A Single-System Ectopic Ureter in a Child: A Challenge for Early Diagnosis.

An ectopic ureter is an uncommon anomaly, usually associated with a duplicated urinary system. Up to 20% of ectopic ureters occur in a single system. In females, only 25% of ectopic ureters insert into the vagina and usually cause urinary incontinence, which can be confused with vaginal discharge. The diagnostic investigation includes urinary tract ultrasound, DMSA, and urethrocystography, which evaluate renal morphology and function, determining factors for surgical treatment decision that aims to preserve renal function, prevent the recurrence of infections, and reestablish urinary continence. The rarity of this anomaly and the delay in recognizing symptoms are factors related to late diagnosis.

Transcutaneous Posterior Tibial Nerve Stimulation: An Adjuvant Treatment for Intractable Constipation in Children.

BACKGROUND: Functional constipation can lead to painful defecations, fecal incontinence, and abdominal pain, significantly affecting a child's quality of life. Treatment options include non-pharmacological and pharmacological approaches, but some cases are intractable and require alternative interventions like neuromodulation. A subtype of neuromodulation, called Transcutaneous Posterior Tibial Nerve Stimulation (TPTNS), comprises electrical stimulation at the ankle level, by means of electrodes fixed to the skin. TPTNS is a minimally invasive, easy-to-apply technique that can potentially improve constipation symptoms in the pediatric population by stimulating the sacral nerves. AIM: To evaluate the clinical results and applicability of TPTNS as an adjuvant treatment for children and adolescents with functional constipation. METHODS: Between April 2019 and October 2021, 36 patients diagnosed with functional constipation according to the Rome IV Criteria were invited to participate in the study. The study followed a single-center, uncontrolled, prospective cohort design. Patients received TPTNS for 4 or 8 weeks, with assessments conducted immediately after the periods of TPTNS and 4 weeks after the end of the intervention period. The data normality distribution was determined by the Shapiro-Wilk test. The Wilcoxon test and Student's t-test for paired samples were used to compare quantitative variables, and the McNemar test was used to compare categorical variables. RESULTS: Of the 36 enrolled patients, 28 children and adolescents with intractable function constipation completed the study, receiving TPTNS for 4 weeks. Sixteen patients (57.1%) extended the intervention period for 4 extra weeks, receiving 8 weeks of intervention. TPTNS led to significant improvements in stool consistency, frequency of defecation, and bowel function scores, with a reduction in abdominal pain. Quality of life across physical and psychosocial domains showed substantial enhancements. The quality of life-related to bowel habits also improved significantly, particularly in lifestyle, behavior, and embarrassment domains. The positive effects of this intervention are seen relatively early, detected after 4 weeks of intervention, and even 4 weeks after the end of the intervention. TPTNS was well-tolerated, with an adherence rate of approximately 78%, and no adverse effects were reported. CONCLUSIONS: TPTNS is an adjuvant treatment for intractable functional constipation, improving bowel function and quality of life. The effects of TPTNS were observed relatively early and sustained even after treatment cessation.

Association between Clinical and Histopathological Findings in Intestinal Neuronal Dysplasia Type B: An Advance towards Its Definition as a Disease.

INTRODUCTION: Intestinal neuronal dysplasia type B (IND-B) is a controversial entity that affects the submucosal nerve plexus of the distal intestine. The lack of definition of the causal relationship between histological findings and clinical symptoms has been identified as the primary point to be elucidated in the scientific investigation related to IND-B, which is essential for it to be considered a disease. OBJECTIVE: To investigate the relationship between histopathological findings and symptoms in a series of patients with IND-B. METHODS: Twenty-seven patients with histopathological diagnosis of IND-B, according to the Frankfurt Consensus (1990), who underwent surgical treatment through colorectal resections were included. Data from medical records regarding the clinical picture of the patients at the time of diagnosis, including the intestinal symptom index (ISI) and a detailed histopathological analysis of the rectal specimens, were retrieved. Exploratory factor analysis was performed, applying the principal components method for clusters with Varimax rotation. RESULTS: Two factors were determined: the first, determined by histopathological and clinical variables, and the second, composed of the main symptoms presented in patients with IND-B, including ISI. Factorial rotation showed the association between the two factors and, through a graph, demonstrated the proximity between ISI values and histopathological alterations. CONCLUSION: There was evidence of an association between the clinical features presented by patients with IND-B and the histopathological findings of the rectal samples. These results support the understanding of IND-B as a disease.

