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Frontiers in Endocrinology 2024
Topics: Humans; Autophagy; Aging; Metabolic Diseases; Endocrine System Diseases; Animals
PubMed: 38952396
DOI: 10.3389/fendo.2024.1439492 -
Frontiers in Endocrinology 2024Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be...
UNLABELLED
Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time.
DESIGN AND PATIENTS
National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235).
RESULTS
The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered.
CONCLUSIONS
Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.
Topics: Humans; Central Nervous System Cysts; Female; Male; Spain; Adult; Middle Aged; Young Adult; Adolescent; Treatment Outcome; Aged; Pituitary Neoplasms; Disease Progression; Follow-Up Studies; Neoplasm Recurrence, Local; Child
PubMed: 38952395
DOI: 10.3389/fendo.2024.1413810 -
Frontiers in Endocrinology 2024Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence... (Review)
Review
Insulin resistance (IR) is becoming a worldwide medical and public health challenge as an increasing prevalence of obesity and metabolic disorders. Accumulated evidence has demonstrated a strong relationship between IR and a higher incidence of several dramatically vision-threatening retinal diseases, including diabetic retinopathy, age-related macular degeneration, and glaucoma. In this review, we provide a schematic overview of the associations between IR and certain ocular diseases and further explore the possible mechanisms. Although the exact causes explaining these associations have not been fully elucidated, underlying mechanisms of oxidative stress, chronic low-grade inflammation, endothelial dysfunction and vasoconstriction, and neurodegenerative impairments may be involved. Given that IR is a modifiable risk factor, it may be important to identify patients at a high IR level with prompt treatment, which may decrease the risk of developing certain ocular diseases. Additionally, improving IR through the activation of insulin signaling pathways could become a potential therapeutic target.
Topics: Humans; Insulin Resistance; Retina; Diabetic Retinopathy; Animals; Retinal Diseases; Eye Diseases; Oxidative Stress; Macular Degeneration; Glaucoma; Risk Factors
PubMed: 38952394
DOI: 10.3389/fendo.2024.1415521 -
Frontiers in Endocrinology 2024Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in...
UNLABELLED
Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in neoplastic development.
AIM
This study assesses the effectiveness of CEUS as a supplementary tool to TIRADS in enhancing the ultrasound-based diagnosis of thyroid cancer.
METHODS AND MATERIALS
Over one year, 157 nodules in 133 patients, with predominantly solid thyroid nodules, were examined using ultrasound and CEUS and underwent thyroidectomy, allowing for a comparison of ultrasound findings with pathological reports.
RESULTS
Thyroid cancer was identified in 31.21% (49/157) of cases. Significant CEUS high-risk features included inhomogeneous enhancement, enhancement defects, and complete hypoenhancement (AUC 0.818, 0.767, 0.864 respectively). Nodules exhibiting any of these features were classified as high-risk in CEUS. The diagnostic performance of TIRADS improved when combined with CEUS, with AUC increasing from 0.707 to 0.840 and improved sensitivity.
CONCLUSION
The integration of CEUS with TIRADS significantly enhances the diagnostic accuracy and specificity in identifying thyroid cancer. This combination proves to be a more effective method for risk stratification and diagnosis, highlighting the value of CEUS as an adjunctive tool in thyroid cancer evaluation.
Topics: Humans; Thyroid Nodule; Male; Female; Ultrasonography; Thyroid Neoplasms; Middle Aged; Adult; Contrast Media; Aged; Thyroidectomy
PubMed: 38952390
DOI: 10.3389/fendo.2024.1417449 -
Frontiers in Endocrinology 2024To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine...
Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors.
OBJECTIVES
To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs).
METHODS
A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed.
RESULTS
A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts.
CONCLUSION
A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.
Topics: Humans; Machine Learning; Pancreatic Neoplasms; Endosonography; Female; Male; Middle Aged; Insulinoma; Adult; Neuroendocrine Tumors; Diagnosis, Differential; Aged; Nomograms; Radiomics
PubMed: 38952387
DOI: 10.3389/fendo.2024.1383814 -
Veterinary Medicine and Science Jul 2024Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight... (Comparative Study)
Comparative Study
Application of ultrasonographic human estimated foetal weight formulas to cynomolgus monkeys (Macaca fascicularis) at 129-132 days of gestation: A comparative study of estimated and actual birthweight.
BACKGROUND
Cynomolgus monkeys (Macaca fascicularis) are essential in biomedical research, including reproductive studies. However, the application of human estimated foetal weight (EFW) formulas using ultrasonography (USG) in these non-human primates is not well established.
