF-1alpha and HIF-2alpha wild-type mice, pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were lower in HIF-1alpha(+/-) and similar in HIF-2alpha(+/-) mice. Pneumoperitoneum did not enhance adhesion formation in HIF-1alpha(+/-) or in HIF-2alpha(+/-) mice. Therefore, in comparison with the correspondent wild-type mice, pneumoperitoneum-enhanced adhesions were lower in HIF-1alpha(+/-) and HIF-2alpha(+/-) mice. CONCLUSION(S): These data confirm that CO(2) pneumoperitoneum enhances adhesion formation and indicate that this effect is mediated, at least in part, by an up-regulation of HIF-1alpha and HIF-2alpha.

Role of vascular endothelial growth factor and placental growth factor in basal adhesion formation and in carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.

OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Female wild-type mice and transgenic mice (n = 110), expressing exclusively VEGF-A(164) (VEGF-A(164/164)) or deficient for VEGF-B (VEGF-B(-/-)) or for PlGF (PlGF(-/-)). INTERVENTION(S): Adhesions were induced during laparoscopy. To evaluate "basal adhesions" and "CO(2) pneumoperitoneum-enhanced adhesions," the pneumoperitoneum was maintained for a minimum (10 minutes) or prolonged (60 minutes) period. The role of PlGF was also evaluated by administration of antibodies. MAIN OUTCOME MEASURE(S): Adhesions were blindly scored after 7 days. RESULT(S): In all wild-type mice, CO(2) pneumoperitoneum enhanced adhesion formation. In comparison with wild-type mice, basal adhesions were higher in VEGF-A(164/164) mice and similar in VEGF-B(-/-) and PlGF(-/-) mice. Pneumoperitoneum did not enhance adhesions in any of these transgenic mice. The effects observed in PlGF(-/-) mice were confirmed in PlGF antibody-treated mice. CONCLUSION(S): The data demonstrate that the VEGF family plays a role in adhesion formation and confirm that CO(2) pneumoperitoneum enhances adhesions. VEGF-A(164) has a direct role in basal adhesions. Absence of pneumoperitoneum-enhanced adhesions in VEGF-A(164/164), VEGF-B(-/-), and PlGF(-/-) mice indicates up-regulation of VEGF-A(164), VEGF-B, and PlGF by CO(2) pneumoperitoneum as a mechanism for pneumoperitoneum-enhanced adhesion formation.

Role of the plasminogen system in basal adhesion formation and carbon dioxide pneumoperitoneum-enhanced adhesion formation after laparoscopic surgery in transgenic mice.

OBJECTIVE: To evaluate the role of plasminogen activator inhibitor-1 (PAI-1), urokinase plasminogen activator (uPA), and tissue-type plasminogen activator (tPA) in adhesion formation after laparoscopic surgery. DESIGN: Prospective, randomized study. SETTING: Academic research center. ANIMAL(S): Seventy female wild-type and transgenic knockout mice for PAI-1 (PAI-1(-/-)), uPA (uPA(-/-)) or tPA (tPA(-/-)). INTERVENTION(S): Standardized lesions to induce peritoneal adhesions were performed during laparoscopy. To evaluate basal adhesions and pneumoperitoneum-enhanced adhesions, the pneumoperitoneum was maintained for 10 minutes or 60 minutes, respectively. Peritoneal biopsy samples were obtained during and after 60 minutes of carbon dioxide pneumoperitoneum. MAIN OUTCOME MEASURE(S): Adhesions were blindly scored after 7 days. Concentrations of PAI-1 and tPA were measured by using enzyme-linked immunosorbent assay. RESULT(S): In PAI-1, uPA, and tPA wild-type mice, pneumoperitoneum enhanced adhesions. Compared with wild-type mice, basal adhesions were fewer in PAI-1(-/-) mice and more in uPA(-/-) and tPA(-/-) mice. Pneumoperitoneum did not enhance adhesions in these transgenic mice. PAI-1 concentration increased after 60 minutes of pneumoperitoneum whereas tPA concentration did not change. CONCLUSION(S): Impaired fibrinolysis increases basal adhesions. The absence of pneumoperitoneum-enhanced adhesions in PAI-1(-/-), uPA(-/-), and tPA(-/-) mice and the increase in PAI-1 expression indicate that PAI-1 up-regulation by carbon dioxide pneumoperitoneum is a mechanism of pneumoperitoneum-enhanced adhesion formation.

[Frontal dysexecutive syndromes]. / Syndromes frontaux et dysexécutifs.

Investigation of executive functions is an approach which began with the early description of behavioral disorders induced by frontal damage. The development of neuropsychology has led to the description of a large variety of cognitive disorders. This type of approach has generated a large number of tests which are still used in clinical practice. More recently, theoretical approaches have proposed an organization of executive processes and have documented the diversity of executive functions and related anatomy. These studies have deeply influenced the clinical approach, the assessment and the diagnosis of executive disorders. For clinical practice, these data favor specific assessment of certain key behavioral and cognitive deficits investigated with a battery of tests.

A European survey on awareness of post-surgical adhesions among gynaecological surgeons.

The present survey was conducted among gynaecological surgeons from several European countries to assess the actual knowledge and practice related to post-surgical adhesions and measures for reduction. From September 1, 2012 to February 6, 2013, gynaecological surgeons were invited to answer an 18-item online questionnaire accessible through the ESGE website. This questionnaire contained eight questions on care settings and surgical practice and ten questions on adhesion formation and adhesion reduction. Four hundred fourteen surgeons participated; 70.8 % agreed that adhesions are a source of major morbidity. About half of them declared that adhesions represented an important part of their daily medical and surgical work. About two thirds informed their patients about the risk of adhesion. Most cited causes of adhesions were abdominal infections and extensive tissue trauma, and endometriosis and myomectomy surgery. Fewer surgeons expected adhesion formation after laparoscopy (18.9 %) than after laparotomy (40.8 %); 60 % knew the surgical techniques recommended to reduce adhesions; only 44.3 % used adhesion-reduction agents on a regular basis. This survey gives a broad picture of adhesion awareness amongst European gynaecological surgeons, mainly from Germany and the UK. The participants had a good knowledge of factors causing adhesions. Knowledge of surgical techniques recommended and use of anti-adhesion agents developed to reduce adhesions need to be improved.