Spinocerebellar ataxia 38: structure-function analysis shows ELOVL5 G230V is proteotoxic, conformationally altered and a mutational hotspot.

Fatty acid elongase ELOVL5 is part of a protein family of multipass transmembrane proteins that reside in the endoplasmic reticulum where they regulate long-chain fatty acid elongation. A missense variant (c.689G>T p.Gly230Val) in ELOVL5 causes Spinocerebellar Ataxia subtype 38 (SCA38), a neurodegenerative disorder characterized by autosomal dominant inheritance, cerebellar Purkinje cell demise and adult-onset ataxia. Having previously showed aberrant accumulation of p.G230V in the Golgi complex, here we further investigated the pathogenic mechanisms triggered by p.G230V, integrating functional studies with bioinformatic analyses of protein sequence and structure. Biochemical analysis showed that p.G230V enzymatic activity was normal. In contrast, SCA38-derived fibroblasts showed reduced expression of ELOVL5, Golgi complex enlargement and increased proteasomal degradation with respect to controls. By heterologous overexpression, p.G230V was significantly more active than wild-type ELOVL5 in triggering the unfolded protein response and in decreasing viability in mouse cortical neurons. By homology modelling, we generated native and p.G230V protein structures whose superposition revealed a shift in Loop 6 in p.G230V that altered a highly conserved intramolecular disulphide bond. The conformation of this bond, connecting Loop 2 and Loop 6, appears to be elongase-specific. Alteration of this intramolecular interaction was also observed when comparing wild-type ELOVL4 and the p.W246G variant which causes SCA34. We demonstrate by sequence and structure analyses that ELOVL5 p.G230V and ELOVL4 p.W246G are position-equivalent missense variants. We conclude that SCA38 is a conformational disease and propose combined loss of function by mislocalization and gain of toxic function by ER/Golgi stress as early events in SCA38 pathogenesis.

Transcutaneous Neuromodulation for Constipation and Fecal Incontinence in Children: A Systematic Review and Meta-Analysis.

INTRODUCTION: Constipation is a disorder with a multifactorial origin. Constipation has a varied clinical presentation, including infrequent defecation of bulky stools and episodes of retentive fecal incontinence. Neuromodulation has been used to treat many health problems, with promising results. OBJECTIVE: To conduct a systematic review of randomized clinical trials based on the effects of transcutaneous neuromodulation in treating constipation and retentive fecal incontinence in children and adolescents. METHODS: A systematic review of randomized clinical trials was performed. Medline (PubMed), PEDro, SciELO, Cochrane (CENTRAL), Embase, and Scopus databases were searched from March 2000 to August 2022. We included clinical trials evaluating transcutaneous neuromodulation in children with constipation and fecal incontinence compared or associated with other types of treatment. Two reviewers independently selected relevant studies, assessed the methodological quality, and extracted the data. RESULTS: Three studies with 164 participants were included in this review. Two meta-analyses were generated based on these studies. These analyses revealed that transcutaneous neuromodulation is an effective adjuvant treatment modality that improves children's constipation and retentive fecal incontinence. The methodological quality of the included studies was classified as high based on the assessment of the quality of evidence, with a high degree of confidence based on the GRADE system. CONCLUSIONS: Transcutaneous neuromodulation is an effective adjuvant treatment modality for children with constipation and retentive fecal incontinence.

