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Pediatric Neurology May 2024Isolated tumefactive demyelinating lesions (≥2 cm) may be difficult to distinguish from contrast-enhancing brain tumors, central nervous system infections, and...
BACKGROUND
Isolated tumefactive demyelinating lesions (≥2 cm) may be difficult to distinguish from contrast-enhancing brain tumors, central nervous system infections, and (rarely) tissue dysgenesis, which may all occur with increased signal on T2-weighted images. Establishing an accurate diagnosis is essential for management, and we delineate our single-center experience.
METHODS
We performed a retrospective review of medical records, imaging, and biopsy specimens for patients under 18 years presenting with isolated tumefactive demyelination over a 10-year period.
RESULTS
Ten children (eight female) met inclusion criteria, with a median age of 14.1 years. Lesions were most likely to involve the thalamus (six of 10), brainstem (five of 10), basal ganglia (four of 10), or corpus callosum (four of 10). Eighty percent had perilesional edema at presentation, and 60% had midline shift. Biopsies demonstrated demyelination with perivascular lymphocytic infiltration and axonal damage ranging from mild to severe. All patients were initially treated with high-dose corticosteroids, and eight of 10 required additional medical therapies such as intravenous immunoglobulin, plasmapheresis, cyclophosphamide, or rituximab. Increased intracranial pressure was managed aggressively with two of 10 patients requiring decompressive craniectomies. Clinical outcomes varied.
CONCLUSIONS
Solitary tumefactive demyelinating lesions are rare, and aggressive management of inflammation and increased intracranial pressure is essential. Biopsy is helpful to evaluate for other diagnoses on the differential and maximize therapies. Treatment beyond initial therapy with corticosteroids is often required. Isolated tumefactive demyelinating lesions are uncommon; multicenter natural history studies are needed to better delineate differential diagnoses and optimal therapies.
PubMed: 38917518
DOI: 10.1016/j.pediatrneurol.2024.05.012 -
Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.Orphanet Journal of Rare Diseases Jun 2024Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials...
BACKGROUND
Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials.
METHODS
We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed.
RESULTS
Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective.
CONCLUSION
5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen.
PubMed: 38918870
DOI: 10.1186/s13023-024-03219-5 -
BMC Health Services Research Jun 2024Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant...
BACKGROUND
Latin America (LATAM) encompasses a vast region with diverse populations. Despite publicly funded health care systems providing universal coverage, significant socioeconomic and ethno-racial disparities persist in health care access across the region. Breast cancer (BC) incidence and mortality rates in Brazil are comparable to those in other LATAM countries, supporting the relevance of Brazilian data, with Brazil's health care policies and expenditures often serving as models for neighboring countries. We evaluated the impact of mobility on oncological outcomes in LATAM by analyzing studies of patients with BC reporting commuting routes or travel distances to receive treatment or diagnosis.
METHODS
We searched MEDLINE (PubMed), Embase, Cochrane CENTRAL, LILACS, and Google Scholar databases. Studies eligible for inclusion were randomized controlled trials and observational studies of patients with BC published in English, Portuguese, or Spanish and conducted in LATAM. The primary outcome was the impact of mobility or travel distance on oncological outcomes. Secondary outcomes included factors related to mobility barriers and access to health services. For studies meeting eligibility, relevant data were extracted using standardized forms. Risk of bias was assessed using the Newcastle-Ottawa Scale. Quantitative and qualitative evidence synthesis focused on estimating travel distances based on available data. Heterogeneity across distance traveled or travel time was addressed by converting reported travel time to kilometers traveled and estimating distances for unspecified locations.
RESULTS
Of 1142 records identified, 14 were included (12 from Brazil, 1 from Mexico, and 1 from Argentina). Meta-analysis revealed an average travel distance of 77.8 km (95% CI, 49.1-106.48) to access BC-related diagnostic or therapeutic resources. Nonetheless, this average fails to precisely encapsulate the distinct characteristics of each region, where notable variations persist in travel distance, ranging from 88 km in the South to 448 km in the North.
CONCLUSION
The influence of mobility and travel distance on access to BC care is multifaceted and should consider the complex interplay of geographic barriers, sociodemographic factors, health system issues, and policy-related challenges. Further research is needed to comprehensively understand the variables impacting access to health services, particularly in LATAM countries, where the challenges women face during treatment remain understudied.
TRIAL REGISTRATION
CRD42023446936.
PubMed: 38918823
DOI: 10.1186/s12913-024-11222-6 -
Journal of Orthopaedic Surgery and... Jun 2024Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB...
Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort...
