Highly conserved bifidobacteria in the human gut: Bifidobacterium longum subsp. longum as a potential modulator of elderly innate immunity.

Aging is a physiological and immunological process involving the deterioration of human health, characterised by the progressive alteration of organs and their functions. The speed and extent of such decline are dependent on lifestyle, environment, and genetic factors. Moreover, with advancing age, humans become progressively more fragile and prone to acute and chronic diseases. Although the intestinal microbiota is predisposed to perturbations that accompany aging and frailty, it is generally accepted that the gut microbiota engages in multiple interactions that affect host health throughout the host life span. In the current study, an exhaustive in silico investigation of gut-associated bifidobacteria in healthy individuals from birth to old age revealed that Bifidobacterium longum subsp. longum is the most prevalent member, especially during infancy and in centenarians. Moreover, B. longum subsp. longum genome reconstruction and strain tracing among human gut microbiomes allowed the identification of prototypes of this taxon in the human gut microbiota of healthy elderly individuals. Such analyses guided culturomics attempts to isolate B. longum subsp. longum strains that matched the genomic content of B. longum subsp. longum prototypes from healthy elderly individuals. The molecular effects of selected B. longum subsp. longum strains on the human host were further investigated using in vitro microbe-host interactions, revealing differences in the host immune system transcriptome, with a reduction in gene expression of inflammation-related cytokines. These intriguing findings support the potential anti-aging effects of elderly associated prototypes of B. longum subsp. longum.

Apheresis treatment of cryoglobulinemic vasculitis: A multicentre cohort study of 159 patients.

OBJECTIVE: To assess the effectiveness of apheresis therapy (AT) in treating the clinical manifestations of patients with complicated cryoglobulinemic vasculitis (CV). METHODS: A retrospective cohort study of 159 CV patients attending 22 Italian Centers who underwent at least one AT session between 2005 and 2015. The response to AT was evaluated on the basis of a defined grading system. RESULTS: Peripheral neuropathy was the most frequent clinical condition leading to AT. Therapeutic plasma exchange was used in 70.4% of cases. The outcome of AT was rated very good in 19 cases, good in 64, partial/transient in 40, and absent/not assessable in 36. Life-threatening CV-related emergencies and renal impairment independently correlated with failure to respond to AT. The independent variables associated with an increased risk of death were age at the time of the first AT session, multi-organ life-threatening CV, the presence of renal impairment and failure to respond to AT. The time-dependent probability of surviving until CV-related death in the second year was 84%, with an AHR in patients with absent/not assessable response to AT of 11.25. CONCLUSION: In this study AT is confirmed to be a safe procedure in patients with CV. Early AT should be considered in patients with severe CV, especially in cases with impending renal involvement, in order to prevent irreversible kidney damage. Although its efficacy in patients with multi-organ failure is limited, AT is the only treatment that can rapidly remove circulating cryoglobulins, and should be considered an emergency treatment.

The synergistic effect between Positivity, socio-demographic factors and smoking cessation: results of a cohort study.

OBJECTIVE: To examine the extent to which a effect does exist between Positivity (POS), smoking and socio-demographic factors in determining quitting smoking in subjects participating in a Group Counselling Program (GCP) for smoking cessation. METHODS: 481 subjects were contacted through a telephone call. A logistic regression analysis was carried out. Possible interaction between sociodemographic variables and POS level was tested using the Synergism Index (SI). RESULTS: For individuals with a POS level over or equal to 3.4 the odds of being smoker was significantly higher among females (OR = 1.55), who smoked at home (OR = 2.16) and lower if there had children at home (OR = 0.53). For individuals with a POS level under 3.4, the only significant variable associated with smoking was beinga female (OR = 2.58). As far concerns the synergistic effect between the variables considered does exist between POS levels and having children at home (SI=1.13) and female gender (SI = 2.8). CONCLUSIONS: The synergistic effect between POS and sociodemographic factors adds evidence on the use of POS as possible determinants of individual happiness.

Laparoscopic pancreaticoduodenectomy for tumors of the head of pancreas; 10 cases for a single center experience.