Hirschsprung Disease and Intestinal Neuronal Dysplasia Type B: Is There a Difference in the Clinical Presentation of These Two Diseases?

BACKGROUND: Although the signs and symptoms that comprise the clinical presentation of Hirschsprung disease (HD) and intestinal neuronal dysplasia type B (IND-B) are well established, no studies have specifically compared the clinical characteristics presented by patients with these diseases. We compared the clinical pictures of patients with HD and IND-B at the time of histopathological diagnosis. METHODS: This was a single-center, retrospective, analytical, and comparative study. We included 119 patients aged 0-15 years diagnosed with HD or IND-B. Information from the medical records of these patients was retrieved to obtain demographic and clinical information at the time of diagnosis. The data were compared statistically according to the characteristics of the variables. RESULTS: Sixty-nine patients (58.0%) were diagnosed with HD, and 50 (42.0%) had IND-B. The HD group had significantly more individuals with symptom onset in the neonatal period (p = 0.001), delayed meconium clearance (p < 0.001), failure to thrive (p = 0.02), and acute complications, such as enterocolitis (p = 0.049) or acute abdominal obstruction (p = 0.031), more commonly requiring emergency surgery (p < 0.001). Patients with IND-B were diagnosed at a significantly older age (p = 0.002). They more commonly had chronic constipation as their main symptom (p = 0.004), with local complications, such as evacuation bleeding (p = 0.007). CONCLUSION: There were significant differences between the clinical pictures of patients with HD and IND-B. Knowledge of each disease's most common signs and symptoms can help direct diagnostic susception and initial management.

Agreement between histopathological and intraoperative classifications for pediatric appendicitis and its relationship with the post-operative clinical outcome.

Introduction: Some studies have shown poor agreement between intraoperative and histopathological classifications for appendicitis, despite their routine use in clinical practice. Objective: To investigate the agreement between histopathological and intraoperative classifications for pediatric appendicitis and evaluate the predictive potential of these classifications for the post-operative outcome. Methods: A retrospective, longitudinal, observational single-center study, carried out with 485 patients up to15 years of age, with a confirmed diagnosis of acute appendicitis by histopathological evaluation. The histopathological results classified the appendices as uncomplicated appendicitis when there was confirmation of the diagnosis of appendicitis without necrosis or perforation and complicated appendicitis when there was extensive necrotic tissue in the outer layer of the appendix or signs of perforation. The intraoperative findings were classified as uncomplicated appendicitis when the appendix presented with hyperemia and edema or fibrinous exudate and complicated appendicitis when the appendix showed necrosis, abscess, or perforation. The kappa index determined the agreement and the prediction relationships using a generalized linear model. Results: 43.9% of cases were classified as complicated appendicitis by histopathological evaluation and 49.7% by intraoperative classification. The agreement analysis between the histopathological and intraoperative classification showed a moderate agreement, with a Kappa index of 0.419 (0.337-0.501). There was an association (P < 0.05) between the intraoperative classification and the post-operative clinical outcomes (time to start feeding, fever, intraabdominal collection, length of stay, the need for antibiotic therapy changing, and need for ICU). There was no association between histopathological classification and post-operative outcomes. Conclusion: The agreement between the two classifications was moderate, and the intraoperative classification was able to predict the post-operative clinical outcomes.

CD38 Expression by Circulating and Skin-Infiltrating Lymphocytes from Sezary Syndrome Patients: A Flow Cytometry and Immunohistochemistry Study.

