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Scientific Reports Jun 2024Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin,...
Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19-84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34-49.88) months by the Kaplan-Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS.
Topics: Humans; Myelodysplastic Syndromes; Male; Aged; Female; Middle Aged; Prognosis; Aged, 80 and over; Adult; Retrospective Studies; Hemoglobins; Young Adult; ROC Curve; Blood Platelets; Lymphocytes; Platelet Count
PubMed: 38879594
DOI: 10.1038/s41598-024-64166-6 -
BMC Medical Genomics Jun 2024Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft...
BACKGROUND
Fibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis.
CASE PRESENTATION
A three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother's persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition).
CONCLUSION
This report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways.
Topics: Humans; Myositis Ossificans; Female; Hallux Valgus; Infant; Bone Morphogenetic Protein Receptors, Type I
PubMed: 38879467
DOI: 10.1186/s12920-024-01931-6 -
BMC Pregnancy and Childbirth Jun 2024To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised...
BACKGROUND
To investigate the prognosis of the remaining fetus in twin pregnancy after experiencing one fetal demise in the first trimester according to the location of the demised fetus.
METHODS
This was a retrospective study of twin pregnancies with one fetal demise after the first trimester (14 weeks of gestation) delivered between September 2004 and September 2022. The study population was divided into two groups based on the location of the demised fetus as determined by the last recorded ultrasonography results: Group 1 included twin pregnancies where the presenting fetus was demised (n = 36) and Group 2 included twin pregnancies where the non-presenting fetus was demised (n = 44). The obstetric and neonatal outcomes were also reviewed.
RESULTS
A total of 80 pregnant women were included. The median gestational age for the diagnosis of fetal demise was 24.1 weeks. The gestational age of the demised fetus was not different between Groups 1 and 2; however, the gestational age of the remaining fetus at delivery was significantly earlier in Group 1 than it was in Group 2 (33.8 vs. 37.3 weeks, P = .004). The rate of preterm birth before 28 weeks was almost five times higher in Group 1 than in Group 2 (22.2% vs. 4.5%, P = .037). Regression analysis demonstrated significant differences between Groups 1 and 2. Respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, retinopathy of prematurity, and jaundice were more common in Group 1 than in Group 2; however, the association was not significant after adjusting for gestational age at delivery.
CONCLUSIONS
When the presenting fetus is demised in a twin pregnancy, the remaining fetus tends to be delivered earlier than when the non-presenting fetus is demised.
Topics: Humans; Female; Pregnancy; Pregnancy, Twin; Retrospective Studies; Adult; Fetal Death; Gestational Age; Prognosis; Infant, Newborn; Premature Birth; Pregnancy Outcome; Pregnancy Trimester, First; Ultrasonography, Prenatal; Fetus
PubMed: 38877391
DOI: 10.1186/s12884-024-06621-w -
The Knee Jun 2024In recent years, coronal lower leg alignment has received significant attention. Two classifications recently described the variability in both femoral and tibial...
BACKGROUND
In recent years, coronal lower leg alignment has received significant attention. Two classifications recently described the variability in both femoral and tibial morphology, resulting in differing native lower limb alignment. The native trochlea and the variability in morphology has received less attention.
METHODS
This is a prospective cohort study of 200 patients undergoing robotically assisted TKA. Preoperative transverse CT scans were used to determine the posterior condylar axis (PCA), transepicondylar axis (TEA), lateral trochlear inclination (LTI), the sulcus angle (SA) and the anterior trochlear line (ATL). Outliers were defined as values > 1.5 IQR from median value. Trochlea dysplasia was defined as LTI < 12°. Gender differences were compared.
RESULTS
In total, 99 patients were female (49.4%). SA had a median of 137.0° (IQR 12°), ATL 4° (IQR 4), LTI 18° (IQR 7°). Median TEA-PCA was 5° external (IQR 3°). There were 5.0% outliers in SA, 3.0% of outliers in ATL, 3.5% outliers in LTI and 4.5% outliers in the TEA-PCA. Trochlear dysplasia was present in 11.5% of the measurements. There was no difference in any of the angles between the genders.
CONCLUSION
The present study demonstrates no difference in trochlea morphology between the genders, rather a significant number of overall outliers in trochlear morphology. Larger cohorts but also, more investigations, are needed to better understand the trochlear morphology of patients undergoing total knee arthroplasty. The personalized alignment strategies and implants need to account for this variability in the population.
PubMed: 38876083
DOI: 10.1016/j.knee.2024.06.002 -
PloS One 2024We aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and...
OBJECTIVE
We aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and validating the associated ferroptosis-related genes to explore new directions for treating BPD.
