Methods for diagnosing bile acid malabsorption: a systematic review

Background: Bile acid malabsorption (BAM) and bile acid-related diarrhea represent an under-recognized cause of chronic diarrhea mainly because of limited guidance on appropriate diagnostic and laboratory tests. We aimed to perform a systematic review of the literature in order to identify and compare the diagnostic accuracy of different diagnostic methods for patients with BAM, despite a proven gold standard test is still lacking. Methods: A PubMed literature review and a manual search were carried out. Relevant full papers, evaluating the diagnostic accuracy of different methods for BAM, were assessed. Available data were analyzed to estimate the sensitivity and specificity of each published test. Results: Overall, more than one test was considered in published papers on BAM. The search strategy retrieved 574 articles; of these, only 16 were full papers (with a total of 2.332 patients) included in the final review. Specifically, n = 8 studies used 75Selenium-homotaurocholic-acid-test (75SeHCAT) with a < 10% retention threshold; n = 8 studies evaluated fasting serum 7-α-hydroxy-4-cholesten-3-one (C4); n = 3 studies involved total fecal bile acid (BA) excretion over 48 h; n = 4 studies assessed fibroblast growth factor 19 (FGF19). 75SeHCAT showed an average sensitivity and specificity of 87.32 and 93.2%, respectively, followed by serum C4 (85.2 and 71.1%) and total fecal BA (66.6 and 79.3%). Fasting serum FGF19 had the lowest sensitivity and specificity (63.8 and 72.3%). All the extracted data were associated with substantial heterogeneity. Conclusions: Our systematic review indicates that 75SeHCAT has the highest diagnostic accuracy for BAM, followed by serum C4 assay. The diagnostic yield of fecal BA and FGF19 assays is still under investigation. Our review reinforces the need for novel biomarkers aimed to an objective detection of BAM and therefore improving the management of this condition

Characterization of the Pathogenic Potential of the Beach Sand Microbiome and Assessment of Quicklime as a Remediation Tool

Beach sand may act as a reservoir for potential human pathogens, posing a public health risk. Despite this, the microbiological monitoring of sand microbiome is rarely performed to determine beach quality. In this study, the sand microbial population of a Northern Adriatic Sea beach sand was profiled by microbiological (CFU counts) and molecular methods (WGS, microarray), showing significant presence of potential human pathogens including drug-resistant strains. Consistent with these results, the potential of quicklime as a restoring method was tested in vitro and on-field. Collected data showed that adding 1-3% quicklime (w/w) to sand provided an up to -99% of bacteria, fungi, and viruses, in a dose- and time-dependent manner, till 45 days post-treatment. In conclusion, data suggest that accurate monitoring of sand microbiome may be essential, besides water, to assess beach quality and safety. Moreover, first evidences of quicklime potential for sand decontamination are provided, suggesting its usage as a possible way to restore the microbiological quality of sand in highly contaminated areas

Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management

Anti-CD117 CAR T cells incorporating a safety switch eradicate human acute myeloid leukemia and hematopoietic stem cells

Discrimination between hematopoietic stem cells and leukemic stem cells remains a major challenge for acute myeloid leukemia immunotherapy. CAR T cells specific for the CD117 antigen can deplete malignant and healthy hematopoietic stem cells before consolidation with allogeneic hematopoietic stem cell transplantation in absence of cytotoxic conditioning. Here we exploit non-viral technology to achieve early termination of CAR T cell activity to prevent incoming graft rejection. Transient expression of an anti-CD117 CAR by mRNA conferred T cells the ability to eliminate CD117+ targets in vitro and in vivo. As an alternative approach, we used a Sleeping Beauty transposon vector for the generation of CAR T cells incorporating an inducible Caspase 9 safety switch. Stable CAR expression was associated with high proportion of T memory stem cells, low levels of exhaustion markers, and potent cellular cytotoxicity. Anti-CD117 CAR T cells mediated depletion of leukemic cells and healthy hematopoietic stem cells in NSG mice reconstituted with human leukemia or CD34+ cord blood cells, respectively, and could be terminated in vivo. The use of a non-viral technology to control CAR T cell pharmacokinetic properties is attractive for a first-in-human study in patients with acute myeloid leukemia prior to hematopoietic stem cell transplantation

Employment of Oligodeoxynucleotide plus Interleukin-2 Improves Cytogenetic Analysis in Splenic Marginal Zone Lymphoma

