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2.
Hum Genet ; 143(3): 211-232, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38396267

ABSTRACT

Spinocerebellar ataxia subtype 37 (SCA37) is a rare disease originally identified in ataxia patients from the Iberian Peninsula with a pure cerebellar syndrome. SCA37 patients carry a pathogenic intronic (ATTTC)n repeat insertion flanked by two polymorphic (ATTTT)n repeats in the Disabled-1 (DAB1) gene leading to cerebellar dysregulation. Herein, we determine the precise configuration of the pathogenic 5'(ATTTT)n-(ATTTC)n-3'(ATTTT)n SCA37 alleles by CRISPR-Cas9 and long-read nanopore sequencing, reveal their epigenomic signatures in SCA37 lymphocytes, fibroblasts, and cerebellar samples, and establish new molecular and clinical correlations. The 5'(ATTTT)n-(ATTTC)n-3'(ATTTT)n pathogenic allele configurations revealed repeat instability and differential methylation signatures. Disease age of onset negatively correlated with the (ATTTC)n, and positively correlated with the 3'(ATTTT)n. Geographic origin and gender significantly correlated with age of onset. Furthermore, significant predictive regression models were obtained by machine learning for age of onset and disease evolution by considering gender, the (ATTTC)n, the 3'(ATTTT)n, and seven CpG positions differentially methylated in SCA37 cerebellum. A common 964-kb genomic region spanning the (ATTTC)n insertion was identified in all SCA37 patients analysed from Portugal and Spain, evidencing a common origin of the SCA37 mutation in the Iberian Peninsula originating 859 years ago (95% CI 647-1378). In conclusion, we demonstrate an accurate determination of the size and configuration of the regulatory 5'(ATTTT)n-(ATTTC)n-3'(ATTTT)n repeat tract, avoiding PCR bias amplification using CRISPR/Cas9-enrichment and nanopore long-read sequencing, resulting relevant for accurate genetic diagnosis of SCA37. Moreover, we determine novel significant genotype-phenotype correlations in SCA37 and identify differential cerebellar allele-specific methylation signatures that may underlie DAB1 pathogenic dysregulation.


Subject(s)
Alleles , Cerebellum , DNA Methylation , Genetic Association Studies , Spinocerebellar Ataxias , Humans , Spinocerebellar Ataxias/genetics , Female , Male , Cerebellum/pathology , Cerebellum/metabolism , Middle Aged , Adult , Mutagenesis, Insertional , Aged , Age of Onset
3.
Clin Transl Oncol ; 26(5): 1129-1138, 2024 May.
Article in English | MEDLINE | ID: mdl-37872422

ABSTRACT

PURPOSE: Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach. METHODS: This retrospective study included all the available (FP) treatments, performed in patients of childbearing age between 2006 and 2022. RESULTS: 1556 patients were referred to the FPP: 332 oocyte vitrification cycles, 115 ovarian cortex cryopreservation with 11 orthotopic autotransplantations, 175 gonadotropin-releasing hormone (GnRH) agonist treatments, 109 fertility-sparing treatments for gynaecological cancer, and 576 sperm cryopreservation were performed. Malignancy was the main indication for FP (the main indications being breast cancer in women and haematological malignancies in men), although non-oncological pathologies, such as endometriosis and autoimmune diseases, have increased in recent years. Currently, the most widely used FP technique is oocyte vitrification, the increase of which has been associated with a decrease in the use of cortex CP and GnRH agonists. CONCLUSIONS: The increase in FP treatment reflects the implementation of reproductive counselling in oncology programmes. A multidisciplinary approach in a tertiary public hospital allows individualised FP treatment for each patient. In recent years, there has been a change in trend with the introduction of new indications for FP and a change in techniques due to their optimisation.