BACKGROUND
Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB (EPTB) has received little attention. Diagnosis of EPTB remains challenging due to the invasive procedures required for sample collection. Spinal TB (STB) accounts for 10% of EPTB and often leads to lifelong debilitating disease due to devastating spinal deformation and compression of neural structures. Little is known about the extent of disease, although both isolated STB and a disseminated form of STB have been described. In our Spinal TB X cohort study, we aim to describe the clinical phenotype of STB using whole-body FDG-PET/CT, identify a specific gene expression profile for different stages of dissemination and compare findings to previously described gene expression signatures for latent and active pulmonary TB.
METHODS
A single-centre, prospective cohort study will be established to describe the distributional pattern of STB detected by whole-body FDG-PET/CT and gene expression profile of patients with suspected STB on magnetic resonance imaging (MRI) at point of diagnosis, six months, and 12 months. Blood biobanking will be performed at these time points. Specimens for microbiology will be obtained from sputum/urine, from easily accessible sites of disease (e.g., lymph nodes, abscess) identified in the first FDG-PET/CT, from CT-guided biopsy and/or surgery. Clinical parameters and functional scores will be collected at every physical visit. Data will be entered into RedCap® database; data cleaning, validation and analysis will be performed by the study team. The University of Cape Town Ethics Committee approved the protocol (243/2022).
DISCUSSION
The Spinal TB X cohort study is the first prospective cohort study using whole-body 18FDG-PET/CT scans in patients with microbiologically confirmed spinal tuberculosis. Dual imaging techniques of the spine using FDG-PET/CT and magnetic resonance imaging as well as tissue diagnosis (microbiology and histopathology) will allow us to develop a virtual biopsy model. If successful, a distinct gene-expression profile will aid in blood-based diagnosis (point of care testing) as well as treatment monitoring and would lead to earlier diagnosis of this devastating disease.
TRIAL REGISTRATION
The study has been registered on ClinicalTrials.gov (NCT05610098).
PubMed: 38918806
DOI: 10.1186/s13018-024-04840-7 -
Asian Pacific Journal of Cancer... Jun 2024Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by...
INTRODUCTION
Lung cancer is one of the commonest cause of cancer associated mortality worldwide. Platelets have emerged as key players in cancer development and progression by supporting tumor growth, and dissemination. In the present systematic review, we analyzed RNA transfer between cancer cells and platelets and explored potential role of different platelet RNA profiles as onco-signature in diagnosis, subtyping, disease progression and treatment monitoring in carcinoma lung carcinoma.
MATERIALS AND METHODS
The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Cochrane Manual of Systematic Reviews and Meta-analysis that included seven studies on patients with lung cancer, with data on tumor-educated platelets, and control group. The outcome measured was based on sensitivity, specificity, and ROC. PUBMED, SCOPUS, Central Cochrane Registry of Controlled Trials and Science Direct databases were searched using specific search terms until October 2023. QUADAS - 2 tool was used to assess quality, risk of bias and applicability concerns.
RESULTS
The analysis revealed AUC > 70% for different platelet mRNAs, with sensitivity and specificity of more than 60 %. AUC and sensitivity were highest for ITGA2B (AUC 0.922; sensitivity 92.8%). lncRNA GTF2H2-1 was the most specific platelet RNA. On QUADAS-2 tool, 3/7 articles were unclear in reference standards, patient flow timing, and 1/7 had high bias in both aspects. For applicability, 1/7 studies were unclear in reference standards, and 2/7 in index tests.
CONCLUSION
TEP RNA can aid in early diagnosis of lung cancer and of proven utility in its early-stage detection. TEP RNA can also monitor disease progression and treatment response.
PubMed: 38918651
DOI: 10.31557/APJCP.2024.25.6.1911 -
Nature Medicine Jun 2024Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African...
Diabetes complications occur at higher rates in individuals of African ancestry. Glucose-6-phosphate dehydrogenase deficiency (G6PDdef), common in some African populations, confers malaria resistance, and reduces hemoglobin A1c (HbA1c) levels by shortening erythrocyte lifespan. In a combined-ancestry genome-wide association study of diabetic retinopathy, we identified nine loci including a G6PDdef causal variant, rs1050828 -T (Val98Met), which was also associated with increased risk of other diabetes complications. The effect of rs1050828 -T on retinopathy was fully mediated by glucose levels. In the years preceding diabetes diagnosis and insulin prescription, glucose levels were significantly higher and HbA1c significantly lower in those with versus without G6PDdef. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, participants with G6PDdef had significantly higher hazards of incident retinopathy and neuropathy. At the same HbA1c levels, G6PDdef participants in both ACCORD and the Million Veteran Program had significantly increased risk of retinopathy. We estimate that 12% and 9% of diabetic retinopathy and neuropathy cases, respectively, in participants of African ancestry are due to this exposure. Across continentally defined ancestral populations, the differences in frequency of rs1050828 -T and other G6PDdef alleles contribute to disparities in diabetes complications. Diabetes management guided by glucose or potentially genotype-adjusted HbA1c levels could lead to more timely diagnoses and appropriate intensification of therapy, decreasing the risk of diabetes complications in patients with G6PDdef alleles.
