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Clinical Genitourinary Cancer Jun 2024Bacteriuria may affect the response to adjuvant therapy in non-muscle invasive bladder cancer (NMIBC). The main aim of this study was to examine the effect of recurrent... (Observational Study)
Observational Study
PURPOSE
Bacteriuria may affect the response to adjuvant therapy in non-muscle invasive bladder cancer (NMIBC). The main aim of this study was to examine the effect of recurrent bacteriuria (RB) on the prognosis of NMIBC in women receiving intravesical therapy.
MATERIALS AND METHODS
We designed a prospective observational study from 2012 to 2019. We included women with bladder cancer treated with transurethral resection of the bladder (TURB) and adjuvant intravesical treatment. Significant bacteriuria was defined as a presence in urine cultures at or above 100,000 colony-forming units per millilitre. The recurrent bacteriuria group included patients with significant bacteriuria in at least two determinations in 6 months or in 3 or more determinations in a year. The institutional board approved the study.
RESULTS
One hundred thirty-six patients diagnosed with NMIBC participate in the study, of whom 100 met the inclusion criteria. During follow-up, 48 were categorized in the RB group and 52 formed the non-bacteriuria group (NB).
RB GROUP HAD A BETTER OUTCOME
Eight patients (16.67%) experiencing a recurrence of the same grade, with no progression to a higher-grade tumor or muscle-invasive tumor. In the NB group, 18 (34.6%) patients presented a recurrence (P = .001) and 22 (42.3%) progressed to a higher-grade tumor or muscular invasion (P = .001). The presence of RB was identified as a predictor of good response in multivariate regression with a relative risk of 0.13 (P = .018) CONCLUSIONS: Female patients with RB had a better response to adjuvant treatment for NMIBC. The RB group showed lower rates of tumor recurrences and progression.
Topics: Humans; Urinary Bladder Neoplasms; Female; Aged; Bacteriuria; Prospective Studies; Prognosis; Middle Aged; Neoplasm Recurrence, Local; Administration, Intravesical; Neoplasm Invasiveness; Chemotherapy, Adjuvant; Treatment Outcome; Aged, 80 and over; Non-Muscle Invasive Bladder Neoplasms
PubMed: 38430858
DOI: 10.1016/j.clgc.2024.01.020 -
Cancer Communications (London, England) Apr 2024The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory, anaplastic lymphoma...
BACKGROUND
The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib-refractory, anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study.
METHODS
In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two-sided 95% confidence intervals (CIs). Next-generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management.
RESULTS
At the data cut-off date (August 31, 2022), with a median follow-up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3-53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks.
CONCLUSION
Ensartinib led to a favorable OS in patients with advanced, crizotinib-resistant, and ALK-positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.
Topics: Humans; Anaplastic Lymphoma Kinase; Carcinoma, Non-Small-Cell Lung; Circulating Tumor DNA; Crizotinib; Lung Neoplasms; Neoplasm Proteins; Piperazines; Protein Kinase Inhibitors; Pyridazines; Drug Resistance, Neoplasm
PubMed: 38421881
DOI: 10.1002/cac2.12524 -
Journal of Circulating Biomarkers 2024For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA...
BACKGROUND
For patients with mCRPC, PSMA-targeted radioligand treatment has significantly improved the clinical outcome. A blood-based liquid biopsy assay for recognizing PSMA protein expression on circulating tumor cells may be beneficial for better informing therapeutic decision-making and identifying the patients most likely to benefit from PSMA-targeted radioligand therapy.
METHODS
Using high-throughput imaging and digital AI pathology algorithms, a four-color immunofluorescence assay has been developed to find PSMA protein expression on CTCs on a glass slide. Cell line cells (LNCaP/PC3s/22Rv1) spiked into healthy donor blood were used to study the precision, specificity, sensitivity, limit of detection, and overall accuracy of the assay. Clinical validation and low-pass whole-genome sequencing were performed in PSMA-PET-positive patients with high-risk mCRPC (N = 24) utilizing 3 mL of blood.
RESULTS
The PSMA CTC IF assay achieved analytical specificity, sensitivity, and overall accuracy above 99% with high precision. In the clinical validation, 76% (16/21) of the cases were PSMA positive with CTC heterogeneity, and 88% (21/24) of the patients contained at least one conventional CTC per milliliter of blood. Thirty-six low-pass-sequenced CTCs from 11 individuals with mCRPC frequently exhibited copy number increases in and and losses in , and locus.
