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1.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38473962

RESUMO

Colorectal cancer is the third leading cause of death from neoplasia worldwide. Thanks to new screening programs, we are now seeing an increase in Early Onset of ColoRectal Cancer (EOCRC) in patients below the age of 50. Herein, we report a clinical case of a woman affected by EOCRC. This case illustrates the importance of genetic predisposition testing also in tumor patients. Indeed, for our patient, we used a combined approach of multiple molecular and cellular biology technologies that revealed the presence of an interesting novel variant in the SMARCA4 gene. The latter gene is implicated in damage repair processes and related, if mutated, to the onset of various tumor types. In addition, we stabilized Patient-Derived Organoids from the tumor tissue of the same patient and the result confirmed the presence of this novel pathogenic variant that has never been found before even in early onset cancer. In conclusion, with this clinical case, we want to underscore the importance of including patients even those below the age of 50 years in appropriate screening programs which should also include genetic tests for predisposition to early onset cancers.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Colorretais/patologia , Neoplasias do Colo/genética , Testes Genéticos , Predisposição Genética para Doença , DNA , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética
2.
Open Biol ; 14(2): 230319, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38350611

RESUMO

Transient abnormal myelopoiesis (TAM) is a Down syndrome-related pre-leukaemic condition characterized by somatic mutations in the haematopoietic transcription factor GATA-1 that result in exclusive production of its shorter isoform (GATA-1S). Given the common hallmark of altered miRNA expression profiles in haematological malignancies and the pro-leukaemic role of GATA-1S, we aimed to search for miRNAs potentially able to modulate the expression of GATA-1 isoforms. Starting from an in silico prediction of miRNA binding sites in the GATA-1 transcript, miR-1202 came into our sight as potential regulator of GATA-1 expression. Expression studies in K562 cells revealed that miR-1202 directly targets GATA-1, negatively regulates its expression, impairs GATA-1S production, reduces cell proliferation, and increases apoptosis sensitivity. Furthermore, data from TAM and myeloid leukaemia patients provided substantial support to our study by showing that miR-1202 down-modulation is accompanied by increased GATA-1 levels, with more marked effects on GATA-1S. These findings indicate that miR-1202 acts as an anti-oncomiR in myeloid cells and may impact leukaemogenesis at least in part by down-modulating GATA-1S levels.


Assuntos
Síndrome de Down , Leucemia Mieloide , Reação Leucemoide , MicroRNAs , Humanos , Síndrome de Down/genética , Síndrome de Down/complicações , Síndrome de Down/patologia , Leucemia Mieloide/genética , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Reação Leucemoide/complicações , MicroRNAs/genética , MicroRNAs/metabolismo
3.
Histopathology ; 84(3): 440-450, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37903647

RESUMO

AIMS: Very early-onset inflammatory bowel disease (VEO-IBD) is a clinical umbrella term referring to IBD-like symptoms arising in children before the age of 6 years, encompassing both 'pure' IBD, such as ulcerative colitis (UC) and Crohn's disease (CD) and monogenic diseases (MDs), the latter often involving genes associated with primary immunodeficiencies. Moreover, histological features in gastrointestinal (GI) biopsies in MD can also have IBD-like morphology, making differential diagnosis difficult. Correct diagnosis is fundamental, as MDs show a more severe clinical course and their inadequate/untimely recognition leads to inappropriate therapy. METHODS AND RESULTS: Biopsy samples from the lower and upper GI tract of 93 clinically diagnosed VEO-IBD children were retrospectively selected in a multicentre cohort and histologically re-evaluated by 10 pathologists blinded to clinical information. Each case was classified according to morphological patterns, including UC-like; CD-like; enterocolitis-like; apoptotic; eosinophil-rich; and IBD-unclassified (IBD-U). Nine (69%) MD children showed IBD-like morphology; only the IBD-U pattern correlated with MD diagnosis (P = 0.02) (available in 64 cases: 51 non-MD, true early-onset IBD/other; 13 MD cases). MD patients showed earlier GI symptom onset (18.7 versus 26.9 months) and were sent to endoscopy earlier (22 versus 37 months), these differences were statistically significant (P < 0.05). Upper GI histology was informative in 37 biopsies. CONCLUSIONS: The diagnosis of the underlying cause of VEO-IBD requires a multidisciplinary setting, and pathology, while being one of the fundamental puzzle pieces, is often difficult to interpret. A pattern-based histological approach is therefore suggested, thus aiding the pathologist in VEO-IBD reporting and multidisciplinary discussion.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Trato Gastrointestinal Superior , Criança , Humanos , Estudos Retrospectivos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Endoscopia Gastrointestinal , Trato Gastrointestinal Superior/patologia , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/patologia
4.
Eur J Radiol ; 168: 111116, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37801998