OBJECTIVES
This study aims to evaluate the applicability of human EFW formulas for estimating foetal weight in cynomolgus monkeys at approximately 130 days of gestation.
METHODS
Our study involved nine pregnant cynomolgus monkeys. We measured foetal parameters, including biparietal diameter, head circumference, abdominal circumference and femur length using USG. The EFW was calculated using 11 human EFW formulas. The actual birthweight (ABW) was recorded following Cesarean section, the day after the EFW calculation. For comparing EFW and ABW, we employed statistical methods such as mean absolute percentage error (APE) and Bland-Altman analysis.
RESULTS
The ABW ranged between 200.36 and 291.33 g. Among the 11 formulas, the Combs formula showed the lowest APE (4.3%) and highest correlation with ABW (p < 0.001). Notably, EFW and ABW differences for the Combs formula were ≤5% in 66.7% and ≤10% in 100% of cases. The Bland-Altman analysis supported these results, showing that all cases fell within the limits of agreement.
CONCLUSIONS
The Combs formula is applicable for estimating the weight of cynomolgus monkey fetuses with USG at approximately 130 days of gestation. Our observations suggest that the Combs formula can be applied in the prenatal care and biomedical research of this species.
Topics: Animals; Macaca fascicularis; Female; Birth Weight; Fetal Weight; Pregnancy; Ultrasonography, Prenatal; Humans
PubMed: 38952271
DOI: 10.1002/vms3.1521 -
European Journal of Sport Science Jul 2024World Rugby supports dedicated women's welfare, injury surveillance and medical/technical interventions, yet breast health has received limited attention. This article... (Review)
Review
World Rugby supports dedicated women's welfare, injury surveillance and medical/technical interventions, yet breast health has received limited attention. This article aims to provide insights into breast health issues in rugby, including breast impacts and injuries. We discuss how breast anatomy and position may be problematic in rugby. Breast volume relates to body size, which may be increasing in women's rugby, suggesting increased breast surface area and mass, potentially increasing injury risk. Breast health issues in rugby have been reported previously, with 58% of contact footballers (including rugby) experiencing breast injuries. There are damaging effects related to these breast health issues, with breast impacts often causing pain and swelling. Breast impacts may lead to haematomas, cysts and fat necrosis which can calcify over time making them difficult to distinguish from breast carcinoma, causing further investigation and anxiety. In sport, poor bra fit and insufficient support are associated with pain, skin strain and performance decrements. This article reports the potential implications of these breast health issues on performance in rugby. Recent breast-related projects supported by rugby communities may address recommendations identified in the literature for robust breast injury classifications, updated injury surveillance systems and prospective data collection on breast injury prevalence, severity and impact in rugby. These data should inform breast injury care pathways and intervention research, including evidence-based bra design. Understanding the implications of breast impacts on tissue properties, health and wellbeing is vital. Finally, data should inform rugby-specific breast education, raising awareness of this aspect of athlete health.
PubMed: 38952063
DOI: 10.1002/ejsc.12128 -
Microbiome Jul 2024Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer...
BACKGROUND
Endometrial cancer is a multifactorial disease with inflammatory, metabolic and potentially microbial cues involved in disease pathogenesis. The endometrial cancer microbiome has been poorly characterised so far and studies have often overestimated bacterial biomass due to lack of integration of appropriate contamination controls. There is also a scarcity of evidence on the functionality of microbial microenvironments in endometrial cancer. This work addresses that knowledge gap by interrogating the genuine, contamination-free microbial signatures in the female genital tract and rectum of women with endometrial cancer and the mechanistic role of microbiome on carcinogenic processes.
RESULTS
Here we sampled different regions of the reproductive tract (vagina, cervix, endometrium, fallopian tubes and ovaries) and rectum of 61 patients (37 endometrial cancer; 24 benign controls). We performed 16S rRNA gene sequencing of the V1-V2 hypervariable regions and qPCR of the 16S rRNA gene to qualitatively and quantitatively assess microbial communities and used 3D benign and endometrial cancer organoids to evaluate the effect of microbial products of L. crispatus, which was found depleted in endometrial cancer patients following primary analysis, on endometrial cell proliferation and inflammation. We found that the upper genital tract of a subset of women with and without endometrial cancer harbour microbiota quantitatively and compositionally distinguishable from background contaminants. Endometrial cancer was associated with reduced cervicovaginal and rectal bacterial load together with depletion of Lactobacillus species relative abundance, including L. crispatus, increased bacterial diversity and enrichment of Porphyromonas, Prevotella, Peptoniphilus and Anaerococcus in the lower genital tract and endometrium. Treatment of benign and malignant endometrial organoids with L. crispatus conditioned media exerted an anti-proliferative effect at high concentrations but had minimal impact on cytokine and chemokine profiles.
