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ACS Applied Materials & Interfaces Jun 2024Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive...
Polypyrrole (Ppy) is a biologically compatible polymer that is used as a matrix, in which drugs and enzymes can be incorporated by doping. Here, we suggest an inventive application of Ppy as a biorecognition film encapsulated with an antibody (Ab) as an alternative strategy for the on-site multistep functionalization of thiol-based self-assembled monolayers. The fabrication steps of the recognition films were followed by dropping pyrrole and Ab mixed solutions onto the electrode and obtaining a thin film by direct current electropolymerization. The efficiency of Ab immobilization was studied by using fluorescence microscopy and electrochemical (EC) methods. Finally, the Ab density was increased and immobilized in 1 min, and the sensing performance as an EC immunosensor was demonstrated using α-fetoprotein with a limit of detection of 3.13 pg/mL and sensing range from 1 pg/mL to 100 ng/mL. This study demonstrates the potential for electrochemical functionalization of biomolecules with high affinity and rapidity.
Topics: Pyrroles; Immunoassay; Polymers; Electrochemical Techniques; Antibodies, Immobilized; Biosensing Techniques; Polymerization; alpha-Fetoproteins; Electrodes; Limit of Detection; Humans
PubMed: 38857116
DOI: 10.1021/acsami.4c00730 -
Journal of Visualized Experiments : JoVE May 2024This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial...
This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Neoadjuvant Therapy; Embolization, Therapeutic; Yttrium Radioisotopes; Male; Retrospective Studies; Immune Checkpoint Inhibitors; Middle Aged; Aged; Radiopharmaceuticals
PubMed: 38856215
DOI: 10.3791/66407 -
Neurology. Genetics Apr 2024This study investigates atypical late-onset ataxia-telangiectasia (AT) cases in a Korean family, diagnosed via Nanopore long-read sequencing, diverging from the typical...
OBJECTIVES
This study investigates atypical late-onset ataxia-telangiectasia (AT) cases in a Korean family, diagnosed via Nanopore long-read sequencing, diverging from the typical early childhood onset caused by biallelic pathogenic ATM variants.
METHODS
A 52-year-old Korean woman exhibiting dystonia and tremor, with a family history of similar symptoms in her older sister, underwent comprehensive tests including routine laboratory tests, neuropsychological assessments, and neuroimaging. Genetic analysis was conducted through targeted sequencing of 29 dystonia-associated genes and Nanopore long-read sequencing to assess the configuration of 2 gene variants.
RESULTS
Routine blood tests and brain imaging studies returned normal results, except for elevated α-fetoprotein levels. Neurologic examination revealed dystonia in the face, hand, and trunk, along with cervical dystonia in the proband. Her sister exhibited similar symptoms without evident telangiectasia. Genetic testing revealed 2 heterozygous pathogenic gene variants (p.Glu2014Ter and p.Glu2052Lys). Nanopore long-read sequencing confirmed these variants were in configuration, establishing a definite molecular diagnosis in the proband.
DISCUSSION
This report expands the known clinical spectrum of AT, highlighting a familial case of atypical AT. Moreover, it underscores the clinical utility of Nanopore long-read sequencing in phasing variant haplotypes, essential for diagnosing autosomal recessive disorders, especially beneficial for cases without parental samples.
PubMed: 38854973
DOI: 10.1212/NXG.0000000000200141 -
Beyoglu Eye Journal 2024This study aimed to evaluate serum biomarker values measured during second-trimester aneuploidy screening in terms of their predictive ability for the development of...
OBJECTIVES
This study aimed to evaluate serum biomarker values measured during second-trimester aneuploidy screening in terms of their predictive ability for the development of retinopathy of prematurity (ROP) in premature infants.
METHODS
This retrospective cohort study evaluated the data of 1985 idiopathic premature infants who underwent ROP screening from 2016 to 2022. The infants were divided into two groups according to the presence of ROP, and those with ROP were further evaluated in two subgroups based on the presence of proliferation. Comparisons were made concerning the serum multiple of the median values of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and alpha-fetoprotein (AFP) among aneuploidy screening biomarkers.
