Serum Cardiac Biomarkers in Asymptomatic Hemodialysis Patients: Role of Soluble Suppression of Tumorigenicity-2.

INTRODUCTION: Cardiovascular events (CVE) remain the leading cause of mortality in hemodialysis (HD) patients. The ability to assess the risk of short-term CVE is of great importance. Soluble suppression of tumorogenicity-2 (sST2) is a novel biomarker that better stratifies risk of CVE than troponins in patients with heart failure. Few studies have investigated the role of sST2 in the HD population. The aim of this single-center study was to assess the predictive ability of sST2 on CVE in comparison to high-sensitive cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) in HD patients. METHODS: This study used a prospective, observational cohort design. We enrolled 40 chronic HD patients asymptomatic for chest pain and without recent history of acute coronary syndrome. We tested sST2 pre-/post-HD, hs-cTnI, and BNP. Demographic/dialytic/echocardiographic data were evaluated. We recorded the number of CVE for 12 months. The patients were classified into 2 groups: those who developed CVE and those who did not. RESULTS: Ten of the 40 patients (25%) developed CVE during a 12-month follow-up. Increased sST2 levels (p < 0.0001) as well as hs-cTnI and BNP are predictive of CVE. When analyzing biomarkers as binary variables for values above or below the normal range, the correlation remained significant only for sST2 (p = 0.001). A small variation in sST2 levels before and after HD sessions was found (-2.1 ng/mL). sST2 was correlated with left ventricular (LV) echocardiographic data: LV mass index (p = 0.0001), LV ejection fraction (p = 0.01), and diastolic bulging of septum (p = 0.015). BNP and sST2 combination increased the prediction of CVE in a statistical model. CONCLUSION: Our study confirms that sST2 is useful for stratifying CV risk in the HD population. sST2 can be evaluated simply as a dichotomous value higher or lower than the normal range, making it easily interpretable. Dialysis and residual diuresis did not affect significantly sST2. A multimarker approach that incorporates sST2 and BNP may improve the prediction of CVE.

Combined Analysis of Intragastric Malignant Exfoliation and Ca 72.4 Concentration in Stomach Adenocarcinoma: The "GL1 Ca 72.4" Parameter.

INTRODUCTION/OBJECTIVE: Differently from other digestive malignancies, gastric cancer (GC) pathobiology is still little known and understood. Recently, cytopathology and molecular biology on gastric juice/gastric lavage (GJ/GL) of GC patients have provided novel and interesting results in terms of screening, diagnosis, prognosis, and therapy. However, entertaining cytologic examination and molecular test as a unified solo-run test is previously unreported. Our aim was to assess the new parameter "GL Ca 72.4" for GC patients. METHODS: Between April 2012 and July 2013, GJ/GL obtained from 37 surgical GC patients were tested for the presence/absence (GL1/GL0) of exfoliated malignant cells along with the intragastric concentration of Ca 72.4 (normal value <6.49 ng/mL: Ca 72.4n; elevated level ≥6.49 ng/mL: Ca 72.4+). RESULTS: At a median follow-up of 79.3 months, all the GC alive patients were "GL0 Ca 72.4n." The "GL1 Ca 72.4+" parameter, in comparison with GL0 Ca 72.4n, strongly correlated with deeper tumor invasion (p = 0.027), severe nodal metastasis (p = 0.012), worst metastatic node ratio (p = 0.041), higher number of metastatic lymph nodes (30 vs. 20 nodes, p = 0.014), angiolymphatic invasion (p = 0.044), advanced stage (p = 0.034), and adjuvant therapy (p = 0.044). The Kaplan-Meier model showed that GL1 Ca 72.4+ subjects had shorter overall survival (OS) than GL0 Ca 72.4n cases (9.7 vs. 43.2 months, respectively, p = 0.042). At univariate analysis, the GL1 Ca 72.4+ parameter resulted a significant prognostic factor for OS (p = 0.023). CONCLUSIONS: The combined cyto-molecular parameter "GL1 Ca 72.4+" appears to be a strong indicator of aggressive tumor behavior and a significant prognostic factor of poor survival for GC patients.

