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The Journal of Clinical Endocrinology... Jun 2024Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs,...
UNLABELLED
Medical treatment of acromegaly is currently performed through a trial-error approach using first generation somatostatin receptor ligands (fgSRLs) as first-line drugs, with an effectiveness of about 50%, and subsequent drugs are indicated through clinical judgment. Some biomarkers can predict fgSRLs response. Here we report the results of the ACROFAST study, a clinical trial in which a protocol based on predictive biomarkers of fgSRLs was evaluated.
METHODS AND SUBJECTS
prospective trial (21 university hospitals) comparing the effectiveness and time-to control of two treatment protocols during 12 months: A) A personalized protocol in which first option were fgSRLs as monotherapy or in combination with pegvisomant or, pegvisomant as monotherapy depending on the short Acute Octreotide Test (sAOT) results, tumor T2 Magnetic Resonance (MRI) signal or immunostaining for E-cadherin and, B) A control group with treatment always started by fgSRLs and the other drugs included after demonstrating inadequate control.
RESULTS
Eighty-five patients participated; 45 in the personalized and 40 in the control group. More patients in the personalized protocol achieved hormonal control compared to those in the control group (78% vs 53%, p < 0.05). Survival analysis revealed a hazard ratio for achieving hormonal control adjusted by age and sex of 2.53 (CI 1.30-4.80). Patients from personalized arm were controlled in a shorter period of time (p = 0.01).
CONCLUSION
Personalized medicine is feasible using a relatively simple protocol and allows a higher number of patients achieving control in a shorter period of time.
PubMed: 38943661
DOI: 10.1210/clinem/dgae444 -
International Endodontic Journal Jun 2024The osteogenic potential of new premixed calcium-silicate-containing bioceramic sealers (Ca-Si sealers) was tested with porcine vascular wall-mesenchymal stem cells...
AIM
The osteogenic potential of new premixed calcium-silicate-containing bioceramic sealers (Ca-Si sealers) was tested with porcine vascular wall-mesenchymal stem cells (pVW-MSCs).
METHODOLOGY
Two Ca-Si-containing sealers: Ceraseal (MetaBiomed, Cheong-si, South Korea) and AH Plus Bioceramic (Maruchi, Wonju-si, South Korea), and an epoxy resin sealer (AH Plus; Dentsply, Konstanz, Germany) as a control, were prepared according to the manufacturers' indications. All samples were allowed to set for 100% of their setting time in a sterile humid cabinet at 37°C and 95% relative humidity. pVW-MSC seeding efficiency and osteogenic differentiation were analysed as marker of gene/protein expression for up to 12 days. Mineralization assay and immunofluorescence staining were performed and evaluated over a period of 21 days. Statistical analyses were conducted using one-way analysis of variance (p < .05). Additional samples were prepared and stored under the same conditions and inspected using an environmental scanning electron microscope equipped with an energy dispersive X-ray spectroscopy system.
RESULTS
Significantly higher cell seeding efficiency (p < .05) was observed for both Ca-Si sealers from day 8. pVW-MSCs showed a significant shift towards the osteogenic lineage only when seeded in contact with Ca-Si sealers. Gene expression of osteopontin was upregulated significantly. Collagen I and osteocalcin were clearly expressed by cells in contact with Ca-Si sealers. Mineralization granules were observed in Alizarin red assays and confocal laser scanning microscopy analysis of both Ca-Si sealers. No gene expression or granule mineralization were observed on the epoxy resin sealer.
CONCLUSIONS
Premixed Ca-Si sealers displayed a higher potential for osteogenic activity on pVW-MSCs. Epoxy resin sealer was unable to induce any osteogenic activity. The properties of both Ca-Si sealers suggest their potential as osteoinductive platforms for vascular MSCs in periapical bone.
PubMed: 38943551
DOI: 10.1111/iej.14098 -
Neuro-oncology Jun 2024IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically...
BACKGROUND
IDH-wildtype (-wt) status is a pre-requisite for the diagnosis of glioblastoma (GBM); however, IDH-wt gliomas with low grade or anaplastic morphology have historically been excluded from GBM trials and may represent a distinct prognostic entity. While alkylating agent chemotherapy improves overall survival (OS) and progression-free survival (PFS) for IDH-wt GBM and also IDH-mutant gliomas, irrespective of grade, the benefit for IDH-wt diffuse histologic lower grade gliomas is unclear.
METHODS
We performed a meta-analysis of randomized clinical trials for World Health Organization (WHO) grade 2-3 gliomas (2009 to present) to determine the effect of alkylating chemotherapy on IDH-wt and -mutant gliomas using a random-effects model with inverse-variance pooling.
