Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation.

Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS) 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex II (CII) and I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking RET in pro-inflammatory myeloid cells protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo . Our data show that RET in myeloid cells is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders 3 .

Complete absence of GLUT1 does not impair human terminal erythroid differentiation.

The Glucose transporter 1 (GLUT1) is one of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (Vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR-mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates for the first-time generation of enucleated human reticulocytes lacking GLUT1. The GLUT1-deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1-deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMPK-signalling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1 deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anaemia in GLUT1 deficiency syndrome.

Improvements in one severe progressive multiple sclerosis patient quality of life after an intensity fluid dynamic treatment.

Clinical case: A 49-year-old man (MM72) affected by Secondary Progressive Multiple Sclerosis (SP-MS) since 1998. On last 3 years, neurologists valued 9.0 the patient MM72's EDSS. Methods: MM72 was treated by acoustic waves, modulated in frequency and power by the MAM device, according to an ambulatory intensive protocol. Patient's treatments schedule was organized in thirty cycles of DrenoMAM and AcuMAM, and manual cervical spinal adjustments. Before and after treatments, MSIS-29, Barthel, FIM, EDSS, ESS, and FSS questionnaires were administered to the patient. Results: MM72 patient had improvements in all index score (MSIS-29, Barthel, FIM, EDSS, ESS and FSS) after 30 treatments by MAM plus cervical spine chiropractic adjustments. He showed a significative improvement of his disability and the restore of many functions. After MAM treatments, MM72's cognitive sphere improved of 370%. Fur-thermore, after 5 years of paraplegy, he regained his lower limbs and feet fingers movements with an increase of 230%. Conclusion: We suggest ambulatory intensive treatments by fluid dynamic MAM protocol in SP-MS patients. Statistical analyses are in progress on a larger sample of SP-MS patients.

The incidence of the multiple sclerosis in Italy: 2011-2015.

Introduction: There are very few scientific papers (and only on de-limited areas) about incidence and prevalence of the multiple sclerosis (MS) in Italy. We analysed 2011-2015 national data by correlating INPS database with ISTAT data. Materials: we assessed 10,725 MS invalids. We compared geographical distribution of MS patients with the Italian census. Results: We found a MS mean incidence equal to 3.54 patients every 100,000 Italian residents. The female MS mean incidence was 4.52 versus the male mean incidence of 2.52 (p<0.001). MS incidence is growing up from 2011 to 2015. Incidence values, for 100,000 inhabitants, become from 2.8 to 4.0 (female from 3.6 to 5.2 and male from 1.9 to 2.7). During 2011-2015 period, the MS patients median age decreases of two years (p<0.01). Conclusions: We couldn't calculate the MS prevalence because we do not have an official database managed by a national authority. This work wishes to be a stimulus to investigate more deeply and to promote public health in the care of the multiple sclerosis patients. We propose our work to realize a base more appropriate health planning on the national and regional territories for MS patients care.

High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: a matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation.

BACKGROUND: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. METHODOLOGY: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. RESULTS: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. CONCLUSION: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

Neutrophil-to-lymphocyte ratio but not monocyte-to-HDL cholesterol ratio nor platelet-to-lymphocyte ratio correlates with early stages of lower extremity arterial disease: an ultrasonographic study.

OBJECTIVE: The role of inflammatory markers as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-high-density lipoprotein-cholesterol ratio (MHR), and platelet-to-lymphocyte ratio (PLR) in cardiovascular diseases has been widely investigated in recent years. In the context of lower extremity arterial disease (LEAD), this association has been mainly studied in the advanced stages. The aim of our study was to investigate the role of these inflammatory markers in all stages of LEAD, including early ones, using ultrasonography as diagnostic tool, together with ankle-brachial index (ABI) determination. PATIENTS AND METHODS: In this cross-sectional observational study, we enrolled 240 patients undergoing ultrasonographic evaluation of the lower limb arteries and ABI determination because of symptoms suggestive of LEAD or presence of known cardiovascular risk factors. RESULTS: In our study population, we found that ultrasonographic categories of LEAD were associated with NLR, but not with MHR and PLR. CONCLUSIONS: These results confirm that a specific pattern of inflammation can be found in all stages of LEAD, including early ones.

Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel.