CONCLUSIONS
Our findings provide evidence that the upper female reproductive tract of some women contains detectable levels of bacteria, the composition of which is associated with endometrial cancer. Whether this is a cause or consequence of cancer pathophysiology and what is the functional significance of this finding remain to be elucidated to guide future screening tools and microbiome-based therapeutics. Video Abstract.
Topics: Humans; Female; Endometrial Neoplasms; RNA, Ribosomal, 16S; Microbiota; Middle Aged; Bacteria; Endometrium; Aged; Rectum; Vagina; Adult
PubMed: 38951935
DOI: 10.1186/s40168-024-01821-0 -
Journal of Experimental & Clinical... Jul 2024Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the...
BACKGROUND
Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion.
METHODS
The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma.
RESULTS
We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma.
CONCLUSIONS
Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.
Topics: Multiple Myeloma; Humans; Mice; Animals; Signal Transduction; Receptors, Immunologic; NF-kappa B; Membrane Glycoproteins; Cell Line, Tumor; Osteoclasts; Xenograft Model Antitumor Assays
PubMed: 38951916
DOI: 10.1186/s13046-024-03110-y -
Breast Cancer Research : BCR Jun 2024HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising...
PURPOSE
HER3, a member of the EGFR receptor family, plays a central role in driving oncogenic cell proliferation in breast cancer. Novel HER3 therapeutics are showing promising results while recently developed HER3 PET imaging modalities aid in predicting and assessing early treatment response. However, baseline HER3 expression, as well as changes in expression while on neoadjuvant therapy, have not been well-characterized. We conducted a prospective clinical study, pre- and post-neoadjuvant/systemic therapy, in patients with newly diagnosed breast cancer to determine HER3 expression, and to identify possible resistance mechanisms maintained through the HER3 receptor.
EXPERIMENTAL DESIGN
The study was conducted between May 25, 2018 and October 12, 2019. Thirty-four patients with newly diagnosed breast cancer of any subtype (ER ± , PR ± , HER2 ±) were enrolled in the study. Two core biopsy specimens were obtained from each patient at the time of diagnosis. Four patients underwent a second research biopsy following initiation of neoadjuvant/systemic therapy or systemic therapy which we define as neoadjuvant therapy. Molecular characterization of HER3 and downstream signaling nodes of the PI3K/AKT and MAPK pathways pre- and post-initiation of therapy was performed. Transcriptional validation of finings was performed in an external dataset (GSE122630).
RESULTS
Variable baseline HER3 expression was found in newly diagnosed breast cancer and correlated positively with pAKT across subtypes (r = 0.45). In patients receiving neoadjuvant/systemic therapy, changes in HER3 expression were variable. In a hormone receptor-positive (ER +/PR +/HER2-) patient, there was a statistically significant increase in HER3 expression post neoadjuvant therapy, while there was no significant change in HER3 expression in a ER +/PR +/HER2+ patient. However, both of these patients showed increased downstream signaling in the PI3K/AKT pathway. One subject with ER +/PR -/HER2- breast cancer and another subject with ER +/PR +/HER2 + breast cancer showed decreased HER3 expression. Transcriptomic findings, revealed an immune suppressive environment in patients with decreased HER3 expression post therapy.
CONCLUSION
This study demonstrates variable HER3 expression across breast cancer subtypes. HER3 expression can be assessed early, post-neoadjuvant therapy, providing valuable insight into cancer biology and potentially serving as a prognostic biomarker. Clinical translation of neoadjuvant therapy assessment can be achieved using HER3 PET imaging, offering real-time information on tumor biology and guiding personalized treatment for breast cancer patients.
Topics: Humans; Female; Breast Neoplasms; Neoadjuvant Therapy; Middle Aged; Receptor, ErbB-3; Prospective Studies; Adult; Aged; Biomarkers, Tumor; Receptor, ErbB-2; Receptors, Estrogen; Gene Expression Regulation, Neoplastic; Signal Transduction; Positron-Emission Tomography
PubMed: 38951909
DOI: 10.1186/s13058-024-01859-w