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Computers in Biology and Medicine Apr 2022Atrial fibrillation (AF) is the most sustained arrhythmia in the heart and also the most common complication developed after cardiac surgery. Due to its progressive...
Atrial fibrillation (AF) is the most sustained arrhythmia in the heart and also the most common complication developed after cardiac surgery. Due to its progressive nature, timely detection of AF is important. Currently, physicians use a surface electrocardiogram (ECG) for AF diagnosis. However, when the patient develops AF, its various development stages are not distinguishable for cardiologists based on visual inspection of the surface ECG signals. Therefore, severity detection of AF could start from differentiating between short-lasting AF and long-lasting AF. Here, de novo post-operative AF (POAF) is a good model for short-lasting AF while long-lasting AF can be represented by persistent AF. Therefore, we address in this paper a binary severity detection of AF for two specific types of AF. We focus on the differentiation of these two types as de novo POAF is the first time that a patient develops AF. Hence, comparing its development to a more severe stage of AF (e.g., persistent AF) could be beneficial in unveiling the electrical changes in the atrium. To the best of our knowledge, this is the first paper that aims to differentiate these different AF stages. We propose a method that consists of three sets of discriminative features based on fundamentally different aspects of the multi-channel ECG data, namely based on the analysis of RR intervals, a greyscale image representation of the vectorcardiogram, and the frequency domain representation of the ECG. Due to the nature of AF, these features are able to capture both morphological and rhythmic changes in the ECGs. Our classification system consists of a random forest classifier, after a feature selection stage using the ReliefF method. The detection efficiency is tested on 151 patients using 5-fold cross-validation. We achieved 89.07% accuracy in the classification of de novo POAF and persistent AF. The results show that the features are discriminative to reveal the severity of AF. Moreover, inspection of the most important features sheds light on the different characteristics of de novo post-operative and persistent AF.
PubMed: 35124441
DOI: 10.1016/j.compbiomed.2022.105270 -
Cancers Oct 2023De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since... (Review)
Review
De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5-10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities for de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have modified the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road toward personalized treatment for de novo mHSPC is still long, considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that did not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as a predictive biomarker requires further validation, and it remains to be ascertained how the genomic variants detected in mHSPC, which are regarded as predictive in the castration-resistant disease, can be exploited in the mHSPC setting.
PubMed: 37894312
DOI: 10.3390/cancers15204945 -
Prostate International Sep 2021Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we... (Review)
Review
Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.
PubMed: 34692582
DOI: 10.1016/j.prnil.2020.12.003 -
Breast Cancer Research and Treatment Nov 2022This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment...
PURPOSE
This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment era and examined factors related to outcome differentials.
METHODS
Using an institutional database, we examined patient and tumor characteristics, treatment response, and outcome among 232 patients with de novo and 612 patients with recurrent MBC diagnosed between 2011 and 2017.
RESULTS
De novo MBC had 9-month (m) longer overall survival (OS) than recurrent MBC (36.4 vs 27.4 m, p < 0.001). Contributions to this difference included nearly twofold more HER2-positive (29.3% vs 15.2%) and significantly fewer triple-negative breast cancers (20.3% vs 32.4%, both p < 0.001) in de novo compared with recurrent MBC cohorts. Stratified by clinical subtype, progression-free survival (PFS) on first-line therapy was significantly longer in de novo MBC in all but the triple-negative subtype, 25.5 vs 11.6 m (p < 0.001) among 390 patients with hormone receptor-positive, HER2-negative, 11.4 vs 5.4 m (p = 0.002) among 142 patients with HER2-positive, and 4.0 vs 3.0 m (p = 0.121) among 162 with triple-negative MBC. In multivariable analysis, de novo status remained independently associated with improved OS (hazard ratio 0.63, 95% CI 0.49-0.80), regardless of subtype and other features.
CONCLUSION
Patients with de novo MBC have better outcomes than those with recurrent MBC. Differences in clinical subtype and response to therapy in the metastatic setting contribute to, but do not fully explain, this difference. Longer PFS to first-line therapy in de novo MBC suggests biologic differences compared to recurrent MBC, which may be intrinsic or due to acquired resistance from treatment for prior localized breast cancer in recurrent disease.