RESULTS
We identified six trials with 1,204 patients (430 IDH-wt, 774 IDH-mutant) that evaluated alkylating chemoradiotherapy versus radiotherapy alone, allowing us to perform an analysis focused on the value of adding alkylating chemotherapy to radiotherapy. For patients with IDH-wt tumors, alkylating chemotherapy added to radiotherapy was associated with improved PFS (HR:0.77 [95%CI 0.62-0.97], P=.03) but not OS (HR:0.87 [95%CI 0.64-1.18], P=.17). For patients with IDH-mutant tumors, alkylating chemotherapy added to radiotherapy improved both OS (HR:0.52 [95%CI 0.42-0.64], P<.001) and PFS (HR=0.47 [95%CI 0.39-0.57], P<.001) compared to radiotherapy alone. The magnitude of benefit was similar for IDH-mutant gliomas with or without 1p19q-codeletion.
CONCLUSIONS
Alkylating chemotherapy reduces mortality by 48% and progression by 53% for patients with IDH-mutant gliomas. Optimal management of IDH-wt diffuse histologic lower grade gliomas remains to be determined, as there is little evidence supporting an OS benefit from alkylating chemotherapy.
PubMed: 38943513
DOI: 10.1093/neuonc/noae102 -
Bratislavske Lekarske Listy 2024To create a new mucoadhesive dosage form based on PluronicF127 followed by transformation into a gel form upon intranasal administration for targeted delivery to brain...
OBJECTIVES
To create a new mucoadhesive dosage form based on PluronicF127 followed by transformation into a gel form upon intranasal administration for targeted delivery to brain tissueMETHODS: Citicoline, cytidine diphosphocholine, designated as CDP-choline, was purchased as a white powder with the molecular weight of 510.31 g/mol. The triblock copolymers of polyethylene glycol-block-polypropylene glycol-block-polyethylene glycol (PEG-PPG-PEG), branded as Pluronic F127, was used.
RESULTS
When instilled into the nasal cavity, Pluronic F127 for intranasal administration is transformed into a gel that remains retained for 45-55 minutes, which promotes better penetration of drugs into the brain tissue.
CONCLUSION
The polymer's gelling and adhesive properties performed well, which is crucial for further research at the preclinical stage (Tab. 1, Fig. 5, Ref. 28).
Topics: Administration, Intranasal; Poloxamer; Brain; Drug Delivery Systems; Animals; Cytidine Diphosphate Choline; Gels; Polyethylene Glycols; Nasal Mucosa
PubMed: 38943505
DOI: 10.4149/BLL_2024_67 -
Bratislavske Lekarske Listy 2024A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes.
OBJECTIVE
A retrospective analysis of invasive and metastatic hydatidiform moles (HM) in the Slovak Republic (SR)‒epidemiology, patient characteristics and treatment outcomes.
BACKROUND
Invasive and metastatic mole is a highly curable type of gestational trophoblastic neoplasia. Both invasive and metastatic HM may be cured by hysterectomy without adjuvant chemotherapy.
METHODS
Nineteen cases of histopathologically confirmed HM (10 invasive and 9 metastatic) were treated in SR from 1993 to 2022. Patients were divided into two groups according to treatment modality (hysterectomy only ‒ 8; hysterectomy and chemotherapy ‒ 11). The parameters included in the analysis were patient age, antecedent pregnancy, human chorionic gonadotropin level, tumor size and time to remission.
RESULTS
The incidence of invasive and metastatic HM in the SR was 1:121,253 pregnancies, or 1:86,589 live births. The overall cure rate was 100%, without recurrence. Hysterectomy was performed as first-line therapy in 14 patients, with a cure rate of 57.1%. 4 out of 8 patients (50%) with metastatic moles, who underwent first-line hysterectomy, were cured without chemotherapy. There was no statistically significant difference between the two groups in all selected parameters.
CONCLUSION
First-line hysterectomy may lead to remission without adjuvant chemotherapy or reduce the number of chemotherapies in invasive and metastatic HM (Tab. 4, Fig. 2, Ref. 21).
Topics: Humans; Female; Slovakia; Hysterectomy; Pregnancy; Uterine Neoplasms; Adult; Retrospective Studies; Hydatidiform Mole; Hydatidiform Mole, Invasive; Young Adult; Middle Aged; Incidence; Treatment Outcome
PubMed: 38943503
DOI: 10.4149/BLL_2024_65 -
Bratislavske Lekarske Listy 2024True aneurysm of the radial artery is very rare. Aneurysmal expansion of arteries due to degenerative changes, possibly infections, primarily affects the abdominal and...