To compare the efficiency of novel mitogenic agents and traditional mitosis inductors, 18 patients with splenic marginal zone lymphoma (SMZL) were studied. Three cultures using oligodeoxynucleotide (ODN) plus interleukin-2 (IL-2), or TPA, or LPS were setup in each patient. Seventeen/18 cases with ODN + IL2 had moderate/good proliferation (94, 4%) as compared with 10/18 cases with TPA and LPS (55%) (P = .015); 14/18 (77, 7%) cases with ODN + IL2 had sufficient good quality of banding as compared with 8/18 cases (44, 4%) with TPA and LPS. The karyotype could be defined from ODN + IL2-stimulated cultures in all 18 patients, 14 of whom (77, 7%) had a cytogenetic aberration, whereas clonal aberrations could be documented in 9 and in 3 cases by stimulation with LPS and TPA, respectively. Recurrent chromosome aberrations in our series were represented by aberrations of chromosome 14q in 5 patients, by trisomy 12 and 7q deletion in 4 cases each, and by abnormalities involving 11q and 13q in two cases each. These findings show that stimulation with ODN + IL2 offers more mitotic figures of better quality and results in an increased rate of clonal aberrations in SMZL, making this method ideal for prospective studies aiming at the definition of the prognostic impact of cytogenetic aberrations in this disorder

Adipose micro-grafts enhance tendinopathy healing in ovine model: An in vivo experimental perspective study

In Europe, approximatively 100 000 to 500 000 tendon repairs are performed every year. These procedures are associated with a considerable rate of postoperative complications (from 6% to 11%). Autologous micro-grafts (AAMG) and stromal vascular fraction (SVF) have been shown to improve tendon healing in 60% to 70% of treated rodents. The purpose of this study was to evaluate the effects of AAMG in a sheep model with tendinopathy. We used sheep models because, as a large animal, they are more comparable to humans. The hypothesis was that SVF injection would improve tendon healing compared with the control group, reducing inflammatory and matrix degrading, while increasing anti-inflammatory expression and collagen synthesis in the early stage of tendon injury. Sixteen Apennine sheep aged 2 to 5 years underwent 500 UI type I collagenase injection into both common calcaneal tendons (CCT) to induce tendinopathy. After 15 days (T0), one CCT in every ovine underwent randomly to 2.5 mL of AAMG obtained by mechanical disruption and the contralateral CCTs received no treatment. Clinical, ecographic, and sonographic evaluations were performed after 4 weeks (T1) and 8 weeks (T2). Histological, immunohistochemical, real-time polymerase chain reaction (RT-PCR), and biomechanical evaluations were performed at T2. At T2, the treated group showed a final tendon diameter (9.1 ± 1.4 mm) and a hardness expression (62%) that were similar to the original healthy tendon (8.1 ± 1.1 mm; 100%), with a significant recovery compared with the control group (9.5 ± 1.7 mm; 39%). Moreover, histological analysis of the treated group revealed an improvement in the fiber orientation score, fiber edema score, infiltrative-inflammatory process, and necrosis score (4.3 ± 3.3) compared with control group (8.8 ± 2.9). Immunohistochemically, the treated group showed high expression of collagen 1, Factor VIII and significantly low expression of collagen 3. These data were confirmed by RT-PCR analysis. The study findings suggested that AAMGs obtained through mechanical disruption present a safe, efficient, and reliable technique, enhancing tendon healing

Gender, age and diagnosis effect on self-perceived pain in hematological patients: retrospective analysis of two case series.

We have read with great interest the paper by Ahmed and colleagues (1), entitled " Does gender affect self-perceived pain in cancer patients? -A meta-analysis "

The Matter of Future Heritage

In 2018, for the first time, the University of Bologna’s Board of PhD in Architecture and Design Culture assigned second-year PhD students the task of developing and managing an international conference and publishing its works. The organisers of the first edition of this initiative – Giacomo Corda, Pamela Lama, Viviana Lorenzo, Sara Maldina, Lia Marchi, Martina Massari and Giulia Custodi – have chosen to leverage the solid relationship between the Department of Architecture and the Municipality of Bologna to publish a call having to do with the European Year of Cultural Heritage 2018, in which the Municipality was involved. The theme chosen for the call, The Matter of Future Heritage, set itself the ambitious goal of questioning the future of a field of research – Cultural Heritage (CH) – that is constantly being  redefined. A work that was made particularly complex in Europe by the development of the H2020 programme, where the topic entered, surprisingly, not as a protagonist but rather as an articulation of other subjects that in the vision of the programme seemed evidently more urgent and, one might say, dominant. The resulting tensions have been considerable and with both negative and positive implications, all the more evident if we refer to the issues that are closest to us namely the city and the landscape

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs