Effectiveness and safety of 1L PEG-ASC preparation for colonoscopy in patients with inflammatory bowel diseases.

INTRODUCTION: The effectiveness of bowel cleansing is a key element for high-quality colonoscopy. Recently, a 1 L polyethylene glycol plus ascorbate (PEG-ASC) solution has been introduced, but effectiveness and safety of this preparation have not been assessed in IBD patients. This study aims to evaluate effectiveness and safety of 1 L PEG-ASC solution in patients with IBD compared to controls. METHODS: We retrospectively analysed prospectively collected data on a cohort of 411 patients performing a colonoscopy after preparation with 1 L PEG-ASC, consecutively enrolled in 5 Italian centres. RESULTS: Overall, 185/411 (45%) were patients with IBD and 226/411 (55%) served as controls. A significantly higher cleansing success was achieved in IBD patients (92.9% vs 85.4%, p = 0.02). The multiple regression model showed that presence of IBD (OR=2.514, 95%CI=1.165-5.426; P = 0.019), lower age (OR=0.981, 95%CI=0.967-0.996; P = 0.014), split preparation (OR=2.430, 95%CI=1.076-5.492; P = 0.033), absence of diabetes (OR=2.848, 95%CI=1.228-6.605; P = 0.015), and of chronic constipation (OR=3.350, 95%CI=1.429-7.852; P = 0.005), were independently associated with cleansing success. The number of treatment-emergent adverse events (TEAEs) (51 vs 62%, p = 0.821), and of patients with TEAEs (22.2% vs 21.2%, p = 0.821), were similar in IBD patients and in controls, respectively. CONCLUSIONS: Results from this study support the effectiveness and safety of 1 L PEG-ASC solution in IBD patients, which may improve the definition of endoscopic outcomes both in Crohn's disease and ulcerative colitis.

Italian SARS-CoV-2 patients in intensive care: towards an identikit for subjects at risk?

OBJECTIVE: To investigate patient characteristics and factors that increase the risk of being admitted to intensive care and that influence survival in cases of SARS-CoV-2 pneumonia. PATIENTS AND METHODS: One-hundred and ninety-one SARS-CoV-2 patients were admitted to the "Fondazione Poliambulanza di Brescia" Hospital (Brescia, Lombardy, Italy) in the period 1st March 2020 to 11th April 2020. Data on demographics, clinical presentation at admission, co-morbidities, pharmacological treatment, admission to intensive care and death was recorded. Logistic regression and survival analysis were carried out to investigate the risk of being admitted to intensive care and the risk of death. RESULTS: The mean age of the study cohort was 64.6±9.9 years (range 20-88). Median BMI was 28.5±5 kg/m2. Fever (81%) and dyspnea (65%) were the most common symptoms on admission. Most of patients (63%) had at least one co-existing disease. The 157 (82%) patients admitted to intensive care were more likely to be of intermediate age (60-69 years; OR 3.23, 95% CI 1.32-8.38), overweight (OR 2.66, 95% CI 1.02-7.07) or obese (OR 5.63, 95% CI 1.73-21.09) and with lymphocytopenia (OR 2.75, 95% CI 1.17-6.89) than the 34 patients admitted to the ordinary ward. During intensive care, 50% of patients died and their death was associated with older age (HR 2.06, 95% CI 1.07-3.97), obesity (HR 2.23, 95% CI 1.15-4.35) and male gender (HR 1.9, 95% CI 1.02-3.57). CONCLUSIONS: We found that admission to intensive care and poor survival were associated with advanced age and higher body mass index, albeit with differences in statistical significance. Pre-existing diseases and symptoms on admission were not associated with different clinical outcomes. Interestingly, male gender was more prevalent among SARS-CoV-2 patients and was related negatively to survival, but it was not associated with more frequent admission to intensive care.

Impact of the COVID-19 pandemic on Gastroenterology Divisions in Italy: A national survey.

BACKGROUND: In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. AIMS: to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. CONCLUSION: This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases.