Omega 3 polyunsaturated fatty acids (PUFAs) influence metabolism and thermogenesis in non-hibernators. How omega 3 PUFAs influence Arctic Ground Squirrels (AGS) during hibernation is unknown. Prior to hibernation we fed AGS chow composed of an omega 6:3 ratio approximately 1:1 (high in omega 3 PUFA, termed Balanced Diet), or an omega 6:3 ratio of 5:1 (Standard Rodent Chow), and measured the influence of diet on core body temperature (Tb), brown adipose tissue (BAT) mass, fatty acid profiles of BAT, white adipose tissue (WAT) and plasma as well as hypothalamic endocannabinoid and endocannabinoid-like bioactive fatty acid amides during hibernation. Results show feeding a diet high in omega 3 PUFAs, with a more balanced omega 6:3 ratio, increases AGS Tb in torpor. We found the diet-induced increase in Tb during torpor is most easily explained by an increase in the mass of BAT deposits of Balanced Diet AGS. The increase in BAT mass is associated with elevated levels of metabolites DHA and EPA in tissue and plasma suggesting that these omega 3 PUFAs may play a role in thermogenesis during torpor. While we did not observe diet-induced change in endocannabinoids, we do report altered hypothalamic levels of some endocannabinoids, and endocannabinoid-like compounds, during hibernation.

Gastrointestinal symptoms and digestive comorbidities in an Italian cohort of patients with COVID-19.

OBJECTIVE: The Coronavirus Disease 2019 (COVID-19) pandemic mainly involves respiratory symptoms, though gastrointestinal (GI) symptoms are increasingly being recognized. In this context, the presence of comorbidities appears to be associated with adverse outcomes. However, the role of digestive manifestations is not yet well defined. The primary aim of this study was to assess the prevalence of GI symptoms and digestive comorbidities in a cohort of patients with COVID-19 compared to controls. The secondary aim was to determine the association of GI-symptoms and digestive comorbidities with clinical outcomes. PATIENTS AND METHODS: Inpatients with COVID-19 and controls with similar symptoms and/or radiological findings were enrolled. Symptoms at admission and throughout hospitalization were collected as they were comorbidities. The measured clinical outcomes were mortality, intensive care unit admission and cumulative endpoint. RESULTS: A total of 105 patients were included: 34 with COVID-19 and 71 controls. At admission, the prevalence of GI symptoms among COVID-19 patients was 8.8%. During hospitalization, the frequency of GI symptoms was higher in patients with COVID-19 than in controls (p=0.004). Among patients with COVID-19, the mortality and a cumulative endpoint rates of those with GI symptoms were both lower than for those without GI symptoms (p=0.016 and p=0.000, respectively). Finally, we found digestive comorbidities to be associated with a milder course of COVID-19 (p=0.039 for cumulative endpoint). CONCLUSIONS: Our results highlighted the non-negligible frequency of GI symptoms in patients with COVID-19, partly attributable to the therapies implemented. In addition, the presence of GI symptoms and digestive comorbidities is associated with better outcomes. Most likely, digestive comorbidities do not hinder the host's immune response against SARS-COV-2, and the occurrence of GI symptoms might be linked to a faster reduction of the viral load via the faecal route.

Trans-stomal single-port laparoscopic Hartmann's reversal is an efficacious and efficient procedure: a case-controlled study.

BACKGROUND: Hartman's reversal remains challenging and is associated with a widely variable success rate. In a previous study, we reported that laparoscopy may lower the mortality and morbidity rates of the procedure. The aim of the current study was to assess the operative results of single-port laparoscopic Hartmann's reversal (SP-HR) as compared to the more standard, multi-port laparoscopic variant (MP-HR). METHODS: We performed a retrospective, non-randomized, case-controlled study of 44 consecutive patients who had SP-HR (Group A) compared to 44 patients who had MP-HR (Group B). The study was conducted in a high-volume colorectal unit in a 1200-bed university affiliated hospital, The Poissy-Saint Germain Medical Complex, France. RESULTS: Preoperative patients' characteristics (sex, body mass index, American Society of Anesthesiologists status, prior surgery, comorbidities, colonic disease) were comparable in both groups. The conversion rate was 13.6% and 4.5% in Group A and in Group B, respectively (p = 0.084) and consisted of placement of any additional ports. Conversion to open surgery did not occur in any patient in either group (p = 1). Mean operative time was shorter in Group A than in in Group B, (105 vs. 155 min; p = 0.0133). The mortality rate was 2.2% in Group A and 0% in Group B (p = 0.3145). The overall morbidity rate was 11.4% in Group A and 18.2% in Group B (p = 0.5344). The median length of hospital stay was significantly shorter in Group than in Group B (4.8 vs. 6.8 days; p = 0.0102). CONCLUSIONS: The SP-HR technique was found to be safe and efficient. It compares favorably with MP-HR. Moreover, indirect cost savings could be induced by the reduction in the length of hospital stay.

Production of cheese from donkey milk as influenced by addition of transglutaminase.

Donkey milk is characterized by low contents of total solids, fat, and caseins, especially κ-casein, which results in formation of a very weak gel upon renneting. The objective of this study was to evaluate the effect of fortification of donkey milk with microbial transglutaminase (MTGase) for cheesemaking in relation to different enzyme addition protocols (patterns, PAT). Four independent trials were performed using MTGase (5.0 U/g of milk protein) according to the following experimental patterns: control (no MTGase addition); MTGase addition (40°C) 15 min before starter inoculation (PAT1); addition of MTGase to milk simultaneously with starter culture (40°C) (PAT2); and MTGase addition simultaneously with rennet (42°C) in acidified milk (pH 6.3) (PAT3). Evolution of pH during acidification, cheesemaking parameters, and proximal composition and color of cheese at 24 h were recorded. The protein fractions of cheese and whey were investigated by urea-PAGE and sodium dodecyl sulfate-PAGE. Addition of MTGase had no significant effect on moisture, protein, fat, or cheese yield. The addition of MTGase with rennet (PAT3) improved curd firmness compared with the control. Among the different patterns of MTGase addition, PAT3 reduced gel formation time, time between rennet addition and cheese molding, and weight loss of cheese at 24 h. The PAT3 treatment also resulted in the lowest lightness and highest yellowness color values of the cheese. Sodium dodecyl sulfate-PAGE of cheeses revealed that MTGase modified the protein pattern in the high-molecular-weight zone (range 37-75 kDa) compared with the control. Of the MTGase protocols, PAT3 showed better casein retention in cheese, as confirmed by the lanes of α- and ß-caseins in the electropherogram of the whey, which was subtler for this protocol. In conclusion, MTGase may be used in cheese production from donkey milk to improve curd firmness; MTGase should be added simultaneously with the rennet.

Preliminary experience with umbilical stoma in transumbilical single-port colorectal surgery.

BACKGROUND: The umbilicus, an embryological natural orifice, is increasingly used as the only access route during single-incision laparoscopic surgery (SILS) for colorectal disease. As a part of some of these procedures, a temporary, diverting ostomy could be exteriorized through the umbilicus itself. Theoretical advantages include better preservation of the abdominal wall and potentially superior cosmetic results. The aim of the present study was to evaluate our preliminary experience in SILS colorectal resection with umbilical stoma (u-stoma). METHODS: We retrospectively reviewed all colorectal patients operated using SILS for benign or malignant disease at Paris Poissy Medical Center. Patients were selected for consideration of u-stoma with our stoma therapists. RESULTS: Between January 2010 and December 2016, 234 patients underwent colorectal SILS procedures. In 74 patients (31.6%), an ileostomy (n = 41) or a colostomy (n = 33) was fashioned. Of these, 20 (27% of all ostomies) were umbilical stomas. The 20 u-stoma patients, 10 men and 10 women, received either a loop ileostomy (n = 14) or an end (n = 4) or loop (n = 2) colostomy. The mean age was 52 years (range 29-81 years). There was no mortality. Operative stoma-related morbidity occurred in only 5% of patients (n = 1: ileal torsion volvulus). Median follow-up after stoma formation was 30 months (range 12-59 months). Adjustment to the stoma and quality of life were satisfactory as estimated by both the patient and the stoma therapist. All stomas were reversed. At a median follow-up of 27.5 months (range 7-55 months) after stoma reversal, two patients had reoperation for incisional hernia. CONCLUSION: This preliminary experience showed that u-stoma is a feasible and safe alternative to more conventional ostomy after SILS.

Effect of water restriction on milk yield and quality in Lacaune breed ewes.

