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Cancer Management and Research 2024As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their...
Efficacy and Safety of Chidamide in Combination with PD-1 Inhibitor and Radiotherapy for HER2-Negative Advanced Breast Cancer: Study Protocol of a Single Arm Prospective Study.
PURPOSE
As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer.
PATIENTS AND METHODS
This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored.
CONCLUSION
As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.
PubMed: 38948681
DOI: 10.2147/CMAR.S464677 -
Frontiers in Veterinary Science 2024Synthesis and secretion of bile acids (BA) is a key physiological function of the liver. In pathological conditions like portosystemic shunt, hepatic insufficiency,...
Synthesis and secretion of bile acids (BA) is a key physiological function of the liver. In pathological conditions like portosystemic shunt, hepatic insufficiency, hepatitis, or cirrhosis BA metabolism and secretion are disturbed. Quantification of total serum BA is an established diagnostic method to assess the general liver function and allows early detection of abnormalities, liver disease progression and guidance of treatment decisions. To date, data on comparative BA profiles in dogs are limited. However, BA profiles might be even better diagnostic parameters than total BA concentrations. On this background, the present study analyzed and compared individual BA profiles in serum, plasma, urine, and feces of 10 healthy pups and 40 adult healthy dogs using ultra-high performance liquid chromatography coupled to electrospray ionization mass spectrometry. Sample preparation was performed by solid-phase extraction for serum, plasma, and urine samples or by protein precipitation with methanol for the feces samples. For each dog, 22 different BA, including unconjugated BA and their glycine and taurine conjugates, were analyzed. In general, there was a great interindividual variation for the concentrations of single BA, mostly exemplified by the fact that cholic acid (CA) was by far the most prominent BA in blood and urine samples of some of the dogs (adults and pups), while in others, CA was under the detection limit. There were no significant age-related differences in the BA profiles, but pups showed generally lower absolute BA concentrations in serum, plasma, and urine. Taurine-conjugated BA were predominant in the serum and plasma of both pups (68%) and adults (74-75%), while unconjugated BA were predominant in the urine and feces of pups (64 and 95%, respectively) and adults (68 and 99%, respectively). The primary BA chenodeoxycholic acid and taurocholic acid and the secondary BA deoxycholic acid and lithocholic acid were the most robust analytes for potential diagnostic purpose. In conclusion, this study reports simultaneous BA profiling in dog serum, plasma, urine, and feces and provides valuable diagnostic data for subsequent clinical studies in dogs with different kinds of liver diseases.
PubMed: 38948668
DOI: 10.3389/fvets.2024.1380920 -
Journal of Family Medicine and Primary... May 2024Dengue disease severity and progression are determined by the host immune response, with both pro- and anti-inflammatory cytokines are key mediators.
CONTEXT
Dengue disease severity and progression are determined by the host immune response, with both pro- and anti-inflammatory cytokines are key mediators.
AIMS
To study pro- and anti-inflammatory cytokines across dengue severity and as a biomarker for predicting severe dengue infection.
SETTINGS AND DESIGN
Hospital-based cross-sectional study was conducted on 125 dengue-positive subjects across the 5-60 years age group of either gender in 2022.
METHODS AND MATERIALS
Haematological parameters and blood samples were drawn to measure cytokines IL6, IL-10 and TNF alpha using the ELISA technique.
STATISTICAL ANALYSIS
One-way ANOVA and the Kruskal - Wallis test were used to compare the dependent variables across categories of the dengue spectrum. Receiver operating characteristic curve was drawn to calculate the predictability of the cytokines as a predictor of severe dengue. A < 0.05 was considered significant.
RESULTS
34.4% of cases had severe dengue infection with 53.2% of severe cases reported in >40 years of age. Only IL-6 levels significantly increased ( < 0.01) across the spectrum of dengue infection across age groups >20 years with a consistent and significant fall in platelet levels ( < 0.01). The accuracy of IL-6 to predict severe dengue was 74.4% and platelet count was 16.2%.
CONCLUSIONS
Only IL-6 cytokine levels were significantly increased across the spectrum of dengue infection observed in age >20 years and can significantly predict the probability of severe dengue by 74% (sensitivity 81.4%). A significant decrease in platelet values is consistent with the severity but is not a good predictor for severe dengue infection.