BACKGROUND: Reports on the expression of CD38 in Sézary syndrome (SS), erythrodermic primary cutaneous T cell lymphoma with leukemic involvement, are limited. The aim of the present study is the analysis of the expression of CD38 by skin-infiltrating mononuclear cells and circulating T lymphocytes in a cohort of SS patients. METHODS: SS patients diagnosed since 1985 in our clinic were retrospectively analyzed for CD38 expression in biopsy and blood samples by immunohistochemistry and flow cytometry, respectively. RESULTS: SS patients show a predominant CD38-negative phenotype on both skin and blood. A subgroup of patients was found expressing CD38 (12 cases) in either the skin (>25% cell infiltrate) or blood (CD4+CD38+ >50%), among whom 4 in the blood, 7 in the skin, and 1 in both blood and skin. CONCLUSION: The implications of these observations may be twofold: the relevance in basic science is related to a potential role in immune defense regulation, whilst in perspective CD38 may become a target for antibody therapy, considering the availability of different anti-CD38 monoclonal antibodies.

Sézary Syndrome: Different Erythroderma Morphological Features with Proposal for a Clinical Score System.

Sézary syndrome is a rare subtype of cutaneous T-cell lymphoma characterized by erythroderma, peripheral lymphadenopathies, and circulating atypical cerebriform T-cells. To date, no definite staging system has been developed for these patients. In this retrospective analysis of the archive of the Dermatological Clinic of the University of Turin, Italy, erythrodermic SS patients were classified according to clinical records and photographs into three main presentations: erythematous, infiltrated, or melanodermic. The pattern of erythroderma was found to be associated with disease outcome, as better survivals were recorded in patients with erythematous and infiltrative erythroderma. Patients in the melanodermic group, though less represented in our investigation, seemed to show a worse trend in survival. According to this preliminary evidence, a new prognostic classification, with a revised score specific for Sézary syndrome patients, can be proposed to usefully integrate the current staging system. The correlation displayed in our research will be hopefully confirmed by prospective studies with larger cohorts, with the aim of identifying significant prognostic features in this subset of cutaneous T-cell lymphoma patients.

CD157 signaling promotes survival of acute myeloid leukemia cells and modulates sensitivity to cytarabine through regulation of anti-apoptotic Mcl-1.

CD157/BST-1 (a member of the ADP-ribosyl cyclase family) is expressed at variable levels in 97% of patients with acute myeloid leukemia (AML), and is currently under investigation as a target for antibody-based immunotherapy. We used peripheral blood and bone marrow samples from patients with AML to analyse the impact of CD157-directed antibodies in AML survival and in response to cytarabine (AraC) ex vivo. The study was extended to the U937, THP1 and OCI-AML3 AML cell lines of which we engineered CD157-low versions by shRNA knockdown. CD157-targeting antibodies enhanced survival, decreased apoptosis and reduced AraC toxicity in AML blasts and cell lines. CD157 signaling activated the PI3K/AKT/mTOR and MAPK/ERK pathways and increased expression of Mcl-1 and Bcl-XL anti-apoptotic proteins, while decreasing expression of Bax pro-apoptotic protein, thus preventing Caspase-3 activation. The primary CD157-mediated anti-apoptotic mechanism was Bak sequestration by Mcl-1. Indeed, the Mcl-1-specific inhibitor S63845 restored apoptosis by disrupting the interaction of Mcl-1 with Bim and Bak and significantly increased AraC toxicity in CD157-high but not in CD157-low AML cells. This study provides a new role for CD157 in AML cell survival, and indicates a potential role of CD157 as a predictive marker of response to therapies exploiting Mcl-1 pharmacological inhibition.

Brazilian Portuguese version of the Amsterdam infant stool scale: a valid and reliable scale for evaluation of stool from children up to 120 days old.

