291 Colon cancer screening program in adult CF patients: an Italian cross-sectional pilot study

Objectives: Adult CF patients have a significantly increased risk of colon adenomatous polyps, yet there is currently no consensus about the optimal screening protocol. The aim of this study is to evaluate the prevalence of colon precancerous abnormalities in CF patient by a systematic colonoscopic screening and surveillance program. Methods: In a cross-sectional design, each individual out of 184 CF patients aged 40+ followed by the Regional CF Centre of Ancona (Marche), Verona (Veneto) and Atri (Abruzzo) is being asked to undergo within the next six months a screening colonoscopy after execution of Fecal Occult Blood Test (FOBT). Assessed outcomes: probability of having at least one polyp, 3+ polyps, one adenoma with severe dysplasia, a colon cancer diagnosis; positive and negative predictive value of FOBT for colonic mucosa lesions. Additional risk factors, such as familiarity for colorectal or breast cancer, IBD and cumulative dose of NSAIDs in the last five years, are being recorded. Results: Until nowadays, 20 patients out of 184 have been evaluated, with 4 positive for polyps (histology in progress). The results of the screening program will be available in the next months. Conclusion: Preliminary data show an increase of potentially evolutionary colonic lesions in CF adults. The precise burden, the optimal screening strategies, the influence of conventional or disease-associated risk factors must be clarified for an effective program. Our study is one of the first pilot experiences to address this aspect

Predictive value of interleukin 6 (IL-6), interleukin 8 (IL-8) and gastric intramucosal pH (pH-i) in major abdominal surgery

Objective. To study plasma concentrations of interleukin 6 (IL-6) and interleukin 8 (IL-8) in patients with splanchnic hypoxia, as documented by gastric intramucosal measurements (pH-i), during major abdominal surgery and the relationship between IL-6 and IL-8 concentrations and postoperative complications as well as clinical outcome. Design: A prospective study. Patients: Twelve patients scheduled for major abdominal surgery with no evidence of coexisting infectious disease. Results: Six out of seven samples from patients with postoperative complications showed intraoperative pH-i levels lower than 7.32 and IL-6 levels higher than 300 pg/ml. Seven out of nine samples from patients without complications showed pH-i levels higher than 7.32 and IL-6 levels lower than 300 pg/ml. The difference in the pattern of distribution was statistically significant (p < 0.01). Only two out of seven samples of patients with postoperative complications showed intraoperative pH-i levels lower than 7.32 and IL-8 levels higher than 60 pg/ml. It was not possible to identify a clear distribution pattern of data points for IL-6 and IL-8 during the postoperative period. Conclusions: Intraoperative splanchnic ischemia, as documented by gastric intramucosal pH-i, is directly correlated to the increase of IL-6 plasma levels and to the incidence of postoperative complications, while IL-8 levels showed no correlation with surgical complications

Two novel and correlated CF-causing insertions in the (TG)mTn tract of the CFTR gene

Two novel and related pathogenic variants of the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene were structurally and functionally characterized. These alterations have not been previously described in literature. Two patients with diagnosis of Cystic Fibrosis (CF) based on the presence of one mutated allele, p.Phe508del, pathological sweat test and clinical symptoms were studied. To complete the genotypes of both patients, an extensive genetic and functional analysis of the CFTR gene was performed. Extensive genetic characterization confirmed the presence of p.Phe508del pathogenic variant and revealed, in both patients, the presence of an insertion of part of intron 10 in intron 9 of the CFTR gene, within the (TG)m repeat, with a variable poly-T stretch. The molecular lesions resulted to be very similar in both patients, with only a difference in the number of T in the poly-T stretch. The functional characterization at RNA level revealed a complete anomalous splicing, without exon 10, from the allele with the insertion of both patients. Consequently, the alleles with the insertions are expected not to contribute to the formation of a functional CFTR protein. Molecular and functional features of these alterations are compatible with the definition of novel CF-causing variants of the CFTR gene. This also allowed the completion of the genetic characterization of both patients

A comparison among portal lactate, intramucosal sigmoid pH, and Delta CO2 (Paco(2) regional Pco(2)) as indices of complications in patients undergoing abdominal aortic aneurysm surgery