The effect of water restriction on body weight, body condition score, milk yield, and milk composition and rheological characteristics in intensively reared Lacaune ewes was evaluated. After 7 days of adaptation, the trial lasted 28 days. Thirty lactating ewes (48 ± 5 months of age; mean value ± standard deviation) at the beginning of third lactation month were divided into three groups (n = 10), corresponding to the following water restriction treatment: a group control received no drinking water restriction (W100), and two groups received water to the extent of 80% and 60% of W100 daily consumption (W80 and W60 group respectively). The effects of water restriction were assessed at the beginning of experiment (D0), at D14 and D28. The W60 group resulted in a significant decrease in body weight, body condition score, milk yield and feed consumption of hay due to the experimental treatment; whereas a marked increase in both W60 and W80 groups of milk lactose, urea, sodium, sodium chloride content and titratable acidity was observed. Rheological parameters of milk, rennet coagulation time and curd-firming time were positively affected by water restriction treatments, with a decrease in both experimental groups of the time required for the formation of a stable and firm curd. Results highlight the importance of water consumption in dairy sheep. The scarce availability of water, significantly affecting ewes milk production, is worthy of particular attention in arid area where water stress-resistant breeds should be considered. This study underlines that milk yield, being closely linked to the availability of water of the breeding habitat due to its high water content (about 81%), could be reached in area where water is not a limiting factor without reducing the genetic expression of the animals. Less severe water restrictions, such as 20% of daily voluntary water intake, produce no detrimental effect on milk yield.

Choosing the individual rehabilitation program for patients with intermittent claudication.

This study is aimed at identifying the collateral circulation in case of femoral-aorta-iliac axis obstruction, with the purpose of a more correct therapeutic indication being either medical or surgical or physiotherapeutic or combined.

Specific dyspeptic symptoms are associated with poor response to therapy in patients with gastroesophageal reflux disease.

INTRODUCTION: In patients with gastroesophageal reflux disease (GORD), co-existence of functional dyspepsia (FD) is known to be associated with poor response to proton pump inhibitors (PPIs), but the contribution of specific dyspepsia symptoms has not yet been systematically investigated. OBJECTIVE: We aimed to characterize the impact of dyspepsia symptoms on response to PPIs in patients with GORD. METHODS: The enrolled subjects were consecutive patients with a diagnosis of GORD. All patients underwent a 24 hour pH-impedance test, while on PPI therapy. Patients were divided into two groups, refractory and responders, according to the persistence of GORD symptoms. A standardized questionnaire for FD was also administered to assess presence of dyspepsia symptoms. RESULTS: In the subgroup of refractory patients FD was more prevalent than in responders, with post-prandial fullness, nausea, vomiting, early satiation and epigastric pain being significantly prevalent in refractory GORD patients. In the multivariate analysis only early satiation and vomiting were significantly associated with poor response to PPIs. CONCLUSION: Co-existence of FD is associated with refractory GORD. We showed that only early satiation and vomiting are risk factors for poor response to therapy with PPIs. Our findings suggest that symptoms of early satiation and vomiting would help to identify the subset of PPI-refractory GORD patients.

Dietary verbascoside supplementation in donkeys: effects on milk fatty acid profile during lactation, and serum biochemical parameters and oxidative markers.

Various uses of donkeys' milk have been recently proposed for human consumption on the basis of its nutritional characteristics. Improvements in milk fatty acid profile and animal oxidative status can be induced through dietary supplementation of phenolic compounds. The study aimed to evaluate in donkeys the effects of dietary supplementation with verbascoside (VB) on: (i) the fatty acid profile and vitamins A and E contents of milk during a whole lactation, and (ii) blood biochemical parameters and markers of oxidative status of the animals. At foaling, 12 lactating jennies were subdivided into two groups (n 6): control, without VB supplement; VB, receiving a lipid-encapsulated VB supplement. Gross composition, fatty acid profile and vitamins A and E contents in milk were assessed monthly over the 6 months of lactation. Serum total cholesterol, high-density lipoproteins cholesterol and low-density lipoproteins cholesterol, tryglicerides, non-esterified fatty acid, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase, reactive oxygen metabolites, thiobarbituric acid reactive substances (TBARs), vitamin A and vitamin E were evaluated at 8 days after foaling (D0) and then at D90, D105 and D120 of lactation. In milk, the VB supplementation decreased the saturated fatty acids (P<0.05) and increased the monounsaturated fatty acids (P<0.05), and vitamins A and E (P<0.01) values. On the serum parameters, the VB supplementation decreased total cholesterol (P<0.01), tryglicerides, bilirubin, ALT and TBARs, and increased (P<0.01) vitamin E. In conclusion, the VB dietary supplementation affects the nutritional quality of donkey's milk with a benefit on the oxidative status and serum lipidic profile of the animals.

