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2.
Hellenic J Cardiol ; 2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39245435

ABSTRACT

BACKGROUND: The precise triggers for atherosclerotic plaque rupture and the underlying pathophysiology of coronary thrombogenesis remain elusive. Polymorphonuclear neutrophils, particularly their formation of neutrophil extracellular traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). METHODS: For this study, 336 consecutive STEMI patients undergoing pPCI were considered for TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. RESULTS: Manual TA was selectively performed in 72 cases with increased thrombotic burden, and 60 thrombi were suitable for analysis and included in the current study. Most thrombi specimens displayed lytic features (63%), and almost three out of four were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 min), OR = 10.29 (95% CI 2.11-42.22, p = 0.001), and stress-induced hyperglycemia OR = 6.58 (95% CI 1.23-52.63, p < 0.01) after multivariate regression analysis. Additionally, distal embolization, and left ventricular ejection fraction ≤40% were more frequent among patients with an elevated NETs burden OR = 16.9 (95% CI 4.23-44.52, p < 0.01) and OR = 3.2 (95% CI 1.05-12.1, p = 0.05), respectively. CONCLUSION: Elevated NETs burden in STEMI thrombi may be due to delayed reperfusion and stress-induced hyperglycemia, and it is associated with an increased risk of distal embolization and lower left ventricular ejection fraction. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

3.
Case Rep Hematol ; 2024: 5597263, 2024.
Article in English | MEDLINE | ID: mdl-39015771

ABSTRACT

Hodgkin lymphoma (HL) is an uncommon malignancy that is characterized by Hodgkin or Reed-Sternberg cells. Cardiac implications of HL remain one of the least investigated subjects. There are few case reports in the literature of cardiac tamponade in HL patients. We describe a case of a 21-year-old female patient who presented with cardiac tamponade as an initial presentation of HL. Any pericardial effusion significant for tamponade requires immediate drainage and fluid analysis for thorough investigation. Prompt identification and timely intervention are crucial in effectively addressing these complex situations. Therefore, clinicians should maintain heightened awareness in such cases.

4.
Medicina (Kaunas) ; 60(7)2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39064602

ABSTRACT

Background and Objectives: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous malignancy influenced by various genetic and environmental factors. Mast cells (MCs), typically associated with allergic responses, have recently emerged as key regulators of the HNSCC tumor microenvironment (TME). This systematic review explores the role of MCs in HNSCC pathogenesis and their potential as prognostic markers and therapeutic targets. Materials and Methods: A systematic search was conducted in the PubMed, Scopus and ClinicalTrials.gov databases until 31 December 2023, using "Mast cells" AND "Head and neck squamous cell carcinoma" as search terms. Studies in English which reported on MCs and HNSCC were included. Screening, data extraction and analysis followed PRISMA guidelines. No new experiments were conducted. Results: Out of 201 articles, 52 studies met the inclusion criteria, 43 of which were published between 2020 and 2023. A total of 28821 HNSCC and 9570 non-cancerous tissue samples had been examined. MC density and activation varied among normal tissues and HNSCC. Genetic alterations associated with MCs were identified, with specific gene expressions correlating with prognosis. Prognostic gene signatures associated with MC density were established. Conclusions: MCs have arisen as multifaceted TME modulators, impacting various aspects of HNSCC development and progression. Possible site-specific or HPV-related differences in MC density and activation should be further elucidated. Despite conflicting findings on their prognostic role, MCs represent promising targets for novel therapeutic strategies, necessitating further research and clinical validation for personalized HNSCC treatment.


Subject(s)
Head and Neck Neoplasms , Mast Cells , Squamous Cell Carcinoma of Head and Neck , Tumor Microenvironment , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/immunology , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Tumor Microenvironment/immunology , Prognosis
5.
Rom J Morphol Embryol ; 65(2): 267-271, 2024.
Article in English | MEDLINE | ID: mdl-39020541