PubMed: 38948604
DOI: 10.4103/jfmpc.jfmpc_1576_23 -
Journal of Family Medicine and Primary... May 2024Biomarkers to predict the onset and progression of chronic kidney disease (CKD) in children are lacking, and no such definite biomarkers have been implicated in the...
BACKGROUND
Biomarkers to predict the onset and progression of chronic kidney disease (CKD) in children are lacking, and no such definite biomarkers have been implicated in the diagnosis of CKD. We conducted this study to evaluate copeptin as a CKD marker and predict the disease progression by estimating the copeptin levels at baseline and 12 months follow-up in children with CKD stage 2 and above.
MATERIALS AND METHODS
This prospective single-centre cohort study was conducted in children under 14 years with CKD stages 2-4. Blood and urine samples were collected at enrolment and 1-year follow-up for routine investigations and serum copeptin, cystatin C and urinary neutrophil gelatinase-associated lipocalcin (uNGAL) estimation.
RESULTS
A total of 110 children (60 cases and 50 controls) were enrolled in the study. The mean estimated glomerular filtration rate (eGFR) of cases was 58.3 ± 18.7 ml/min/1.73 m. Among the cases, there was a significant rise in the serum copeptin levels from baseline 483.08 ± 319.2 pg/ml to follow-up at 1 year, that is, 1046.82 ± 823.53 pg/ml ( < 0.0001). A significant difference was noted in the baseline values of serum cystatin C, that is, 1512.98 ± 643.77 ng/ml and 719.68 ± 106.96 ng/ml ( < 0.0001), and uNGAL, that is, 13.53 ± 11.72 and 1.76 ± 2.37 ng/ml ( < 0.0001) between the cases and controls. There was no significant correlation (correlation coefficient = 0.10) between change in eGFR and copeptin levels during 12 months of follow-up.
CONCLUSION
No significant correlation was found between the change in eGFR and copeptin levels during 12 months of follow-up. This can be due to the slow deterioration of renal functions, as most of the cases had underlying congenital anomalies of the kidney and urinary tract (CAKUT), which is known to have a slow progression of CKD and a small sample size.
PubMed: 38948594
DOI: 10.4103/jfmpc.jfmpc_1707_23 -
Journal of Family Medicine and Primary... May 2024Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to...
Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition because in the early stages, it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay.
PubMed: 38948565
DOI: 10.4103/jfmpc.jfmpc_518_24 -
Journal of Family Medicine and Primary... May 2024Erroneous blood pressure measurement could lead to improper treatment and hence progression of chronic kidney disease (CKD). In routine clinical practice, there is poor...
Comparison of routine office blood pressure measurement versus standardized attended manually activated oscillometric office blood pressure measurement in patients with chronic kidney disease.
CONTEXT
Erroneous blood pressure measurement could lead to improper treatment and hence progression of chronic kidney disease (CKD). In routine clinical practice, there is poor adherence to the various steps to be followed during blood pressure measurement. Automated oscillometric BP measurement is difficult to perform in routine clinical practice due to several practical limitations.
AIMS
To evaluate the quality of blood pressure measurement and to compare routine office blood pressure measurement with standardized attended manually activated oscillometric blood pressure measurement in patients with CKD attending the nephrology outpatient department (OPD) of a tertiary care referral center.
SETTINGS AND DESIGN
This cross-sectional study was conducted in patients aged more than 18 years with CKD stage 3-5ND, and previously diagnosed hypertension, in the nephrology OPD of a tertiary care referral center between July 2022 and September 2022.
METHODS AND MATERIAL
The quality of blood pressure measurement was evaluated using a questionnaire. The study participants had their blood pressure checked by both methods-routine office blood pressure and standardized attended manually activated oscillometric blood pressure.
RESULTS
Standardized attended manually activated oscillometric blood pressure measurement yielded a significantly higher systolic blood pressure (SBP) compared to routine office blood pressure measurement (Mean SBP: 139.53 ± 29.1 vs 132.57 ± 23.59; < 0.001). However, the diastolic blood pressure did not differ significantly between the two methods of measurement.
CONCLUSIONS
Standardized attended manually activated oscillometric BP measurement yields a higher systolic BP compared to routine office BP measurement. Further studies are required to compare the standardized attended oscillometric BP measurement used in this study with unattended automated oscillometric BP measurement and ambulatory BP measurement.
