To calculate the accuracy (A) and establish the best cutoff value for ophthalmic artery (OA) Doppler velocimetry indexes in patients diagnosed with preeclampsia (PE), compared with healthy pregnant ...women.
This prospective experimental study enrolled 268 women: 133 with PE and 135 healthy pregnant women. All patients were evaluated by OA Doppler sonography, bilaterally, to assess their pulsatility index (PI), resistance index (RI), peak systolic velocity (PVS), second peak systolic velocity (P2), end-diastolic velocity (EDV), and peak ratio (PR). Means were compared using Student's T-test. Receiver Operating Characteristics (ROC) curve was used to establish the cutoff value and estimate the sensitivity (S), specificity (Sp), accuracy (A) of all variables, and a significance of 95% was adopted.
ROC curve analysis showed that P2 and PR were superior to the other parameters for PE diagnosis. We tested two cutoff values: (1) using PR ≥0.70, obtained A: 88.72%, S: 81.95%, and Sp: 95.48% and (2) using PR ≥0.75, and A: 86.24%, S: 74.43%, and Sp: 99.24%. By adopting P2 ≥ 21.5 cm/s, we obtained A: 87.59%, S: 84.96%, and Sp: 90.22% and when the cutoff point was P2 ≥ 22 cm/s, there was a slight decrease in A to 86.46% and S to 81.20%, with Sp: 91.89.3%.
Ophthalmic artery Doppler demonstrated to be an effective and high-performance imaging method for the diagnosis of PE and the indexes P2 and PR demonstrated superior accuracy to the other Doppler parameters assessed. Higher performance occurred when the cutoff values with greater specificity were adopted, PR ≥ 0.75 and P2 ≥ 22 cm/s, considering that the proposed OA Doppler is to be a complementary method for preeclampsia.
The influence of a nanodispersion of TiO2 in water (nanoparticle size: 40 nm, polydispersity index: 0.25), brushed on a Paraloid film and subjected to UV–Vis irradiation was evaluated. The TiO2 ...nanodispersions showed a tendency to reduce the molecular weight of Paraloid due to its photocatalytic properties. FTIR and GPC analyses and SEM images suggested the degradation of the polymer, while chromatic variations of the films were scarcely detected. This study is very remarkable in the perspective of using this material for the removal of polymeric films used in conservation.
Uterine leiomyosarcoma (uLMS) is characterized by aggressive behavior associated with a high risk of relapse and mortality. Several therapeutic agents have been employed in the treatment of ...metastatic disease, with a poor objective response rate. Pazopanib, approved in 2012, is a multi-targeted, orally active small molecule that exerts its effects by inhibiting several tyrosine kinases. To date, poor research on real-life data has been conducted. We aimed to assess the effectiveness and safety of the drug in everyday clinical practice.
We present results of multicenter retrospective data on 38 patients with heavily pretreated metastatic uLMS who underwent oral pazopanib during their therapeutic journey.
At a median follow-up of 8.6 months, the disease control rate was 55.2%, with 17% partial responses and 15 patients (39.5%) with stable disease. At a median follow-up of 8.6 months, median progression-free survival was 4 months, and median overall survival was 19.8 months. The most common grade 3 adverse events (AEs) drug-related were hepatic toxicities, diarrhea, hypertension, nausea, and vomiting (all of them with an incidence of 5% considering the whole study cohort). No grade 4 AEs occurred.
Pazopanib in everyday clinical practice is safe and shows a good disease control rate with prolonged survival.
Background:
Previous data, mostly from clinical trials, reported that HER2-low status is associated with low pathological complete response (pCR), and favourable prognosis. Since these findings ...suggest the existence of an additional breast cancer subtype, we questioned if the predictive/prognostic value of HER2-low was also relevant in the real world.
Methods:
Data from non-metastatic breast cancer patients treated with neoadjuvant chemotherapy and surgery (2009–2020) were retrieved from our institutional prospectively-maintained registry. Univariable and multivariable logistic models were implemented to study the association between pCR and baseline HER2 status. Univariable analysis of disease-free survival (DFS) was performed through Kaplan-Meier survival curves and log-rank tests.
Results:
Starting from a total of 790 consecutive cases, we identified 444 newly-diagnosed breast cancer patients featuring HER2 immunohistochemistry (IHC) 0 (HER2-0,
n
= 109), and 1 + or IHC 2+/
in situ
hybridization negative (HER2-low,
n
= 335) receiving anthracycline and taxane-based regimens in 88.9% of cases. Most of the patients were diagnosed with stage II (67.3%) and there was no difference of disease presentation according to HER2-status. pCR was attained by 71 (16.0%) patients and was significantly associated with increased DFS (
p
= 0.031). Compared to HER2-0, HER2-low cases were more likely hormone receptor-positive (81.2% vs. 43.1%,
p
< 0.001), well-differentiated (47.5% vs. 26.6%,
p
= 0.001), less proliferative (21.5% vs. 8.3%,
p
= 0.001) and less responsive to treatment (pCR 11.6% vs. 29.4%,
p
< 0.0001). There was no difference in DFS according to HER2 status, though hormone-receptor (HR) negative/HER2-low cases tended to have a worse prognosis compared to HR-negative/HER2-0. By pCR achievement, 3-years DFS was 87.5.% (75.1–100%) vs. 71.6% (65.9–77.8%) (
p
= 0.161) in HER2-low and 89.1% (75.8–100%) vs. 72.1% (59.7–87.0%) (
p
= 0.092) in HER2-0.