4.
Hum Genet ; 142(12): 1747-1754, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37957369

ABSTRACT

Machado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG)n expansion. MJD has two major ancestral backgrounds: the Machado lineage, found mainly in Portuguese families; and the Joseph lineage, present in all five continents, probably originating in Asia. MJD has been described in a few African and African-American families, but here we report the first diagnosed in Sudan to our knowledge. The proband presented with gait ataxia at age 24; followed by muscle cramps and spasticity, and dysarthria, by age 26; he was wheel-chair bound at 29 years of age. His brother had gait problems from age 20 years and, by age 21, lost the ability to run, showed dysarthria and muscle cramps. To assess the mutational origin of this family, we genotyped 30 SNPs and 7 STRs flanking the ATXN3_CAG repeat in three siblings and the non-transmitting father. We compared the MJD haplotype segregating in the family with our cohort of MJD families from diverse populations. Unlike all other known families of African origin, the Machado lineage was observed in Sudan, being shared with 86 Portuguese, 2 Spanish and 2 North-American families. The STR-based haplotype of Sudanese patients, however, was distinct, being four steps (2 STR mutations and 2 recombinations) away from the founder haplotype shared by 47 families, all of Portuguese extraction. Based on the phylogenetic network constructed with all MJD families of the Machado lineage, we estimated a common ancestry at 3211 ± 693 years ago.


Subject(s)
Machado-Joseph Disease , Male , Humans , Young Adult , Adult , Machado-Joseph Disease/genetics , Machado-Joseph Disease/diagnosis , Portugal , Muscle Cramp , Dysarthria , Phylogeny , Africa, Eastern
5.
Gastrointest Endosc ; 98(6): 953-964, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37473969

ABSTRACT

BACKGROUND AND AIMS: Data on how to teach endosonographers needle-based confocal laser endomicroscopy (nCLE)-guided histologic diagnosis of pancreatic cystic lesions (PCLs) are limited. Hence, we developed and tested a structured educational program to train early-career endosonographers in nCLE-guided diagnosis of PCLs. METHODS: Twenty-one early-career nCLE-naïve endosonographers watched a teaching module outlining nCLE criteria for diagnosing PCLs. Participants then reviewed 80 high-yield nCLE videos, recorded diagnoses, and received expert feedback (phase 1). Observers were then randomized to a refresher feedback session or self-learning at 4 weeks. Eight weeks after training, participants independently assessed the same 80 nCLE videos without feedback and provided histologic predictions (phase 2). Diagnostic performance of nCLE to differentiate mucinous versus nonmucinous PCLs and to diagnose specific subtypes were analyzed using histopathology as the criterion standard. Learning curves were determined using cumulative sum analysis. RESULTS: Accuracy and diagnostic confidence for differentiating mucinous versus nonmucinous PCLs improved as endosonographers progressed through nCLE videos in phase 1 (P < .001). Similar trends were observed with the diagnosis of PCL subtypes. Most participants achieved competency interpreting nCLE, requiring a median of 38 assessments (range, 9-67). During phase 2, participants independently differentiated PCLs with high accuracy (89%), high confidence (83%), and substantial interobserver agreement (κ = .63). Accuracy for nCLE-guided PCL subtype diagnoses ranged from 82% to 96%. The learned nCLE skills did not deteriorate at 8 weeks and were not impacted by a refresher session. CONCLUSIONS: We developed a practical, effective, and durable educational intervention to train early-career endosonographers in nCLE-guided diagnosis of PCLs.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Pancreatic Cyst , Humans , Prospective Studies , Microscopy, Confocal , Pancreatic Cyst/diagnostic imaging , Pancreatic Cyst/pathology , Lasers
6.
Sensors (Basel) ; 23(10)2023 May 10.
Article in English | MEDLINE | ID: mdl-37430551

ABSTRACT

LED lighting has become the standard solution for illumination purposes thanks to its energy efficiency. Nowadays, there is growing interest in the use of LEDs for data transmission to develop future-generation communication systems. The low cost and widespread deployment of phosphor-based white LEDs make them the best candidate for visible light communications (VLC), although they have a limited modulation bandwidth. This paper presents a simulation model of a VLC link based on phosphor-based white LEDs and a method to characterize the VLC setup used to perform the data transmission experiments. Specifically, the simulation model incorporates the frequency response of the LED, the noise levels coming from the lighting source and the acquisition electronics, and the attenuation due to both the propagation channel and the angular misalignment between the lighting source and the photoreceiver. In order to validate the suitability of the model for VLC, carrierless amplitude phase (CAP) and orthogonal frequency division multiplexing (OFDM) modulation signals were employed for data transmission, and simulations with the proposed model and measurements over the equivalent scenario show high agreement.