RESUMO

PURPOSE: To build and validate a predictive model of placental accreta spectrum (PAS) in patients with placenta previa (PP) combining clinical risk factors (CRF) with US and MRI signs. METHOD: Our retrospective study included patients with PP from two institutions. All patients underwent US and MRI examinations for suspicion of PAS. CRF consisting of maternal age, cesarean section number, smoking and hypertension were retrieved. US and MRI signs suggestive of PAS were evaluated. Logistic regression analysis was performed to identify CRF and/or US and MRI signs associated with PAS considering histology as the reference standard. A nomogram was created using significant CRF and imaging signs at multivariate analysis, and its diagnostic accuracy was measured using the area under the binomial ROC curve (AUC), and the cut-off point was determined by Youden's J statistic. RESULTS: A total of 171 patients were enrolled from two institutions. Independent predictors of PAS included in the nomogram were: 1) smoking and number of previous CS among CRF; 2) loss of the retroplacental clear space at US; 3) intraplacental dark bands, focal interruption of the myometrial border and placental bulging at MRI. A PAS-prediction nomogram was built including these parameters and an optimal cut-off of 14.5 points was identified, showing the highest sensitivity (91%) and specificity (88%) with an AUC value of 0.95 (AUC of 0.80 in the external validation cohort). CONCLUSION: A nomogram-based model combining CRF with US and MRI signs might help to predict PAS in PP patients, with MRI contributing more than US as imaging evaluation.


Assuntos
Placenta Acreta , Placenta Prévia , Gravidez , Humanos , Feminino , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/patologia , Placenta Prévia/diagnóstico por imagem , Placenta/patologia , Estudos Retrospectivos , Cesárea , Imageamento por Ressonância Magnética/métodos
5.
Abdom Radiol (NY) ; 48(10): 3207-3215, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37439841

RESUMO

PURPOSE: To retrospectively evaluate the performance of different manual segmentation methods of placenta MR images for predicting Placenta Accreta Spectrum (PAS) disorders in patients with placenta previa (PP) using a Machine Learning (ML) Radiomics analysis. METHODS: 64 patients (n=41 with PAS and n= 23 without PAS) with PP who underwent MRI examination for suspicion of PAS were retrospectively selected. All MRI examinations were acquired on a 1.5 T using T2-weighted (T2w) sequences on axial, sagittal and coronal planes. Ten different manual segmentation methods were performed on sagittal placental T2-weighted images obtaining five sets of 2D regions of interest (ROIs) and five sets of 3D volumes of interest (VOIs) from each patient. In detail, ROIs and VOIs were positioned on the following areas: placental tissue, retroplacental myometrium, cervix, placenta with underneath myometrium, placenta with underneath myometrium and cervix. For feature stability testing, the same process was repeated on 30 randomly selected placental MRI examinations by two additional radiologists, working independently and blinded to the original segmentation. Radiomic features were extracted from all available ROIs and VOIs. 100 iterations of 5-fold cross-validation with nested feature selection, based on recursive feature elimination, were subsequently run on each ROI/VOI to identify the best-performing method to classify instances correctly. RESULTS: Among the segmentation methods, the best performance in predicting PAS was obtained by the VOIs covering the retroplacental myometrium (Mean validation score: 0.761, standard deviation: 0.116). CONCLUSION: Our preliminary results show that the VOI including the retroplacental myometrium using T2w images seems to be the best method when segmenting images for the development of ML radiomics predictive models to identify PAS in patients with PP.


Assuntos
Placenta Acreta , Placenta Prévia , Gravidez , Humanos , Feminino , Placenta , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos
7.
Br J Pharmacol ; 180(2): 235-251, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36168728

RESUMO

BACKGROUND AND PURPOSE: Transient receptor potential melastatin type-8 (TRPM8) is a cold-sensitive cation channel protein belonging to the TRP superfamily of ion channels. Here, we reveal the molecular mechanism of TRPM8 and its clinical relevance in colorectal cancer (CRC). EXPERIMENTAL APPROACH: TRPM8 expression and its correlation with the survival rate of CRC patients was analysed. To identify the key pathways and genes related to TRPM8 high expression, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted in CRC patients. TRPM8 functional role was assessed by using Trpm8-/- mice in models of sporadic and colitis-associated colon cancer. TRPM8 pharmacological targeting by WS12 was evaluated in murine models of CRC. KEY RESULTS: TRPM8 is overexpressed in colon primary tumours and in CD326+ tumour cell fraction. TRPM8 high expression was related to lower survival rate of CRC patients, Wnt-Frizzled signalling hyperactivation and adenomatous polyposis coli down-regulation. In sporadic and colitis-associated models of colon cancer, either absence or pharmacological desensitization of TRPM8 reduced tumour development via inhibition of the oncogenic Wnt/ß-catenin signalling. TRPM8 pharmacological blockade reduced tumour growth in CRC xenograft mice by reducing the transcription of Wnt signalling regulators and the activation of ß-catenin and its target oncogenes such as C-Myc and Cyclin D1. CONCLUSION AND IMPLICATIONS: Human data provide valuable insights to propose TRPM8 as a prognostic marker with a negative predictive value for CRC patient survival. Animal experiments demonstrate TRPM8 involvement in colon cancer pathophysiology and its potential as a drug target for CRC.


Assuntos
Neoplasias Colorretais , Canais de Cátion TRPM , Via de Sinalização Wnt , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/metabolismo , Prognóstico , Canais de Cátion TRPM/genética , Canais de Cátion TRPM/metabolismo , Via de Sinalização Wnt/genética
8.
Biomedicines ; 10(12)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36551759

RESUMO

The aim of this study was, firstly, to analyze the histopathological characteristics of placentas in women with uneventful pregnancies and affected by COVID-19 at the time of delivery; and secondly, to correlate histological findings to maternal and neonatal characteristics. In our single-center prospective observational study, 46 placentas from term uncomplicated singleton pregnancies of patients with a documented SARS-CoV-2 infection at the time of delivery underwent histological examination. Despite a normal feto-maternal outcome, most of the placentas (82.6%) presented signs of maternal vascular malperfusion, while features of fetal vascular malperfusion were found in 54% of cases. No correlation was detected between maternal and neonatal characteristics and the severity of blood circulation disease, and abnormal findings were also described in asymptomatic patients. Moreover, we did not find any maternal symptoms or clinical details allowing for the prediction of abnormal placental findings in pregnancy complicated by COVID-19 infection. Our results suggest that SARS-CoV-2 infection during pregnancy could lead to acute placental dysfunction.

9.
J Clin Med ; 11(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36233742

RESUMO

Antiphospholipid Antibody Syndrome (APS) is a systemic autoimmune disease characterized by acquired hypercoagulability with the possible development of venous, arterial, and microvascular thrombosis. We report a rare case of Libman-Sacks tricuspid valve endocarditis in a 38-year-old pregnant woman at 15 weeks gestation with unknown primary antiphospholipid syndrome. During a routine cardiac examination and echocardiography performed for a previous episode of pleuropericarditis, a large, mobile mass with irregular edges was found at the level of the tricuspid valve. Three main differential diagnoses for intramyocardial mass were examined: tumor, infective endocarditis, and nonbacterial thrombotic endocarditis (NTBE). Cardiac magnetic resonance imaging (CMR) with contrast raised the suspicion of a thrombus. The woman was hospitalized urgently at the Cardiac Intensive Care Unit of the Federico II University Hospital, and anticoagulant and antiplatelet therapy were started. The thrombophilic screening performed and medical history confirmed the diagnosis of primary antibody syndrome (APS). A multidisciplinary consultation with obstetricians, cardiologists, anesthetists, and cardiac surgeons was required. The patient decided not to terminate the pregnancy despite the risk to her health and to undergo cardiac surgery during pregnancy. Histological examination confirmed the presence of nonbacterial thrombotic endocarditis. Weekly obstetric scans were performed after surgery to verify fetal well-being. An emergency cesarean section was performed at the 35th week of gestation due to repeated deceleration and abnormal short-term variability on c-CTG in a pregnancy complicated by fetal growth restriction and gestational hypertension. A newborn weighing 1290 g was born. She was hospitalized in Neonatal Intensive Care and discharged after two months; currently, she enjoys good health. The management of patients with antiphospholipid antibody syndrome has not yet been standardized, but there is a general consensus that patients who do not have thrombocytopenia, thromboembolic phenomena, or pregnancy should not undergo any treatment or should take only low doses of acetylsalicylic acid. In the presence of any of the above conditions, various treatment regimens have been used based on the severity and individuality of the case.