Does DCD Donor Time-to-Death Affect Recipient Outcomes? Implications of Time-to-Death at a High-Volume Center in the United States.

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single-center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0-1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1-2 h. Five-year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5-year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait-time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.

Predicting Donor Death: Early Changes in Oxygen Saturation After Withdrawal of Support Predict Successful Donation During Donation After Circulatory Death.

BACKGROUND: We have previously shown that approximately 27% of patients do not progress to death in time to donate organs after attempted donation after circulatory death (DCD). As such, nearly 1000 transplants per year are not possible. One way to convert unsuccessful donations to successful donations is to increase procurement team "stand-down" times; however, increased stand-down times may predispose transplantable organs to increased ischemic damage. METHODS: Hemodynamics for successful and unsuccessful donations, occurring between 2011 and 2014, were characterized to determine if some unsuccessful DCDs could have donated successfully, had procurement teams waited longer. RESULTS: Analysis of 169 DCDs demonstrated statistically significant differences in hemodynamic profiles after withdrawal of support (WOS) between successful and unsuccessful donations. Early decreases in oxygen saturation were predictive of successful organ donation. We observed that for unsuccessful DCDs, patients who died in more than 2 hours but less than 12 hours were agonal within 10 minutes of WOS, suggesting that increasing stand-down times would result in prohibitive warm ischemia time. CONCLUSIONS: Early changes in oxygen saturation after withdrawal of support predict donor death. Alternative approaches that convert unsuccessful DCDs to successful DCDs but that do not result in low-quality organs should be explored.

Double loop reconstruction following pancreaticoduodenectomy for malignant tumor: Short-term outcome.

BACKGROUND: To evaluate the use of a double loop reconstruction following pylorus preserving proximal pancreaticoduodenectomy (PPPPD). METHODS: Morbidity and mortality were evaluated in 55 patients undergoing PPPPD for malignant tumors, followed by a double loop reconstruction. RESULTS: The mean intra-operative blood loss was 908mL±531. In-hospital mortality was 5.4% (3/55 pts). The mean length of hospital stay was 17±5 days (range 12-45 days). Postoperative complications occurred in 25 patients (46.2%). Five patients developed an anastomotic leak, one biliary and four pancreatic (4/55; 7%). Delayed gastric emptying occurred in 8 patients (14.5%). Reoperation was required in two patients for hemorrhage. CONCLUSIONS: A double loop alimentary reconstruction following PPPPD led to a low incidence of DGE and pancreatic fistula. Although mortality rate was higher than that reported by referral centres, this technique has been performed in a not specialized unit attaining acceptable results.

Enteric glia: A new player in inflammatory bowel diseases.

In addition to the well-known involvement of macrophages and neutrophils, other cell types have been recently reported to substantially contribute to the onset and progression of inflammatory bowel diseases (IBD). Enteric glial cells (EGC) are the equivalent cell type of astrocyte in the central nervous system (CNS) and share with them many neurotrophic and neuro-immunomodulatory properties. This short review highlights the role of EGC in IBD, describing the role played by these cells in the maintenance of gut homeostasis, and their modulation of enteric neuronal activities. In pathological conditions, EGC have been reported to trigger and support bowel inflammation through the specific over-secretion of S100B protein, a pivotal neurotrophic factor able to induce chronic inflammatory changes in gut mucosa. New pharmacological tools that may improve the current therapeutic strategies for inflammatory bowel diseases (IBD), lowering side effects (i.e. corticosteroids) and costs (i.e. anti-TNFα monoclonal antibodies) represent a very important challenge for gastroenterologists and pharmacologists. Novel drugs capable to modulate enteric glia reactivity, limiting the pro-inflammatory release of S100B, may thus represent a significant innovation in the field of pharmacological interventions for inflammatory bowel diseases.