BACKGROUND: For newborns and infants wearing diapers the difficulties in characterizing the appearance of the stool are significant, since the changes in consistency, quantity, and color of the stool are higher than in other age groups. The Amsterdam Infant Stool Scale (AISS) was created and validated in 2009, providing a specific tool for the evaluation of the stool of children up to 120 days old. However, to be used in clinical practice and scientific investigations in Brazil, it is mandatory to perform the translation and cross-cultural adaptation process for Brazilian Portuguese language. Thus, we aim to perform the translation and cross-cultural adaptation of AISS into Brazilian Portuguese and to evaluate the psychometric properties of the translated version. METHODS: The process of translation and cross-cultural adaptation was performed according to the internationally accepted methodology, including: translation, summary of translations, backtranslation, preparation of the pre-final version, application of the pre-test and determination of the final version. The evaluation of the psychometric properties was performed through the application of Brazilian Portuguese AISS, by five examiners (including child health field specialists and a literate adult lay on the subject), analyzing 238 stool photographs of children under 120 days old. The intra and inter-examiner agreement values were determined using kappa statistic. The validity of the criterion was investigated through correlation analysis (Kendall's coefficient) between the classifications determined by the non-specialist examiner and the expert examiners. RESULTS: In all 30 tests performed between different examiners, there was an agreement considered as at least moderate (kappa values above 0.40). The intra-examiner reliability was considered as substantial (kappa> 0.6). There was a statistically significant correlation (p <  0.05) between the classifications determined by the examiners considered as specialists and the examiner considered as non-specialist. CONCLUSION: The Brazilian Portuguese AISS version proved to be valid and reliable to be used by healthcare professionals and the general public in the evaluation of stool from children up to 120 days old.

Rectal Biopsy Technique for the Diagnosis of Hirschsprung Disease in Children: A Systematic Review and Meta-Analysis.

ABSTRACT: The diagnosis of Hirschsprung disease (HD) depends on the histopathological analysis of rectal biopsies. This review aims to define the best rectal biopsy technique. A systematic literature review and proportional meta-analysis of the available case series studies of rectal biopsies were performed in this study. All case series with more than five rectal biopsies in children younger than 18 years of age suspected of HD that described at least one type of rectal biopsy were included. The studies that did not specify the rate of conclusive results and the rate of complications of the biopsy procedures were excluded. According to the literature review, there were four different techniques of rectal biopsy: open, suction, punch, and endoscopic. In the title and abstract screening process, we assessed 496 articles, 159 fulfilled the eligibility criteria, and 71 studies reported our outcomes of interest and were included in the meta-analysis. The pooled proportion of conclusive results was 94% in open biopsies (95% CI 0.89-0.98), 95% in punch (95% CI 0.90-0.98), and 88% in suction group (95% CI 0.85-0.92). The pooled proportion of complication rates was 2% in open biopsies (95% CI 0.00031-0.04), 0.039% in suction (95% CI 0.00023-0.0006), and 2% in punch biopsies (95% CI 0.00075-0.04). Suction, punch, and open techniques presented comparable rates of conclusive results. In the suction group, the association between different methods of histopathological analysis increased conclusive results rates; however, the punch biopsy was associated with significantly higher complication rates than the suction technique.

What should be the treatment for intestinal neuronal dysplasia type B? A comparative long-term follow-up study.

PURPOSE: To present the long-term follow-up outcomes of patients with intestinal neuronal dysplasia type B (IND-B) managed either conservatively or surgically. METHODS: We conducted an ambispective, observational, longitudinal, and comparative study. Clinical data were reviewed at the start of treatment. After a minimum period of five years, the patients participated in semi-structured interviews in which the bowel function score (BFS) was applied to assess intestinal function, a proposed intestinal symptom index (ISI) to assess clinical symptoms, and a classification of clinical prognosis to assess treatment success. Comparisons between the two types of treatment were performed by evaluating pre- and post-treatment criteria. RESULTS: Fifty patients diagnosed with IND-B were included in the study. Thirty-eight patients underwent surgical treatment (26 elective surgical treatment for primary colorectal resection and 12 emergency colostomies for intestinal obstruction or enterocolitis). Twelve patients were managed conservatively. With the exception of the patients who required an emergency operation (n = 12), the two groups were composed of patients with severe constipation who had similar clinical and functional characteristics at the time of IND-B diagnosis. A better clinical response was observed in patients submitted to conservative treatment, with a greater increase in the BFS (16.5 [-4/+18] versus 4 [-15/+17]; p = 0.001), indicating better bowel function and a more pronounced drop in ISI (-6 [-7/-4] versus -4 [-6/+1]; p = 0.015), suggesting fewer symptoms. The percentage of patients who had a successful treatment was higher in the group treated conservatively (72.7% versus 42.3%; p = 0.03). CONCLUSION: Conservative management showed better long-term outcomes than surgical management in children with IND-B.