10.
Microorganisms ; 10(7)2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35889153

RESUMO

The variety of placental morphological findings with SARS-CoV-2 maternal infections has raised the issue of poor agreement in histopathological evaluation. The aims of this study were: to describe the histopathological placental features of a large sample of SARS-CoV-2-positive women who gave birth in Italy during the COVID-19 pandemic, to analyse the factors underlying these lesions, and to analyse the impact of placental impairment on perinatal outcomes. From 25 February 2020 to 30 June 2021, experienced perinatal pathologists examined 975 placentas of SARS-CoV-2-positive mothers enrolled in a national prospective study, adopting the Amsterdam Consensus Statement protocol. The main results included the absence of specific pathological findings for SARS-CoV-2 infections, even though a high proportion of placentas showed signs of inflammation, possibly related to a cytokine storm induced by the virus, without significant perinatal consequences. Further research is needed to better define the clinical implications of placental morphology in SARS-CoV-2 infections, but the results of this large cohort suggest that placentas do not seem to be a preferential target for the new Coronavirus infection.

11.
Healthcare (Basel) ; 10(5)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35627942

RESUMO

BACKGROUND: Tailgut cysts are rare congenital lesions that develop in the presacral space. As they can potentially conceal primary neuroendocrine tumors, surgical excision is suggested as the treatment of choice. However, specific management guidelines have yet to be developed. A posterior approach is usually preferred for cysts extending to the third sacral vertebral body. Conversely, a transabdominal approach is preferred for lesions extending upward to achieve an optimal view of the surgical field and avoid injuries. CASE REPORT: Here, we report a case of a 48-year-old man suffering from perianal pain and constipation. Digital rectal examination and magnetic resonance imaging revealed a presacral mass below the third sacral vertebral body. A laparoscopic transabdominal presacral tumor excision was performed. The final histological diagnosis was a rare primary neuroendocrine tumor arising from a tailgut cyst. The postoperative course was uneventful, and no signs of recurrence were observed at the six-month follow-up. CONCLUSIONS: This study may help establish more well-grounded recommendations for the surgical management of rectal tumors, demonstrating that the laparoscopic transabdominal technique is safe and feasible, even for lesions below the third sacral vertebral body. This approach provided an adequate view of the presacral space, facilitating the preservation of cyst integrity, which is essential in cases of malignant pathologies.

12.
Front Surg ; 9: 793858, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310433

RESUMO

Introduction: Although carcinomatous degeneration is a rare occurrence, some authors support the need for a histopathological examination after pilonidal cyst excision. Today, minimally invasive techniques are widely spread for the treatment of pilonidal sinus disease but opposed to standard procedures, these techniques could not allow to perform a histopathological examination because of the absence of a specimen. The aim of this two-institutions study is to evaluate whether histopathological examination of the pilonidal sinus excision material can be successfully performed after an endoscopic ablation of the cyst. Materials and Methods: We identified all consecutive patients from January 2021 to September 2021 with diagnosis of pilonidal sinus disease who underwent Video Assisted Ablation of Pilonidal Sinus (VAAPS) followed by histopathological examination. Results: A total of 45 patients were included in the study. All patients were Caucasians and aged below 50 years. Nine of them underwent surgery due to recurrence of PSD. No evidence of malignancy was detected in the histopathological examination of the pilonidal sinus sampling material. Discussion: We were able to send pilonidal sinus sampling material for a histopathological examination in all patients who underwent minimally invasive technique for the treatment of pilonidal sinus disease. No evidence of malignancy was found in any of the 45 samples. Our findings prove that minimally invasive ablation of pilonidal sinus does not preclude histopathological examination of the cysts.