OBJECTIVE: The tumors of the head of the pancreas are one of the leading causes of cancer-related death in Western countries. The current gold standard for these tumors is a Whipple procedure. This procedure did not change in its surgical steps since when it was initially introduced in 1935. More recently, a laparoscopic approach with similar outcomes has been described. The aim of this paper is to describe the laparoscopic surgical technique performed in our unit, reporting single center postoperative outcomes. PATIENTS AND METHODS: From the 1st January 2013 to the 31st December 2015 a database was created. Data about patients who underwent a laparoscopic pancreaticoduodenectomy (LPD) were collected prospectively. All patients were preoperatively assessed with blood samples, tumor markers, CT chest abdomen and pelvis and/or MRI pancreas. Only patients with specific characteristics were considered eligible for an LPD: performance status 0, body mass index (BMI) less than 30 kg/m2, a small neoplastic lesion (< 3.5 cm) confined to the pancreas, the absence of infiltrated organs and/or blood vessels (T1 or T2). Postoperative data and complications were recorded and described according to the Clavien-Dindo classification and the international study group of pancreatic surgery definitions. RESULTS: In a time interval of 36 months, 31 patients with an initially considered resectable pancreatic cancer were referred. 11 patients were found to have metastasis during the preoperative workout. Only 10 patients were considered eligible for a LPD. Six of them were men (60%). The mean BMI was 25.01 kg/m2 (19.6-29.8). 5 patients, who underwent to LPD did not have any comorbidities. An overall 50% of all patients were jaundice at the time of diagnosis with a mean bilirubin level of 181.3 µmol/L (119.7-307.8). All patients with a direct bilirubin greater than 250 µmol/L underwent a preoperative percutaneous biliary drainage. In the majority of the LPD performed (50%), the histology reported a pancreatic adenocarcinoma. Other postoperative histology described were: IPMN (20%), ampullar neoplasia (20%) and neuroendocrine tumor (10%). Neo-adjuvant chemotherapy was never considered indicated. The reported postoperative complications were: 1 anastomotic bleeding, 2 pancreatic fistula, 1 infected intra-abdominal collection and 1 delay gastric emptying. The pancreatic fistulas were considered grade A and grade B. One fatality after LPD occurred because of an uncontrollable, diffuse severe hemorrhagic gastritis associated with a GJ anastomosis bleeding in the POD 25. The mean hospital stay was 12.3 days (8-25). The mean operative time was 224 min (170-310). There were no intraoperative complications. The main intraoperative blood loss was 220 ml (180-400) and intraoperative blood transfusions were not required. The resection margins were negative (R0) in 100% of cases and the mean lymph nodes harvested were 24 (18-40). The LPD is still a not common practice. Our results are comparable with those reported in literature about the open technique. These remarkable surgical outcomes are probably related to the extremely careful preoperative patient selection performed. The indication for a laparoscopic vs. an open pancreaticoduodenectomy was based on a CT scan pancreas performed less than 30 days before the planned date of surgery and a careful preoperative assessment. A low complication rate and a relative short stay in hospital were associated to a good quality of life in the early postoperative period and an early referral for postoperative chemotherapy. Good clinical outcomes were associated with outstanding oncological results. CONCLUSIONS: Laparoscopic pancreaticoduodenectomy is a feasible surgical procedure. Remarkable oncological and surgical outcomes can be achieved with a morbidity and mortality rate in line with the data reported by the large series of open procedures.

Effect of canine mesenchymal stromal cells loaded with paclitaxel on growth of canine glioma and human glioblastoma cell lines.

This study investigated whether canine mesenchymal stromal cells (cMSCs) are able to take up and release paclitaxel (PTX) in active form, and therefore whether they have potential as a tool for therapeutic delivery of this drug. cMSCs from bone marrow and adipose tissue were isolated, expanded and characterised phenotypically. cMSCs were loaded with PTX (cMSCs-PTX) and their capacity for release of PTX was determined by their effect on proliferation of cancer cells. cMSCs-PTX derived from bone marrow and adipose tissue were able to take up and then release active PTX. cMSCs-PTC inhibited proliferation of the canine glioma cell line J3T, and the human glioblastoma cell lines T98G and U87MG. The potential of canine cMSCs-PTX for treatment of canine gliomas should be investigated further.

Recurrent acute pancreatitis in bowel malrotation.

OBJECTIVE: Recurrent acute pancreatitis is an uncommon diagnosis in teenagers. Excluded alcohol and biliary stones, more prevalent aetiologies in these group of patients are genetic pancreatitis, pancreatic duct system abnormalities, neoplasia, traumas and congenital abnormalities of the duodenum such as duodenal duplication or diverticulum. Two reported cases of recurrent pancreatitis associated to midgut malrotation were described in English literature. Bowel malrotation is a difficult diagnosis in a teenager or a young adult and a common delay is documented. Ladd's procedure is largely recognized to be the standard treatment for a symptomatic malrotation. CASE REPORT: Our Report describes in details a case of recurrent pancreatitis, where a late diagnosis of midgut malrotation was obtained and an endoscopic management was attempted. A literature review and an analysis of two previously reported cases were performed to explore a possible aetiopathogenesis of the recurrent acute pancreatitis in patients with midgut malrotation. RESULTS: 24 months of follow-up showed an asymptomatic patient on a free diet, with a mild deranged Liver Functional Tests and a normal Amylase and Lipase. The recurrence of acute pancreatitis has not been observed until the present day. CONCLUSIONS: Recurrent episodes of acute pancreatitis in young adults, without a history of alcohol abuse or evidence of gallstones, might be an atypical presentation of midgut malrotation and it should be in the differential diagnosis. In this case, a Ladd's operation is beneficial and an endoscopic procedure does not obtain advantages.

Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery.

BACKGROUND: Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the 'Trojan Horse' concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new 'horses' in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. AIM: To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. METHODS: hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. RESULTS: hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake-release mechanism with PTX was not affected. CONCLUSIONS: hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis.

First on-line survey of an international multidisciplinary working group (MightyMedic) on current practice in diagnosis, therapy and follow-up of dyslipidemias.

The MightyMedic (Multidisciplinary International Group for Hemapheresis TherapY and MEtabolic DIsturbances Contrast) Working Group has been founded in 2013. The leading idea was to establish an international network of interdisciplinary nature aimed at working to cross national borders research projects, clinical trials, educational initiatives (meetings, workshops, summer schools) in the field of metabolic diseases, namely hyperlipidemias, and diabetes, preventive cardiology, and atherosclerosis. Therapeutic apheresis, its indications and techniques, is a parallel field of investigation. The first on-line survey of the Group has been completed in the first half of 2014. The survey included # 24 Centers in Italy, Germany, Greece, UK, Sweden, Japan and USA. Relevant data have been collected on current practice in diagnosis, therapy and follow-up of dyslipidemias. 240 subjects with hyperlipidemia and treated with lipoprotein apheresis have been reported in the survey, but a large percentage of patients (35%) who could benefit from this therapeutic option are still treated by conventional drug approach. Genetic molecular diagnosis is performed in only 33% of patients while Lipoprotein(a) (Lp(a)) is included in cardiovascular disease risk assessment in 71% of participating Centers. New detailed investigations and prospective multicenter studies are needed to evaluate changes induced by the impact of updated indications and strategies, as well as new treatment options, targeting standardization of therapeutic and diagnostic approaches.

Horse adipose-derived mesenchymal stromal cells constitutively produce membrane vesicles: a morphological study.

Mesenchymal stromal cells (MSCs) are multipotent somatic cells that can differentiate into a variety of mature cell types. Over recent years, their biological in vitro and in vivo properties have elicited great expectations in the field of regenerative medicine, immunotherapy and tumour treatment. An increasing number of experimental observations suggest that their biological effects are probably related to a paracrine mechanism via the release of trophic factors and cytokines as well as through the production of membrane vesicles (MVs). These are nanometric membrane-bound structures, comprising shedding vesicles (SV) and exosomes (Ex), that enclose and transfer signalling molecules to target cells. We hypothesized that MVs may be implicated in the biological effects of MSCs from horse adipose tissue (E-AdMSCs), a type of MSC that has been extensively studied in recent years for its remarkable efficacy in tissue regeneration. By means of electron microscopy, we ascertained, for the first time, that equine adipose-derived MSCs constitutively produce MVs (E-Ad-MSCs). The analysis of MVs separated by ultracentrifugation allowed us to describe their general morphological features. Through the examination of cell monolayers by TEM, additionally, we distinguished the different pathways of SV and Ex formation, demonstrating that both fractions are produced by E-AdMSC. The accurate description of MV heterogeneous morphological characteristics led us to emphasize the possible implications of the relationship between different morphologies versus different functions. The data presented in this paper has an additional value, as they can be noteworthy for horses as well as for other mammalian species, including humans.