METHODS
The dataset GSE32472 on BPD was downloaded from the public genome database. Using R language, differentially expressed genes (DEGs) between the BPD and normal group were screened. In the present study, we adopted weighted gene correlation network analysis (WGCNA) for identifying BPD-related gene modules and ferroptosis-related genes were extracted from FerrDb. Their results were intersected to obtain the hub genes. After that, to explore the hub gene-related signaling pathways, the hub genes were exposed to gene ontology enrichment analysis. With the purpose of verifying the mRNA expression of the hub genes, a single-gene gene set enrichment analysis and quantitative reverse transcription polymerase chain reaction were conducted. Immune cell infiltration in BPD was analyzed using the CIBERSORT inverse fold product algorithm.
RESULTS
A total of 606 DEGs were screened. WGCNA provided the BPD-related gene module darkgreen4. The intersection of DEGs, intramodular genes, and ferroptosis-related genes revealed six ferroptosis-associated hub genes (ACSL1, GALNT14, WIPI1, MAPK14, PROK2, and CREB5). Receiver operating characteristic curve analysis demonstrated that the hub genes screened for BPD were of good diagnostic significance. According to the results of immune infiltration analysis, the proportions of CD8, CD4 naive, and memory resting T cells and M2 macrophage were elevated in the normal group, and the proportions of M0 macrophage, resting mast cell, and neutrophils were increased in the BPD group.
CONCLUSIONS
A total of six ferroptosis-associated hub genes in BPD were identified in this study, and they may be potential new therapeutic targets for BPD.
Topics: Ferroptosis; Bronchopulmonary Dysplasia; Humans; Computational Biology; Gene Regulatory Networks; Gene Expression Profiling; Databases, Genetic; Gene Ontology
PubMed: 38875180
DOI: 10.1371/journal.pone.0291583 -
Journal of the Korean Society of... May 2024Developmental dysplasia of the hip is a condition characterized by hip joint instability due to acetabular dysplasia in infancy, necessitating precise ultrasound... (Review)
Review
Developmental dysplasia of the hip is a condition characterized by hip joint instability due to acetabular dysplasia in infancy, necessitating precise ultrasound examination. Legg-Calvé-Perthes disease is caused by a temporary disruption in blood flow to the femoral head during childhood, progressing through avascular, fragmentation, re-ossification, and residual stages. Slipped capital femoral epiphysis is a condition where the femoral head shifts medially along the epiphyseal line during adolescence due to stress, such as weight-bearing. Differentiating between transient hip synovitis and septic arthritis may require joint fluid aspiration. Osteomyelitis can be associated with soft tissue edema and osteolysis. When multiple lesions are present, it is essential to distinguish between Langerhans cell histiocytosis and metastatic neuroblastoma. This review will introduce imaging techniques and typical findings for these conditions.
PubMed: 38873372
DOI: 10.3348/jksr.2024.0021 -
Pathology Oncology Research : POR 2024Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric...
BACKGROUND
Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the cause, classification, and clinicopathological features of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms.
METHODS
37 cases diagnosed with GEN-FGMLs were included in this study. H&E-stained slides were reviewed and clinicopathological parameters were recorded. Immunohistochemical staining was conducted for MUC2, MUC5AC, MUC6, CD10, CD56, synaptophysin, chromograninA, p53, Ki67, pepsinogen-I, H/K-ATPase and Desmin.
RESULTS
The patients' ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between OGA, GA-FG, and GA-FGM. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. These cells resembled fundic gland cells. None of the OGA invaded the submucosal layer. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Non-atrophic gastritis was observed in more than half of the background mucosa. All cases were diffusely positive for MUC6 and pepsinogen-I on immunohistochemistry. H/K-ATPase staining was negative or showed a scattered pattern in most cases. MUC5AC was expressed on the surface of GA-FGMs. p53 was focally expressed and the Ki67 index was low (1%-20%). Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view ( < 0.05) and had larger sizes ( < 0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA ( < 0.0001). Specimens with Ki-67 proliferation indices >2.5% and size >4.5 mm are more likely to be diagnosed with GA-FG and GA-FGM than OGA.
CONCLUSION
GEN-FGMLs are group of well-differentiated gastric tumors with favourable biological behaviours, low cellular atypia, and low proliferation. Immunohistochemistry is critical for confirming diagnosis. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. Pathologists and endoscopists should be cautious to prevent misdiagnosis and overtreatment, especially in biopsy specimens.
Topics: Humans; Stomach Neoplasms; Male; Female; Middle Aged; Aged; Adult; Ki-67 Antigen; Gastric Mucosa; Biomarkers, Tumor; Adenocarcinoma; Gastric Fundus; Adenoma; Prognosis
PubMed: 38873175
DOI: 10.3389/pore.2024.1611734 -
Cancer Medicine Jun 2024Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other...
OBJECTIVES
Visual inspection with acetic acid (VIA) is a low-cost approach for cervical cancer screening used in most low- and middle-income countries (LMICs) but, similar to other visual tests, is subjective and requires sustained training and quality assurance. We developed, trained, and validated an artificial-intelligence-based "Automated Visual Evaluation" (AVE) tool that can be adapted to run on smartphones to assess smartphone-captured images of the cervix and identify precancerous lesions, helping augment VIA performance.