7.
Dig Dis Sci ; 68(5): 1747-1753, 2023 05.
Article in English | MEDLINE | ID: mdl-36355334

ABSTRACT

BACKGROUND/AIM: Training endoscopists to perform endoscopic retrograde cholangiopancreatography (ERCP) is critical to address the increasing patient population with pancreatobiliary diseases. Concerns remain about ERCP safety and success involving trainees. We compared the technical success and immediate adverse events between ERCP with and without trainee involvement. METHODS: Retrospective analysis of 28,271 ERCP procedures in a national sample of the United States over 12 years. Demographics, procedure and fluoroscopy time, visualization and cannulation of main structures, adverse events, and technical success rates were compared between ERCP with and without trainees. Categorical variables were compared using Pearson's chi-square test and continuous variables using a standard t-test. Univariate and multivariate regressions were performed adjusting for age, gender, ethnicity, US region, ASA class and clinical setting. RESULTS: Approximately 49.5% of ERCPs had a trainee involved. The ampulla was visualized in 97.4% with trainee vs. 97.3% without trainee involvement (P = 0.858). The common bile duct was visualized and cannulated in 90.4% with trainees vs. 91.7% without trainees involved (P < 0.001). The ERCP was incomplete in 5.9% of cases with trainees vs. 6.4% without trainees involved (P = 0.207). Trainee participation added 8.7 min to average procedure time (aOR: 1.02, P < 0.001) and 2.0 min to fluoroscopy time (aOR: 1.00, P = 0.796). Adverse events (aOR: 0.89, P = 0.704) and technical success (aOR: 0.83, P = 0.571) were similar in both groups. CONCLUSIONS: Trainee involvement leads to increased procedure duration but is not associated with increased immediate adverse events, or technical failure. Our study supports ERCP safety and success with trainee participation.


Subject(s)
Catheterization , Cholangiopancreatography, Endoscopic Retrograde , Humans , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Cholangiopancreatography, Endoscopic Retrograde/methods , Retrospective Studies , Catheterization/methods , Common Bile Duct
8.
Biomed Pharmacother ; 156: 113987, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36411654

ABSTRACT

INTRODUCTION: small-cell lung cancer (SCLC) is one of the most lethal malignancies. Its management is complex due to the lack of biomarkers and limited therapies. Galectin-1 (Gal-1) plays a major role in cancer development and progression. The aim of this study is to assess whether Gal-1 has a predictive role in the disease evolution and its therapeutic potential. MATERIAL AND METHODS: The expression level of Gal-1 was examined by using a public RNA-sequencing (77 SCLC patients) and in-house immunohistochemistry (IHC) performed on biopsies from 81 patients. Survival curves and Cox regression analysis were used to assess the prognostic potential of Gal-1. In addition, a SCLC-PDX model was carried out and treated with either OTX008, an inhibitor of Gal-1, or vehicle to assess the effects of Gal-1 inhibition on this disease in vivo. RESULTS: Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcome in SCLC patients with advanced disease (p = 0.007). IHC unveiled that overall survival (OS) was significantly lower among extensive-stage SCLC (ES-SCLC) patient group with increased level of Gal-1 and platelet-to-lymphocyte ratio (PLR) (HR=3.07, 95% CI: 1.62, 5.79, p < 0.001). The SCLC-PDX model showed a significant reduction in tumor size (tumor growth inhibition [TGI] index 73%) without side effects. DISCUSSION: in this study, high levels of Gal-1 and PLR were associated with poorer OS in SCLC patients, supporting their utility as clinical prognostic biomarkers. Moreover, the in vivo model suggests the inhibition of Gal-1 as a novel potential therapy for this disease with very poor prognosis.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Galectin 1/genetics , Small Cell Lung Carcinoma/drug therapy , Benzamides , Lung Neoplasms/drug therapy
9.
Int J Mol Sci ; 23(20)2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36293256