RESULTS
While 1628 premature infants were in the non-ROP group, 357 were in the ROP group. Of the infants with ROP, 72 were in the proliferative ROP group and 285 in the non-proliferative ROP group. There was no significant difference in the multiple of the median values of the evaluated serum biomarkers (uE3, hCG, and AFP) between the ROP and non-ROP groups or between the proliferative ROP, non-proliferative ROP, and non-ROP groups.
CONCLUSION
The multiple of the median values of second-trimester aneuploidy screening serum biomarkers were not able to predict the development of ROP in premature infants. This result may have been caused by the fact that the blood tests were taken only once and in the same weeks.
PubMed: 38854900
DOI: 10.14744/bej.2024.81598 -
Nihon Shokakibyo Gakkai Zasshi = the... 2024An 86-year-old male patient with sustained virological response of chronic hepatitis type C was diagnosed with hepatocellular carcinoma (HCC) in hepatic segment 3. He...
An 86-year-old male patient with sustained virological response of chronic hepatitis type C was diagnosed with hepatocellular carcinoma (HCC) in hepatic segment 3. He was treated with transcatheter arterial chemoembolization (TACE) and radiation therapy because the tumor was located at the edge of the liver and umbilical portion of the portal vein. The value of alpha-fetoprotein (AFP) which is a serological tumor marker decreased, and the tumor size did not increase;however, another tumor was recognized at S3 of the liver 15 months post-TACE. The patient underwent a second TACE, and computed tomography revealed HCC recurrence at S3, S8/4, and S1 of the liver 6 months later. The patient refused to undergo another treatment, but the AFP and Des-γ-carboxy prothrombin values and the tumor size decreased 3 months postrecurrence. Two months after multiple recurrences of HCC, he received the third dose of messenger RNA-based vaccine for severe acute respiratory syndrome coronavirus 2. Tumor regression may occur after an immune-inflammatory response induced by messenger RNA-based vaccine.
Topics: Humans; Male; Carcinoma, Hepatocellular; Liver Neoplasms; Aged, 80 and over; COVID-19 Vaccines; COVID-19; Vaccination
PubMed: 38853019
DOI: 10.11405/nisshoshi.121.497 -
Talanta Jun 2024In this study, a quartz crystal microbalance (QCM) aptasensor for carcinoembryonic antigen (CEA), a well-known biomarker for various cancer types, was reported,...
In this study, a quartz crystal microbalance (QCM) aptasensor for carcinoembryonic antigen (CEA), a well-known biomarker for various cancer types, was reported, utilizing two different aptamers. To achieve this, a nanofilm of 4-mercaptophenyl was electrochemically attached to gold-coated QCM crystal surfaces via the reduction of 4-mercaptobenzenediazonium salt (4 MB-DAT) using cyclic voltammetry. Subsequently, gold nanoparticles (AuNP) were affixed to this structure, and then aptamers (antiCEA1 and antiCEA2) modified with SH-functional ends bound to AuNPs completed the modification. The analytical performance of the CEA sensor was evaluated through simultaneous QCM measurements employing CEA solutions ranging from 0.1 ng/mL to 25 ng/mL. The detection limit (LOD) for CEA was determined to be 102 pg/mL for antiCEA1 and 108 pg/mL for antiCEA2 aptamers. Interday and intraday precision and accuracy tests yielded maximum results of 4.3 and + 3.8, respectively, for both aptasensors, as measured by relative standard deviation (RSD%) and relative error (RE%). The kinetic data of the aptasensors resulted in affinity values (K) of 0.43 ± 0.14 nM for antiCEA1 and 0.75 ± 0.42 nM for antiCEA2. These values were lower than the reported values of 3.9 nM and 37.8 nM for both aptamers, respectively. The selectivity of the aptasensor was evaluated by measuring the signal changes caused by alpha-fetoprotein (AFP), cancer antigen (CA-125), and vascular endothelial growth factor (VEGF-165) individually and together at a concentration of 500 ng/mL, resulting in a maximum 4.1 % change, which was comparable to precision and accuracy values reported in the literature. After confirming the selectivity of the aptamers, recovery experiments were conducted using spiked commercial serum samples to simulate real samples, and the lowest recovery value obtained was 95.4 %. It was determined that two different aptasensors could be successfully used for the QCM-based detection of CEA in this study.
PubMed: 38852341
DOI: 10.1016/j.talanta.2024.126376 -
BMC Cancer Jun 2024Although radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major...