13.
Br J Pharmacol ; 179(8): 1679-1694, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34791641

RESUMO

BACKGROUND AND PURPOSE: N-Acylethanolamine acid amidase (NAAA) is a lysosomal enzyme accountable for the breakdown of N-acylethanolamines (NAEs) and its pharmacological inhibition has beneficial effects in inflammatory conditions. The knowledge of NAAA in cancer is fragmentary with an unclarified mechanism, whereas its contribution to colorectal cancer (CRC) is unknown to date. EXPERIMENTAL APPROACH: CRC xenograft and azoxymethane models were used to assess the in vivo effect of NAAA inhibition. Further, the tumour secretome was evaluated by an oncogenic array, CRC cell lines were used for in vitro studies, cell cycle was analysed by cytofluorimetry, NAAA was knocked down with siRNA, human biopsies were obtained from surgically resected CRC patients, gene expression was measured by RT-PCR and NAEs were measured by LC-MS. KEY RESULTS: The NAAA inhibitor AM9053 reduced CRC xenograft tumour growth and counteracted tumour development in the azoxymethane model. NAAA inhibition affected the composition of the tumour secretome inhibiting the expression of EGF family members. In CRC cells, AM9053 reduced proliferation with a mechanism mediated by PPAR-α and TRPV1. AM9053 induced cell cycle arrest in the S phase associated with cyclin A2/CDK2 down-regulation. NAAA knock-down mirrored the effects of NAAA inhibition with AM9053. NAAA expression was down-regulated in human CRC tissues, with a consequential augmentation of NAE levels and dysregulation of some of their targets. CONCLUSION AND IMPLICATIONS: Our results show novel data on the functional importance of NAAA in CRC progression and the mechanism involved. We propose that this enzyme is a valid drug target for the treatment of CRC growth and development.


Assuntos
Neoplasias Colorretais , Etanolaminas , Amidoidrolases , Azoximetano , Neoplasias Colorretais/tratamento farmacológico , Etanolaminas/metabolismo , Humanos
15.
Minerva Obstet Gynecol ; 74(4): 356-363, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33944524

RESUMO

INTRODUCTION: Krukenberg tumor (KT) is defined as a secondary neoplasm of the ovary. While ovarian metastases account for about 30% of ovarian tumors, KTs are rare, accounting for about 1-2% of the total. The rarity of KT is at least in part responsible for the lack of a precise clinic-pathological characterization of these tumors. Clinically, KT may have a subtle clinical presentation, with few symptomatic manifestations and nonspecific clinical signs, even though in literature there is disagreement about the clinical presentation of these patients; such difficulties in the diagnostic framework often leads to a delayed diagnosis with serious consequences on the patient outcome. We aimed to provide a clinico-pathological characterization of Krukenberg Tumor (KT) through a systematic review and meta-analysis to improve the diagnosis and management of KT. EVIDENCE ACQUISITION: Electronic databases were searched for all studies assessing clinico-pathological features of KT series. Pooled prevalence of each clinical or pathological factor was calculated according to the random-effect model. EVIDENCE SYNTHESIS: Forty-eight studies with 3025 KT patients were included; 39.7% of patients were ≥50 and 39.8% were postmenopausal. The most common primary tumor sites were stomach (42.5%), colon-rectum (26.1%), breast (9.3%), and appendix (5%); 48.7% of KTs were synchronous with the primary tumor, 64.3% were bilateral, 40.5% had a diameter ≥10 cm; 55.3% showed extraovarian extent and 49% showed peritoneal involvement. The most common presenting symptoms were ascites (51.7%), palpable mass (31.3%), pain (29.3%), abdominal distention (28.7%), irregular bleeding (9.1%), asymptomatic (11.2%). CONCLUSIONS: KT shows a highly variable presentation. Understanding the prevalence of clinico-pathological factors may be helpful to improve the diagnosis and management of KT.