Topics: Biological Products; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2
PubMed: 36008651
DOI: 10.1007/s10549-022-06700-6 -
BMC Biology Nov 2023Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth....
BACKGROUND
Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Particularly, de novo gene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms that lead to functionalization are poorly understood, and estimated rates of de novo gene birth remain contentious. Here, we address this problem within a model that takes into account mutations and structural variation, allowing us to estimate the likelihood of emergence of new functions at non-functional loci.
RESULTS
Assuming biologically reasonable mutation rates and mutational effects, we find that functionalization of non-genic loci requires the realization of strict conditions. This is in line with the observation that most de novo genes are localized to the vicinity of established genes. Our model also provides an explanation for the empirical observation that emerging proto-genes are often lost despite showing signs of adaptation.
CONCLUSIONS
Our work elucidates the properties of non-genic loci that make them fertile for adaptation, and our results offer mechanistic insights into the process of de novo gene birth.
Topics: Evolution, Molecular; Mutation; Biological Evolution
PubMed: 37957718
DOI: 10.1186/s12915-023-01745-5 -
Biomarker Research Sep 2023Population-based data comparing the outcomes of patients with transformed follicular lymphoma (t-FL) and de novo diffuse large B-cell lymphoma (DLBCL) are lacking. The...
Population-based data comparing the outcomes of patients with transformed follicular lymphoma (t-FL) and de novo diffuse large B-cell lymphoma (DLBCL) are lacking. The objective of this study was to compare the survival of patients with t-FL and de novo DLBCL diagnosed in the United States between 2010-2018. We hypothesized that patients with t-FL would have an inferior survival compared to patients with de novo DLBCL. The study outcomes were relative survival (RS), overall survival (OS), and lymphoma-specific survival (LSS) compared between t-FL and de novo DLBCL. Flexible parametric survival models were used to estimate the study outcomes. There were 569 cases of t-FL and 44,706 cases of de novo DLBCL. Patients with t-FL had an estimated 5-year RS of 54% [95% confidence interval (CI), 49-59%) compared to 67% (95% CI, 66-67%) for those with de novo DLBCL (adjusted hazard ratio, 1.29; 95% CI, 1.11-1.50; P = 0.001). The corresponding 5-year OS estimates were 49% (95% CI, 44-53%) and 57% (95% CI, 57-58%), respectively (adjusted hazard ratio, 1.23; 95% CI, 1.07-1.42; P = 0.004). The corresponding 5-year LSS estimates were 54% (95% CI, 50-59%) and 66% (95% CI, 65-66%), respectively (adjusted hazard ratio, 1.34; 95% CI, 1.15-1.56; P < 0.001). This population-based registry analysis shows that patients with t-FL continue to have an inferior survival in the modern era and should be prioritized for enrollment in clinical trials.
PubMed: 37759262
DOI: 10.1186/s40364-023-00525-1 -
Genes Mar 2022Most genetic variants are rare and specific to the population, highlighting the importance of characterizing local population genetic diversity. Many countries have...
Most genetic variants are rare and specific to the population, highlighting the importance of characterizing local population genetic diversity. Many countries have initiated population-based whole-genome sequencing (WGS) studies. Genomic variation within Lithuanian families are not available in the public databases. Here, we describe initial findings of a high-coverage (an average of 36.27×) whole genome sequencing for 25 trios of the Lithuanian population. Each genome on average carried approximately 4,701,473 (±28,255) variants, where 80.6% (3,787,626) were single nucleotide polymorphisms (SNPs), and the rest 19.4% were indels. An average of 12.45% was novel according to dbSNP (build 150). The WGS structural variation (SV) analysis identified on average 9133 (±85.10) SVs, of which 95.85% were novel. De novo single nucleotide variation (SNV) analysis identified 4417 variants, where 1.1% de novo SNVs were exonic, 43.9% intronic, 51.9% intergenic, and the rest 3.13% in UTR or downstream sequence. Three potential pathogenic de novo variants in the , , and genes were identified. Our findings provide useful information on local human population genomic variation, especially for de novo variants, and will be a valuable resource for further genetic studies, and medical implications.
