Early Stages Of Disease Research Articles

Baseline Clinical and Blood Biomarkers in Patients With Preataxic and Early-Stage Disease Spinocerebellar Ataxia 1 and 3.

Baseline Clinical and Blood Biomarkers in Patients With Preataxic and Early-Stage Disease Spinocerebellar Ataxia 1 and 3.

Characteristics and variations in young adults with cutaneous melanoma: A national cancer database analysis.

Many cancers in young adulthood differ in terms of biology, histologic variation, and prognosis compared to cancer in other older age groups. Differences in cutaneous melanoma among young adults compared to other older age groups, as well as between sexes in young adults are not well studied. The National Cancer Database was queried for patients diagnosed with cutaneous melanoma between 2004 and 2017. Patient characteristics, disease factors, and treatment were stratified by age-based cohorts and compared using standard univariate statistics. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between age-based cohorts and young adult sexes. Of the 329 765 patients identified, 10.5% were between 18 and 39 years of age at diagnosis. Compared with other older age groups, young adult patients were more likely to be female and uninsured with higher proportions of superficial spreading melanoma, melanoma of the trunk and extremities, and earlier-stage disease. Young adults had improved OS compared to other older age groups. Young male patients had a greater proportion of no insurance, nodular melanoma, higher-stage disease, and decreased OS compared to young female patients. Additionally, while the 5-year OS difference was statistically significant across all stages of disease between young males and females, the clinical significance is likely limited to later stages. Age and sex-specific differences in cutaneous melanoma highlight distinct patterns and characteristics, emphasizing the need for tailored approaches to screening, diagnosis, and treatment.

Curcumin and its Analogues in Oral Squamous Cell Carcinoma: State-of-the-art and Therapeutic Potential.

Oral Squamous Cell Carcinoma (OSCC) is the most common cancer arising from squamous epithelium in the oral cavity and is characterized by high aggressiveness and metastatic potential, which together with a late diagnosis results in a 5-year survival rate of only 50% of patients. The therapeutic options for OSCC management are limited and largely influenced by the cancer stage. While radical surgery can be curative in early stage of disease, most cases require adjuvant therapies, including chemotherapy and radiotherapy which, however, often achieve poor curative rates and are associated with important negative effects. Therefore, there is an urgent need to discover new alternative treatment strategies to improve patients' outcomes. Several medicinal herbs are being studied for their preventive or therapeutic effect in several diseases, including cancer. In particular, the Indian spice curcumin, largely used in oriental countries, has been studied as a chemopreventive or adjuvant agent for different malignancies. Indeed, curcumin is characterized by important biological properties, including antioxidant, anti-inflammatory, and anticancer effects, which could also be exploited in OSCC. However, due to its limited bioavailability and poor aqueous solubility, this review is focused on studies designing new synthetic analogues and developing novel types of curcumin delivery systems to improve its pharmacokinetic and biological properties. Thus, this review analyses the potential therapeutic role of curcumin in OSCC by providing an overview of current in vitro and in vivo studies demonstrating the beneficial effects of curcumin and its analogues in OSCC.

Histopathologic Predictors for Locoregional Recurrence in Patients With Oral Squamous Cell Carcinoma - A Single-Center Retrospective Study.

Oral squamous cell carcinoma (OSCC) is known for its aggressive behavior and the high potential for locoregional recurrence (LRR), contributing to poor prognostic outcomes. The aim of this study was to investigate the role of histologic parameters in predicting LRR in patients with OSCC. A retrospective analysis was performed on 58 OSCC patients treated between January 2018 and December 2022. Data were collected from medical records, focusing on demographics, clinicopathologic features, and treatment details. Different histopathologic factors such as depth of invasion, tumor stage (T), pathologic node stage (N), histologic grade of differentiation, perineural invasion, lymphovascular invasion, extranodal extension (ENE), and margin of resection were correlated with LRR. Out of 58 patients, 20 (34.4%) reported LRR within the first year of follow-up. In the recurrence group, 14 patients succumbed to death within 24 months. Among all the histopathologic parameters, our study found a statistically significant correlation between higher pathologic node stage, presence of ENE, and closest margin of resection (≤5mm) with LRR. Higher pathologic node stage, presence of ENE, and closest margin of resection (≤5mm) were the histopathologic factors associated with LRR, and can serve as deciding prognostic factors. Treatment intensification in early-stage disease with higher pathologic nodal stage, presence of ENE, and closest margin of resection (≤5mm) may improve survival outcomes.