DESIGN
Prospective study.
SETTING
Eight public health facilities in Zambia.
PARTICIPANTS
A total of 8204 women aged 25-55.
INTERVENTIONS
Cervical images captured on commonly used low-cost smartphone models were matched with key clinical information including human immunodeficiency virus (HIV) and human papillomavirus (HPV) status, plus histopathology analysis (where applicable), to develop and train an AVE algorithm and evaluate its performance for use as a primary screen and triage test for women who are HPV positive.
MAIN OUTCOME MEASURES
Area under the receiver operating curve (AUC); sensitivity; specificity.
RESULTS
As a general population screening tool for cervical precancerous lesions, AVE identified cases of cervical precancerous and cancerous (CIN2+) lesions with high performance (AUC = 0.91, 95% confidence interval [CI] = 0.89-0.93), which translates to a sensitivity of 85% (95% CI = 81%-90%) and specificity of 86% (95% CI = 84%-88%) based on maximizing the Youden's index. This represents a considerable improvement over naked eye VIA, which as per a meta-analysis by the World Health Organization (WHO) has a sensitivity of 66% and specificity of 87%. For women living with HIV, the AUC of AVE was 0.91 (95% CI = 0.88-0.93), and among those testing positive for high-risk HPV types, the AUC was 0.87 (95% CI = 0.83-0.91).
CONCLUSIONS
These results demonstrate the feasibility of utilizing AVE on images captured using a commonly available smartphone by nurses in a screening program, and support our ongoing efforts for moving to more broadly evaluate AVE for its clinical sensitivity, specificity, feasibility, and acceptability across a wider range of settings. Limitations of this study include potential inflation of performance estimates due to verification bias (as biopsies were only obtained from participants with visible aceto-white cervical lesions) and due to this being an internal validation (the test data, while independent from that used to develop the algorithm was drawn from the same study).
Topics: Humans; Female; Uterine Cervical Neoplasms; Smartphone; Zambia; Adult; Early Detection of Cancer; Prospective Studies; Middle Aged; Sensitivity and Specificity; Papillomavirus Infections; Algorithms; Uterine Cervical Dysplasia; Mass Screening; ROC Curve; Artificial Intelligence
PubMed: 38872398
DOI: 10.1002/cam4.7355 -
Revue Medicale de Liege Jun 2024Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health... (Review)
Review
Prematurity remains a leading cause of mortality and morbidity in neonates and children. Prevention of preterm birth and of its complications is a major public health issue. From before conception to long term follow up, many health actors are engaged in this preventive strategy with the same goal : to give the best quality of life for these vulnerable young patients. We will review different preventive aspects during antenatal and perinatal period, during NICU (Neonatal Intensive Care Unit) stay and after discharge. Prevention of prematurity's complications requires a global approach including respiratory, nutritional and infectious aspects among others. Neuroprotective strategies are a key point of this global approach.
Topics: Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Premature; Pregnancy; Female; Premature Birth
PubMed: 38869136
DOI: No ID Found -
International Journal of... Apr 2024Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal...
Myelodysplastic syndromes (MDS) are determined by ineffective hematopoiesis and bone marrow cytological dysplasia with somatic gene mutations and chromosomal abnormalities. Accumulating evidence has revealed the pivotal role of NLRP3 inflammasome activation and pyroptotic cell death in the pathogenesis of MDS. Although MDS can be diagnosed with a variety of morphologic and cytogenetic tests, most of these tests have limitations or problems in practice. In the present study, we evaluated the expression of genes that form the inflammasome () in bone marrow specimens of MDS patients and compared the results with those of other leukemias to evaluate their diagnostic value for MDS. Primary samples of this observational cohort study were collected from aspiration samples of patients with myelodysplastic syndromes (27 cases) and patients with non-myelodysplastic syndrome hematological cancers (45 cases). After RNA extraction and c.DNA synthesis, candidate transcripts and housekeeping transcripts were measured by real-time PCR method (SYBER Green assay). Using Kruskal-Wallis the relative gene expressions were compared and differences with value less than 0.05 were considered as significant. Discrimination capability, cut-off, and area under curve (AUC) of all markers were analyzed with recessive operation curve (ROC) analysis. We found that Caspase-1 and ASC genes expressed at more levels in MDS specimens compared to non-MDS hematological malignancies. A relative average expression of 10.22 with of 0.001 and 1.86 with =0.019 was detected for Caspase-1 and ASC, respectively. ROC curve analysis shows an AUC of 0.739 with =0.0001 for Caspase-1 and an AUC of 0.665 with =0.0139 for ASC to MDS discrimination. Our results show that Caspase-1 and ASC gene expression levels can be used as potential biomarkers for MDS diagnosis. Prospective studies with large sample numbers are suggested.
PubMed: 38868810
DOI: 10.18502/ijhoscr.v18i2.15371