Adipose tissue-derived stromal cells primed in vitro with paclitaxel acquire anti-tumor activity.

Many strategies, including those based on genetically modified Mesenchymal Stromal Cells (MSCs), have been developed in recent years in order to obtain high concentrations of anticancer drugs effective on tumor mass. In previous studies, we showed that human and murine bone marrow-derived MSCs (BM-MSCs) and human skin-derived stromal fibroblasts (hSDFs) acquired strong anti-tumor capacity, both in vitro and in vivo, once primed with Paclitaxel (PTX). In this report we investigate whether adipose tissue-derived MSCs (AT-MSCs) behave similarly to BM-MSCs in their uptake and release of PTX in sufficient amounts to inhibit tumor proliferation in vitro. According to a standardized procedure, PTX primed AT-MSCs (AT-MSCsPTX) were washed and then subcultured to harvest their conditioned medium, which was then tested to evaluate its in vitro anti-tumor potential. We observed that AT-MSCsPTX were able to uptake PTX and release it in a time-dependent manner and that the released drug was active in vitro against proliferation of leukemia, anaplastic osteosarcoma, prostatic carcinoma and neuroblastoma cell lines. These data confirm that AT-MSCs, as well as BM-MSCs, can be loaded in vitro with anti-cancer drugs. While the harvesting of BM-MSCs requires invasive procedures, AT-MSCs can be prepared from fat samples taken with little patient discomfort. For this reason, this source of stromal cells represents an important alternative to BM-MSCs in developing new tools for carrying and delivering anti-cancer drugs into tumor microenvironments.

The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.

Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL- Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot be considered either specific nor, selective. In PEX the whole blood is separated into plasma and its corpuscular components usually through centrifugation or rather filtration. The corpuscular components mixed with albumin solution plus saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins, but also other essential plasma proteins, such as albumin, immunoglobulins, and hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma separation and removal of plasma proteins through double filtration. During the CF two hollow-fiber filters with pores of different diameter are used to eliminate the plasma components of different weight and molecular diameter. A CF system uses a first polypropylene filter with 0.55 µm diameter pores and a second one of diacetate of cellulose with 0.02 µm pores. The first filter separates the whole blood, and the plasma is then perfused through a second filter which allows the recovery of molecules with a diameter lower than 0.02 µm, and the removal of molecules larger in diameter as apoB100-containing lipoproteins. Since both albumin and immunoglobulins are not removed, or to a negligible extent, plasma-expanders, substitution fluids, and in particular albumin, as occurs in PEX are not needed. CF however, is characterized by lower selectivity since removes also high density lipoprotein (HDL) particles which have an antiatherogenic activity. In the 80's, a variation of Lipid-apheresis has been developed which allows the LDL-cholesterol (LDLC) (-61%) and Lp(a) (-60%) removal from plasma through processing 3 liters of filtered plasma by means of lipid-specific thermofiltration, LDL immunoadsorption, heparin-induced LDL precipitation, LDL adsorption through dextran sulphate. More recently (90's) the DALI®, and the Liposorber D® hemoperfusion systems, effective for apoB100- containing lipoproteins removal have been developed. All the above mentioned systems are established LDL-apheresis techniques referable to the generic definition of LDLa. However, this last definition cannot describe in an appropriate manner the removal of another highly atherogenic lipoprotein particle: the Lp(a). Thus it would be better to refer the above mentioned techniques to the wider scientific and technical concept of lipoprotein apheresis.

First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis.

BACKGROUND: The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes. METHODS: Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined. RESULTS: In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups. CONCLUSIONS: Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Psychological well-being (PWB): a natural life outlook? An Italian twin study on heritability of PWB in young adults.