ABSTRACT

Male germ cells experience a drastic chromatin remodeling through the nucleo-histone to nucleo-protamine (NH-NP) transition necessary for proper sperm functionality. Post-translational modifications (PTMs) of H4 Lys5, such as acetylation (H4K5ac), play a crucial role in epigenetic control of nucleosome disassembly facilitating protamine incorporation into paternal DNA. It has been shown that butyrylation on the same residue (H4K5bu) participates in temporal regulation of NH-NP transition in mice, delaying the bromodomain testis specific protein (BRDT)-dependent nucleosome disassembly and potentially marking retained nucleosomes. However, no information was available so far on this modification in human sperm. Here, we report a dual behavior of H4K5bu and H4K5ac in human normal spermatogenesis, suggesting a specific role of H4K5bu during spermatid elongation, coexisting with H4K5ac although with different starting points. This pattern is stable under different testicular pathologies, suggesting a highly conserved function of these modifications. Despite a drastic decrease of both PTMs in condensed spermatids, they are retained in ejaculated sperm, with 30% of non-colocalizing nucleosome clusters, which could reflect differential paternal genome retention. Whereas no apparent effect of these PTMs was observed associated with sperm quality, their presence in mature sperm could entail a potential role in the zygote.


Subject(s)
Chromatin , Nucleosomes , Humans , Male , Mice , Animals , Chromatin/metabolism , Acetylation , Nucleosomes/metabolism , Histones/metabolism , Semen/metabolism , Spermatogenesis/physiology , Spermatozoa/metabolism , Chromatin Assembly and Disassembly , Protein Processing, Post-Translational , Spermatids/metabolism , Protamines/metabolism
10.
Hum Reprod ; 37(8): 1712-1726, 2022 07 30.
Article in English | MEDLINE | ID: mdl-35678707

ABSTRACT

STUDY QUESTION: Is histone H4 acetylation (H4ac) altered in the seminiferous tubules of patients affected by testicular tumours? SUMMARY ANSWER: A considerable dysregulation of H4ac was detected in the cells of the seminiferous tubules adjacent to testicular tumours of different aetiology and prior to any treatment, while no comparable alterations were observed in patients with disrupted spermatogenesis. WHAT IS KNOWN ALREADY: Altered H4ac levels have been associated with a variety of testicular pathological conditions. However, no information has been available regarding potential alterations in the spermatogenic cells adjacent to the neoplasia in testicular tumour patients. STUDY DESIGN, SIZE, DURATION: A retrospective analysis using testicular sections from 33 men aged between 21 and 74 years old was performed. Three study groups were defined and subjected to double-blind evaluation: a control group with normal spermatogenesis (n = 6), patients with testicular tumours (n = 18) and patients with spermatogenic impairments (n = 8). One additional sample with normal spermatogenesis was used as a technical internal control in all evaluations. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunohistochemistry against H4ac and, when needed, Placental-like alkaline phosphatase and CD117, was performed on testicular sections. The H4ac H-score, based on the percentage of detection and signal intensity, was used as the scoring method for statistical analyses. Protein expression data from the Human Protein Atlas were used to compare the expression levels of predicted secreted proteins from testicular tumours with those present in the normal tissue. MAIN RESULTS AND THE ROLE OF CHANCE: We revealed, for the first time, a dramatic disruption of the spermatogenic H4ac pattern in unaffected seminiferous tubule cells from different testicular tumour patients prior to any antineoplastic treatment, as compared to controls (P < 0.05). Since no similar alterations were associated with spermatogenic impairments and the in silico analysis revealed proteins potentially secreted by the tumour to the testicular stroma, we propose a potential paracrine effect of the neoplasia as a mechanistic hypothesis for this dysregulation. LIMITATIONS, REASONS FOR CAUTION: Statistical analyses were not performed on the hypospermatogenesis and Leydig cell tumour groups due to limited availability of samples. WIDER IMPLICATIONS OF THE FINDINGS: To the best of our knowledge, this is the first report showing an epigenetic alteration in cells from active seminiferous tubules adjacent to tumour cells in testicular tumour patients. Our results suggest that, despite presenting spermatogenic activity, the global epigenetic dysregulation found in the testicular tumour patients could lead to molecular alterations of the male germ cells. Since testicular tumours are normally diagnosed in men at reproductive age, H4ac alterations might have an impact when these testicular tumour patients express a desire for fatherhood. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the European Union Marie Curie European Training Network actions and by grants to R.O. from the 'Ministerio de Economía y Competividad (Spain)' (fondos FEDER 'una manera de hacer Europa', PI13/00699, PI16/00346 and PI20/00936) and from EU-FP7-PEOPLE-2011-ITN289880. J.C. was supported by the Sara Borrell Postdoctoral Fellowship, Acción Estratégica en Salud, CD17/00109. J.C. is a Serra Húnter fellow (Universitat de Barcelona, Generalitat de Catalunya). F.B. has received grants from the Ministerio de Educación, Cultura y Deporte para la Formación de Profesorado Universitario (Spain) (FPU15/02306). A.d.l.I. is supported by a fellowship of the Ministerio de Economía, Industria y Competitividad (Spain) (PFIS, FI17/00224). M.J. is supported by the Government of Catalonia (Generalitat de Catalunya, pla estratègic de recerca i innovació en salut, PERIS 2016-2020, SLT002/16/00337). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Histones , Seminiferous Tubules , Testicular Neoplasms , Acetylation , Adult , Aged , Double-Blind Method , Histones/metabolism , Humans , Male , Middle Aged , Retrospective Studies , Seminiferous Tubules/physiopathology , Spermatogenesis , Testicular Neoplasms/pathology , Testis/metabolism , Young Adult
11.
Neuroradiology ; 64(12): 2315-2322, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35583667