CONCLUSIONS
The analytical validation utilizing Epic Sciences' liquid biopsy CTC platform demonstrated the potential to detect PSMA protein expression in CTCs from patients with mCRPC. This assay is positioned as an effective research tool to evaluate PSMA expression, heterogeneity, and therapeutic response in many ongoing clinical studies to target tumors that express PSMA.
PubMed: 38415240
DOI: 10.33393/jcb.2024.2636 -
Molecular and Clinical Oncology Apr 2024Anti-programmed cell death 1 immuno-monotherapy has become the second-line standard treatment for advanced esophageal squamous cell carcinoma (ESCC) after the failure of...
Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second‑line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study.
Anti-programmed cell death 1 immuno-monotherapy has become the second-line standard treatment for advanced esophageal squamous cell carcinoma (ESCC) after the failure of first-line chemotherapy. However, new biomarkers are still needed to identify patients at risk of tumor progression and to select patients with advanced ESCC who are likely to benefit from immunotherapy. A total of 12 patients with advanced ESCC treated with tislelizumab were prospectively enrolled and endoscopic biopsy samples were collected. Plasma was obtained prior to and after every 2-3 treatment cycles with tislelizumab and when disease progression occurred. Targeted sequencing of 425 genes from plasma cell-free DNA, DNA from leukocytes and fixed esophageal tumor biopsies was performed. The patients underwent imaging analyses every 6-8 weeks until disease progression. The association between status of circulating tumor DNA (ctDNA) or changes in ctDNA following tislelizumab immunotherapy and response, tumor progression and survival was determined. All patients had evaluable next-generation sequencing results at the time of analysis. The results showed that patients with ESCC with liver metastasis had a significantly shorter median progression-free survival (mPFS: 1.4 vs. 11.7 months; P=0.037). TSC complex subunit 2 [11.7 months vs. not reached (NR); P=0.004] and zinc finger protein 217 (11.7 months vs. NR; P=0.022) gene mutations were the independent and negative prognostic factors for median overall survival (OS), respectively. Of note, ctDNA dynamic changes expressed as ∆ mutant molecules per milliliter of plasma (∆MMPM; MMPM detected at the first monitoring time-point after the first infusion of tislelizumab as baseline MMPM) predicted progression-free survival (PFS) and OS more accurately compared to the ctDNA change of an individual gene. ∆MMPM <20% was an independent predictor of PFS (2.8 vs. 14.6 months; P=0.029), although there was no significant difference for OS (16.7 vs. 17.6 months; P=0.830). In conclusion, changes in ctDNA levels were associated with anti-tumor effects, progression and disease-specific survival. ctDNA sequencing is promising for predicting response and progression after tislelizumab immunotherapy as second-line monotherapy for advanced ESCC [the present study was part of the RATIONALE-302 study (ClinicalTrials.gov identifier no. NCT03430843; 29.01.2018)].
PubMed: 38414510
DOI: 10.3892/mco.2024.2727 -
Hernia : the Journal of Hernias and... Apr 2024Heavyweight polypropylene (HWPP) mesh is thought to increase inflammatory response and delay tissue integration compared to mediumweight (MWPP). Reactive fluid volume... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Heavyweight polypropylene (HWPP) mesh is thought to increase inflammatory response and delay tissue integration compared to mediumweight (MWPP). Reactive fluid volume (i.e., drain output) may be a reasonable surrogate for integration. We hypothesized that daily drain output is higher with HWPP compared to MWPP in open retromuscular ventral hernia repair (VHR).
METHODS
This is a post-hoc analysis of a multicenter, randomized clinical trial conducted March 2017-April 2019 comparing MWPP and HWPP for VHR. Retromuscular drain output in milliliters was measured at 24-h intervals up to postoperative day seven. Univariate analyses compared differences in daily drain output and time to drain removal. Multivariable analyses compared total drain output and wound morbidity within 30 days and hernia recurrence at 1 year.
RESULTS
288 patients were included; 140 (48.6%) HWPP and 148 (51.4%) MWPP. Daily drain output for days 1-3 was higher for HWPP vs. MWPP (total volume: 837.8 mL vs. 656.5 mL) (p < 0.001), but similar on days 4-7 (p > 0.05). Median drain removal time was 5 days for both groups. Total drain output was not predictive of 30-day wound morbidity (p > 0.05) or hernia recurrence at 1 year (OR 1, p = 0.29).
CONCLUSION
While HWPP mesh initially had higher drain outputs, it rapidly returned to levels similar to MWPP by postoperative day three and there was no difference in clinical outcomes. We believe that drains placed around HWPP mesh can be managed similarly to MWPP mesh.