Colorectal cancer in patients with type 2 diabetes mellitus: a single-center experience.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of colorectal cancer (CRC). The aim of the study is to evaluate the prevalence of CRC in a cohort of Caucasian patients with T2DM and the association with other variables previously known to be related with increased risk of CRC. We retrospectively evaluated the data of 741 consecutive Caucasian patients with T2DM who underwent colonoscopic screening in our tertiary referral center. A control cohort of 333 patients with thyroid disease was selected to evaluate the difference in the incidence of CRC. At a median follow-up of 132.5 months (range 33.3-175.7), 67 cases of cancer (prevalence 9%) occurred; among these, 14 cases of CRC were reported (prevalence 1.88%) among the diabetic patients, while only two case (one of these was a CRC) (overall prevalence 0.006%, prevalence of CRC 0.003%) occurred in the control group; the difference between the prevalence of CRC was statistically significant (chi-square 4.21, p=0.04). The median duration of T2DM to CRC diagnosis was 168 months (range 12-768). At the univariate analysis, older age (p=0.001, r 0.138) and diabetes duration (p=0.001, r 0.138) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0.07, r -0.098). In the subset of patients with CRC, the age (RR = 2.25; 95% CI: 0.30 - 17.31; p less than 0.001), the diabetes duration (RR = 1.93; 95% CI: 0.25 – 14.77; p = 0.001) and the sulphonylureas treatment (RR = 2.33; 95% CI: 0.78 – 7.38; p = 0.007) were independently correlated with CRC. In our study, the prevalence of CRC in the cohort of patients with T2DM was higher compared to that from the National Tumor Register in 2010 (0.5%). Furthermore, we could speculate that sulphonylureas may play a role in CRC carcinogenesis impairing the physiological insulin secretion.

Focal active colitis as a predictor of inflammatory bowel disease: results from a single-center experience.

The term focal active colitis (FAC) is conventionally used to describe the presence of isolated cryptitis, characterized by an inflammatory infiltrate consisting of intraepithelial neutrophils and/or neutrophils invading the lumen of the criptae, with no other microscopic alteration of the colonic mucosa and, in particular, without the presence of signs of chronic inflammation. To date, only four studies, including one conducted in a pediatric population, have been performed to evaluate the clinical significance of this disease. The aim of this retrospective study on prospectively-collected data is to evaluate the clinical implications of the focal active colitis, since there still remains a marked uncertainty regarding this topic and about how often such a diagnosis will presage a diagnosis of inflammatory bowel disease (IBD). Clinical, endoscopic, and pathological data were retrospectively reviewed from 30 patients with focal active colitis, who had no other diagnostic findings on colorectal biopsy and no history of chronic inflammatory bowel disease. The histological findings were correlated with clinical diagnoses. Thirty patients (11 males, 19 females; age 24-80 years, median 56 years) (0.5%) out of 5,600 undergoing colonoscopy between January 2012 and December 2016 presented a definitive diagnosis of FAC. Follow-up ranged from 6 to 60 months (median 24 months). At endoscopy, 19 patients (63%) had mild and non-specific changes, such as mild mucosal erythema, while 11 (37%) had normal findings. Eight patients were documented as having irritable bowel syndrome, while nine cases could be attributed to the effects of drugs, five presented FAC as incidental finding, one a diagnosis of infectious colitis, and seven a diagnosis of IBD (4 with Crohn’s disease). FAC was confirmed to be a more significant predictor of IBD than the previous literature would indicate, even if larger prospective studies, targeted to study this relationship, are needed to understand more clearly its clinical significance.

Intra-axonal calcium changes after axotomy in wild-type and slow Wallerian degeneration axons.

Calcium accumulation induces the breakdown of cytoskeleton and axonal fragmentation in the late stages of Wallerian degeneration. In the early stages there is no evidence for any long-lasting, extensive increase in intra-axonal calcium but there does appear to be some redistribution. We hypothesized that changes in calcium distribution could have an early regulatory role in axonal degeneration in addition to the late executionary role of calcium. Schmidt-Lanterman clefts (SLCs), which allow exchange of metabolites and ions between the periaxonal and extracellular space, are likely to have an increased role when axon segments are separated from the cell body, so we used the oxalate-pyroantimonate method to study calcium at SLCs in distal stumps of transected wild-type and slow Wallerian degeneration (Wld(S)) mutant sciatic nerves, in which Wallerian degeneration is greatly delayed. In wild-type nerves most SLCs show a step gradient of calcium distribution, which is lost at around 20% of SLCs within 3mm of the lesion site by 4-24h after nerve transection. To investigate further the association with Wallerian degeneration, we studied nerves from Wld(S) rats. The step gradient of calcium distribution in Wld(S) is absent in around 20% of the intact nerves beneath SLCs but 4-24h following injury, calcium distribution in transected axons remained similar to that in uninjured nerves. We then used calcium indicators to study influx and buffering of calcium in injured neurites in primary culture. Calcium penetration and the early calcium increase in this system were indistinguishable between Wld(S) and wild-type axons. However, a significant difference was observed during the following hours, when calcium increased in wild-type neurites but not in Wld(S) neurites. We conclude that there is little relationship between calcium distribution and the early stages of Wallerian degeneration at the time points studied in vivo or in vitro but that Wld(S) neurites fail to show a later calcium rise that could be a cause or consequence of the later stages of Wallerian degeneration.