Elevated Gastric Juice Carbohydrate Antigen 72.4 (Ca 72.4) Is an Independent Prognostic Factor of Poor Survival for Gastric Cancer Patients.

BACKGROUND/AIM: As of 2020, carbohydrate antigen 72.4 (Ca 72.4) has been rarely investigated in the gastric juice (GJ) of patients with gastric cancer (GC). Our aim was to analyze the significance and role of this tumor antigen in the GJ of our GC population. PATIENTS AND METHODS: Between April 2012 and July 2013, 37 patients with operable GC were prospectively investigated to determine the GJ Ca 72.4 levels before surgical manipulation. RESULTS: GJ Ca 72.4 ≥6.49 ng/ml strongly correlated with the traditional categories of aggressive cancer (advanced tumor depth and stage, lymph node invasion and metastatic lymphatic ratio, indication to adjuvant treatment). It also associated with shorter survival (p=0.049) and is, thus, suggested as an independent factor of poor prognosis in GC patients (p=0.047). CONCLUSION: The GJ Ca 72.4 parameter should be considered an indicator of an aggressive tumor phenotype and should be used in the prognostic assessment of GC patients.

Urinary and exhaled biomarkers of exercise-induced bronchoconstriction in atopic asthmatic children.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) reflects poor asthma control. Assessing noninvasive biomarkers associated with EIB could help to monitor patients in the pediatric age. AIMS: To test exhaled and urinary biomarkers for assessing EIB in atopic asthmatic children. METHODS: In 45 atopic patients (11.1 ± 1.8 years, 25 males) we measured the fractional exhaled nitric oxide (FENO ), its alveolar (CaNO), and bronchial (J'awNO) components corrected for the trumpet shape of the airways and axial NO diffusion (TMAD), concentrations of urinary adenosine and 8-hydroxy-2'-deoxyguanosine (8-OxodG), blood eosinophils count, total immunoglobulin E , skin prick tests, and baseline spirometry before a treadmill exercise challenge. Forty healthy control subjects participated solely to baseline measurements. RESULTS: Patients yielded higher FENO and urinary adenosine concentrations than healthy controls. After the challenge, 18 patients (40%) had EIB; these patients had higher levels of CaNO, CaNO TMAD, and urinary adenosine than patients without EIB. Baseline spirometry, FE NO , JawNO, JawNO TMAD, urinary 8-OxodG, allergy, and blood eosinophil counts were found similar in both groups. In multiple linear regression, the fall in FEV 1 was explained by CaNO TMAD, urinary adenosine and blood eosinophil count, whereas the fall in FEF 25-75 was explained by CaNO TMAD and blood eosinophil count. Both CaNO TMAD ≥10.5 ppb and urinary adenosine ≥406 nmol/mmol Cr predicted a fall in FEV 1 ≥10%, while only CaNO TMAD ≥10.5 ppb predicted a fall in FEF 25-75 ≥26%. CONCLUSION: Concentrations of peripheral airway NO are complementary with urinary adenosine for assessing EIB and promising tools of asthma control in pediatric patients with the atopic phenotype.

Lack of evidence for post-vaccine onset of autoimmune/lymphoproliferative disorders, during a nine-month follow-up in multiply vaccinated Italian military personnel.

Anecdotal case reports, amplified by mass media and internet-based opinion groups, have recently indicated vaccinations as possibly responsible for autoimmunity/lymphoproliferation development. Multiply vaccinated Italian military personnel (group 1, operating in Italy, group 2, operating in Lebanon) were followed-up for nine months to monitor possible post-vaccine autoimmunity/lymphoproliferation onset. No serious adverse event was noticed in both groups. Multivariate analysis of intergroup differences only showed a significant association between lymphocyte increase and tetanus/diphtheria vaccine administration. A significant post-vaccine decrease in autoantibody positivity was observed. Autoantibodies were also studied by microarray analysis of self-proteins in subjects exposed to ≥4 concurrent vaccinations, without observing significant difference among baseline and one and nine months post-vaccine. Moreover, HLA-A2 subjects have been analyzed for the possible CD8T-cell response to apoptotic self-epitopes, without observing significant difference between baseline and one month post-vaccine. Multiple vaccinations in young adults are safe and not associated to autoimmunity/lymphoproliferation onset during a nine-month-long follow-up.