True aneurysm of the radial artery is very rare. Aneurysmal expansion of arteries due to degenerative changes, possibly infections, primarily affects the abdominal and thoracic aorta, intra and extracranial sections of cerebral arteries, popliteal artery, and visceral arteries. Published literature does not address the aneurysm on the distal sections of the arteries of upper or lower limb. Unlike the classic symptoms of aneurysmally altered arteries such as rupture, thrombosis and embolization, we encounter more often vascular compression syndrome in distal peripheral aneurysms. We demonstrate the case management of a patient with over 20 years increasing wrist resistance. A fusiform aneurysm of the distal section of the radial artery was identified by sonography. Under general anesthesia, we performed aneurysm resection and artery reconstruction using an interpositum from the ipsilateral cephalic vein. The histological examination of the resected tissue confirmed the presence of all three layers of the vascular wall, confirming the true aneurysm of the radial artery. No complications developed in the patient in the postoperative period and all problems related to the aneurysm subsided (Fig. 4, Ref. 23). Keywords: aneurysm, arteria radialis, surgical reconstruction.
Topics: Humans; Aneurysm; Radial Artery; Male; Syndrome; Middle Aged; Upper Extremity; Female
PubMed: 38943502
DOI: 10.4149/BLL_2024_64 -
Otolaryngology--head and Neck Surgery :... Jun 2024To assess the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in detecting second primary... (Review)
Review
OBJECTIVE
To assess the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in detecting second primary malignancies (SPMs) in patients with treatment naïve head and neck squamous cell carcinoma (HNSCC).
DATA SOURCES
Medline, Embase, Cochrane Library, and Scopus searched from 1946 to December 2022.
REVIEW METHODS
Studies reporting the performance of FDG-PET/CT in patients with treatment-naïve, index HNSCC for detection of SPMs were included. The reference standard was histopathology, clinical follow-up over the duration of study, and other imaging modalities. Multiple investigators completed depth full-text analysis. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed. Methodologic and diagnostic accuracy data were abstracted independently by multiple investigators. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies tool independently. Bivariate random-effects model meta-analysis and multivariable meta-regression modeling were used.
RESULTS
Seventeen studies examining 4624 patients with a total of 475 SPMs were included in the final analysis. Eleven studies were found to be at low risk for bias, while the rest were in the high-risk category. FDG-PET/CT demonstrated pooled sensitivity and specificity of 0.73 (95% confidence interval [CI]: 0.49-0.88) and 0.99 (95% CI: 0.98-1.00) in detecting SPMs. Further subsite analysis revealed varied diagnostic performance across different anatomical regions, with sensitivity and specificity of esophageal SPMs being 0.47 (0.30-0.64) and 0.99 (0.98-1.00), and sensitivity and specificity of 0.86 (0.73-0.94) and 0.99 (0.98-1.00) for head and neck SPMs. Finally, this imaging modality showed sensitivity and specificity of 0.92 (0.84-0.96) and 0.99 (0.98-1.00) for lung SPMs.
CONCLUSION
The findings of this study suggest varied accuracy of FDG-PET/CT in detecting SPMs during initial workup for HNSCC, highlighting the importance of screening modalities such as esophagoscopy in high-risk patients.
PubMed: 38943453
DOI: 10.1002/ohn.879 -
Technology and Health Care : Official... Apr 2024Chronic kidney disease (CKD) is a major public health problem, so it is particularly important to quantitatively assess and intervene in the degree of early renal damage...
BACKGROUND
Chronic kidney disease (CKD) is a major public health problem, so it is particularly important to quantitatively assess and intervene in the degree of early renal damage in CKD.
OBJECTIVE
The objective of the research is to establish reference values for kidney elasticity by using real-time shear wave elastography (RT-SWE) technology to quantify Young's modulus values in the renal cortex of normal adults. The intention is to provide a foundation for evaluating renal function and structural changes in patients with CKD. Furthermore, this research investigates the role of RT-SWE in the early detection of renal fibrosis in CKD, providing insights into its diagnostic value for detecting pathological changes at an early stage.
METHODS
Between August 2019 and December 2021, we collected a sample of 100 healthy people (55 men with an average age of 43.5 ± 15.2 years and 45 women with an average age of 41.6 ± 19.8 years) for medical evaluations at our hospital's Department of Ultrasound Medicine. In addition, 97 individuals with CKD1-3 stage were considered. Following the removal of contraindications and relevant confounding variables, we included a final cohort of 80 individuals in the research (45 men and 35 females, with an average age of 39.1 ± 19.2 years). The RENAL mode was selected and a convex array probe S6-1 operating at a frequency of 3.5-5.5 MHz was used in the research, which made use of the French Supersonic AixPlorer ultrasonic diagnostic instrument. Renal RT-SWE elastography was performed after conventional two-dimensional and color Doppler ultrasonography. The study used RT-SWE technology to assess the mean Young's modulus of the cortex in healthy individuals (Emean), with data analysis and comparisons based on age and gender. Furthermore, the Emean values of CKD stage 1-3 patients were determined, and analyses were performed about 24-hour urine protein quantitative (24hUTP), serum creatinine concentration (SCr), and renal biopsy pathology, specifically the degree of interstitial fibrosis.