ABSTRACT

PURPOSE: To qualitatively and quantitatively compare synthetic and conventional MRI sequences acquired on a 1.5-T system for patients with multiple sclerosis (MS). METHODS: Prospective study that involved twenty-seven consecutive relapsing-remitting MS patients scanned on a 1.5-T MRI scanner. The MRI protocol included 2D transverse conventional spin-echo sequences: proton density-weighted (PD), T2-weighted, T2-FLAIR, and T1-weighted. Synthetic images were generated using 2D transverse QRAPMASTER and SyMRI software with the same voxel size, repetition, echo, and inversion times as the conventional sequences. Four raters performed a crosstab qualitative analysis that involved evaluating global image quality, contrast, flow artefacts, and confidence in lesion assessment introducing the concepts of predominance, agreement, and disagreement. A quantitative analysis was also performed and included evaluating the number of lesions (periventricular, juxtacortical, brainstem, and cerebellum) and the contrast-to-noise ratio between regions (CSF, white matter, grey matter, lesions). RESULTS: The global image quality assessment showed predominance for better scores for conventional sequences over synthetic sequences, whereas contrast, confidence in lesion assessment, and flow artefacts showed predominance for agreement between sequences. There was predominance for disagreement between all pairs of raters in most of the evaluated qualitative parameters. Synthetic PD and T2-FLAIR images showed higher contrast-to-noise ratios than the corresponding conventional images for most comparison between regions. There were no significant differences in the number of lesions detected for most of the study regions between conventional and synthetic images. CONCLUSION: Synthetic MRI can be potentially used as an alternative to conventional brain MRI sequences in the assessment of MS.


Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/diagnostic imaging , Multiple Sclerosis/pathology , Prospective Studies , Magnetic Resonance Imaging/methods , Brain/diagnostic imaging , Brain/pathology , Artifacts
12.
Brain Commun ; 4(2): fcac030, 2022.
Article in English | MEDLINE | ID: mdl-35310830

ABSTRACT

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Z max = 3.43; θ = 0.00; P < 3.53 × 10-5). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients' fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions.