Stage-related increase in PIM2 expression in mycosisfungoides.

The oncogene PIM2 is upregulated in several malignancies but has never been investigated in mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma (CTCL). PIM2 is a well-known oncogene and is regulated by cell signaling pathways like the JAK/STAT- and NF-kB-pathway, key regulators in the pathogenesis of CTCL. The aim of this study was to examine the role of PIM2 in MF. PIM2 gene expression was measured in 81 formalin-fixed paraffin-embedded skin biopsies from patients with MF and 46 control biopsies from healthy skin (HS) and benign inflammatory skin disease (BID). Validation of PIM2 protein expression was performed on selected biopsies with immunohistochemical staining. We found a significant difference in gene expression levels between both early stage MF and HS (p < 0.0001), and BID (p < 0.0001). In addition, the PIM2 gene expression was higher in advanced-stage MF compared to early stage disease (p = 0.0001). No significant difference in gene expression levels was found between patients with and without disease progression. In conclusion, we found PIM2 expression is significantly increased in MF compared to controls, and in advanced-stage MF compared to early stage MF. These findings could potentially have diagnostic value in discriminating early stage MF from BID.

Pine Wilt Disease Segmentation with Deep Metric Learning Species Classification for Early-Stage Disease and Potential False Positive Identification

Pine Wilt Disease Segmentation with Deep Metric Learning Species Classification for Early-Stage Disease and Potential False Positive Identification

Medial temporal lobe gray matter microstructure in preclinical Alzheimer's disease.

Typical MRI measures of neurodegeneration have limited sensitivity in early disease stages. Diffusion MRI (dMRI) microstructural measures may allow for detection in preclinical stages. Participants had dMRI and either beta-amyloid PET or plasma biomarkers of Alzheimer's pathology within 18 months of MRI. Microstructure was measured in portions of the medial temporal lobe (MTL) with high neurofibrillary tangle (NFT) burden based on a previously developed post mortem 3D-map. Regressions examined relationships between microstructure and markers of Alzheimer's pathology in preclinical disease and then across disease stages. There was higher isometric volume fraction in amyloid-positive compared to amyloid-negative cognitively unimpaired individuals in high tangle MTL regions. Similarly, plasma biomarkers and 18F-flortaucipir were associated with microstructural changes in preclinical disease. Additional microstructural effects were seen across disease stages. Combining a post mortem atlas of NFT pathology with microstructural measures allows for detection of neurodegeneration in preclinical Alzheimer's disease. Highlights Typical markers of neurodegeneration are not sensitive in preclinical Alzheimer's. dMRI measured microstructure in regions with high NFT. Microstructural changes occur in medial temporal regions in preclinical disease. Microstructural changes occur in other typical Alzheimer's regions in later stages. Combining post mortem pathology atlases with in vivo MRI is a powerful framework.

Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

Idiopathic pulmonary fibrosis (IPF) affects subpleural lung, but is considered to spare small airways. Micro-CT studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. We use EB-OCT to evaluate small airways in early IPF and control subjects in vivo. EB-OCT was performed in 12 IPF and 5 control subjects (matched by age, sex, smoking-history, height, BMI). IPF subjects had early disease with mild restriction (FVC: 83.5% predicted), diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for UIP present) and less affected (some but not all criteria for UIP present) sites. Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. Compared to control subjects (mean: 11.2 bronchioles/cm3; SD: 6.2), there was significant bronchiole reduction in IPF subjects (42% loss; mean: 6.5/cm3; SD: 3.4; p=0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; p<0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; p=0.024) sites. Stereology metrics showed IPF affected small airways were significantly larger and more distorted/irregular than in IPF less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (p=0.36-1.0). EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30 and 50%), even in areas minimally affected by disease, compared to matched controls. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Montelukast improves disease outcome in SOD1G93A female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial. Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK. Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.