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

BACKGROUND: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. METHODS: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. CONCLUSIONS: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

Measuring Intragastric Tumor Markers in Gastric Cancer Patients: a Systematic Literature Review on Significance and Reliability.

As of 2017, no serum tumor marker has shown high levels of sensitivity or specificity for early detection, classification, staging, prediction and prognosis of patients affected by gastric cancer. In this regard, since 1975 several authors have investigated the gastric juice or gastric lavage of patients with gastric adenocarcinoma in order to determine the concentrations of intragastric tumor markers and discover the perfect antigen for this cancer. To date, however, a systematic review of the literature on intragastric tumor markers is still unreported. After a thorough search, we found important as well as unimportant findings and have come to clearly defined conclusions. We believe that describing the current state of knowledge achieved by the scientific community in this particular field of research could augment information on the complex pathobiology of gastric cancer and entail a deeper understanding of its unpredictable malignant behavior.

Circulating neuregulin-1 and galectin-3 can be prognostic markers in breast cancer.

BACKGROUND: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. METHODS: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab. RESULTS: NRG1 and Gal-3 were significantly more elevated in cancer patients than in healthy controls; furthermore, NRG1 and Gal-3 were significantly increased after chemotherapy and were predictive of mortality at 1 year. CONCLUSIONS: Circulating NRG1 and Gal-3 can be additional biomarkers indicative of prognosis and outcomes for breast cancer patients.

Comparison Between Soluble ST2 and High-Sensitivity Troponin I in Predicting Short-Term Mortality for Patients Presenting to the Emergency Department With Chest Pain.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) and the soluble isoform of suppression of tumorigenicity 2 (sST2) are useful prognostic biomarkers in acute coronary syndrome (ACS). The aim of this study was to test the short term prognostic value of sST2 compared with hs-cTnI in patients with chest pain. METHODS: Assays for hs-cTnI and sST2 were performed in 157 patients admitted to the Emergency Department (ED) for chest pain at arrival. In-hospital and 30-day follow-up mortalities were assessed. RESULTS: The incidence of ACS was 37%; 33 patients were diagnosed with ST elevation myocardial infarction (STEMI), and 25 were diagnosed with non-ST elevation myocardial infarction (NSTEMI). Compared with the no acute coronary syndrome (NO ACS) group, the median level of hs-cTnI was higher in ACS patients: 7.22 (5.24-14) pg/mL vs 68 (15.33-163.50) pg/mL (P<0.0001). In all patients, the sST2 level at arrival showed higher independent predictive power than hs-cTnI (odds ratio [OR] 20.13, P<0.0001 and OR 2.61, P<0.0008, respectively). sST2 at ED arrival showed a greater prognostic value for cardiovascular events in STEMI (area under the curve [AUC] 0.80, P<0.001) than NSTEMI patients (AUC 0.72, P<0.05). Overall, 51% of the STEMI patients with an sST2 value>35 ng/mL at ED arrival died during the 30-day follow-up. CONCLUSIONS: sST2 has a greater prognostic value for 30-day cardiac mortality after discharge in patients presenting to the ED for chest pain compared with hs-cTnI. In STEMI patients, an sST2 value >35 ng/mL at ED arrival showed the highest predictive power for short-term mortality.

Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients.