PubMed: 38948560
DOI: 10.4103/jfmpc.jfmpc_1619_23 -
Frontiers in Endocrinology 2024Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical,...
BACKGROUND
Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy.
METHODS
Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT.
RESULTS
Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year ( < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level ( < 0.05) for patients with progressive disease.
CONCLUSION
We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients.
Topics: Humans; Neuroendocrine Tumors; Male; Female; MicroRNAs; Middle Aged; Intestinal Neoplasms; RNA, Messenger; Aged; Follow-Up Studies; Adult; Prognosis; Biomarkers, Tumor; Somatostatin; Receptors, Peptide; Radiopharmaceuticals; Lutetium; Radioisotopes
PubMed: 38948517
DOI: 10.3389/fendo.2024.1385079 -
Frontiers in Endocrinology 2024Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10%...
Ectopic ACTH syndrome (EAS) remains one of the most demanding diagnostic and therapeutic challenges for endocrinologists. Thymic neuroendocrine tumors account for 5%-10% of all EAS cases. We report a unique case of a 31-year-old woman with severe EAS caused by primary metastatic combined large-cell neuroendocrine carcinoma and atypical carcinoid of the thymus. The patient presented with severe hypercortisolemia, which was successfully controlled with continuous etomidate infusion. Complex imaging initially failed to detect thymic lesion; however, it revealed a large, inhomogeneous, metabolically active left adrenal mass infiltrating the diaphragm, suspected of primary disease origin. The patient underwent unilateral adrenalectomy, which resulted in hypercortisolemia resolve. The pathology report showed an adenoma with adrenal infarction and necrosis. The thymic tumor was eventually revealed a few weeks later on follow-up imaging studies. Due to local invasion and rapid progression, only partial resection of the thymic tumor was possible, and the patient was started on radio- and chemotherapy.
Topics: Humans; Female; Adult; Thymus Neoplasms; Cushing Syndrome; Carcinoma, Neuroendocrine; Adrenal Gland Neoplasms; ACTH Syndrome, Ectopic; Adrenalectomy; Neoplasms, Multiple Primary
PubMed: 38948516
DOI: 10.3389/fendo.2024.1399930 -
F1000Research 2023To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Case series. Three women (27 ±...
To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Case series. Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.
Topics: Humans; Female; Polycystic Ovary Syndrome; Adult; Meibomian Glands; Estrogens; Progesterone; Young Adult; Dry Eye Syndromes
PubMed: 38948507
DOI: 10.12688/f1000research.139229.1 -
Frontiers in Pharmacology 2024Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated...
Pancreatoblastoma (PB), a neoplasm derived from pancreatic follicular cells, primarily affects the pediatric population. Although infrequent in adults, it is associated with a considerably worse prognosis. Approximately one-third of patients are diagnosed with metastatic disease, with liver metastases being the most prevalent. Diagnosis relies on histopathological alterations including squamous vesicles, positive staining for CK8/CK18/CK19, and nuclear displacement of β-catenin. Additionally, liver metastases demonstrate substantial enhancement during the arterial phase of a contrast-enhanced computed tomography (CT) scan. Surgical resection serves as the principal therapeutic approach for addressing primary lesions and liver metastatic PB. In instances where surgical intervention is not viable, patients may derive benefits from systemic therapy and radiotherapy. This particular case report presents the clinical details of a 27-year-old female patient diagnosed with PB, who subsequently developed multiple liver metastases following a pancreaticoduodenectomy. Genomic examinations revealed the presence of ERBB2 amplification, RAD54L deletion, low TMB-L, and MSS in the patient. Despite the patient undergoing chemotherapy and Her-2 targeted therapy in conjunction with immunotherapy, no reduction in lesion size was observed until the administration of surufatinib. Subsequently, a notable outcome ensued, where the metastatic lesions were effectively excised via surgical intervention. Surufatinib has demonstrated a progression-free survival (PFS) of no less than 14 months, and the patient's survival has endured for a duration of 33 months. This indicates the potential efficacy of surufatinib as a viable therapeutic alternative for adult patients afflicted with PB.
PubMed: 38948477
DOI: 10.3389/fphar.2024.1361628