ABSTRACT

AIM: To investigate the immunohistochemical (IHC) expression and the diagnostic value of c-MYC, Cyclin D1, and Ki-67∕MIB-1 in follicular adenomas (FAs), follicular carcinomas (FCs), and anaplastic carcinomas (ACs) of the thyroid gland, as well as in their corresponding adjacent, non-neoplastic thyroid tissue (NNTT). MATERIALS AND METHODS: We conducted a retrospective study of patients who were pathologically diagnosed with FA, FC, or AC after total thyroidectomy. Tissue microarrays with cores taken from neoplastic and adjacent NNTT were constructed. Immunohistochemistry for anti-c-MYC, anti-Cyclin D1, and anti-Ki-67∕MIB-1 antibodies was performed, and the positivity was evaluated. RESULTS: Twenty-eight specimens were included. Nuclear c-MYC positivity was observed in 4∕11 FCs, and 3∕4 ACs, whereas cytoplasmic c-MYC positivity was found in 16∕24 NNTTs. Globally, there were statistically significant differences between neoplasms and NNTTs, with higher nuclear c-MYC and Cyclin D1 expression observed in neoplasms (p=0.017 and p=0.001, respectively). In contrast, cytoplasmic positivity was seen solely in NNTTs (p=0.001). Cyclin D1 positivity was noted in 11∕13 FAs, 7∕11 FCs, 2∕4 ATCs, and only in one NNTT. A statistically significant correlation was found between MIB1 and c-MYC nuclear positivity (p=0.040). CONCLUSIONS: Our findings exhibit a clear difference in the IHC expression of c-MYC and Cyclin D1 between different types of thyroid tumors, as well as between the neoplastic and NNTT. Nuclear c-MYC positivity excludes the benign nature of a thyroid lesion, in contrast to cytoplasmic positivity, which demonstrates normal or hyperplastic nature.


Subject(s)
Cyclin D1 , Ki-67 Antigen , Proto-Oncogene Proteins c-myc , Thyroid Gland , Thyroid Neoplasms , Humans , Cyclin D1/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Female , Male , Ki-67 Antigen/metabolism , Thyroid Gland/metabolism , Thyroid Gland/pathology , Middle Aged , Retrospective Studies , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Thyroid Neoplasms/diagnosis , Adult , Immunohistochemistry/methods , Aged
6.
Cureus ; 16(5): e60361, 2024 May.
Article in English | MEDLINE | ID: mdl-38882980

ABSTRACT

Oncocytes are frequently encountered in routine thyroidectomies. The distinction between oncocytic hyperplastic nodules and oncocytic adenomas (OAs) may be challenging. Although both entities are benign, a precise diagnosis is essential. We present two cases of solitary oncocytic lesions carrying pathogenic mutations in the p53 and NRAS genes, respectively, leading to a histological diagnosis of oncocytic hyperplastic nodules. Additionally, similar oncocytic nodules from two cases of autoimmune thyroiditis did not show any significant findings on molecular analysis (next-generation sequencing, NGS). Hence, this brief investigative series study is of particular diagnostic interest because it prompts pathologists to use the term adenoma when a solitary oncocytic nodule is encountered, regardless of the established criteria for the diagnosis of adenoma. This viewpoint leads to the possible need for the reevaluation of the histological criteria of adenomas when it comes to oncocytic lesions in order to gain a common diagnostic approach and nomenclature among pathologists and overcome any controversies in such cases.

7.
Cancers (Basel) ; 16(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38893213

ABSTRACT

Triple Negative Breast Cancer (TNBC) is characterized by distinct molecular subtypes with unique biological and clinical features. This systematic review aimed to identify articles examining the differences in the tumor immune microenvironment (TIME) across different TNBC molecular subtypes. Six studies meeting inclusion criteria were analyzed, utilizing gene expression profiling and bioinformatic analyses to classify TNBC samples into molecular subtypes, as well as immunohistochemistry and cell deconvolution methods to characterize the TIME. Results revealed significant heterogeneity in immune cell composition among TNBC subtypes, with the immunomodulatory (IM) subtype demonstrating robust immune infiltration, composed mainly of adaptive immune cells along with an increased density of CTLA-4+ and PD-1+ TILs, high PD-L1 tumor cell expression, and upregulation of FOXP3+ Tregs. A more immunosuppressive TIME with a predominance of innate immune cells and lower levels of tumor-infiltrating lymphocytes (TILs) was observed in luminal androgen receptor (LAR) tumors. In mesenchymal stem-like (MSL) tumors, the TIME was mainly composed of innate immune cells, with a high number of M2 tumor-associated macrophages (TAMs), while the BL and M tumors displayed poor adaptive and innate immune responses, indicating an "immune-cold" phenotype. Differential activation of signaling pathways, genomic diversity, and metabolic reprogramming were identified as contributors to TIME heterogeneity. Understanding this interplay is crucial for tailoring therapeutic strategies, especially regarding immunotherapy.

8.
Diagnostics (Basel) ; 14(11)2024 May 29.
Article in English | MEDLINE | ID: mdl-38893658

ABSTRACT

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches.