BACKGROUND: To date, the genetic and environmental architecture of the dimensions of psychological well-being (PWB) remains unexplored. METHOD: PWB of 742 twins aged 23-24 years and enrolled in the Italian Twin Registry was assessed with the three-item version of Ryff's Scales of Psychological Well-Being (SPWB). These scales include items for evaluating the PWB dimensions of self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth. A twin design was used to obtain correlations in the PWB dimensions for monozygotic (MZ) and dizygotic (DZ) twins and to estimate the contribution of genetic and environmental factors to variation and covariation in the dimensions. RESULTS: Genetic factors explained moderate to substantial proportions of variance in the six SPWB dimensions, with heritability estimates between 37% and 64%. The estimates of genetic correlations were very high (range 0.77-0.99), indicating that genetic factors that influence the expression of the different dimensions of PWB may be shared to a large extent. Non-shared environmental correlations ranged from substantial to high, with the exception of the correlation between autonomy and the dimensions of purpose in life, self-acceptance and personal growth. CONCLUSIONS: This study presents a twin analysis of PWB measured by the SPWB dimensions; it was found that both genes and non-shared environment play a role in individual differences. The genetic and non-shared environmental correlations between SPWB dimensions suggest that common underlying genetic and non-shared environmental factors influence the expression of the different facets of PWB.

Laparoscopic sleeve gastrectomy as first stage or definitive intent in 300 consecutive cases.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) was originally used as a bridge to definitive surgery in high-risk patients. Recently it has been considered as a stand-alone procedure due to its effectiveness on weight loss and comorbidities resolution. This study was designed to evaluate the results of SG on complications, body mass index (BMI), and comorbidities resolution in 300 consecutive obese patients and to analyze the lesson learned from this experience. METHODS: From October 2002 to November 2009, 300 patients underwent SG. In the first 100 cases (group 1: mean BMI, 54.4±9.3), SG was intended as a first stage of biliopancreatic diversion with duodenal switch in high risk super-obese patients. In the last 200 cases (group 2: mean BMI, 45.5±7.3), SG was intended as a definitive procedure. No routine reinforcement was performed in group 1. In group 2, oversewn reinforcement was performed routinely. SG was redo surgery in 21 patients (7%). RESULTS: Mean operative time was 119±48.6 min in group 1 and 72±33.8 in group 2. Conversion rate was 0.6% (massive hepatomegaly). Mortality was 0.6%. Major postoperative complications were registered in 15 patients in group 1 and 11 in group 2. In 3 cases, a reoperation was needed. The mean BMI in group 1 was 46, 43, 39, and 31 at 6, 12, 24, and 36 months, respectively. In group 2, the mean BMI was 32.9, 30.6, and 31.7 at 6, 12, and 18 months. At 12 months, the diabetes, hypertension, and OSAS were cured on 69%, 62%, and 50% in group 1 and 88%, 57%, and 58% in group 2. In group 2, no patient required second stage. CONCLUSIONS: SG is a safe and effective treatment for morbid obesity at mid-term follow-up. SG is effective for comorbidities resolution, especially for the treatment of diabetes. Suture line reinforcement allows a significant reduction of bleeding.

Long-term effects of laparoscopic sleeve gastrectomy, gastric bypass, and adjustable gastric banding on type 2 diabetes.

BACKGROUND: This study aimed to compare the efficacy of laparoscopic sleeve gastrectomy (SG) with that of laparoscopic gastric bypass (GBP) and laparoscopic adjustable gastric banding (AGB) for glucose homeostasis in morbidly obese subjects with type 2 diabetes mellitus (T2DM) at a 3-year follow-up assessment and to elucidate the role of weight loss in the T2DM resolution after SG. METHODS: For this study, 60 morbidly obese T2DM patients (44 females and 16 males) who underwent AGB (24 patients), GBP (16 patients), or SG (20 patients) between 1996 and 2008 were retrospectively analyzed. Age, sex, body mass index (BMI), estimated weight loss (EWL), fasting glycemia, HbA1c, euglycemic hyperinsulinemic clamp, discontinuation of diabetes treatment, and time until interruption of therapy were evaluated. RESULTS: In the study, 54 patients received oral hypoglycemic agents for at least 12 months before surgery, and 6 patients received insulin. The mean follow-up period was 36 months. The resolution rate was 60.8% for the AGB patients, 81.2% for the GBP patients, and 80.9% for the SG patients. The postoperative time until interruption of therapy was 12.6 months for the AGB patients, 3.2 months for the GBP patients, and 3.3 months for the SG patients. The hyperinsulinemic euglycemic clamp test was performed 12 months after surgery for the cured patients. Insulin resistance was restored to normal values in all the patients. The greatest improvement from preoperative values occurred in the SG group. For the not-cured GBP and SG patients, an improvement of 120 mg/dl in fasting plasma glucose was observed 3 months after the surgery, suggesting an enhancement in insulin sensitivity, which determines better medical control. The resolution rate remained constant at the 36-month follow-up evaluation in both the GBP and SG groups. CONCLUSIONS: All three bariatric procedures are effective in treating diabetes, with a 3-year follow-up evaluation showing an effect that lasts. The AGB procedure was the least effective. The antidiabetic effect was similarly precocious after GBP and SG compared with AGB. This difference may indicate that a hormonal mechanism may be involved, independent of weight loss.

Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study.

LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m²) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004 vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was present in 21%. 52.6% were physically active. Patients with coronary artery disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5% (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had both CAD and extra-coronary artery disease. This multicentre study confirmed that long-term treatment with LDLa was at least able to stabilize CAD in the majority of the individuals with symptomatic HyperLp(a).

A new completely flexible ring for mitral valve annuloplasty: the "Rama-Valvuloplasty-Ring". Five-year Pitié Salpétrière experience.

The aim of this study was to analyze the effects about the use of a new completely flexible ring for mitral valve anuloplasty, the "Rama-Valvuloplasty-ring", in 182 patients operated on in the Pitié-Salpétrière Hospital, Paris, France for mitral valve regurgitation (MVR). From January 1998 to December 2003, 182 patients with mitral regurgitation (MR) underwent mitral reconstructive surgery at our institution with the "Rama-Valvuloplasty-Ring". This group was made up of 117 men (64.3%) and 65 women (35.7%). The age ranged from 19 to 87 years (mean 62.51 +/- 8.2 years). The patients surviving the operation were the subject of a prospective follow-up. In the preoperative stage sinus rhythm was found in 71.97% (131) of patients and atrial fibrillation in the remaining 28.03% (51) of patients. The mean NYHA FC was 2.9 +/- 1.7 and subdivided as follows: 65 patients in FC I-II (35.72%), 104 patients in FC III (57.14%) and 13 patients in FC IV (7.14%). Most of the patients have shown, in the preoperative echocardiogram, grade II M.R. (46.15% N. 84) and grade III M.R. (29.12%, N.53); 24.72% of the patients (N. 45) had grade IV M.R. The mean E.F. was 42.8 +/- 9.7%. Left ventricular end diastolic diameter (LVEDD) was 57.7 +/- 9.7 mm. The causes of mitral valve insufficiency were degenerative disease in 141 patients (77.47%), post-ischemic disease in 21 patients (11.53%), rheumatic valvular disease in 11 patients (6.05%) and infectious endocarditis in 9 patients (4.95%). All the patients were operated using the Rama-Valvuloplasty-Ring. Ring sizes most commonly used were 30 mm and 32 mm, respectively in 92 patients (50.55%) and 41 patients (22.54%), followed by 28 mm (43 patients, 23.62%), 34 mm (5 patients, 2.74%), 36 mm (1 patient, 0.55%). The surgical tecnique was valve quadrangular resection in 103 patients (56.60%), triangular resection in 57 patients (31.32%) and no valve resection in 22 patients (12.08%). Among the above, 89 patients (48.90%) underwent an associated intervention as follows: 44 patients (24.18%) underwent coronary revascularization: 18 patients (9.89%) with single by-pass surgery, 21 patients (11.54%) with double by-pass, 5 patients with triple by-pass (2.75%); 42 patients (23.07) underwent aortic valve replacement (AVR); 3 patients (1.65%) underwent aortic repair. Early postoperative mortality was 2.19% (4 of 182 patients). Early postoperative echocardiographic control showed MR grade 0 in 142 patients (79.78%) and grade I in 36 (20.22%) with mean grade 0.4 +/- 0.12; no patients with grade III or IV. Therefore, there was no mitral annuloplasty failure requiring valve replacement (MVR). During the follow-up there were 12 late deaths (12 of 178 patients, 6.74%). Only one death was valve-related (thrombosis) whereas the other 11 ones were non cardiac-related deaths (subdural frontal haematoma, septic shock). Postoperative transthoracic echocardiogram data were available in 166 patients at 5 years: the presence of postoperative MR was evaluated and severity was graded as mild in 33 patients (19.88%), moderate in 18 patients (10.84%), severe in 3 (1.81%) patients. There was no MR in the other 112 patients (67.47%); LVEDD was 49.4 +/- 6.5 mm; EF was 51.8 +/- 4.3%. The mean NYHA FC was 0.8 +/- 0.4. Only one patient was reoperated on during the follow-up because of mitral annuloplasty failure with MVR. In conclusion, mid-term 5-years follow up is good for patients operated on with the new completely flexible Rama-Valvuloplasty-Ring for mitral annuloplasty. This study has also verified the advantage about the Rama-Valvuloplasty-Ring use in the preservation of native valve apparatus.