Topics: Humans; Polypropylenes; Surgical Mesh; Herniorrhaphy; Hernia, Ventral; Drainage
PubMed: 38409571
DOI: 10.1007/s10029-024-02972-7 -
Marine Drugs Jan 2024Marine fungi, such as species from the and genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been... (Review)
Review
Marine fungi, such as species from the and genera, are prolific producers of a diversity of natural products with cytotoxic properties. These fungi have been successfully isolated and identified from various marine sources, including sponges, coral, algae, mangroves, sediment, and seawater. The cytotoxic compounds derived from marine fungi can be categorized into five distinct classes: polyketides, peptides, terpenoids and sterols, hybrids, and other miscellaneous compounds. Notably, the pre-eminent group among these compounds comprises polyketides, accounting for 307 out of 642 identified compounds. Particularly, within this collection, 23 out of the 642 compounds exhibit remarkable cytotoxic potency, with IC values measured at the nanomolar (nM) or nanogram per milliliter (ng/mL) levels. This review elucidates the originating fungal strains, the sources of isolation, chemical structures, and the noteworthy antitumor activity of the 642 novel natural products isolated from marine fungi. The scope of this review encompasses the period from 1991 to 2023.
Topics: Fungi; Aspergillus; Antineoplastic Agents; Biological Products; Polyketides
PubMed: 38393041
DOI: 10.3390/md22020070 -
Antibiotics (Basel, Switzerland) Feb 2024One of the greatest challenges to the use of molecular methods for diagnostic purposes is the detection of target DNA that is present only in low concentrations. One...
One of the greatest challenges to the use of molecular methods for diagnostic purposes is the detection of target DNA that is present only in low concentrations. One major factor that negatively impacts accuracy, diagnostic sensitivity, and specificity is the sample matrix, which hinders the attainment of the required detection limit due to the presence of residual background DNA. To address this issue, various methods have been developed to enhance sensitivity through targeted pre-amplification of marker sequences. Diagnostic sensitivity to the single molecular level is critical, particularly when identifying bloodstream infections. In cases of clinically manifest sepsis, the concentration of bacteria in the blood may reach as low as one bacterial cell/CFU per mL of blood. Therefore, it is crucial to achieve the highest level of sensitivity for accurate detection. In the present study, we have established a method that fills the analytical gap between low concentrations of molecular markers and the minimum requirements for molecular testing. For this purpose, a sample preparation of whole blood samples with a directly downstream pre-amplification was developed, which amplifies specific species and resistance markers in a multiplex procedure. When applying pre-amplification techniques, the sensitivity of the pathogen detection in whole blood samples was up to 100 times higher than in non-pre-amplified samples. The method was tested with blood samples that were spiked with several Gram-positive and Gram-negative bacterial pathogens. By applying this method to artificial spiked blood samples, it was possible to demonstrate a sensitivity of 1 colony-forming unit (CFU) per millilitre of blood for and . A detection limit of 28 and 383 CFU per ml of blood was achieved for and , respectively. If the sensitivity is also confirmed for real clinical blood samples from septic patients, the novel technique can be used for pathogen detection without cultivation, which might help to accelerate diagnostics and, thus, to decrease sepsis mortality rates.
PubMed: 38391548
DOI: 10.3390/antibiotics13020161 -
Frontiers in Veterinary Science 2024Anthelmintic drug resistance has proliferated across Europe in sheep gastrointestinal nematodes (GINs). Sheep welfare and health are adversely impacted by these...
Anthelmintic drug resistance has proliferated across Europe in sheep gastrointestinal nematodes (GINs). Sheep welfare and health are adversely impacted by these phenomena, which also have an impact on productivity. Finding alternatives for controlling GINs in sheep is thus of utmost importance. In this study, the anthelmintic effectiveness (AE) of a Calabrian ethnoveterinary aqueous macerate based on (whole fruits) was assessed in Comisana pregnant sheep. Furthermore, an examination, both qualitative and quantitative, was conducted on milk. Forty-five sheep were selected for the investigation. The sheep were divided by age, weight, physiological state (pluripara at 20 days before parturition), and eggs per gram of feces (EPG) into three homogeneous groups of 15 animals each: PG received a single oral dosage of macerate at a rate of 50 mL per sheep; AG, treated with albendazole, was administered orally at 3.75 mg/kg/bw; and CG received no treatment. Timelines were as follows: D0, treatments, group assignment, fecal sampling, and AE assessment; D7, D14, D21, fecal sampling, and AE evaluation. The FLOTAC technique was used to evaluate the individual GIN fecal egg count (FEC) using a sodium chloride flotation solution (specific gravity = 1.20) and 100 × (1-[T2/C2]) as the formula for evaluating FEC reduction. Following the lambs' weaning, milk was collected on the following days (DL) in order to quantify production: DL35, DL42, DL49, DL56, DL63, DL70, DL77, and DL84. The amount of milk produced by every animal was measured and reported in milliliters (ml) for quantitative evaluations. Using MilkoScan TM fT + foss electric, Denmark, the quality of the milk (casein, lactose, protein concentration, and fat, expressed as a percentage) was assessed. The macerate demonstrated a considerable AE (51.8%). Moreover, its use has resulted in higher milk production rates quantitatively (15.5%) and qualitatively (5.12% protein, 4.12% casein, 4.21% lactose, and 8.18% fat). The study showed that green veterinary pharmacology could be the easiest future approach to counteracting anthelmintic resistance in sheep husbandry.
