Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult- and pediatric-onset inflammatory bowel disease in Italy

AIM： To investigate gene variants in a large Italian inflammatory bowel disease （IBD） cohort, and to analyze the correlation of sub-phenotypes （including age at diagnosis） and epistatic interaction with other IBD genes. METHODS： Total of 763 patients with Crohn＇s disease （CD, 189 diagnosed at age 〈 19 years）, 843 with ulcerative colitis （UC, 179 diagnosed 〈19 years）, 749 healthy controls, and 546 healthy parents （273 trios） were included in the study. The rs2241880 [autophagy-related 16-like 1 （ATG16L1）], rs11209026 and rs7517847 [interleukin 23 receptor （IL23R）], rs2066844, rs2066845, rs2066847 （CARD15）, rs1050152 （OCTN1）, and rs2631367 （OCTN2） gene variants were genotyped. RESULTS： The frequency of G allele of ATG16L1 SNP （Ala197Thr） was increased in patients with CD compared with controls （59% vs 54% respectively） （OR = 1.25, CI = 1.08-1.45, P = 0.003）, but not in UC （55%）. The frequency of A and G （minor） alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD （4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P 〈 0.01）, compared with controls （6% and 38%, respectively）. The A allele （but not G） was also reduced signifi cantly in UC （4%, OR = 0.69, CI = 0.5-0.94, P = 0.019）. No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION： The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.     

Social,functional and health status influences on mortality: Consideration of a multidimensional inquiry in a large elderly population

Health status, functional status, and social influences were analyzed as risk factors associated with mortality in 1201 elderly subjects (70–75 years old), living in the center of Brescia, Northern Italy, followed up for three years.Mortality was positively associated with degree of impairment in health status, functional status, and mental status as measured by cognitive function and mood depression. Among social conditions no relation was found between mortality and living alone, education, or income, while a significant inverse relationship has been found between mortality and activities. In defining risk factors of mortality in aged people not only health status and cognitive function have to be taken into account but also social activities; these latter may act as protective factors buffering the organism from the effects of noxious stimuli.Paper originally presented at the XIVth International Congress of Gerontology, Acapulo, Mexico 18–23 June 1989.     

Effect of N-Acetyl-Cysteine (NAC) Added to Fenoldopam or Dopamine on End-Tidal Carbon Dioxide and Mean Arterial Pressure at Time of Renal Artery Declamping During Cadaveric Kidney Transplantation

N-Acetyl-cysteine (NAC) is known to be a powerful antioxidant used to prevent renal damage. Our deceased-donor kidney transplantation protocol administered an NAC bolus at the time of declamping of the renal artery to reduce the potential oxidative damage with ischemia-reperfusion. The aim of injury this study was to compare the effects of NAC added to a continuous infusion of either fenoldopam or dopamine during kidney recipient anesthesia on mean arterial pressure (MAP) and end-tidal carbon dioxide (ECO₂), which were assumed to be expressions of oxidative and acid-base status. One hundred forty patients undergoing deceased donor kidney transplantation were enrolled in the study. Using a standardized perioperative anesthesia protocol, the patients were divided into 4 groups: group N, receiving an NAC (50 mg/kg) bolus just before renal artery declamping (n = 40); group C, not receiving any NAC or other infusion (n = 20); group NF, same treatment as group N plus fenoldopam (0.1 μg/kg/min) continuous infusion (n = 40); and group ND, same treatment as group N plus dopamine (3 μg/kg/min) continuous infusion (n = 40). We recorded the duration of kidney cold and warm ischemia and EtCO₂ and MAP values before and after arterial declamping, as well as subjective evaluations of graft perfusion and the incidence of early or delayed graft function and adverse events. EtCO₂ was higher and MAP lower in group C compared with group N; comparing groups N, ND, and NF, the NF regimen resulted in lower EtCO₂ and higher MAP values and a greater incidence of early graft function. Subjective evaluation of graft perfusion was more favorable for groups N, ND, and NC, particularly for NF. No significant periprocedural adverse events were recorded in the groups. In our experience, the association of an NAC bolus at the time of renal artery declamping and continuous infusion of fenoldopam resulted in a minor, though non-significant, increase in EtCO₂ values, higher MAP, and greater incidence of early graft function during deceased-donor kidney transplantation compared with no NAC or NAC plus renal-dose dopamine. Further studies are necessary to better define the potential role of oxidative damage in renal ischemia- reperfusion injury, including implications for outcome, as well as the potential role of the combination of NAC plus fenoldopam as a nephroprotective and outcome-modulating regimen.     