An effective role-oriented binary Walrus Grey Wolf approach for feature selection in early-stage chronic kidney disease detection.

In clinical decision-making for chronic disorders like chronic kidney disease, high variability often leads to uncertainty and negative outcomes. Deep learning techniques have been developed as useful tools for minimizing the chance and improving clinical decision-making. Moreover, traditional techniques for chronic kidney disease recognition frequently the accuracy is compromised as it relies on limited sets of biological attributes. Therefore, in the proposed work, a combination of deep radial bias network and the puma optimization algorithm is suggested for precised chronic kidney disease classification. Initially, the accessed data undergo preprocessing using Spectral Z score Bag Boost K-Means SMOTE transformation, which includes robust scaling, data cleaning, balancing, encoding, handling missing values, min-max scaling, and z-standardization. Feature selection is then conducted using the hybrid methodology of Role-oriented Binary Walrus Grey Wolf Algorithm to choose discriminative features for improving classification accuracy. Then, Auto Encoder with Patch-Based Principal Component Analysis is employed for dimensionality reduction to minimize the processing time. Finally, the proposed classification method utilizes deep radial bias and the puma optimization search algorithm for effective chronic kidney disease classification. The introduced scheme is tested on two datasets: the risk factor prediction of chronic kidney disease dataset and chronic kidney disease dataset, which provides accuracies of 99.02%, and 99.15%, respectively. Experiments demonstrate that the proposed model identifies chronic kidney disease more accurately than the existing approaches.

Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients. From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes. Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group. Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.

Long-term clinical outcomes in patients with CIS treated with interferon beta-1b: results from the 15-year follow up of the BENEFIT trial.

Multiple sclerosis (MS) treatment intervention with immunomodulating therapy at early disease stage improves short term clinical outcomes. The objective of this study is to describe the long-term outcomes and healthcare utilization of patients with clinically isolated syndrome (CIS) included in the Betaferon®/Betaseron® in Newly Emerging MS for Initial Treatment (BENEFIT) randomized, parallel group trial. In BENEFIT patients were assigned to "early" IFNB-1b treatment or placebo ("delayed" treatment). After 2years or conversion to clinically definite multiple sclerosis (CDMS), all patients were offered IFNB-1b and were reassessed 15years later. Of 468 patients, 261 (55.8%) were enrolled into BENEFIT 15 (161 [55.1%] from the early, 100 [56.8%] from the delayed treatment arm). In the full BENEFIT analysis set, risk of conversion to CDMS remained lower in the early treatment group ( - 30.5%; hazard ratio 0.695 [95% CI, 0.547-0.883]; p = 0.0029) with a 15.7% lower risk of relapse than in the delayed treatment group (p = 0.1008). Overall, 25 patients (9.6%; 9.9% early, 9.0% delayed) converted to secondary progressive multiple sclerosis. Disability remained low and stable with no significant difference between groups in Expanded Disability Status Scale score or MRI metrics. Paced Auditory Serial Addition Task-3 scores were better in the early treatment group (p = 0.0036 for treatment effect over 15years). 66.3% of patients were still employed at Year 15 versus 74.7% at baseline. In conclusion, results 15years from initial randomization support long-term benefits of early treatment with IFNB-1b.

Magnetic Resonance Imaging, Computed Tomographic and Radiographic Findings in the Metacarpophalangeal Joints of 31 Warmblood Showjumpers in Full Work and Competing Regularly

There is a limited description of magnetic resonance imaging (MRI) and no information on computed tomographic (CT) findings in the fetlock of non-lame, non-racing sports horses. This study aimed to document comparative CT, MRI and radiographic findings in the metacarpophalangeal joints of showjumpers in full work. Clinical and gait assessments, low-field MRI, fan-beam CT and radiographic examinations of both metacarpophalangeal joints were performed on 31 showjumpers. Images were analysed descriptively. In most limbs (53/62, 85.5%), there were CT and MRI changes consistent with densification in the sagittal ridge and/or condyles of the third metacarpal bone (McIII). Hypoattenuation (subchondral bone resorption) was seen in CT reconstructions in the metacarpal condyle dorsoproximally (n = 2) and dorsodistally (n = 1), in the sagittal groove (n = 2) and medial fovea (n = 1) of the proximal phalanx. The McIII resorptive lesions were detected on MR images but not the proximal phalanx lesions. None were identified on radiographs. In conclusion, MRI and CT abnormalities previously associated with lameness were seen in the front fetlocks of showjumpers without relevant lameness. Densification in the sagittal ridge and the metacarpal condyles likely reflects an adaptive change to exercise. Subchondral bone resorption may indicate an early stage of disease; follow-up information is needed to establish its clinical significance.