9.
Medicina (Kaunas) ; 60(3)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38541194

ABSTRACT

Background and Objectives: Incidental thyroid cancers (ITCs) are often microcarcinomas. The most frequent histologic type is a papillary microcarcinoma. Papillary thyroid microcarcinomas are defined as papillary thyroid tumours measuring less than 10 mm at their greatest diameter. They are clinically occult and frequently diagnosed incidentally in histopathology reports after a thyroidectomy. The aim of this study is to evaluate the rate of papillary thyroid microcarcinomas (PTMC) in patients who were thyroidectomised with indications of benign disease. Materials and Methods: We retrospectively evaluated the histological incidence of PTMC in 431 consecutive patients who, in a 5 year period, underwent a thyroidectomy with benign indications. Patients with benign histology and with known or suspected malignancy were excluded. Results: Histopathology reports from 540 patients who underwent a total thyroidectomy in our department between 2016 and 2021 were reviewed. A total of 431 patients were thyroidectomised for presumed benign thyroid disease. A total of 395 patients had confirmed benign thyroid disease in the final histopathology, while 36 patients had incidental malignant lesions (33 PTMC-7.67%, one multifocal PTC without microcarcinomas-0.23%, two follicular thyroid carcinoma-0.46%). Out of the PTMC patients, 29 were female and four were male (7.2:1 female-male ratio). The mean age was 54.2 years old. A total of 24 out of 33 patients had multifocal lesions, 11 of which co-existed with macro PTC. Nine patients had unifocal lesions. A total of 21 of these patients were initially operated on for multinodular goitre (64%), while 13 were operated on for Hashimoto/Lymphocytic thyroiditis (36%). Conclusions: PTMC-often multifocal-is not an uncommon, incidental finding after thyroidectomy for benign thyroid lesions (7.67% in our series) and often co-exists with other incidental malignant lesions (8.35% in our series). The possibility of an underlying papillary microcarcinoma should be taken into account in the management of patients with benign-especially nodular-thyroid disease, and total thyroidectomy should be considered.


Subject(s)
Carcinoma, Papillary , Thyroid Diseases , Thyroid Neoplasms , Humans , Male , Female , Middle Aged , Thyroidectomy , Retrospective Studies , Thyroid Neoplasms/epidemiology , Thyroid Neoplasms/surgery , Thyroid Diseases/pathology
10.
Breast ; 73: 103668, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176305

ABSTRACT

BACKGROUND: Dose-dense sequential (dds) chemotherapy has changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a currently widely used chemotherapeutic regimen. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. PATIENTS AND METHODS: Totally, 1054 patients were prospectively enrolled in the current study with 1024 patients being eligible, while adequate tissue was available for 596 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. RESULTS: Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. Importantly, the 10-year DFS and OS rates were 78.4% (95% CI 75.0-81.5) and 81.7% (95% CI 79.0-84.1), respectively. Interestingly, higher CD8+ T cells as well as TILs in the tumor microenvironment were associated with an improved long-term survival outcome. CONCLUSIONS: In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of TILs and infiltrating CD8+ lymphocytes in BC patients with early-stage disease.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Epirubicin , Docetaxel/therapeutic use , CD8-Positive T-Lymphocytes/pathology , Lymphocytes, Tumor-Infiltrating/pathology , Cyclophosphamide , Prognosis , Disease-Free Survival , Tumor Microenvironment
11.
Cureus ; 15(9): e46085, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37900389

ABSTRACT

BACKGROUND: Emerging data indicate that the cellular microenvironment and interleukins (IL) play a crucial role in mycosis fungoides (MF). We aimed to explore the potential association between the composition of the cellular microenvironment and the expression of IL-22 and IL-17A in MF skin lesions. METHODS: The study encompassed 16 cases of MF of different stages, for which sufficient skin tissue for immunohistochemistry and frozen tissue for reverse transcription-polymerase chain reaction, both taken from the same lesion, were available. Histological evaluation of eosinophils, neutrophils, CD20+, CD4+, CD8+, FOXP3+, CD56+, and CD1a+ cells was conducted. Additionally, mRNA expression levels of IL-22 and IL-17 mRNA were quantified using reverse transcription-quantitative polymerase chain reaction. SPSS version 28 (IBM Corp., Armonk, NY) was utilized for statistical analysis. RESULTS: Among the cases examined, three were in the patch stage, eight in the plaque stage, and five in the transformation to high-grade large cell lymphoma (t-LCL). B-lymphocytes, neutrophils, and eosinophils were primarily observed in t-LCL cases. IL-22 levels displayed a significant association with IL-17A levels (Pearson's r = 0.961, p < 0.001), FOXP3+ cells (Pearson's r = 0.851, p < 0.001), and neutrophil density (Pearson's r = 0.586, p = 0.014). No correlation was detected between IL-17A levels and the evaluated subtypes of microenvironmental cells. CONCLUSION: The microenvironment of MF lesions with t-LCL is noticeably different from early MF in terms of cellular composition. Histopathological identification of the cellular microenvironment may serve as an indicator of IL-22 tissue levels. These results implicate certain types of cells in IL-22 expression in the MF microenvironment and may contribute to advancing our knowledge on the pathogenesis and progression of the disease.