Assuntos
Tumor de Krukenberg , Neoplasias Ovarianas , Feminino , Humanos , Tumor de Krukenberg/diagnóstico , Neoplasias Ovarianas/diagnóstico
16.
J Matern Fetal Neonatal Med ; 35(25): 8169-8175, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34470111

RESUMO

OBJECTIVES: To investigate the use of computerized cardiotocography (cCTG) parameters in Intrauterine Growth Restriction (IUGR) pregnancies for the prediction of 1) complication with preeclampsia; 2) placental histological abnormalities, and 3) neonatal outcomes. . STUDY DESIGN: A single-center observational retrospective case-control study was performed by reviewing medical records, cCTG databases and pathological reports of women with singleton pregnancy and IUGR uncomplicated (controls) and complicated by preeclampsia (cases). Primary endpoint was the association between cCTG parameters and preeclampsia in IUGR. Secondary endpoints were the association between cCTG parameters and 1) placental abnormalities, and 2) neonatal outcomes. The one-way ANOVA test was used to compare cCTG parameters in cases and controls. t-test was applied to compare neonatal outcomes and placental abnormalities in both groups. The Spearman Test value Correlation coefficients between the cCTG parameters and neonatal outcome in the two groups. A p value < .05 was considered significant for all analyses. RESULTS: Among all cCTG parameters, a significant association with preeclampsia in IUGR was found for Fetal Heart Rate (FHR, p = .008), Delta (p = .018), Short Term Variability (STV, p = .021), Long Term Variability (LTV, p = .028), Acceleration Phase Rectified Slope (APRS, p = .018) and Deceleration Phase Rectified Slope (DPRS, p = .038). Of all placental histologic abnormalities, only vascular alterations at least moderate were significantly associated with increased FHR (p = .02). About neonatal outcomes, all cCTG parameters were significantly associated with birth weight, Apgar index at 1 and 5 min, pH and pCO2. FHR, LTI, Delta, Approximate Entropy (ApEn) and LF were significantly associated with pO2; LTI, Interval Index (II) and ApEn with base excess. Among controls, Delta, ApEn, Low Frequency (LF) and High Frequency (HF) were significantly associated with pCO2, while among cases, STV and Delta were significantly associated with pH; STV, LTI, Delta, ApEn, LF and HF with pCO2; STV, LTI, Delta and ApEn with pO2; HF with base excess; FHR and LF with lactates. CONCLUSIONS: cCTG parameters may be useful to detect complication with preeclampsia in IUGR pregnancies. Regarding placental status, cCTG parameters may detect overall circulation alterations, but not specific histological abnormalities. Lastly, all cCTG parameters may predict neonatal outcomes, helping to tailor the patients' management.


Assuntos
Retardo do Crescimento Fetal , Pré-Eclâmpsia , Recém-Nascido , Feminino , Gravidez , Humanos , Retardo do Crescimento Fetal/etiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Placenta , Cardiotocografia , Frequência Cardíaca Fetal/fisiologia
17.
J Vasc Res ; 59(1): 61-68, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34535602

RESUMO

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value <0.05). The Mann-Whitney U test was used for comparison between the 2 groups. For the first time, our study revealed that in fetal aortas obtained from hypercholesterolemic mothers, the SREBF2 gene shows 4 significant differentially hypermethylated sites in the 5'UTR-CpG island. This finding indicates that more effective long-term primary cardiovascular prevention programs need to be designed for the offspring of mothers with hypercholesterolemia. Further studies should be conducted to clarify the epigenetic mechanisms underlying the association between early atherogenesis and maternal hypercholesterolemia during pregnancy.