Conclusion:
Our real-world data show that HER2-low breast cancer patients represent roughly a half of the cases treated with neoadjuvant therapy, and have poor treatment response. In absence of pCR, HER2-low breast cancer patients have a dismal prognosis, especially when primary tumor hormone receptor status is negative. Studies are therefore needed to define the biology of these tumors for new therapeutic targets and to incorporate HER2-targeting agents in early-stage treatment.
Inflammation and immunity are linked to intestinal adenoma (IA) and colorectal cancer (CRC) development. The gut microbiota is associated with CRC risk. Epithelial barrier dysfunction can occur, ...possibly leading to increased intestinal permeability in CRC patients. We conducted a case-control study including 100 incident histologically confirmed CRC cases, and 100 IA and 100 healthy subjects, matched to cases by center, sex and age. We performed 16S rRNA gene analysis of blood and applied conditional logistic regression. Further analyses were based on negative binomial distribution normalization and Random Forest algorithm. We found an overrepresentation of blood 16S rRNA gene copies in colon cancer as compared to tumor-free controls. For high levels of gene copies, community diversity was higher in colon cancer cases than controls. Bacterial taxa and operational taxonomic unit abundances were different between groups and were able to predict CRC with an accuracy of 0.70. Our data support the hypothesis of a higher passage of bacteria from gastrointestinal tract to bloodstream in colon cancer. This result can be applied on non-invasive diagnostic tests for colon cancer control.
Biliary tract cancers (BTCs) have poor prognosis and limited therapeutic options. The impact of O6‐methylguanine‐DNA methyltransferase (MGMT) inactivation in advanced BTC patients is not established. ...We investigated the prevalence, prognostic, and predictive impact of MGMT inactivation in two multicenter cohorts. MGMT inactivation was assessed through PCR and immunohistochemistry (IHC) in an Italian cohort; the results were then externally validated using RNA sequencing (RNA‐seq) data from the BTC subcohort of the Molecularly Aided Stratification for Tumor Eradication Research (MASTER) precision oncology program of the National Center for Tumor Diseases Heidelberg and the German Cancer Consortium. Among 164 Italian cases, 18% presented MGMT promoter hypermethylation (> 14%) and 73% had negative MGMT protein expression. Both were associated with worse overall survival (OS; HR 2.31; P < 0.001 and HR 1.99, P = 0.012, respectively). In the MASTER cohort, patients with lower MGMT mRNA expression showed significantly poorer OS (median OS mOS 20.4 vs 31.7 months, unadjusted HR 1.89; P = 0.043). Our results suggest that MGMT inactivation is a frequent epigenetic alteration in BTC, with a significant prognostic impact, and provide the rationale to explore DNA‐damaging agents in MGMT‐inactivated BTCs.
The impact of MGMT inactivation in patients with advanced biliary tract cancer (BTC) is not established. We investigated its prevalence, prognostic, and predictive impact, assessed through methylation‐specific PCR and IHC, in a large Italian cohort. Then we evaluated MGMT inactivation through RNA‐seq and DNA methylation analysis in an independent German cohort. Overall, MGMT inactivation or reduced expression consistently resulted in poorer survival.
Patients with solid tumors and mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H) are eligible for immunotherapy. Recently, different reports described patients with poor ...performance status (PS), unrelated to comorbidities, which showed a rapid improvement of their clinical conditions under immunotherapy, which evoked a Lazarus response. Very few data on the efficacy and safety of immunotherapy in patients with gynecological malignancies and poor PS are available. Based on the GARNET trial, Dostarlimab, a monoclonal antibody anti-programmed death receptor-1 (PD-1), has been approved in advanced or recurrent mismatch repair deficient endometrial cancer (EC) which progressed after platinum-based therapy. For the first time, in gynecological oncology, an immune checkpoint inhibitor drastically changed the clinical practice. We collected a multicenter case series of six patients with advanced endometrial carcinoma and PS ECOG 3–4 treated with Dostarlimab, showing exceptionally quick responses and significant improvement of PS to configure a Lazarus response.
Background: In spite of the frequency and clinical impact of BRCA1/2 alterations in high-grade epithelial ovarian cancer (HGEOC), real-world information based on robust data warehouse has been scarce ...to date. Methods: Consecutive patients with BRCA-mutated HGEOC treated between 2011 and 2016 within French comprehensive cancer centers from the Unicancer network were extracted from the ESME database. The main objective of the study was the assessment of clinicopathological and treatments parameters. Results: Out of the 8021 patients included in the ESME database, 266 patients matching the selection criteria were included. BRCA1 mutation was found in 191 (71.8%) patients, while 75 (28.2%) had a BRCA2 mutation only; 95.5% of patients received a cytoreductive surgery. All patients received a taxane/platinum-based chemotherapy (median = six cycles). Complete and partial response were obtained in 53.3% and 20.4% of the cases, respectively. Maintenance therapy was administered in 55.3% of the cases, bevacizumab being the most common agent. After a median follow up of 51.7 months, a median progression-free survival of 28.6 months (95% confidence interval (CI) 26.5; 32.7) and an estimated 5-year median overall survival of 69.2% (95% CI 61.6; 70.3) were reported. Notably, BRCA1- and BRCA2-mutated cases exhibited a trend towards different median progression-free survivals, with 28.0 (95% CI 24.4; 32.3) and 33.3 months (95% CI 26.7; 46.1), respectively (p-value = 0.053). Furthermore, five-year OS for BRCA1-mutated patients was 64.5% (95% CI 59.7; 69.2), while it was 82.5% (95% CI 76.6; 88.5) for BRCA2-mutated ones (p-value = 0.029). Conclusions: This study reports the largest French multicenter cohort of BRCA-mutated HGEOCs based on robust data from the ESME, exhibiting relevant real-world data regarding this specific population.
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