BACKGROUND
Although radical surgical resection is the most effective treatment for hepatocellular carcinoma (HCC), the high rate of postoperative recurrence remains a major challenge, especially in patients with alpha-fetoprotein (AFP)-negative HCC who lack effective biomarkers for postoperative recurrence surveillance. Emerging radiomics can reveal subtle structural changes in tumors by analyzing preoperative contrast-enhanced computer tomography (CECT) imaging data and may provide new ways to predict early recurrence (recurrence within 2 years) in AFP-negative HCC. In this study, we propose to develop a radiomics model based on preoperative CECT to predict the risk of early recurrence after surgery in AFP-negative HCC.
PATIENTS AND METHODS
Patients with AFP-negative HCC who underwent radical resection were included in this study. A computerized tool was used to extract radiomic features from the tumor region of interest (ROI), select the best radiographic features associated with patient's postoperative recurrence, and use them to construct the radiomics score (RadScore), which was then combined with clinical and follow-up information to comprehensively evaluate the reliability of the model.
RESULTS
A total of 148 patients with AFP-negative HCC were enrolled in this study, and 1,977 radiographic features were extracted from CECT, 2 of which were the features most associated with recurrence in AFP-negative HCC. They had good predictive ability in both the training and validation cohorts, with an area under the ROC curve (AUC) of 0.709 and 0.764, respectively. Tumor number, microvascular invasion (MVI), AGPR and radiomic features were independent risk factors for early postoperative recurrence in patients with AFP-negative HCC. The AUCs of the integrated model in the training and validation cohorts were 0.793 and 0.791, respectively. The integrated model possessed the clinical value of predicting early postoperative recurrence in patients with AFP-negative HCC according to decision curve analysis, which allowed the classification of patients into subgroups of high-risk and low-risk for early recurrence.
CONCLUSION
The nomogram constructed by combining clinical and imaging features has favorable performance in predicting the probability of early postoperative recurrence in AFP-negative HCC patients, which can help optimize the therapeutic decision-making and prognostic assessment of AFP-negative HCC patients.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; alpha-Fetoproteins; Neoplasm Recurrence, Local; Middle Aged; Tomography, X-Ray Computed; Contrast Media; Aged; Retrospective Studies; Adult; Hepatectomy; Prognosis; Radiomics
PubMed: 38849749
DOI: 10.1186/s12885-024-12436-x -
ESMO Open Jun 2024Anaemia is frequent in patients with cancer and/or liver cirrhosis and is associated with impaired quality of life. Here, we investigated the impact of anaemia on...
BACKGROUND
Anaemia is frequent in patients with cancer and/or liver cirrhosis and is associated with impaired quality of life. Here, we investigated the impact of anaemia on overall survival (OS) and clinical characteristics in patients with hepatocellular carcinoma (HCC).
MATERIALS AND METHODS
HCC patients treated between 1992 and 2018 at the Medical University of Vienna were retrospectively analysed. Anaemia was defined as haemoglobin level <13 g/dl in men and <12 g/dl in women.
RESULTS
Of 1262 assessable patients, 555 (44.0%) had anaemia. The main aetiologies of HCC were alcohol-related liver disease (n = 502; 39.8%) and chronic hepatitis C (n = 375; 29.7%). Anaemia was significantly associated with impaired liver function, portal hypertension, more advanced Barcelona Clinic Liver Cancer stage and elevated C-reactive protein (CRP). In univariable analysis, anaemia was significantly associated with shorter median OS [9.5 months, 95% confidence interval (95% CI) 7.3-11.6 months] versus patients without anaemia (21.5 months, 95% CI 18.3-24.7 months) (P < 0.001). In multivariable analysis adjusted for age, Model for End-stage Liver Disease, number of tumour nodules, size of the largest nodule, macrovascular invasion, extrahepatic spread, first treatment line, alpha-fetoprotein and CRP, anaemia remained an independent predictor of mortality (adjusted hazard ratio 1.23, 95% CI 1.06-1.43, P = 0.006).