Characterization and differential expression analysis of complete coding sequences of Vitis vinifera L. sirtuin genes.

The sirtuin/Sir2 (Silent information regulator 2) family of NAD+-dependent deacetylases and mono-ADP-ribosyltransferases plays an important role in several cellular processes including gene silencing, cell cycle regulation and life span extension in yeast and animals. Compared to other eukaryotes, plants have relatively fewer SIR2 related genes encoding only two putative SIR2 family proteins. Recently, two putative sirtuin genes were identified also in the grapevine genome. Starting from the predicted coding sequences present in the database, we have been able to obtain two truly expressed coding sequences from the start to the stop codon for both sirtuin genes that were named VvSRT1 and VvSRT2. The search for the expressed coding sequences was performed by comparing the predicted sequences with the recently available grape RNA seq database with the aim to develop the primers to be used in reverse transcriptase PCR reactions to amplify the genes of interest. Finally, in order to better understand the physiological role of both sirtuins, we investigated the expression of these genes in young leaves, mature leaves, and berries sampled at different growing stages. In leaves, usually it has been observed that VvSRT1 is less expresses than VvSRT2, moreover in young leaves VvSRT2 showed the higher expression during setting while in mature leaves during the flowering time. No particular variations have been observed concerning VvSRT1. In berries the two genes showed more similar expression level, and they showed the highest expression during the flowering time. Finally, the expression of VvSRT2 in berries is smaller than in leaves.

Viral-load and B-lymphocyte monitoring of EBV reactivation after allogeneic hemopoietic SCT in children.

EBV-associated post transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication that may occur after hemopoietic SCT. We prospectively screened 80 children on a weekly basis using nested quantitative PCR to evaluate EBV genome copies. EBV viral load <1000 copies per 10(5) PBMC was observed in 63% of transplants, whereas it was between 1000 and 9999 copies per 10(5) PBMC in 13%, and between 10 000 and 19 999 in 10%, with no significant increase in percentage of CD20+ lymphocytes. Viral load reached > or = 20 000 copies per 10(5) PBMC in 14% of patients, and rituximab was administered to 75% of them. None of the patients except one developed a lymphoproliferative disease. Our study found that only 13% of unrelated donor HSCT recipients had a very high risk of EBV-PTLD defined as > or = 20 000 geq per 10(5) PBMC associated with an increase in CD20+ lymphocyte. We suggest that rituximab could be administered in the presence of very high levels of EBV-DNA viral load or in the presence of mid levels of EBV-DNA viral load associated with an increase in the percentage of CD20+ lymphocytes. Through this approach, we significantly reduced the number of patients treated with rituximab, and consequently the acute and chronic adverse events related to this treatment.

WldS can delay Wallerian degeneration in mice when interaction with valosin-containing protein is weakened.

Axon degeneration is an early event in many neurodegenerative disorders. In some, the mechanism is related to injury-induced Wallerian degeneration, a proactive death program that can be strongly delayed by the neuroprotective slow Wallerian degeneration protein (Wld(S)) protein. Thus, it is important to understand the Wallerian degeneration mechanism and how Wld(S) blocks it. Wld(S) location is influenced by binding to valosin-containing protein (VCP), an essential protein for many cellular processes including membrane fusion and endoplasmic reticulum-associated degradation. In mice, the N-terminal 16 amino acids (N16), which mediate VCP binding, are essential for Wld(S) to protect axons, a role which another VCP binding sequence can substitute. In Drosophila, the Wld(S) phenotype is weakened by a similar N-terminal truncation and by knocking down the VCP homologue ter94. Neither null nor floxed VCP mice are viable so it is difficult to confirm the requirement for VCP binding in mammals in vivo. However, the hypothesis can be tested further by introducing a Wld(S) missense mutation, altering its affinity for VCP but minimizing the risk of disturbing other aspects of its structure or function. We introduced the R10A mutation, which weakens VCP binding in vitro, and expressed it in transgenic mice. R10AWld(S) fails to co-immunoprecipitate VCP from mouse brain, and only occasionally and faintly accumulates in nuclear foci for which VCP binding is necessary but not sufficient. Surprisingly however, axon protection remains robust and indistinguishable from that in spontaneous Wld(S) mice. We suggest that either N16 has an additional, VCP-independent function in mammals, or that the phenotype requires only weak VCP binding which may be driven forwards in vivo by the high VCP concentration.

