Peri-operative outcomes of patients with stage IV endometriosis undergoing robotic-assisted laparoscopic surgery

We analyzed peri-operative outcomes of 80 patients who underwent robotic-assisted laparoscopic surgery and were diagnosed with stage IV endometriosis (revised American Society for Reproductive Medicine) between January 2007 and December 2010 at a tertiary gynecologic oncology referral center with a fellowship training program. Eligible women had a combination of one or more factors: pelvic mass, sub-acute or chronic pelvic pain, dysmenorrhea, dyspareunia, elevated serum CA-125, diagnosed with stage IV endometriosis at surgery with robotic-assisted gynecologic procedures using the da Vinci^? Surgical System. The mean age was 43.7?±?7.0?years, body mass index 27.5?±?7.4?kg/m², and 23 (28.9%) patients had prior endometriosis surgery. Presenting symptoms included: chronic pelvic pain (48.8%), dysmenorrhea (40.3%), and dyspareunia (33.8%). Sixty-nine (86%) patients had pelvic masses (43 unilateral and 26 bilateral). Thirty-seven (46.3%) had elevated CA-125 levels (mean 97.9?±?71.6 U/ml). Forty-eight (60%) underwent robotic-assisted laparoscopic hysterectomy (RALH)/bilateral salpingo-oophorectomy (BSO), 9 (11.3%) RALH/unilateral salpingo-oophorectomy (USO), 5 (6.3%) modified radical hysterectomy, and 10 (13%) USO or BSO only. Four (5%) had ovarian cystectomies with excision of endometriotic implants. Three (3.8%) underwent appendectomy and no patient required bowel resection. Four (5%) patients required conversion to laparotomy during the first 15 cases of this series [dense adhesions (3) and ureteral injury (1)]. Mean operative time was 115?±?46?min, blood loss 88?±?67?ml, and length of stay 1.0?±?0.4?days. There were four (5%) complications (ureteral injury, cuff abscess, cuff hematoma, re-admission for nausea and vomiting secondary to narcotics) and no transfusions. One (1.3%) patient underwent a second surgery for pain (dyspareunia). Robotic-assisted surgery for stage IV endometriosis resulted in excellent pain relief, with few laparotomy conversions or complications during a robotic learning-curve experience.     

Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients

Patients with scleroderma receiving Iloprost as a treatment for severe Raynaud's phenomenon report a reduction in skin tightness, suggesting that this drug inhibits skin fibrosis. Connective tissue growth factor (CTGF), a recently described profibrotic cytokine, acts downstream and in concert with TGF-beta to stimulate the fibrotic process and is involved in the fibrosis seen in scleroderma. Here we show that Iloprost, acting by elevation of cAMP, blocks the induction of CTGF and the increase in collagen synthesis in fibroblasts exposed to TGF-beta. The potency of Iloprost with respect to suppression of CTGF far exceeds that of other prostanoid receptor agonists, suggesting that its effect is mediated by the prostacyclin receptor IP. By sampling dermal interstitial fluid using a suction blister device, we show that CTGF levels are greatly elevated in the dermis of scleroderma patients compared with healthy controls and that Iloprost infusion causes a marked decrease in dermal CTGF levels. These studies suggest that Iloprost could be reducing the level of a key profibrotic cytokine in scleroderma patients and that endogenous production of eicosanoids may limit the fibrotic response to TGF-beta.     

Elevated levels of the acute‐phase serum amyloid are associated with heightened lung cancer risk

BACKGROUND:

The authors investigated whether early stage lung cancer could be identified by proteomic analyses of plasma.

METHODS:

For the first case‐control study, plasma samples from 52 patients with lung cancer and from a group of 51 controls were analyzed by surface‐enhanced laser desorption/ionization time‐of‐flight mass spectrometry. In a second case‐control study, a classifier of 4 markers (mass‐to‐charge ratio, 11,681, 6843, 5607, and 8762) also was tested for validation on plasma from 16 consecutive patients with screen‐detected cancer versus 406 healthy individuals. The most relevant marker was identified, and an enzyme‐linked immunosorbent assay‐based analysis revealed that signal intensity was correlated with concentration.

RESULTS:

The classifier had a sensitivity of 94.23% and a specificity of 76.47% in the first study but lost predictive value in the second study. Nevertheless, the 11,681 cluster, which was identified as serum amyloid protein A (SAA), resulted in a multiple logistic regression model that indicated a strong association with lung cancer. When both studies were considered as a together, the odds ratio (OR) for an SAA intensity ≥0.5 was 10.27 (95% confidence interval [CI], 4.64‐22.74), whereas an analysis restricted to stage I cancers (TNM classification) revealed an OR of 8.45 (95% CI, 2.76‐25.83) for T1 lung cancer and 21.22 (95% CI, 5.62‐80.14) for T2 lung cancer.

CONCLUSIONS:

SAA levels were predictive of an elevated risk of lung cancer, supporting the general view that inflammation is implicated in lung cancer development. Cancer 2010. © 2010 American Cancer Society.     

Search superiority in autism within, but not outside the crowding regime

Visual cognition of observers with autism spectrum disorder (ASD) seems to show an unbalance between the complementary functions of integration and segregation. This study uses visual search and crowding paradigms to probe the relative ability of children with autism, compared to normal developments children, to extract individual targets from cluttered backgrounds both within and outside the crowding regime. The data show that standard search follows the same pattern in the ASD and control groups with a strong effect of the set size that is substantially weakened by cueing the target location with a synchronous spatial cue. On the other hand, the crowding effect of eight flankers surrounding a small peripheral target is virtually absent in the clinical sample, indicating a superior ability to segregate cluttered visual items. This data, along with evidence of an impairment to the neural system for binding contours in ASD, bring additional support to the general idea of a shift of the trade-off between integration and segregation toward the latter. More specifically, they show that when discriminability is balanced across conditions, an advantage in odd-man out tasks is evident in ASD observers only within the crowding regime, when binding mechanism might get compulsorily triggered in normal observers.     