Prognostic Value of [99mTc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin-Related Cardiomyopathy and Preserved Left Ventricular Function.

Quantitative 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid ([99mTc]Tc-DPD) SPECT may be used for risk-stratifying patients with amyloid transthyretin-related cardiomyopathy (ATTR-CM). We aimed to analyze the predictive value of quantitative [99mTc]Tc-DPD SPECT/CT in suspected and confirmed ATTR-CM according to different disease stages. Methods: The study enrolled consecutive patients with suspected ATTR-CM who were referred to a single tertiary center and underwent quantitative [99mTc]Tc-DPD SPECT/CT allowing SUVmax and SUVpeak analysis. Patients were divided into 2 groups according to left ventricular ejection fraction (LVEF) at baseline (i.e., ≥50% and <50%). Clinical, laboratory, and echocardiographic parameters and major adverse cardiac events (i.e., all-cause death, sustained ventricular tachyarrhythmia, hospitalization for heart failure, implantation of a cardioverter defibrillator) were investigated for any correlation with quantitative uptake values. Results: In total, 144 patients with suspected ATTR-CM were included in the study (98 with LVEF ≥ 50% and 46 with LVEF < 50%), of whom 99 were diagnosed with ATTR-CM (68.8%; 69 with LVEF ≥ 50% and 30 with LVEF < 50%). A myocardial SUVmax of at least 7 was predictive of major adverse cardiac events at 21.9 ± 13.0 mo of follow-up (hazard ratio, 2.875; 95% CI, 1.23-6.71; P = 0.015) in patients with suspected or confirmed ATTR-CM (global χ2 = 6.892, P = 0.02) and an LVEF of at least 50%. SUVmax was not predictive in patients with an LVEF of less than 50% and suspected or confirmed ATTR-CM. Conclusion: In patients with suspected or confirmed ATTR-CM and preserved LVEF, representing an early disease stage, quantitative [99mTc]Tc-DPD SPECT should be considered to improve early-stage risk stratification.

Polymorphic variants of the &lt;i&gt;PPP1R21&lt;/i&gt; gene associated with the level of sex hormone-binding globulin and the risk of various stages of breast cancer

Aim. To assess the relationship of polymorphic gene variants associated with the level of sex hormone-binding globulin (SHBG) according to genome-wide association studies (GWAS) with the risk of stage I–II and stage III-IV breast cancer. Materials and methods. A comparative genetic analysis was carried out on samples of patients with breast cancer: 254 patients with stages I–II and 91 with stages III–IV, and 1140 females of the control group. The paper considers 4 single nucleotide substitutions associated with the level of circulating SHBG according to GWAS: g.107546375AG PRMT6 (rs17496332), g.27519736TC GCKR (rs780093), g.48419260TC PPP1R21 (rs10454142), g.98364050TA BAIAP2L1 (rs3779195). Results. Differences in the involvement of polymorphic variants of SHBG candidate genes in the development of stages I–II and III–IV breast cancer were revealed. The rs10454142 TC polymorphic variant in the PPP1R21 gene is associated with the risk of stage I–II breast cancer: women with an allelic variant of this locus have a higher risk of early-stage disease (T/T vs. T/C vs. C/C, odds ratio 1.35, 95% confidence interval 1.05-1.75; p=0.021; ppermutat=0.027). Also, an increase in the number of C alleles in the female genotype increased the risk of stage I–II breast cancer by 17–18% per allele. There were no associations of polymorphic variants of SHBG candidate genes with the risk of severe disease (stage III–IV). The single nucleotide substitution rs10454142 TC in the PPP1R21 gene and the single nucleotide polymorphisms strongly linked to it are functionally significant (located in the regions of enhancers and promoters) in the epithelial and myoepithelial cells of the mammary gland and liver, affect the level of genome methylation, and are associated with the level of GTF2A1L gene expression.