Hepatitis B reactivation in allogeneic hemopoietic stem cell transplantation setting: a pediatric experience.

Reactivation of HBV is a well known complication in patients undergoing HSCT. Lamivudine treatment appears to prevent hepatitis B virus reactivation and to decrease the mortality in at risk HSCT patients. We describe HBV reactivation occurred in three allogeneic HSCT pediatric patients coming from Eastern Europe, one of whom was successfully treated with lamivudine. Our experience confirms that HBV-DNA may persist as intra-hepatic infection or in extra-hepatic sites and that HBV reactivation may appear during immunodepression. Careful and complete screening for HBV markers is mandatory before HSCT, especially in children coming from countries at risk for HBV. Furthermore, a treatment with lamivudine could also represent an efficacious prophylaxis in pediatric patients to avoid HBV reactivation and to decrease the development of severe hepatic disease.

Daclizumab as useful treatment in refractory acute GVHD: a paediatric experience.

GVHD remains a serious complication after allogeneic SCT. We describe 13 paediatric patients treated with daclizumab for refractory acute GVHD (aGVHD). After 30 days of daclizumab administration, all patients with cutaneous aGVHD reached complete response. Among patients with gastrointestinal disease, 50 and 30% had complete and partial response, respectively, whereas 11 and 55% of patients with hepatic aGVHD achieved CR and PR, respectively. Overall, complete (46%) and partial (46%) responses were demonstrated in 92% of our patients, whereas the remaining patients (8%) were nonresponders. No life-threatening infectious episodes were recorded within 100 days from transplant in this selected group of paediatric patients. Overall 46% of patients were alive at a median of 461 days from SCT, but 50% of them developed chronic GVHD. In our experience, daclizumab proved to be a useful and safe treatment for refractory and steroid-resistant/dependent aGVHD, in particular for cutaneous and low-moderate intestinal involvement.

Rare viral infections in children receiving hemopoietic stem cell transplant.

Viral infections are a rare complication in autologous hemopoietic stem cell transplant (HSCT) recipients but represent a frequent cause of disease after allogeneic HSCT. In the last years, there has been an increase in the number of viral diseases observed in these patients. This fact may be at least partially due to an improvement in diagnostic facilities, but the increasing number of transplant procedures and the more severe immunosuppression may also have played an important role.

Invasive mycoses in children receiving hemopoietic SCT.

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.

Bacteremias in children receiving hemopoietic SCT.

The incidence of bacteremia following hemopoietic SCT (HSCT) changes over time from the procedure. The first 30 days have the highest incidence, both in autologous and allogeneic HSCT recipients. In the following periods, bacteremia is a frequent complication in allogeneic HSCT, especially from alternative donors. Gram-positive cocci represent the most frequent cause of single-agent bacteremia. Knowledge of epidemiology (incidence and etiology) of bacteremias following HSCT is pivotal for planning management strategies (prevention, diagnosis and therapy) that must be distinct in the different post-transplant period.

Incidence of bacteremias and invasive mycoses in children undergoing allogeneic hematopoietic stem cell transplantation: a single center experience.

We performed a retrospective single center study to define the epidemiology of bacteremias or invasive mycoses in pediatric allogeneic hematopoietic SCT (HSCT) from matched related donors (MRD) or alternative donors (AD). During 119 213 days of follow-up, 156 infections were observed: 130 bacteremias (27 in MRD-HSCT and 103 in AD-HSCT recipients) and 26 invasive mycoses (8 in MRD-HSCT and 18 in AD-HSCT recipients). Overall, the risk of bacteremia was fivefold that of invasive mycosis (P<0.001). AD-HSCT recipients had a higher percentage of infections (89 vs 27%; P<0.001), a higher rate/100 days of immunosuppression (infection rate (IR): 0.21 vs 0.06; P<0.001) and a higher proportion of repeated infections (44 vs 9%; P=0.001). In AD-HSCT, the relative risk of bacteremia was 2.87 in the pre-engraftment period, 5.84 in the early post-engraftment period and 6.46 in the late post-engraftment period (P<0.001) compared to MRD-HSCT. Only after 1 year did the epidemiology become similar. The epidemiology of invasive mycoses did not differ significantly between the two types of transplant.