The endovascular treatment of traumatic isthmic aortic rupture: three years follow-up.

The isthmic aortic rupture represents the main cause of death in car crash accidents, because of closed chest trauma. Early medical and surgical care and endovascular prosthesis treatment with semi-invasive method can improve short and mid term survival. Nine patients with traumatic isthmic aortic rupture underwent endoprosthesis aortic implantation. All the patients were male, mean age 42.48 +/- 17.66 years. Operations included 5 acute cases and 4 chronic cases (chance diagnosis). In all cases the diagnosis was performed by tomodensitometric exam. Cloth prostheses were used (self-expansible Goretex- or Dacron-stent). Three years after the endoprosthesis implantation, we obtained the complete thrombosis of the false aortic lumen in all patients, both acute and chronic, as well as the levelling of the false aneurysms without complications of any kind.

Morphological and functional changes of cardiovascular system in postmenopausal women.

BACKGROUND: The incidence of cardiovascular events in reproductive age women is 3 times lower than in men, whereas this ratio noticeably changes on menopausal beginning. Postmenopausal women are more exposed to the effects of risk factors, which are present in a noticeably different entity in physiological or surgical menopause; and in the latter whether on substitutive hormonal treatment or not. METHODS: This study, carried out in Rome and Latina, has involved 743 postmenopausal women, of whom 545 with physiological menopause and 198 with iatrogenic menopause. RESULTS: The average blood pressure value as well as the incidence of hypertension, hypercholesterolemia, diabetes mellitus, obesity and smoking have a significantly different trend in physiological versus iatrogenic postmenopausal women; and in the latter whether on substitutive hormonal treatment or not. CONCLUSIONS: Studying life-style and evaluating risk factors in postmenopausal women, and giving an up-to-date view about the prevalence oh health conditions at risk, will allow us to promote both primary and secondary prevention actions.

The postnatal rat aorta contains pericyte progenitor cells that form spheroidal colonies in suspension culture.

Pericytes play an important role in modulating angiogenesis, but the origin of these cells is poorly understood. To evaluate whether the mature vessel wall contains pericyte progenitor cells, nonendothelial mesenchymal cells isolated from the rat aorta were cultured in a serum-free medium optimized for stem cells. This method led to the isolation of anchorage-independent cells that proliferated slowly in suspension, forming spheroidal colonies. This process required basic fibroblast growth factor (bFGF) in the culture medium, because bFGF withdrawal caused the cells to attach to the culture dish and irreversibly lose their capacity to grow in suspension. Immunocytochemistry and RT-PCR analysis revealed the expression of the precursor cell markers CD34 and Tie-2 and the absence of endothelial cell markers (CD31 and endothelial nitric oxide synthase, eNOS) and smooth muscle cell markers (alpha-smooth muscle actin, alpha-SMA). In addition, spheroid-forming cells were positive for NG2, nestin, PDGF receptor (PDGFR)-alpha, and PDGFR-beta. Upon exposure to serum, these cells lost CD34 expression, acquired alpha-SMA, and attached to the culture dish. Returning these cells to serum-free medium failed to restore their original spheroid phenotype, suggesting terminal differentiation. When embedded in collagen gels, spheroid-forming cells rapidly migrated in response to PDGF-BB and became dendritic. Spheroid-forming cells cocultured in collagen with angiogenic outgrowths of rat aorta or isolated endothelial cells transformed into pericytes. These results demonstrate that the rat aorta contains primitive mesenchymal cells capable of pericyte differentiation. These immature cells may represent an important source of pericytes during angiogenesis in physiological and pathological processes. They may also provide a convenient supply of mural cells for vascular bioengineering applications.