Anti-neoplastic chemotherapy can determine various side effects, including cardiotoxicity, and no real guidelines for its early detection and management have been developed. The aim of this study is to find some plasmatic markers able to identify breast cancer patients that are at greater risk of developing cardiovascular complications during chemotherapy, in particular heart failure. A prospective study on 100 breast cancer patients with mean age of 66 years in adjuvant treatment with anthracyclines, taxanes, and trastuzumab was performed. Patients underwent cardiological examination before starting treatment (T0) and at 3 months (T1), 6 months (T2), and 1 year (T3) after treatment. Evaluation of serum cardiac markers and N-terminal pro-brain natriuretic peptide (NT-proBNP) was performed at T0, T1, T2, and T3, simultaneously to electrocardiogram and echocardiogram, showing a significant increase in NT-proBNP concentration (p > 0.0001) at T1, T2, and T3, before left ventricular ejection fraction decrease became evident. Human epidermal growth factor receptor 2 (HER2)-negative patients were more susceptible to mild hematological cardiotoxicity, while HER2-positive patients were more susceptible to severe cardiotoxicity. A significant correlation between NT-proBNP increased values after chemotherapy and prediction of mortality at 1 year was evidenced. From our experience, serum biomarker detection was able to support an early diagnosis of cardiac damage, also in the absence of left ventricular ejection fraction decrease. Therefore, the evaluation of specific plasmatic markers for cardiac damage is more sensitive than echocardiography in the early diagnosis of chemotherapy-related cardiotoxicity; furthermore, it can also add a prognostic value on outcome.

Soluble ST2 has a prognostic role in patients with suspected sepsis.

BACKGROUND: Soluble suppression of tumorigenicity 2 (sST2) has emerged as a novel biomarker for heart failure, and serum sST2 concentrations could be increased in inflammatory diseases. We explored whether sST2 is related to cardiac dysfunction/failure and has a prognostic role in patients with suspected sepsis. METHODS: In a total of 397 patients with suspected sepsis, sST2 concentrations were measured by using the Presage ST2 Assay (Critical Diagnostics, USA). sST2 concentrations were analyzed according to procalcitonin (PCT) concentrations, cardiovascular subscores of the sepsis-related organ failure assessment (SOFA) score, and clinical outcomes. RESULTS: sST2 concentrations were increased significantly according to the five groups of PCT concentrations and cardiovascular subscores of the SOFA score (P<0.000001 and P=0.036, respectively). In-hospital mortality was significantly higher among patients with sST2 concentrations above 35 ng/mL (P=0.0213) and among patients with increased concentrations of both sST2 and PCT (P=0.0028). CONCLUSIONS: sST2 seems to be related to both cardiac dysfunction/failure and severity in sepsis. Measurement of sST2 and PCT in combination would be useful for risk stratification and prognosis prediction in patients with suspected sepsis.

Serum Cystatin C for the Diagnosis of Acute Kidney Injury in Patients Admitted in the Emergency Department.

BACKGROUND: Early diagnosis of acute kidney injury (AKI) at emergency department (ED) is a challenging issue. Current diagnostic criteria for AKI poorly recognize early renal dysfunction and may cause delayed diagnosis. We evaluated the use of serum cystatin C (CysC) for the early and accurate diagnosis of AKI in patients hospitalized from the ED. METHODS: In a total of 198 patients (105 males and 93 females), serum CysC, serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were calculated at 0, 6, 12, 24, 48, and 72 hours after presentation to the ED. We compared two groups according to the presence or absence of AKI. RESULTS: Serial assessment of CysC, sCr, and eGFR was not a strong, reliable tool to distinguish AKI from non-AKI. CysC > 1.44 mg/L at admission, both alone (Odds Ratio = 5.04; 95%CI 2.20-11.52; P < 0.0002) and in combination with sCr and eGFR (Odds Ratio = 5.71; 95%CI 1.86-17.55; P < 0.002), was a strong predictor for the risk of AKI. CONCLUSIONS: Serial assessment of CysC is not superior to sCr and eGFR in distinguishing AKI from non-AKI. Admission CysC, both alone and in combination with sCr and eGFR, could be considered a powerful tool for the prediction of AKI in ED patients.

Manipulation of radiation-induced bystander effect in prostate adenocarcinoma by dose and tumor differentiation grade: in vitro study.

PURPOSE: This in vitro study evaluated the ability of prostate adenocarcinoma (ADC) cells to induce radiation-induced bystander effect (RIBE) exploring the factors that may be responsible and affect its intensity. The idea was to mimic a strong, clinically applicable RIBE that could lead to the development of innovative approaches in modern radiotherapy of prostate cancer, especially for those patients with hormone-refractory ADC in which radiotherapy might have a limited role. MATERIALS AND METHODS: Two human prostate cancer cell lines of different differentiation, PC-3 and DU-145, have been irradiated using wide range of doses to obtain radiation-conditioned medium (RCM), which was used to treat the unirradiated cells and to evaluate the cytokines level. Using a trypan blue dye exclusion method, cell growth was assessed. RESULTS: Prostate ADC cells were able to induce RIBE; intensity depended on dose and cell differentiation. RIBE intensity of DU-145 was not correlated with the cytokines level, while for PC-3 Interleukin-6 (IL-6) correlates with strongest RIBE induced by 20 Gy. CONCLUSIONS: RIBE can be manipulated by modifying radiation dose and depends on cell differentiation status. IL-6 correlates with RIBE after exposure of PC-3 to a very high dose of radiation, thus indicates its possible involvement in bystander signaling.

Structural myocardial alterations in diabetes and hypertension: the role of galectin-3.

BACKGROUND: Galectin-3 is a protein widely distributed in the heart, brain and blood vessels, and has a regulatory role in inflammation, immunology and cancer. Many studies demonstrated that the increased level of galectin-3 is associated with progressive fibrosis and stiffening of the myocardium. The aim of this study was to investigate the role of galectin-3 in patients with type 2 diabetes (T2D) and/or arterial hypertension (HT). METHODS: Study population included 189 patients, with no coronary artery disease, divided into three groups: group 1 (T2D), group 2 (T2D+HT), and group 3 (HT). All subjects underwent routine laboratory tests, as well as specific biomarkers assessment [galectin-3, glycosylated hemoglobin (HbA1c), N- terminal fragment B-type natriuretic peptide (NT-proBNP)]. Cardiological evaluation included physical examination, transthoracic tissue Doppler echocardiography and stress echocardiography. RESULTS: The results of this study demonstrated significantly increased levels of galectin-3, blood glucose, and HbA1c in group 2. Also, echocardiographicaly, left ventricular (LV) diameters and IVS thickness were increased in this group of patients. Furthermore, in the same cohort a positive correlation between galectin-3 and NT-pro BNP, and galectin-3 and LV mass were demonstrated. In addition, a negative correlation between galectin-3 and LV end-diastolic diameter was revealed. CONCLUSIONS: This study revealed that levels of galectin-3 were higher in patients with both T2D and HT, and correlated with LV mass, indicating the potential role of this biomarker for early detection of myocardial structural and functional alterations.

Opinion paper on utility of point-of-care biomarkers in the emergency department pathways decision making.

Overcrowding of the emergency department (ED) is rapidly becoming a global challenge and a major source of concern for emergency physicians. The evaluation of cardiac biomarkers is critical for confirming diagnoses and expediting treatment decisions to reduce overcrowding, however, physicians currently face the dilemma of choosing between slow and accurate central-based laboratory tests, or faster but imprecise assays. With improvements in technology, point-of-care testing (POCT) systems facilitate the efficient and high-throughput evaluation of biomarkers, such as troponin (cTn), brain natriuretic peptide (BNP) and neutrophil gelatinase-associated lipocalin (NGAL). In this context, POCT may help ED physicians to confirm a diagnosis of conditions, such as acute coronary syndrome, heart failure or kidney damage. Compared with classic laboratory methods, the use of cTn, BNP, and NGAL POCT has shown comparable sensitivity, specificity and failure rate, but with the potential to provide prompt and accurate diagnosis, shorten hospital stay, and alleviate the burden on the ED. Despite this potential, the full advantages of rapid delivery results will only be reached if POCT is implemented within hospital standardized procedures and ED staff receive appropriate training.

Peripheral blood lymphocyte typing as a useful tool to objectify the oral mucosa patch test in the diagnosis of allergic contact mucositis to nickel.