14.
J Immunol ; 211(5): 743-754, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37466373

ABSTRACT

Subset #201 is a clinically indolent subgroup of patients with chronic lymphocytic leukemia defined by the expression of stereotyped, mutated IGHV4-34/IGLV1-44 BCR Ig. Subset #201 is characterized by recurrent somatic hypermutations (SHMs) that frequently lead to the creation and/or disruption of N-glycosylation sites within the Ig H and L chain variable domains. To understand the relevance of this observation, using next-generation sequencing, we studied how SHM shapes the subclonal architecture of the BCR Ig repertoire in subset #201, particularly focusing on changes in N-glycosylation sites. Moreover, we profiled the Ag reactivity of the clonotypic BCR Ig expressed as rmAbs. We found that almost all analyzed cases from subset #201 carry SHMs potentially affecting N-glycosylation at the clonal and/or subclonal level and obtained evidence for N-glycan occupancy in SHM-induced novel N-glycosylation sites. These particular SHMs impact (auto)antigen recognition, as indicated by differences in Ag reactivity between the authentic rmAbs and germline revertants of SHMs introducing novel N-glycosylation sites in experiments entailing 1) flow cytometry for binding to viable cells, 2) immunohistochemistry against various human tissues, 3) ELISA against microbial Ags, and 4) protein microarrays testing reactivity against multiple autoantigens. On these grounds, N-glycosylation appears as relevant for the natural history of at least a fraction of Ig-mutated chronic lymphocytic leukemia. Moreover, subset #201 emerges as a paradigmatic case for the role of affinity maturation in the evolution of Ag reactivity of the clonotypic BCR Ig.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Humans , Receptors, Antigen, B-Cell/genetics , Receptors, Antigen, B-Cell/metabolism , Glycosylation , Antigens/metabolism
15.
Eur J Pediatr ; 182(6): 2499-2507, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36988678

ABSTRACT

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle-Ottawa scale was applied for the studies' quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case-control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80-5.71). The heterogeneity was moderate and estimated at 51% with the I-squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle-Ottawa score was 8/9 for all the included reports.  Conclusion: This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80-5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.


Subject(s)
Cryptorchidism , Testicular Neoplasms , Male , Humans , Adolescent , Adult , Cryptorchidism/surgery , Testicular Neoplasms/etiology , Testicular Neoplasms/surgery , Orchiopexy/adverse effects , Risk Factors
16.
World J Clin Oncol ; 13(10): 853-860, 2022 Oct 24.
Article in English | MEDLINE | ID: mdl-36337315

ABSTRACT

BACKGROUND: Retrorectal hamartomas or tailgut cysts (TCs) are rare. In most cases, they are asymptomatic and benign; however, rarely, they undergo malignant transformation, mainly in the form of adenocarcinoma. CASE SUMMARY: A 55-year-old woman presented to our hospital with lower back pain. On magnetic resonance imaging, a large pelvic mass was found, which was located on the right of the ischiorectal fossa, extending to the minor pelvis. The patient underwent extensive surgical resection of the lesion through the right buttock. Histological examination confirmed the diagnosis of a retrorectal mucinous adenocarcinoma originating from a TC. Surgical resection of the tumour was complete, and the patient recovered without complications. The pilonidal sinus was then excised. One year later, semi-annual positron emission tomography-computed tomography and magnetic resonance imaging scans did not reveal any evidence of local recurrence or metastatic disease. CONCLUSION: Preoperative recognition, histological diagnosis, and treatment of TCs pose significant challenges. In addition, the possibility of developing invasive mucinous adenocarcinoma, although rare, should be considered.

17.
Cancers (Basel) ; 14(22)2022 Nov 16.
Article in English | MEDLINE | ID: mdl-36428728

ABSTRACT

Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients' tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.