13.
Endosc Int Open ; 10(2): E178-E182, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35178335

ABSTRACT

Background and study aims Splenic injury (SI) during colonoscopy is an underappreciated adverse event. Our aim was to examine the occurrence and outcomes of patients who developed SI after inpatient colonoscopy using a nationwide dataset. Patients and methods Retrospective, observational study using the National Inpatient Sample (NIS) between 2012 and 2018. All patients with ICD9/10CM procedural codes for colonoscopy with or without SI were included. The primary outcome was the association between SI and inpatient colonoscopy. Secondary outcomes were inpatient morbidity, mortality, resource utilization, splenectomy rates, hospital length of stay and total hospital costs and charges. Comparative analyses were performed between patients with and without SI. Multivariate regression analyses were utilized. Results A total of 2,258,040 of inpatient colonoscopies were included. Of these, 240 had associated SI and 25 patients required splenectomy (10.4 %). The incidence of colonoscopy-associated SI remained relatively stable between 2012 and 2018 (0.033 % versus 0.020 %, respectively). The mean age of patients with and without SI was 63.7 and 64.1 years, respectively. The occurrence of SI was calculated as 10.63 cases per 100,000 inpatient colonoscopies. Patients who had associated SI displayed significantly higher odds of inpatient mortality (aOR: 14.45) and ICU stay (aOR: 10.11) compared to those without SI. Conclusions Splenic injury confers significantly higher odds of inpatient mortality, and resource utilization. The incidence of SI related to colonoscopy remained stable during the study period. Although uncommon, SI should be considered when encountering patients with abdominal pain after colonoscopy.

14.
Microbiol Resour Announc ; 11(2): e0140920, 2022 Feb 17.
Article in English | MEDLINE | ID: mdl-35175110

ABSTRACT

Halomonas sp. strain BLLS135 was isolated from hypersaline soil in Mexico. Here, we present the draft genome of this strain. Its genome has 2,861 protein-coding genes, 63 tRNAs, two 16S rRNAs, five 5S rRNAs, and a single copy of 23S rRNA, with a GC content of 63.5%.

15.
Mult Scler ; 28(8): 1209-1218, 2022 07.
Article in English | MEDLINE | ID: mdl-34859704

ABSTRACT

BACKGROUND: Active (new/enlarging) T2 lesion counts are routinely used in the clinical management of multiple sclerosis. Thus, automated tools able to accurately identify active T2 lesions would be of high interest to neuroradiologists for assisting in their clinical activity. OBJECTIVE: To compare the accuracy in detecting active T2 lesions and of radiologically active patients based on different visual and automated methods. METHODS: One hundred multiple sclerosis patients underwent two magnetic resonance imaging examinations within 12 months. Four approaches were assessed for detecting active T2 lesions: (1) conventional neuroradiological reports; (2) prospective visual analyses performed by an expert; (3) automated unsupervised tool; and (4) supervised convolutional neural network. As a gold standard, a reference outcome was created by the consensus of two observers. RESULTS: The automated methods detected a higher number of active T2 lesions, and a higher number of active patients, but a higher number of false-positive active patients than visual methods. The convolutional neural network model was more sensitive in detecting active T2 lesions and active patients than the other automated method. CONCLUSION: Automated convolutional neural network models show potential as an aid to neuroradiological assessment in clinical practice, although visual supervision of the outcomes is still required.


Subject(s)
Multiple Sclerosis , Humans , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , Prospective Studies
16.
Dig Dis Sci ; 67(2): 423-436, 2022 02.
Article in English | MEDLINE | ID: mdl-33625614

ABSTRACT

Inflammatory bowel disease (IBD) can involve multiple organ systems, and pancreatic manifestations of IBD are not uncommon. The incidence of several pancreatic diseases is more frequent in patients with Crohn's disease and ulcerative colitis than in the general population. Pancreatic manifestations in IBD include a heterogeneous group of disorders and abnormalities ranging from mild, self-limited disorders to severe diseases. Asymptomatic elevation of amylase and/or lipase is common. The risk of acute pancreatitis in patients with IBD is increased due to the higher incidence of cholelithiasis and drug-induced pancreatitis in this population. Patients with IBD commonly have altered pancreatic histology and chronic pancreatic exocrine dysfunction. Diagnosing acute pancreatitis in patients with IBD is challenging. In this review, we discuss the manifestations and possible causes of pancreatic abnormalities in patients with IBD.