Are biopsies always necessary in upper and lower gastrointestinal endoscopy in children? A retrospective 10-year analysis.

Little attention has been given to the efficiency and validity of performing routine endoscopic biopsies in normal areas in children. This study aimed to investigate the need to perform routine biopsies in upper gastrointestinal endoscopy (UDE) and colonoscopy in normal areas by comparing macroscopy and histology. It was a 10-year retrospective analysis with the inclusion of 761 UDEs and 177 colonoscopies. Considering all segments, UDEs showed false-positive result rates of 73.11% and false-negative result rates of 14.34%. The histological results modified the initial management in 53.95% of patients. Considering all segments, colonoscopies showed false-positive result rates of 63.64% and false-negative result rates of 30.97%. The histological results modified the initial management in 34.45% of patients.Conclusion: If biopsies were obtained only in abnormal areas, the diagnosis would be lost in 53.95% of the patients in upper endoscopies and 85.7% of the colonoscopies, which justifies routine maintenance of biopsies in macroscopically normal areas in children. What is Known: • Little attention has been given to the efficiency and validity of endoscopic biopsies of normal areas during pediatric exams. • Only a few pediatric studies have correlated macroscopic and histological findings from endoscopic biopsies, and low sensitivity and specificity, as well as poor agreement, were reported. What is New: • Our study confirms the evidence that routine biopsies from macroscopically normal areas during upper and lower digestive endoscopies can lead to histopathological diagnoses and different medical management. • This is the first research on this topic in a Latin population, from a developing country, reassuring the results obtained in previous papers from other countries.

Ultrastructural analysis of bone formation around dental implants in nondiabetic rats, severe diabetics not controlled and controlled with insulin.

PURPOSE: To evaluate bone formation through ultrastructural analysis around titanium implants in severe alloxanic uncontrolled diabetic rats, and controlled with insulin, in comparison with nondiabetic rats. METHODS: Thirty-six male Wistar rats, weighing between 200 and 300 g, divided into three experimental groups: normal control group (G1), a diabetic group without treatment (G2), and a diabetic group treated with insulin (G3). The animals received titanium implants in the right femur, and osseointegration was evaluated at 7, 14, and 21 days after surgery, through ultrastructural analysis using scanning electron microscopy. RESULTS: The ultrastructural analysis showed a dense bone structure in the G1, few empty spaces and a small number of proteoglycans; G2 presented bone matrix with a loose aspect, irregular arrangement, thin trabeculae, empty spaces and a large number of proteoglycans; G3 obtained similar results to G1, however with a higher number of proteoglycans. CONCLUSION: Severe diabetes caused ultrastructural changes in bone formation, and insulin therapy allowed an improvement in osseointegration, but it was not possible to reach the results obtained in the control group.

A protocol for an interventional study on the impact of transcutaneous parasacral nerve stimulation in children with functional constipation.