Nickel (Ni) exposure through the intestinal mucosa may cause a hypersensitivity reaction recently defined as allergic contact mucositis (ACM). This condition is identifiable by the oral mucosa patch test (omPT), a qualitative and subjective examination that requires clinical expertise. Our aim was to evaluate if a peripheral blood lymphocyte typing performed before and after the omPT for Ni may be able to objectify this examination for diagnostic purposes. Thirty patients with symptoms referable to the ingestion of Ni-rich foods were subjected to omPT for Ni. Before and after the omPT, each patient underwent blood sampling for the typing of total lymphocytes and their subsets (T, T helper or Th, T cytotoxic or Tc, B, natural killer or NK). Statistical analysis was performed by Student t test and receiver operating characteristic (ROC) curve analysis. According to the omPT outcomes, 18 patients were defined as Ni-sensitive and the remaining 12 as controls. In Ni-sensitive patients, the number of total, T, Th, Tc, and B lymphocytes/µL whole blood increased after the omPT (p<0.0001 for the first three, p=0.0004 and p=0.0001 for the last two lymphocyte types). No omPT-dependent lymphocyte increase was observed in controls. The post/pre omPT cell ratio, especially if calculated for Th lymphocytes, appears to be an effective index for diagnostic purposes (sensitivity=100%, specificity=83.3%, Youden index=0.833, area under curve (AUC)=0.926, p<0.0001). In conclusion, the peripheral blood lymphocyte typing with calculation of post/pre omPT cell ratio has the potential to support the omPT in diagnosing ACM, with the advantage of providing quantitative and objective data.

Immunological characterization of the allergic contact mucositis related to the ingestion of nickel-rich foods.

BACKGROUND: The ingestion of nickel (Ni)-rich foods may result in allergic contact mucositis (ACM), a not yet well defined condition identifiable by oral mucosa patch test (omPT). Our aim was to characterize immunologically the ACM taking advantage from the allergen exposure that occurs during the omPT for Ni. METHODS: Thirty-seven symptomatic patients underwent to omPT for Ni. Before and after omPT, serum and urine Ni concentrations were determined by mass spectrometry, the white blood cells were counted by hemochromocytometric assay, the peripheral lymphocyte typing was carried out by flow cytometry, total IgE and cytokine serum concentrations were measured by immunoenzymatic assays. The local lymphocyte typing was performed by immunohistochemistry only after omPT. RESULTS: According to the omPT outcomes, 25 patients were defined as Ni-sensitive and the remaining 12 as controls. After omPT, serum and urine Ni concentrations increased significantly in all patients, while a significant increment of circulating lymphocytes and neutrophils was highlighted, respectively, in Ni-sensitive and control patients. Consistently, the Th and Tc circulating lymphocytes, as well as the Th/Tc ratio increased significantly in Ni-sensitive patients after omPT. No noteworthy increment in serum concentrations of total IgE and selected cytokines was observed in any patient after omPT. The presence of CD3+, CD4+, and CD8+ cells was highlighted on the oral mucosa biopsy samples taken from Ni-sensitive patients after omPT. CONCLUSIONS: In patients with ACM, a local adaptive response with increased lymphocyte trafficking appears to be the most likely mechanism of reaction to Ni administered with the omPT.

Recovery of immunological homeostasis positively correlates both with early stages of right-colorectal cancer and laparoscopic surgery.