PubMed: 38384955
DOI: 10.3389/fvets.2024.1347151 -
La Tunisie Medicale Apr 2023Using a simple 10 to 20 milliliters of blood sample in order to make the diagnosis of lung cancer is the dream of every patient and practitioner. In fact, even if tissue...
Using a simple 10 to 20 milliliters of blood sample in order to make the diagnosis of lung cancer is the dream of every patient and practitioner. In fact, even if tissue samples or bronchial liquid represent the gold standard for microscopic diagnosis, using less invasive procedures represented the aim of many researches published in the literature. The utility of biomarkers has been widely reported in screening context, mainly in association to low dose CT-scan, or in therapeutic context in order to highlight therapeutic targets or to change treatment in a context of resistance to target therapies. The use of biomarkers in a diagnostic context has been recently highlighted in the literature. The authors aimed to present a general review of different biomarkers that could be used in the diagnosis of lung cancer.
Topics: Humans; Lung Neoplasms; Biomarkers; Tomography, X-Ray Computed
PubMed: 38372537
DOI: No ID Found -
BMC Veterinary Research Feb 2024Respiratory tract diseases cause significant economic loss in beef cattle. This study aimed to determine whether the application of hyperimmune serum (HS) containing...
BACKGROUND
Respiratory tract diseases cause significant economic loss in beef cattle. This study aimed to determine whether the application of hyperimmune serum (HS) containing antibodies against selected antigens of Gram-negative bacteria would improve the health and growth of different breeds of beef calves kept on three farms. Two recombinant protein antigens (Histophilus somni rHsp60 and rOMP40) were used to immunize four cows to produce HS. Eighty seven beef calves (Charolaise n = 36, Limousine n = 34, and crossbreed n = 17) were included into study. One hundred milliliters of serum were administered subcutaneously to 43 beef calves (Charolaise n = 18, Limousine n = 17, and crossbreed n = 8) twice, between 1 and 5 and 21-28 days of life. Calves were examined three times, and blood samples were taken to evaluate immunoglobulin M, G, and G2, fibrinogen, serum amyloid A, and haptoglobin concentrations and reactivity of these Ig classes of antibodies against H. somni rHsp60 and rOMP40. Average daily weight gain during the first month and until weaning was calculated.
RESULTS
HS showed higher (p ≤ 0.05) reactivity in calf sera against H. somni rHsp60 and OMP40 in IgG and IgG. In experimental calves, compared to control calves, the reactivity of IgG against rOMP40 in the second sampling was higher in Limousine calves (p ≤ 0.001) and in the other two herds (p ≤ 0.05). Serum IgG antibody activity against H. somni rHsp60 in the second sampling was higher in experimental calves than in control calves in charolaise (p ≤ 0.05) and limousine (p ≤ 0.001) herds. The reactivity of IgG against rOMP40 in the second sampling of experimental calves was higher in herds with Charolaise and Limousine calves (p ≤ 0.001) and in crossbred calves (p ≤ 0.05). In the third sampling, serum IgG antibody reactivity against rOMP40 in Limousine calves was higher (p ≤ 0.05) in the experimental group. Among the other evaluated parameters, only SAA in the second sampling in the herd with Charolaise calves and heart rate in the herd with Limousine calves were significantly higher in the control calves (p ≤ 0.05).
CONCLUSION
The application of HS to calves in all herds had an impact on specific reactivity in IgG and IgG classes against H. somni rOMP40 and rHsp60, antigens which were used for serum production.
Topics: Female; Cattle; Animals; Gram-Negative Bacteria; Recombinant Proteins; Immunoglobulin M; Pasteurellaceae; Immunoglobulin G; Cattle Diseases
PubMed: 38341558
DOI: 10.1186/s12917-024-03895-2