Our aim in this observational, prospective, noncontrolled study was to detect, in 29 patients who underwent abdominal aortic aneurysm (AAA) surgery, correlations between the incidence of postoperative organ failure and intraoperative changes in arterial and portal blood lactate; changes in intramucosal sigmoid pH (pHi); differences between sigmoid P-CO2 and arterial P-CO2 (DeltaCO(2)); and hemoglobin (Hb). Hb, arterial blood lactate concentrations, pHi, and DeltaCO(2) (air tonometry) were recorded at the start of anesthesia (T0), before aorta clamping (T1), 30 minutes after clamping (T2), and at the end of surgery (T3). Portal venous lactate concentrations were recorded at T1 and T2. Patients were stratified into two groups: group A patients had no postoperative organ failure, and group B patients had one or more organ failures. As compared with group A (n = 16), group B patients (n = 13) had a lower pHi value at T2 and T3 and a higher DeltaCO(2) at T3. A pHi value of 28 mm Hg predicted later organ failure with a sensitivity of 92.3%, a specificity of 62.5%, and positive and negative predictive values of 66.6% and 90.9%, respectively. Portal venous lactate concentrations were larger in group B at T2 (P<0.001), and an increase greater than or equal to5 g/dL predicted later postoperative organ failure with a sensitivity of 92.3%, a specificity of 100%, and positive and negative predictive values of 100% and 94.1%, respectively. The comparison of the receiving operator characteristic curves to test the discrimination of each variable and the logistic regression analysis revealed that the increase in portal lactate was the best predictor for the development of postoperative organ failure. Hb concentration was significantly smaller in group B at T0 (13.8 +/- 1.0 g/dL versus 12.2 +/- 2.2 g/dL) and T2 (10.9 +/- 1.2 g/dL versus 9.1 +/- 1.9 g/dL). In conclusion, both pHi and DeltaCO(2) are reasonably sensitive prognostic indices of organ failures after AAA surgery, but they are less specific and accurate than portal venous lactate

[Intraoperative lactic acidosis, can it be treated? Clinico-experimental, prospective, sequential study].

To verify the efficacy and absence of risk attributable to therapy with alkaline solutions for correction of lactic acidosis and to demonstrate the usefulness of L-carnitine in converting lactate into pyruvate in conditions of good blood oxygenation. Prospective study on a consecutive series of patients subdivided into three groups following the use of: alkalinizing therapy (group I), L-carnitine (group II), or saline solution (group III). Groups 1 and 2 were further subdivided into subgroups "a" and "b" according to the type of alkalinizing agent and of L-carnitine somministration. Teaching Hospital-Torrette di Ancona. 65 patients submitted to major vascular surgery with aortic clamping in the time period between January 1992 and August 1993. During aortic clamping patients of: group I received 2 mEq:kg of bicarbonate or tromentamolo according to the specific subgroup. Group II received a bolus of 2 g of L-carnitine, patients of group IIb received further 2 g of carnitine in continuous perfusion until the end of surgery. Group III received no pharmacological intervention. HR BP, arterial blood gases and lactic acid levels were measured at 12 pre-determined times. Only a neutralizing effect of alkalinizing therapy was observed, whereas the lactic acid measurements demonstrated no significant differences between the different groups. These results confirm the data of other Authors concerning the good compliance of alkalinizing therapy, however, there was demonstrated no clear evidence of its effective usefulness. No metabolic stimulation due to L-canitina could be demonstrated in our experimental conditions

[Intraoperative lactic acidosis, can it be treated? Clinico-experimental, prospective, sequential study].

To verify the efficacy and absence of risk attributable to therapy with alkaline solutions for correction of lactic acidosis and to demonstrate the usefulness of L-carnitine in converting lactate into pyruvate in conditions of good blood oxygenation.Prospective study on a consecutive series of patients subdivided into three groups following the use of: alkalinizing therapy (group I), L-carnitine (group II), or saline solution (group III). Groups 1 and 2 were further subdivided into subgroups "a" and "b" according to the type of alkalinizing agent and of L-carnitine somministration.Teaching Hospital-Torrette di Ancona.65 patients submitted to major vascular surgery with aortic clamping in the time period between January 1992 and August 1993.During aortic clamping patients of: group I received 2 mEq:kg of bicarbonate or tromentamolo according to the specific subgroup. Group II received a bolus of 2 g of L-carnitine, patients of group IIb received further 2 g of carnitine in continuous perfusion until the end of surgery. Group III received no pharmacological intervention.HR BP, arterial blood gases and lactic acid levels were measured at 12 pre-determined times.Only a neutralizing effect of alkalinizing therapy was observed, whereas the lactic acid measurements demonstrated no significant differences between the different groups.These results confirm the data of other Authors concerning the good compliance of alkalinizing therapy, however, there was demonstrated no clear evidence of its effective usefulness. No metabolic stimulation due to L-canitina could be demonstrated in our experimental conditions