CONCLUSIONS
Anaemia was significantly associated with mortality in HCC patients, independent of established liver- and tumour-related prognostic factors. Whether adequate management of anaemia can improve outcome of HCC patients needs further evaluation.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Female; Male; Retrospective Studies; Middle Aged; Anemia; Aged; Prognosis
PubMed: 38848660
DOI: 10.1016/j.esmoop.2024.103593 -
International Journal of Surgery... Jun 2024The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation (DDLT) for hepatocellular carcinoma (HCC) can...
BACKGROUND AND AIMS
The practice of intraoperative blood salvage and autotransfusion (IBSA) during deceased donor liver transplantation (DDLT) for hepatocellular carcinoma (HCC) can potentially reduce the need for allogeneic blood transfusion. However, implementing IBSA remains debatable due to concerns about its possible detrimental effects on oncologic recurrence.
METHODS
This study retrospectively enrolled nationwide recipients of DDLT for HCC between 2015 and 2020. The focus was on comparing the cumulative recurrence rate and the recurrence-free survival rate. Propensity score matching was conducted repeatedly for further subgroup comparison. Recipients were categorized based on the Milan criteria, macrovascular invasion, and pre-transplant α-Fetoprotein (AFP) level to identify subgroups at risk of HCC recurrence.
RESULTS
A total of 6196 and 329 patients were enrolled in the non-IBSA and IBSA groups in this study. Multivariable competing risk regression analysis identified IBSA as independent risk factors for HCC recurrence (P<0.05). Post-matching, the cumulative recurrence rate and recurrence-free survival rate revealed no significant difference in the IBSA group and non-IBSA group (22.4% vs. 16.5%, P=0.12; 60.3% vs. 60.9%, P=0.74). Recipients beyond Milan criteria had higher, albeit not significant, risk of HCC recurrence if receiving IBSA (33.4% vs. 22.5%, P=0.14). For recipients with macrovascular invasion, the risk of HCC recurrence has no significant difference between the two groups (32.2% vs. 21.3%, P=0.231). For recipients with an AFP level<20 ng/mL, the risk of HCC recurrence was comparable in the IBSA group and the non-IBSA group (12.8% vs. 18.7%, P=0.99). Recipients with an AFP level ≥20 ng/mL, the risk of HCC recurrence was significantly higher in the IBSA group. For those with an AFP level≥400 ng/mL, the impact of IBSA on the cumulative recurrence rate was even more pronounced (49.8% vs. 21.9%, P=0.011).
CONCLUSIONS
IBSA does not appear to be associated with worse outcomes for recipients with HCC exceeding the Milan criteria or with macrovascular invasion. IBSA could be confidently applied for recipients with a pre-transplant AFP level<20 ng/mL. For recipients with AFP levels≥20 ng/mL, undertaking IBSA would increase the risk of HCC recurrence.
PubMed: 38847771
DOI: 10.1097/JS9.0000000000001683 -
Juntendo Iji Zasshi = Juntendo Medical... 2023A 27-year-old man experienced discomfort in his right testis in early September, 2021, and visited the hospital five days later. Physical examination did not detect any...
A 27-year-old man experienced discomfort in his right testis in early September, 2021, and visited the hospital five days later. Physical examination did not detect any abnormalities in the scrotum. However, an ultrasound revealed a tumor in the central part of the right testis, and a Magnetic Resonance Imaging (MRI) showed a tumor 2.7cm in diameter with clear boundaries and a marginally smooth surface. The level of alpha-fetoprotein, human chorionic gonadotropin, human chorionic gonadotropin-β subunit, and lactate dehydrogenase were within normal limits. A Computed Tomography (CT) scan showed no abnormalities. We can't rule out the possibility of malignancy, right radical orchiectomy was performed with a diagnosis of right testicular tumor in mid-September 2021. The macroscopic lesion was 1.5×1.3 cm in size, and no viable tumorous cells were found pathologically. Atypical cells were observed in the seminiferous tubules from the spermatic cord, which were positively stained with immune-histochemical staining CD117 (c-kit), D2-40, and MIB-1 but negatively with alpha-fetoprotein, human chorionic gonadotropin, and human chorionic gonadotropin-β subunit. The pathological diagnosis was germ cell neoplasia in situ, and no continuity was observed between these cells and bleeding necrosis. The patient has been followed up for 1 year and 4 months after surgery, with no recurrence or metastasis observed.
PubMed: 38845730
DOI: 10.14789/jmj.JMJ23-0016-CR