Royal jelly and its hormonal effects in breast cancer: a literature review.

Breast cancer is the most common cancer in women which can be cured in most individuals with early-stage non-metastatic disease. Imbalance in estrogen signaling pathways and propagating levels of estrogens has important roles in breast cancer development. Targeting the estrogen receptor signaling pathway is linked to breast cancer treatment. Royal jelly is one of the bee products containing 10-hydroxy-2-decenoic acid, a structure similar to mammalian estrogen, allowing it to attach to estrogen receptors. It is considered as a general tonic and immunomodulator which may be helpful in reducing the side effects of cancer treatments. Currently, there are controversial data regarding the pros and cons of royal jelly in cancer. Here we provide an overview of the effects of royal jelly on sex hormones and its possible role in breast cancer. Electronic databases including PubMed, Scopus, and Web of Science were searched with the search terms royal jelly, cancer, and sexual hormones. All preclinical and clinical studies regarding the hormonal effects of royal jelly were included. According to the collected preclinical data, consumption of royal jelly at daily doses below 200mg/kg can be useful to decrease the risk of breast cancer since it reduces the serum level of estrogen; whereas increases progesterone, which subsequently decreases the expression of ERs on the ER-positive cells. Future clinical studies are essential to confirm the safe dose of royal jelly as an adjuvant therapy in breast cancer.

The Long-Term Natural History of Fibrous Dysplasia.

Fibrous dysplasia (FD), a developmental, nonfamilial, benign anomaly of bone development, is characterized by the replacement of normal bone by proliferating fibro-osseous tissue. Marked craniofacial deformities, functional disturbances, and emotional stress are major indications for treatment, and various surgical procedures have been performed; however, excision and regrowth issues have also been reported. While several treatment options are available, no studies have reported the natural history of untreated FD. Here, we report 2 patients, aged 73 and 50 years, respectively, who had not received treatment. Both patients presented to the hospital complaining of noise when moving their heads. Computed tomography scans showed niveau with honeycomb cavities in both patients, indicating abscess formation, and resection was performed. Relatively large cranial FD leads to the development of central necrosis over time. In such cases, surgical intervention should be performed at an early disease stage.

Efficacy of the minimal-invasive vacuum-assisted biopsy under direct visualization with ultrasound for impalpable breast lesions in Taiwanese female: A retrospective case-control study

Abstract Background Although surgical excisional biopsy provides robust diagnostic results, the ultrasound-assisted vacuum-assisted biopsy (VABB) offers an alternative for Asian candidates with dense breasts and lesions which cannot be approached by stereotactic biopsy. The study aims to investigate the efficacy of the ultrasound-assisted VABB for impalpable mammographic-detected lesions. Methods A retrospective case-control study is conducted in a group of Taiwanese female patients who have impalpable breast lesions such as microcalcifications at screening mammography that are limited to BI-RADS category 4. Specifically, the lesions are categorized into three groups: 4a, 4b, 4c, and the histology from B2 through B5. The cases underwent ultrasound-assisted VABB and the controls had lumpectomies. The diagnostic accuracy, rate of discordance, excited tumor size, and the proportion of cancer cases is evaluated and compared using Fisher’s Exact test, Cohen’s kappa test, Chi-Square test, and the use of IBM SPSS statistical programs. Results The histology of the majorities of the collected specimen are B2 benign fibrocystic changes (60-70%). In cases of patients who are diagnosed with breast cancer, most are ductal carcinoma in situ and early-stage diseases. The cancer risks for lesions categorized under BI-RADS 4a, 4b, 4c respectively are consistent with clinical practice. Meanwhile, the diagnostic accuracy of VABB is similar to lumpectomy, as the histologic discordance rate did not differ significantly. Conclusions Ultrasound-assisted VABB does offer an option for patients who are not candidates for stereotactic biopsy, as it has shown to have non-inferior diagnostic values and cosmetic benefits when compared to surgical excision. The use of sonography monitors the biopsy process and guides the needle insertion thus is capable of obtaining samples from multiple directions, without risking the pectoralis muscles underneath. However, VABB may be intended for biopsies in lower-risk findings such as BI-RADS category 4a because doubts persist as complete excisional rates are operator-dependent.