Low-density lipoprotein (LDL) receptor/transferrin fusion protein: in vivo production and functional evaluation as a potential therapeutic tool for lowering plasma LDL cholesterol

A soluble form of human low-density lipoprotein receptor (LDL-R) fused in frame with rabbit transferrin (LDL-Rs(hu)/Tf(rab)) is assessed in vivo as a therapeutic tool for lowering plasma LDL cholesterol. The cDNA encoding LDL-Rs(hu)/Tf(rab) is expressed in mice, using a hydrodynamics-based gene transfer procedure. The transgene is transcribed in the liver of transduced animals and the corresponding protein is secreted into the bloodstream. Circulating LDL-Rs(hu)/Tf(rab) binds LDL specifically, thus indicating that it is correctly processed through the cellular compartments in vivo. More importantly, the expression of LDL-Rs(hu)/Tf(rab) allows the removal of injected human (125)I-labeled LDL ((123)I-LDL) from the bloodstream of transduced CD1 mice, which show faster LDL plasma clearance, anticipating by approximately 90 min the same clearance value observed in control animals. A similar effect is observed in transduced LDL-R(-/-) mice, in which the clearance of injected human LDL depends solely on the presence of circulating LDL-Rs(hu) /Tf(rab). In these animals the extent of plasma LDL clearance is directly related to the concentration of LDL-Rs(hu)/Tf(rab) in the blood. Finally, LDL-Rs(hu)/Tf(rab) does not alter the pattern of LDL organ distribution: in transduced animals, as well as in control animals, liver and bladder are the predominantly labeled organs after (123)I-LDL injection. However, LDL-Rs(hu)/Tf(rab) has a quantitative effect on LDL tissue deposition: in treated animals LDL-Rs(hu)/Tf(rab) determines an increase in radioactivity in the liver at early times after (123)I-LDL injection and a progressive labeling of the bladder, starting 20 min after injection.     

Defibrotide for Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease Prophylaxis in High-Risk Adult Patients: A Single-Center Experience Study

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a serious complication after hematopoietic stem cell transplantation (HSCT). SOS/VOD usually occurs within 3 weeks of HSCT, but the 2016 European Society for Blood and Marrow Transplantation diagnosis criteria have been revised to include late forms. Prophylactic use of defibrotide is recommended in the pediatric setting, but its value remains uncertain in the adult population. We report here a single-center series of 63 adult patients considered at high risk for SOS/VOD who received defibrotide prophylaxis in combination with ursodeoxycholic acid between May 2012 and August 2016. The median duration of defibrotide therapy was 23 days. Bleeding occurred in 14 patients (21.5%). Defibrotide prophylaxis was discontinued in 7 patients (10.8%): 4 cases (6.3%) due to bleeding and 3 cases (4.6%) because of the need for antithrombotic therapy. Overall, SOS/VOD occurred in 4 cases (6.3%) within 21 days after HSCT (days 13 and 14) in 2 cases and late-onset SOS/VOD (days 57 and 58) in the other 2 cases. SOS/VOD was moderate in 1 case, very severe in 3 cases, with 2 deaths related to SOS/VOD. Cumulative incidence of grades II to IV acute graft-versus-host disease and transplant-associated thrombotic microangiopathy were 22.2% and 3.2%, respectively. With a median follow-up of 31 months (range, 10.7 to 60.3), the rates of 2-year overall survival, progression-free survival, incidence of relapse, and nonrelapse mortality were 56.5%, 49%, 28.7%, and 22.3%, respectively. In our experience defibrotide prophylaxis is associated with a low incidence of SOS/VOD after allogeneic HSCT in a high-risk adult population with an acceptable safety profile.     

Validation of the Italian version of the SBMA Functional Rating Scale as outcome measure

The Spinal and Bulbar Muscular Atrophy Functional Rating Scale (SBMAFRS) is an established rating instrument used to assess the functional status of patients with Spinal and Bulbar Muscular Atrophy (SBMA). Our aim was to validate an Italian version of the scale. We administered the SBMAFRS to sixty SBMA patients during routine follow-up of clinical evaluations. To estimate the test stability, the scale was re-administered to a subset of 39 randomly selected patients after 8 weeks. The patients underwent clinical evaluation including 6-min walk. Psychometric analysis included reliability assessment and factorial analysis. To evaluate convergent validity, correlations between SBMAFRS items and muscular force assessed by manual testing, ALSFRS total score and subscales scores, and forced vital capacity, were performed. Internal consistency as measured by Cronbach’s alpha (total scale 0.85) was high. Test–retest reliability assessed by Spearman’s rho was also high. Principal component analysis with varimax rotation yielded a four-factor solution accounting for approximately 79 % of the variance. The scale total score and subscales score were strongly correlated with respective items and subscores of the ALSFRS, with respiratory function and with the 6-min walk test. In conclusion, we performed an Italian validation of the only existing disease-specific Functional Rating Scale for SBMA patients. This scale will be a useful tool not only in the clinical practice but also as an outcome measure in upcoming clinical trials.