In epidemiological trials and in clinical practices, it is relevant to have affordable and reliable methods to measure the main lipid cardiovascular risk factors, and in particular low-density ...lipoprotein cholesterol (LDL-C) plasma level. In this context, we aimed to compare the reliability of the Friedewald's (LDL-Cf) and Sampson's (LDL-Cs) equations with the LDL-value dosed by a validated dosage method (LDL-Cd) in a large cohort of children.
We considered the lipid values of 145 infants, 278 preschoolers, 810 scholar children, and 1372 adolescents (Total N. 2605, 1291 males, 1314 females), with mean total cholesterol (TC) = 169.8 ± 39.7 mg/dL, HDL-Cholesterol = 50.8 ± 12.7 mg/dL, non HDL-Cholesterol = 118.9 ± 35.9 mg/dL, Triglycerides (TG) = 90.3 ± 77.9 mg/dL, LDL-Cd = 106.2 ± 29.9 mg/dL, LDL-Cf = 100.9 ± 33.8 mg/dL, and LDL-Cs = 102.2 ± 33.4 mg/dL. Comparing the distance to the LDL-Cd, Friedewald's equation mildly but significantly underestimated in infants (3.4 ± 5.3 mg/dL), preschoolers (1.5 ± 7.1 mg/dL). Children (1.2 ± 2.2 mg/dL) and adolescents (1.1 ± 5.9 mg/dL) compared to Sampson's equation (all comparisons, p < 0.001).
Our analysis, being carried out on a large population sample, shows that Sampson's equation is more reliable than Friedewald's one at each considered age class and even for extreme TG values.
•The Friedewald's formula is the gold standard to estimate LDL-C plasma level.•The new Sampson's formula seems to be more reliable for extreme LDL-C values.•We tested the reliability of the Sampson's formula in a large children cohort.•Sampson's formula seems to be more reliable than Friedewald's also in children.
Recently, accurate machine learning and deep learning approaches have been dedicated to the investigation of breast cancer invasive disease events (IDEs), such as recurrence, contralateral and second ...cancers. However, such approaches are poorly interpretable.
Thus, we designed an Explainable Artificial Intelligence (XAI) framework to investigate IDEs within a cohort of 486 breast cancer patients enrolled at IRCCS Istituto Tumori "Giovanni Paolo II" in Bari, Italy. Using Shapley values, we determined the IDE driving features according to two periods, often adopted in clinical practice, of 5 and 10 years from the first tumor diagnosis.
Age, tumor diameter, surgery type, and multiplicity are predominant within the 5-year frame, while therapy-related features, including hormone, chemotherapy schemes and lymphovascular invasion, dominate the 10-year IDE prediction. Estrogen Receptor (ER), proliferation marker Ki67 and metastatic lymph nodes affect both frames.
Thus, our framework aims at shortening the distance between AI and clinical practice.
There are several treatments available to newly diagnosed prostate cancer (PCA) patients. Although surgery and radiotherapy (RT) with or without androgen deprivation therapy (ADT) are widely adopted ...treatment options for localized PCA together with active surveillance (AS), there is no consensus nor randomised trials on treatment selection, prospective quality of life (QOL), along with toxicity outcomes and according to treatment modality in the Italian population. The current study aimed to describe clinical-therapeutic features and QOL at PCA diagnosis, according to different treatment patterns in a large prospective, Italian population, enrolled in the Pros-IT CNR study.
The Pros-IT CNR is an on-going national, multicenter, observational, prospective study on patients affected by PCA who have been referred by 97 Italian Urology, Radiation Oncology and Medical Oncology facilities participating in the project. The possible relationships between the treatment patterns reported in the 6 month follow-up case report form and patients' features at diagnosis were evaluated using exploratory multiple correspondence analysis (MCA) and other data analysis method.
At diagnosis, surgery and AS patients were significantly younger, had fewer comorbidities, lower PSA levels and Gleason Score (GS) values; they were also diagnosed at an earlier stage of disease with respect to the RT or ADT patients who showed significantly worse QoL scores at the time of diagnosis.
An analysis of the data collected at baseline and 6 months later uncovered substantial differences in ages, comorbidities, clinical and QOL features in the various treatment groups. These findings do not fully reflect the current PCA treatment guidelines and suggest the need for a multidisciplinary consensus guideline to ameliorate both the counselling and treatments of PCA patients.
Introduction
Staging of the mediastinum lymph nodes involvement in patients with non–small cell lung cancer (NSCLC) is an important prognostic factor determining the most appropriate multimodality ...treatment plan. The objective of this study is to assess ultrasound characteristics of mediastinal lymph nodes metastasis and effectiveness of intraoperative ultrasound‐guided mediastinal nodal dissection in patients with resected NSCLC.
Materials and Methods
All patients undergoing video‐assisted thoracoscopic surgery lobectomy and pulmonary lymphadenectomy from November 2020 to March 2022 at the thoracic surgery department of the Vanvitelli University of Naples underwent intraoperative ultrasound‐guided mediastinal lymph nodal dissection.
Results
This study evaluates whether individual B‐mode features and a compounding thereof can be used to accurately and reproducibly predict lymph node malignancy.