Topics: Genome, Human; Humans; INDEL Mutation; Lithuania; Polymorphism, Single Nucleotide; Whole Genome Sequencing
PubMed: 35456375
DOI: 10.3390/genes13040569 -
The American Surgeon Nov 2023Necrotizing pancreatitis (NP) may result de novo or following procedures such as ERCP or partial pancreatectomy (post-procedural), and may require surgical debridement....
BACKGROUND
Necrotizing pancreatitis (NP) may result de novo or following procedures such as ERCP or partial pancreatectomy (post-procedural), and may require surgical debridement. Video-assisted retroperitoneal debridement (VARD) is a standard approach for NP that employs a 5 cm incision with varying degrees of blind and open debridement. We describe our technique and outcomes of a modified VARD called laparoscopic-assisted pancreatic necrosectomy (LAPN) performed through a single 12 mm incision that uses direct laparoscopic visualization during debridement.
METHODS
At one medical center, all LAPN patients (2012-2020) were assessed for demographics, disease factors, and outcomes. Bivariate logistic regression analyses were performed to identify factors independently associated with recovery after LAPN for patients with vs post-procedural necrosum.
RESULTS
Over 9 years, 60 patients underwent LAPN for NP. Median age was 57 years (IQR: 47-66) and 43 (69%) were men. Pancreas necrosum was in 39 (63%) patients and post-procedural in 23 (37%). NP resolved with a median of 1 LAPN procedure and median hospitalization was 33 days. The LAPN major morbidity rate and in-hospital mortality rate were 47% and 5%. No significant differences were seen between NP etiology cohorts, although post-procedure NP patients trended towards a faster clinical recovery to baseline compared to patients (193 vs 394 days; -value = .07).
CONCLUSIONS
LAPN offers a smaller incision with excellent visualization and non-inferior outcomes, regardless of etiology, with likely faster recovery for patients with post-procedural vs necrotizing pancreatitis.
Topics: Male; Humans; Middle Aged; Female; Debridement; Pancreas; Laparoscopy; Pancreatitis, Acute Necrotizing; Retroperitoneal Space; Drainage; Treatment Outcome
PubMed: 35575200
DOI: 10.1177/00031348221101495 -
Frontiers in Neurology 2021Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the...
Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked recessively inherited neuromuscular disorders caused by deletions, duplications, or small mutations in the gene. With advances in prenatal diagnosis decreasing the number of affected offspring from carrier mothers, the frequency of variants could increase. Therefore, determining the differences between the carrier and variants of the gene, which are rarely explored, is important for trial planning and genetic diagnosis in the future. A total of 440 patients, 349 of whom had DMD and 91 had BMD, diagnosed in our department between 2012 and 2019, along with their respective mothers, were included in this study. Multiplex ligation-dependent probe amplification was used to detected deletions and duplications in patients and their mothers. Small mutations were detected using next-generation sequencing in the patients, followed by Sanger sequencing in the mothers. Deletions, duplications, and small mutations were identified in 204, 46, and 99 of the 349 patients with DMD and in 50, 10, and 31 of the 91 patients with BMD, respectively. deletions were more concentrated in hotspot regions than carrier deletions of DMD/BMD. No clear bias was observed in the variant distribution between carriers, duplications, and small mutations in DMD/BMD. The carrier frequency of DMD (61.6%) was lower than that of BMD (69.2%), but the difference was not statistically significant. The carrier frequency of deletions of the gene (51.2%) was significantly lower than those of duplications (75%) and small mutations (81.5%). Compared to deletions, deletions from carrier mothers had a wider distribution. Moreover, there was no significant difference between the carrier frequencies of DMD and BMD. Duplications and small mutations were more commonly inherited, while deletions were present .
PubMed: 34421809
DOI: 10.3389/fneur.2021.714677 -
Pathology Oncology Research : POR Oct 2020The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in...
The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51 years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2 mm (p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Humans; Male; Melanoma; Middle Aged; Nevus, Pigmented; Prognosis; Retrospective Studies; Skin Neoplasms; Young Adult
PubMed: 32572820
DOI: 10.1007/s12253-020-00858-4