Differences in postoperative outcome and recovery between patients subjected to laparoscopic-assisted versus open surgery for colorectal cancer (CRC) resection have been widely documented, though not specifically for right-sided tumors. We investigated the immunological responses to the different surgical approaches, by comparing postoperative data simultaneously obtained at systemic, local and cellular levels. A total of 25 right-sided CRC patients and controls were managed, assessing -in the immediate followup- the conventional perioperative parameters and a large panel of cytokines on plasma, peritoneal fluids and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) tissue cultures. A general better recovery for patients operated with laparoscopy compared to conventional procedure, as indicated by the analysis of typical pre- and post-surgical parameters, was observed. The synchronous evaluation of 12 cytokines showed that preoperative plasma levels of the proinflammatory cytokines IL-6, IL-8, IL-1ß, TNFα were significantly lower in healthy donors versus CRC patients and that such differences progressively increase with tumor stage. After surgery, the IL-6 and IL-8 increases were significantly higher in open compared to laparoscopic approach only in CRC at early stages. The postsurgical whole panel of cytokine levels were significantly higher in peritoneal fluids compared to corresponding plasma, but with no significant differences depending on kind of surgery or stage of disease. Then we observed that, pre- compared to the corresponding post-surgery derived LPS-stimulated PBMC cultures, produced higher supernatant levels of the whole cytokine panel. In particular IL-6 in vitro production was significantly higher in PBMC derived from patients subjected to laparoscopic versus open intervention, but -again- only in CRC at early stages of disease. Our results thus show that laparoscopy compared to open right resection is associated with a shorter compromission of the immunological homeostasis, mainly in early stages of right-CRC patients.

Inflammation and immune response in acute aortic dissection.

OBJECTIVE: The aim of our study was to evaluate the lymphocyte subpopulations and the cytokines in the peripheral blood of patients with type-A Stanford acute aortic dissection (AAD group) and to determine whether inflammatory cells are present at the site of aortic dissection. METHODS: Thirty-five consecutive patients with type-A Stanford dissection were evaluated for haemochrome and lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD4+CD25+, CD16+CD56+, CD4+CD28-, CD8+CD28-) by flow cytometry. C-reactive protein (CRP), tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, interferon-gamma (IFN-γ), and monocyte chemoattractant protein (MCP)-1 were measured by ELISA. In addition, immunohistochemical staining with cell type-specific antibodies was performed to study the inflammatory cells detected inside the aortic wall. RESULTS: In the AAD group, a significant increase in natural killer (NK) (P = 0.032), B cells (P = 0.022), and CD8+CD28- (P = 0.045) subpopulations was observed, whereas there was a significant decrease in total T lymphocytes (P = 0.004) and T helper fractions (P = 0.005). Moreover, a significant increase in CRP (P < 0.0001), IL-6 (P < 0.0001), IL-8 (P < 0.0001), IL-10 (P < 0.0001), TNF-α (P < 0.0001), and MCP-1 (P < 0.001) was observed; macrophages represented the main population detected inside the media. CONCLUSIONS: Our results strongly support the hypothesis of a pivotal role of innate immunity in type-A Stanford AAD.

[Gastric pacing to treat morbid obesity: two years experience in four patients]. / Il gastric pacing per il trattamento dell'obesità patologica. Esperienza a due anni in 4 pazienti.

BACKGROUND: Gastric pacing to treat morbid obesity has been found to be safe and the implant technique simple to perform. Appetite is reduced and satiety is increased after the implant. There are two components in the Implantable Gastric Stimulation (IGS): (a) an electrical stimulator connected to a (b) bipolar lead that is positioned in the muscle wall of the stomach. We describe the optimal procedure to safely place the components. We present our results after preliminary experiences. METHODS: From August 2005 to January 2006, 4 patients (F) mean age 44 (33-63) underwent to IGS implant. The mean BMI was 41.8 (378-47), mean weight 117.2 Kg (107-133) . The IGS was activated 30 days after implant. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured before and 1, 2, 3 and 6 months after implanting operation. RESULTS: All procedures were successfully completed laparoscopically. There were no major operative complications. Postoperative course was uneventful in all cases. One patient was lost to follow up after six months. Postoperative lead dislodgement and cutaneous decubitus occurred in another patient, making necessary the removing of the device. For the other two patient only in one there was a significant weight loss (49 Kg), in the second weight was unchanged. Plasma ghrelin concentrations were no correlated among patients, and results were not in line with what waited by the producer. CONCLUSION: Morbid obese patients can undergo IGS implantation by laparoscopy with minimal perioperative complications. Attention to technical details is essential. In accordance with the producer (Medtronic) our data demonstrate that gastric pacing is a safe procedure for selected patients supported by adequate psychological treatment, but outcome about weight loss should be evaluated among bigger trial, as our experience didn't give satisfactory results, and therefore discouraged us to carry on with the study.