Discussion
Intraoperative ultrasound, during systematic mediastinal lymph node dissection, is helpful in preventing lesion to mediastinal structures. Pathological nodal sonographic characteristics are round shape, short‐axis diameter, echogenicity, margin, the absence or presence of coagulation necrosis sign, and the absence or presence of central hilar structure, increased color Doppler flow, the absence or presence of calcification, and nodal conglomeration. Operating time was not substantially prolonged. The procedure is simple, safe and highly accurate.
Conclusions
Ultrasonic techniques allow surgeons to detect the relationship between lymph nodes and surrounding large blood vessels during biopsy, improving the safety and simplicity of the operation, increasing the number of harvested lymph nodes, and reducing the risk of intraoperative injury; it is a fast, easily reproducible, and inexpensive method.
Intraoperative ultrasound of mediastinal lymph nodes allows surgeons to detect metastatic lymph nodes during surgery for NSCLC. It can show the relationship between lymph nodes and surrounding structures during biopsy, improving the safety and simplicity of the operation, increasing the number of harvested lymph nodes, and reducing the risk of intraoperative injury. It is a fast, easily reproducible and inexpensive method.
Epigenetic changes have been consistently detected in different cell types in multiple sclerosis (MS). However, their contribution to MS pathogenesis remains poorly understood partly because of ...sample heterogeneity and limited coverage of array-based methods. To fill this gap, we conducted a comprehensive analysis of genome-wide DNA methylation patterns in four peripheral immune cell populations isolated from 29 MS patients at clinical disease onset and 24 healthy controls. We show that B cells from new-onset untreated MS cases display more significant methylation changes than other disease-implicated immune cell types, consisting of a global DNA hypomethylation signature. Importantly, 4,933 MS-associated differentially methylated regions in B cells were identified, and this epigenetic signature underlies specific genetic programs involved in B cell differentiation and activation. Integration of the methylome to changes in gene expression and susceptibility-associated regions further indicates that hypomethylated regions are significantly associated with the up-regulation of cell activation transcriptional programs. Altogether, these findings implicate aberrant B cell function in MS etiology.
To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) ...using the Delphi consensus method.
Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.
Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.
Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.
Mechanisms contributing to disability accumulation in multiple sclerosis (MS) are poorly understood. Blood neurofilament light chain (NfL) level, a marker of neuroaxonal injury, correlates robustly ...with disease activity in people with MS (MS); however, data on the association between NfL level and disability accumulation have been conflicting.
To determine whether and when NfL levels are elevated in the context of confirmed disability worsening (CDW).
This study included 2 observational cohorts: results from the Expression, Proteomics, Imaging, Clinical (EPIC) study at the University of California San Francisco (since 2004) were confirmed in the Swiss Multiple Sclerosis Cohort (SMSC), a multicenter study in 8 centers since 2012. Data were extracted from EPIC in April 2022 (sampling July 1, 2004, to December 20, 2016) and SMSC in December 2022 (sampling June 6, 2012, to September 2, 2021). The study included 2 observational cohorts in tertiary MS centers. All participants of both cohorts with available NfL results were included in the study, and no eligible participants were excluded or declined to participate.
Association between NfL z scores and CDW.
CDW was defined as Expanded Disability Status Scale (EDSS) worsening that was confirmed after 6 or more months and classified into CDW associated with clinical relapses (CDW-R) or independent of clinical relapses (CDW-NR). Visits were classified in relation to the disability worsening events into CDW(-2) for 2 visits preceding event, CDW(-1) for directly preceding event, CDW(event) for first diagnosis of EDSS increase, and the confirmation visit. Mixed linear and Cox regression models were used to evaluate NfL dynamics and to assess the association of NfL with future CDW, respectively.
A total of 3906 EPIC visits (609 participants; median IQR age, 42.0 35.0-50.0 years; 424 female 69.6%) and 8901 SMSC visits (1290 participants; median IQR age, 41.2 32.5-49.9 years; 850 female 65.9%) were included. In CDW-R (EPIC, 36 events; SMSC, 93 events), NfL z scores were 0.71 (95% CI, 0.35-1.07; P < .001) units higher at CDW-R(-1) in EPIC and 0.32 (95% CI, 0.14-0.49; P < .001) in SMSC compared with stable MS samples. NfL elevation could be detected preceding CDW-NR (EPIC, 191 events; SMSC, 342 events) at CDW-NR(-2) (EPIC: 0.23; 95% CI, 0.01-0.45; P = .04; SMSC: 0.28; 95% CI, 0.18-0.37; P < .001) and at CDW-NR(-1) (EPIC: 0.27; 95% CI, 0.11-0.44; P < .001; SMSC: 0.09; 95% CI, 0-0.18; P = .06). Those findings were replicated in the subgroup with relapsing-remitting MS. Time-to-event analysis confirmed the association between NfL levels and future CDW-R within approximately 1 year and CDW-NR (in approximately 1-2 years).
This cohort study documents the occurrence of NfL elevation in advance of clinical worsening and may hint to a potential window of ongoing dynamic central nervous system pathology that precedes the diagnosis of CDW.
We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, ...and we surveyed clinicians' opinion and usual practice for the selected interventions.
MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references.
We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility.
For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up.
We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions.
We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.
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