18.
Medicina (Kaunas) ; 58(8)2022 Aug 18.
Article in English | MEDLINE | ID: mdl-36013583

ABSTRACT

BACKGROUND: Multiple gastrointestinal stromal tumors (GISTs) are extremely rare entities that exist either as spontaneous GISTs or as part of various syndromes, such as Carney's triad and type I neurofibromatosis (NF1). Attenuated familial adenomatous polyposis (AFAP) is a variant of familial adenomatous polyposis (FAP) with a milder clinical presentation. Both GISTs and AFAP have been reported to coexist with colorectal cancer, but the coexistence of GISTs and AFAP has never been reported in the literature before. CASE REPORT: A 45-year-old male patient with known AFAP arrived scheduled for a total colectomy and ileo-rectal anastomosis due to the malignancy of one of the previously biopsied polyps of the upper rectum. Intraoperatively, multiple nodular tumors were found at the jejunum within a length of 45 cm, for which an enterectomy and enteroanastomosis were performed. A histopathological examination of the whole colectomy specimen confirmed the presence of multiple polyps in the large intestine along with a rectal invasive adenocarcinoma. At the same time, in the examined part of the small intestine, 15 GISTs sized from 0.5 to 2.0 cm of prognostic group I, were identified. The patient's postoperative course was uncomplicated. CONCLUSION: Multiple GISTs may present as an asymptomatic disease, and the same thing is true for colorectal cancer. Therefore, the appropriate screening is crucial for entities such as AFAP, since the surgery was performed because of the malignant transformation in one of the polyps and revealed multiple GISTs, as well.


Subject(s)
Adenocarcinoma , Adenomatous Polyposis Coli , Colorectal Neoplasms , Gastrointestinal Stromal Tumors , Rectal Neoplasms , Adenocarcinoma/complications , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenomatous Polyposis Coli/complications , Adenomatous Polyposis Coli/surgery , Colorectal Neoplasms/pathology , Gardner Syndrome , Gastrointestinal Stromal Tumors/complications , Gastrointestinal Stromal Tumors/surgery , Humans , Male , Middle Aged , Rectal Neoplasms/complications , Rectal Neoplasms/pathology , Rectal Neoplasms/surgery
19.
Brief Bioinform ; 23(5)2022 09 20.
Article in English | MEDLINE | ID: mdl-36044248

ABSTRACT

Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio.tools/igidiva.


Subject(s)
Genes, Immunoglobulin , Immunoglobulins , B-Lymphocytes , Clone Cells , High-Throughput Nucleotide Sequencing , Immunoglobulins/genetics
20.
Cardiovasc Diabetol ; 21(1): 140, 2022 07 26.
Article in English | MEDLINE | ID: mdl-35883091

ABSTRACT

BACKGROUND: Stress induced hyperglycemia (SIH) is common among patients with ST-elevation myocardial infarction (STEMI), even in patients without diabetes mellitus. However, evidence regarding its role on the angiographic outcomes and the prognosis of patients presenting with STEMI is scarce. METHODS: This study included 309 consecutively enrolled STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Patients were diagnosed with SIH if blood glucose on admission was > 140 mg/dl. Also, patients had to fast for at least 8 hours before blood sampling. The objective was to assess whether SIH was associated with major adverse cardiovascular and cerebrovascular (MACCE) events and explore its relationship with angiographic predictors of worse prognosis such as poor initial TIMI flow, intracoronary thrombus burden, distal embolization, and presence of residual thrombus after pPCI. RESULTS: SIH in diabetic and non-diabetic patients was associated with a higher incidence of LTB (aOR = 2.171, 95% CI 1.27-3.71), distal embolization (aOR = 2.71, 95% CI 1.51-4.86), and pre-procedural TIMI flow grade = 0 (aOR = 2.69, 95% CI 1.43-5.04) after adjusting for relevant clinical variables. Importantly, during a median follow-up of 1.7 years STEMI patients with SIH with or without diabetes experienced increased occurrence of MACCE both in univariate (HR = 1.92, 95% CI 1.19-3.01) and multivariate analysis (aHR = 1.802, 95% CI 1.01-3.21). CONCLUSIONS: SIH in STEMI patients with or without diabetes was independently associated with increased MACCE. This could be attributed to the fact that SIH was strongly correlated with poor pre-procedural TIMI flow, LTB, and distal embolization. Large clinical trials need to validate SIH as an independent predictor of adverse angiographic and clinical outcomes to provide optimal individualized care for patients with STEMI.


Subject(s)
Hyperglycemia , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Thrombosis , Coronary Angiography , Humans , Hyperglycemia/complications , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Treatment Outcome
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