PubMed: 38918629
DOI: 10.1038/s41591-024-03089-1 -
Scientific Reports Jun 2024Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are... (Randomized Controlled Trial)
Randomized Controlled Trial
Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.
Topics: Humans; Vitiligo; Atorvastatin; Simvastatin; Male; Female; Double-Blind Method; Adult; Pilot Projects; Middle Aged; Administration, Topical; Young Adult; Treatment Outcome; Adolescent
PubMed: 38918590
DOI: 10.1038/s41598-024-65722-w -
British Journal of Cancer Jun 2024This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in...
A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.
BACKGROUND
This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer.
METHODS
We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC.
RESULTS
This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05).
CONCLUSIONS
The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists.
TRIAL REGISTRATION NUMBER
The clinical trial numbers were NCT03154749 and NCT04858529.
PubMed: 38918556
DOI: 10.1038/s41416-024-02726-3 -
Scientific Reports Jun 2024Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR... (Comparative Study)
Comparative Study
Lazertinib is a recently developed third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors used for patients with advanced EGFR T790M-positive non-small-cell lung cancer. We evaluated the effectiveness of lazertinib compared with osimertinib using an external control. We obtained individual patient data for the lazertinib arm from the LASER201 trial and the osimertinib arm from registry data at the Samsung Medical Center. In total, 75 and 110 patients were included in the lazertinib and osimertinib groups, respectively. After propensity score matching, each group had 60 patients and all baseline characteristics were balanced. The median follow-up duration was 22.0 and 29.6 months in the lazertinib and osimertinib group, respectively. The objective response rate (ORR) were 76.7% and 86.7% for lazertinib and osimertinib, respectively (p = 0.08). The median progression-free survival (PFS) was 12.3 months (95% confidence interval [CI] 9.5-19.1) and 14.4 months (95% CI 11.8-18.1) for the lazertinib and osimertinib group, respectively (hazard ratio [HR] 0.97; 95% CI 0.64-1.45, p = 0.86). The median overall survival with lazertinib was not reached and that with osimertinib was 29.8 months (HR 0.44; 95% CI 0.25-0.77, p = 0.005). Our study suggests that lazertinib has an ORR and PFS comparable to those of osimertinib and has the potential for superior survival benefits.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Male; Female; Lung Neoplasms; Aged; Middle Aged; Acrylamides; Aniline Compounds; Protein Kinase Inhibitors; Aged, 80 and over; Treatment Outcome; Progression-Free Survival; Mutation; Adult; Pyrimidines; Indoles; Morpholines; Pyrazoles
PubMed: 38918528
DOI: 10.1038/s41598-024-65220-z -
Scientific Reports Jun 2024Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with...
Hypodense volumes (HDV) in mediastinal masses can be visualized in a computed tomography scan in Hodgkin lymphoma. We analyzed staging CT scans of 1178 patients with mediastinal involvement from the EuroNet-PHL-C1 trial and explored correlations of HDV with patient characteristics, mediastinal tumor volume and progression-free survival. HDV occurred in 350 of 1178 patients (29.7%), typically in larger mediastinal volumes. There were different patterns in appearance with single lesions found in 243 patients (69.4%), multiple lesions in 107 patients (30.6%). Well delineated lesions were found in 248 cases (70.1%), diffuse lesions were seen in 102 cases (29.1%). Clinically, B symptoms occurred more often in patients with HDV (47.7% compared to 35.0% without HDV (p = 0.039)) and patients with HDV tended to be in higher risk groups. Inadequate overall early-F-FDG-PET-response was strongly correlated with the occurrence of hypodense lesions (p < 0.001). Patients with total HDV > 40 ml (n = 80) had a 5 year PFS of 79.6% compared to 89.7% (p = 0.01) in patients with HDV < 40 ml or no HDV. This difference in PFS is not caused by treatment group alone. HDV is a common phenomenon in HL with mediastinal involvement.
Topics: Humans; Male; Female; Hodgkin Disease; Adult; Mediastinal Neoplasms; Middle Aged; Tomography, X-Ray Computed; Young Adult; Aged; Adolescent; Mediastinum; Fluorodeoxyglucose F18; Positron-Emission Tomography; Progression-Free Survival
PubMed: 38918503
DOI: 10.1038/s41598-024-64253-8