Allogeneic haematopoietic cell transplantation for chronic myeloid leukaemia in Switzerland in the face of rapid development of effective drugs.

Until the year 2000, allogeneic haematopoietic cell transplantation (HCT) was the standard treatment for young and fit chronic myeloid leukaemia (CML) patients. CML was the main indication for allogeneic HCT. The introduction of tyrosine kinase inhibitors changed the treatment of CML patients dramatically. Allogeneic HCT was rapidly replaced by tyrosine kinase inhibitors as first-line treatment for CML, and the indication shifted to the treatment of non-responders, patients intolerant to tyrosine kinase inhibitors and patients whose CML is transforming to the accelerated phase and blast crisis. This paper describes changes in the use of transplantation technology for CML patients in the face of rapid drug development. All patients receiving a transplant for CML between 1997 and 2021 in Switzerland were included in the study. For the purpose of this analysis, time periods were analysed in quinquennia, 1997-2001 (Q1), 2002-2006 (Q2), 2007-2011 (Q3), 2012-2016 (Q4) and 2017-2021 (Q5), as the observation period spanned 25 years. Overall, 239 patients received a transplant. These included 96 in Q1, 56 in Q2, 25 in Q3, 34 in Q4 and 28 in Q5. Patient characteristics changed over time: recent patients were older and had a longer interval from diagnosis to transplantation because of tyrosine kinase inhibitor treatment. However, the proportions of patients receiving transplants during an early versus advanced disease stage differed little. Transplant technology changed, as well. Patients received intensive conditioning regimens less often due to higher age and more commonly had peripheral blood as opposed to bone marrow transplants. However, the type of stem cell donor selected did not differ. In a univariable analysis, there were no significant differences in survival, progression-free survival, non-relapse mortality, relapse incidence or incidences of acute and chronic graft-versus-host disease among the five quinquennia. In a multivariable analysis, older age, donors other than HLA-identical siblings and more advanced disease stage, but not the quinquennium, were associated with higher risk of death. Since the introduction of tyrosine kinase inhibitors haematopoietic cell transplantation has been used less frequently to treat CML. Patients in recent cohorts received transplants at an older age and later in the disease course; despite these higher risks, the outcome of allogeneic HCT has not worsened over time but has not improved, either. As the outcome is worse in advanced phases, it is important to conduct transplants before disease progression. Therefore, patients with advanced disease should be monitored closely and receive transplants in time.

Evolution of peripheral nerve changes in early multiple sclerosis-a longitudinal MR neurography study.

Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system. Increasing evidence indicates additional peripheral nerve involvement in early and chronic disease stages. To investigate the evolution of peripheral nerve changes in patients first diagnosed with MS using quantitative MR neurography. This prospective study included 19 patients with newly diagnosed MS according to the revised McDonald criteria (16 female, mean 30.2 ± 7.1 years) and 19 age-/sex-matched healthy volunteers. High-resolution 3 T MR neurography of the sciatic nerve using a quantitative T2-relaxometry sequence was performed, which yielded the biomarkers of T2 relaxation time (T2app) and proton spin density (PSD). Follow-up scans of patients were performed after median of 12 months (range 7-16). Correlation analyses considered clinical symptoms, intrathecal immunoglobulin synthesis, nerve conduction study, and lesion load on brain and spine MRI. Patients showed increased T2app and decreased PSD compared to healthy controls at initial diagnosis and follow-up (p < 0.001 each). Compared to the initial scan, T2app further increased in patients at follow-up (p = 0.003). PSD further declined by at least 10% in 9/19 patients and remained stable in another 9/19 patients. Correlation analyses did not yield significant results. Peripheral nerve involvement in MS appears at initial diagnosis and continues to evolve within 1 year follow-up with individual dynamics. Quantitative MRN provides non-invasive biomarkers to detect and monitor peripheral nerve changes in MS.