RESULTS
Healthy group: a) The average kPa values of the left kidney (4.2 ± 2.3), right kidney (4.3 + 2.5) kPa, both kidneys' average kPa values (4.3 ± 2.4) kPa, and the average kPa values of the left and right kidneys do not differ statistically (p= 0.986). b) There was no difference in the kPa values of healthy male and female kidneys (4.4 + 2.1 and 4.2 + 2.6, respectively. c) There was no difference in the renal kPa values of healthy adults aged 50 (4.4 ± 2.8) kPa and renal kPa of the 50-year-old population (4.2 + 2.1) kPa (p= 0.041). Case group: a) the group of patients with CKD1-3 stage and the group did not vary in their Emean values (both p< 0.05); b) There is a difference between CKD stages 1, 2, and 3 (p< 0.05), however, there is still no difference in the pyEmean value corrected for patient age between patients in stages 1 and 2 (p> 0.05).
CONCLUSION
The study reveals no significant differences in the Emean value of bilateral kidneys in normal people and no differences in the elasticity value of kidneys and gender. However, age-based differences were statistically significant. pyEmean may be useful for comparing CKD stage 1, 2, and 3 patients, and RT-SWE can assess early renal damage.
PubMed: 38943409
DOI: 10.3233/THC-231270 -
Journal of Alzheimer's Disease : JAD Jun 2024With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical...
BACKGROUND
With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer's disease (AD) pathology in preclinical stages.
OBJECTIVE
To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD.
METHODS
We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A-) and to ATN model (A-T-N-; A+T-N-; A+T+N-/A+T+N+).
RESULTS
Performance on the LAM-test was significantly correlated with CSF Aβ ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A- (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer's continuum, with significant differences between ATN groups.
CONCLUSIONS
Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.
PubMed: 38943389
DOI: 10.3233/JAD-240067 -
Nigerian Journal of Clinical Practice Jun 2024Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in...
The Prognostic Significance of Tumor SUVmax Value in Pre- and Post-Chemoradiotherapy 18F-FDG PET/CT Imaging in Patients with Localized and Advanced Head and Neck Squamous Cell Carcinoma.
BACKGROUND
Some parameters of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can predict tumor chemosensitivity and survival in patients with head and neck squamous cell carcinoma (HNSCC).
AIM
The aim of the study was to investigate the prognostic value of pre- and post-treatment maximum standardized uptake values (SUVmax) in 18F-FDG PET/CT imaging for predicting mortality in patients with HNSCC, as well as its prognostic value in terms of disease progression, overall survival (OS), and progression-free survival (PFS).
METHODS
This retrospective study included 37 patients with a histopathological diagnosis of HNSCCs between 2015 and 2018. In patients with HNSCC, the first 18F-FDG PET/CT imaging was performed for pre-treatment staging, and the second imaging was performed to evaluate post-treatment response. In these imaging studies, SUVmax values of the primary tumor before and after treatment were determined. After the second imaging, patients were re-evaluated and followed up. ROC analysis was used to determine the predictive value of 18F-FDG PET/CT SUVmax parameters in terms of death and progression, and Cox regression analysis was used to investigate the prognostic value in terms of OS and PFS.
RESULTS
Cut-off value 15 for SUVmax1 (pre-treatment) had a significant predictive value for mortality (P = 0.02). Cut-off value 3.1 for SUVmax2 (post-treatment) had a significant predictive value for progression (P = 0.024). In univariate analysis, both SUVmax1 and SUVmax2 values were significant prognostic factors for OS (P = 0.047, P = 0.004). However, for PFS, only the SUVmax2 value was a significant prognostic factor (P = 0.001).
CONCLUSION
SUVmax1 value of the primary tumor at diagnosis in HNSCC patients has a predictive value for mortality and a prognostic value for OS. However, the SUVmax2 value in the primary tumor after treatment is a predictive factor for progression and a prognostic factor for both OS and PFS.
Topics: Humans; Fluorodeoxyglucose F18; Male; Positron Emission Tomography Computed Tomography; Female; Middle Aged; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Prognosis; Head and Neck Neoplasms; Aged; Chemoradiotherapy; Adult; Radiopharmaceuticals; Predictive Value of Tests; Disease Progression
PubMed: 38943299
DOI: 10.4103/njcp.njcp_856_23