Assuntos
Aorta/metabolismo , Metilação de DNA , Epigênese Genética , Hipercolesterolemia/genética , Complicações na Gravidez/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Aorta/embriologia , Biomarcadores/sangue , Estudos de Casos e Controles , Colesterol/sangue , Epigenoma , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Idade Gestacional , Humanos , Hipercolesterolemia/sangue , Gravidez , Complicações na Gravidez/sangue , Mapas de Interação de Proteínas
18.
Ital J Pediatr ; 47(1): 149, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215305

RESUMO

BACKGROUND: Besides major clinical/biochemical features, neutropenia and inflammatory bowel disease (IBD) constitute common complications of Glycogen storage disease type Ib (GSD Ib). However, their management is still challenging. Although previous reports have shown benefit of empagliflozin administration on neutropenia, no follow-up data on bowel (macro/microscopic) morphology are available. We herein present for the first time longitudinal assessment of bowel morphology in a GSD Ib child suffering from Crohn disease-like enterocolitis treated with empagliflozin. CASE PRESENTATION: A 14-year-old boy with GSD Ib and severe IBD was (off-label) treated with empagliflozin (20 mg/day) after informed oral and written consent was obtained from the patient's parents. No adverse events were noted. Clinical symptoms and stool frequency improved within the first week of treatment. Pediatric Crohn disease activity index (PCDAI) normalised within the first month of treatment. Abdomen magnetic resonance imaging (MRI) performed 3 months after treatment initiation showed dramatic decrease in disease activity and length. Similar findings were reported on histology at 5.5 months. At 7.5 months hemoglobin levels normalised and fecal calprotectin almost normalised. Improved neutrophil count, metabolic control and quality of life were also noted. G-CSF dose was decreased by 33% and the patient was partly weaned from tube feeding. CONCLUSIONS: This is the first report presenting extensive gastrointestinal morphology follow-up in a GSD Ib patient receiving empagliflozin. The present case suggests that empagliflozin can be safe and effective in inducing IBD remission in GSD Ib patients and can even postpone surgery. Future studies are required to confirm its effect over time and assess its benefit in various disease stages. The development of an international collaborating networks for systematic data collection is worthy.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Enterocolite/tratamento farmacológico , Glucosídeos/uso terapêutico , Doença de Depósito de Glicogênio Tipo I/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Adolescente , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Indução de Remissão
19.
Radiol Med ; 126(9): 1216-1225, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34156592

RESUMO

OBJECTIVES: To predict placental accreta spectrum (PAS) in patients with placenta previa (PP) evaluating clinical risk factors (CRF), ultrasound (US) and magnetic resonance imaging (MRI) findings. METHODS: Seventy patients with PP were retrospectively selected. CRF were retrieved from medical records. US and MRI images were evaluated to detect imaging signs suggestive of PAS. Univariable analysis was performed to identify CRF, US and MRI signs associated with PAS considering histology as standard of reference. Receiver operating characteristic curve (ROC) analysis was performed, and the area under the curve (AUC) was calculated. Multivariable analysis was also performed. RESULTS: At univariable analysis, the number of previous cesarean section, smoking, loss of the retroplacental clear space, myometrial thinning < 1 mm, placental lacunae, intraplacental dark bands (IDB), focal interruption of myometrial border (FIMB) and abnormal vascularity were statistically significant. The AUC in predicting PAS progressively increased using CRF, US and MRI signs (0.69, 0.79 and 0.94, respectively; p < 0.05); the accuracy of MRI alone was similar to that obtained combining CRF, US and MRI variables (AUC = 0.97) and was significantly higher (p < 0.05) than that combining CRF and US (AUC = 0.83). Multivariable analysis showed that only IDB (p = 0.012) and FIMB (p = 0.029) were independently associated with PAS. CONCLUSIONS: MRI is the best modality to predict PAS in patients with PP independently from CRF and/or US finding. It is reasonable to propose the combined assessment of CRF and US as the first diagnostic level to predict PAS, sparing MRI for selected cases in which US findings are uncertain for PAS.


Assuntos
Imageamento por Ressonância Magnética , Placenta Acreta , Placenta Prévia/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Análise de Variância , Área Sob a Curva , Feminino , Humanos , Pessoa de Meia-Idade , Placenta Acreta/diagnóstico por imagem , Gravidez , Curva ROC , Estudos Retrospectivos , Fatores de Risco
20.
Int Med Case Rep J ; 14: 187-190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33814933

RESUMO

Sclerosing mesenteritis (SM) is an idiopathic disorder affecting mesentery, characterized by fat necrosis, chronic inflammation and fibrosis. The clinical presentation varies from asymptomatic cases to acute abdomen. The diagnosis is suggested by imaging but can be definitely established only by biopsies. In this paper, we discuss ultrasonography-based management of SM.

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