INTRODUCTION: Transcutaneous parasacral nerve stimulation (TPNS) via electrodes placed over the sacrum can activate afferent neuronal networks noninvasively, leading to sacral reflexes that may improve colonic motility. Thus, TPNS can be considered a promising, noninvasive, and safe method for the treatment of constipation. However, there is no published study investigating its use in children with functional constipation. This is a single-center, prospective, longitudinal, and interventional study designed to assess the applicability and clinical outcomes of TPNS in functionally constipated children. PATIENT CONCERNS: Parents or guardians of patients will be informed of the purpose of the study and will sign an informed consent form. The participants may leave the study at any time without any restrictions. DIAGNOSIS: Twenty-eight children (7-18 years old) who were diagnosed with intestinal constipation (Rome IV criteria) will be included. INTERVENTIONS: The patients will be submitted to daily sessions of TPNS for a period of 4 or 8 weeks and will be invited to participate in semistructured interviews at 3 or 4 moments: 1 week before the beginning of TPNS; immediately after the 4 and/or 8 weeks of TPNS; and 4 weeks after the end of the intervention period. In these appointments, the aspects related to bowel habits and quality of life will be assessed. OUTCOMES: This study will evaluate the increase in the number of bowel movements and stool consistency, the decrease in the number of episodes of retentive fecal incontinence, and the indirect improvement in the overall quality of life. CONCLUSION: we expect that this study protocol can show the efficacy of this promising method to assist the treatment of children with functional constipation.

MicroRNA expression profiles in the esophagus of children with caustic stenosis: A pathway towards esophageal cancer?

BACKGROUND: Eighty percent of caustic ingestions occur in children and esophageal neoplasms may develop as a late complication of such injury. The identification of biomarkers is a promising strategy to improve early diagnosis of esophageal cancer or caustic lesions that are at an increased risk of progression. STUDY DESIGN/AIMS: This study aimed at identifying global microRNA (miRNA) expression changes in esophageal mucosa from children with caustic stenosis. The study included 27 biopsy samples from 15 patients. Samples were divided into two groups, according to the time elapsed after injury (N = 15 in Group A, with less than five years of follow-up and N = 12 in Group B, with more than five years of follow-up). miRNA expression profiles were determined in each lesion, compared with normal esophageal tissues from control group. We used the TaqMan Human MicroRNA Arrays (Thermo Fisher) platform. Furthermore, bioinformatic algorithms were used to identify miRNA target genes and biological pathways including miRNAs and their target genes potentially associated with esophageal disease. RESULTS: Thirteen miRNAs were significantly deregulated (9 over- and 4 underexpressed) in patients from Group A. In patients from Group B, two miRNAs were over- and two were underexpressed. Of note, miR-374 and miR-574 were deregulated in Group B patients and have been linked to esophageal tumorigenesis. We identified signal transduction and transcription factor networks with genes strongly related to development and progression of esophageal cancer. CONCLUSION: miRNAs identified here contribute to a better understanding of pathways associated with malignant transformation from caustic stenosis to neoplastic lesions. This study may serve as a basis for validation of miRNAs, including miR-374 and miR-574, as potential biomarkers of early cancer detection.

CD157: From Myeloid Cell Differentiation Marker to Therapeutic Target in Acute Myeloid Leukemia.

: Human CD157/BST-1 and CD38 are dual receptor-enzymes derived by gene duplication that belong to the ADP ribosyl cyclase gene family. First identified over 30 years ago as Mo5 myeloid differentiation antigen and 10 years later as Bone Marrow Stromal Cell Antigen 1 (BST-1), CD157 proved not to be restricted to the myeloid compartment and to have a diversified functional repertoire ranging from immunity to cancer and metabolism. Despite being a NAD+-metabolizing ectoenzyme anchored to the cell surface through a glycosylphosphatidylinositol moiety, the functional significance of human CD157 as an enzyme remains unclear, while its receptor role emerged from its discovery and has been clearly delineated with the identification of its high affinity binding to fibronectin. The aim of this review is to provide an overview of the immunoregulatory functions of human CD157/BST-1 in physiological and pathological conditions. We then focus on CD157 expression in hematological tumors highlighting its emerging role in the interaction between acute myeloid leukemia and extracellular matrix proteins and its potential utility for monoclonal antibody targeted therapy in this disease.