Subject(s)
Cholelithiasis/complications , Colitis, Ulcerative/complications , Crohn Disease/complications , Pancreatic Neoplasms/complications , Pancreatitis, Chronic/complications , Pancreatitis/etiology , Anti-Bacterial Agents/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Autoimmune Pancreatitis/complications , Azathioprine/adverse effects , Cholangitis, Sclerosing/complications , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Glucocorticoids/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Marijuana Use/adverse effects , Mesalamine/adverse effects , Pancreatitis/diagnosis , Pancreatitis/therapy , Pancreatitis, Alcoholic/complications , Tumor Necrosis Factor Inhibitors/adverse effects
18.
Clin Endosc ; 55(2): 197-207, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34839621

ABSTRACT

BACKGROUND/AIMS: Endoscopic visualization of the microscopic anatomy can facilitate the real-time diagnosis of pancreatobiliary disorders and provide guidance for treatment. This study aimed to review the technique, image classification, and diagnostic performance of confocal laser endomicroscopy (CLE). METHODS: We conducted a systematic review of CLE in pancreatic and biliary ducts of humans, and have provided a narrative of the technique, image classification, diagnostic performance, ongoing research, and limitations. RESULTS: Probe-based CLE differentiates malignant from benign biliary strictures (sensitivity, ≥89%; specificity, ≥61%). Needlebased CLE differentiates mucinous from non-mucinous pancreatic cysts (sensitivity, 59%; specificity, ≥94%) and identifies dysplasia. Pancreatitis may develop in 2-7% of pancreatic cyst cases. Needle-based CLE has potential applications in adenocarcinoma, neuroendocrine tumors, and pancreatitis (chronic or autoimmune). Costs, catheter lifespan, endoscopist training, and interobserver variability are challenges for routine utilization. CONCLUSION: CLE reveals microscopic pancreatobiliary system anatomy with adequate specificity and sensitivity. Reducing costs and simplifying image interpretation will promote utilization by advanced endoscopists.

19.
JCO Glob Oncol ; 7: 1694-1702, 2021 12.
Article in English | MEDLINE | ID: mdl-34914550

ABSTRACT

PURPOSE: Population-based cancer registries (PBCRs) are critical for national cancer control planning, yet few low- and middle-income countries (LMICs) have quality PBCRs. The Central America Four region represents the principal LMIC region in the Western hemisphere. We describe the establishment of a PBCR in rural Western Honduras with first estimates for the 2013-2017 period. METHODS: The Western Honduras PBCR was established through a collaboration of academic institutions and the Honduras Ministry of Health for collection of incident cancer data from public and private health services. Data were recorded using the Research Electronic Data Capture (REDCap) web-based platform with data monitoring and quality checks. Crude and age-standardized rates (ASRs) were calculated at the regional level, following WHO methodology. RESULTS: The web-based platform for data collection, available ancillary data services (eg, endoscopy), and technical support from international centers (United States and Colombia) were instrumental for quality control. Crude cancer incidence rates were 112.2, 69.8, and 154.6 per 100,000 habitants overall, males, and females, respectively (excluding nonmelanoma skin cancer). The adjusted ASRs were 84.2, 49.6, and 118.9 per 100,000 overall habitants, males, and females, respectively. The most common sites among men were stomach (ASR 26.0, 52.4%), colorectal (ASR 5.11, 10.15%), and prostate (ASR 2.7, 5.4%). The most common sites in women were cervix (ASR 34.2, 36.7%), breast (ASR 11.2, 12.3%), and stomach (ASR 10.8, 11.7%). CONCLUSION: The Copán-PBCR represents a successful model to develop cancer monitoring in rural LMICs. Innovations included the use of the REDCap platform and leverage of Health Ministry resources. This provides the first PBCR data for Honduras and the Central America Four and confirms that infection-driven cancers, such as gastric and cervical, should be priority targets for cancer control initiatives.


Subject(s)
Neoplasms , Central America/epidemiology , Female , Honduras/epidemiology , Humans , Incidence , Male , Neoplasms/epidemiology , Registries
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