Complete Periprostatic Anatomy Preservation During Robot-Assisted Laparoscopic Radical Prostatectomy (RALP): The New Pubovesical Complex-Sparing Technique

Background

Puboprostatic ligament preservation has been proposed as a method to accelerate continence recovery after radical prostatectomy (RP). However, these ligaments present anatomic continuity with the bladder, and there must be interruption at some point to expose the prostatourethral junction.

Objectives

To describe the surgical steps of pubovesical complex (PVC)–sparing robot-assisted laparoscopic RP (RALP) and present the preliminary results of our technique.

Design, setting, and participants

Thirty PVC-sparing RALP procedures were performed in patients <60 yr with clinically localised prostate cancer between 2007 and 2009 by the same surgeon.

Surgical procedure

The principles of bladder neck preservation, tension and energy-free dissection of the bundles as well as seminal vesicle sparing are applied. Ventrally, a plane of dissection is developed between the detrusor apron and the prostate. The soft connective tissue between Santorini's plexus and the prostate is blandly dissected, leaving the plexus intact and in place.

Measurements

The rates and location of positive surgical margins (PSM) as well as functional outcomes are presented.

Results and limitations

Three of 30 patients (10%) had a PSM (two apical margins and one on the left posterolateral side). At catheter removal, 24 of 30 patients (80%) were dry (0 pads), and 6 of 30 patients (20%) needed one security pad. After 3 mo, 22 of 30 patients (73%) presented an International Index of Erectile Function score >17 (with or without phosphodiesterase type 5 inhibitors). Thirteen of 22 potent patients had an Erection Hardness Score of 3, and 9 of 22 patients had a score of 4. Small sample size, low mean age of enrolled patients (52 yr), and the absence of diseases that could impair the continence and potency recovery are some of the limitations of the study. Moreover, it is difficult to quantify the effect of each applied continence-sparing technique.

Conclusions

The holistic preservation of the PVC during RALP is technically feasible. It leads towards an absolute preservation of the periprostatic anatomy that may enhance early functional outcomes. Further studies are needed to confirm our results.     

Very low levels of vitamin D in systemic sclerosis patients

Vitamin D displays many extraosseous immunomodulatory effects. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis (SSc) and to analyze the associations between the concentration of the vitamin and clinical manifestations. In March-April 2009, 65 consecutive SSc patients underwent evaluation of vitamin D concentrations by the LIAISON immunoassay (normal 30-100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency, while concentrations <10 ng/ml as vitamin D deficiency. None of the patients were receiving vitamin D supplementation at the time of or during the year prior to study entry. The mean level of vitamin D was 15.8 ± 9.1 ng/ml. Only three cases showed normal values; vitamin D insufficiency and deficiency were found in 43 and 19 cases, respectively. Patients with vitamin D deficiency showed longer disease duration (13.1 ± 6.8 versus 9.4 ± 5.5 years, P = 0.026), lower diffusing lung capacity for carbon monoxide (63.7 ± 12.4 versus 76.4 ± 20.2, P = 0.014), higher estimated pulmonary artery pressure (28.9 ± 9.9 versus 22.8 ± 10.4, P = 0.037) and higher values of ESR (40 ± 25 versus 23 ± 13 mm/h, P = 0.001) and of CRP (7 ± 7 and 4 ± 2 mg/l, P = 0.004) in comparison with patients with vitamin D insufficiency; moreover, late nailfold videocapillaroscopic pattern was more frequently found (52.6% versus 18.6%, P = 0.013). None of the patients showed evidence of overt mal-absorption. Low levels of vitamin D are very frequent in patients with SSc. Intestinal involvement is not likely the cause of vitamin D deficit; other factors such as skin hyperpigmentation and reduced sun exposition for psychological and social reasons may be implicated. Patients with vitamin D deficiency showed more severe disease in comparison with patients with vitamin D insufficiency, above all concerning lung involvement. Further trials are awaited to determine whether vitamin D could represent a modifiable factor able to interfere with SSc evolution.