Weight gain and metabolic changes have been related to survival of early breast cancer patients (EBC). ‘’However, factors influencing metabolism post-diagnosis are not fully understood. We measured ...anthropometric body mass index (BMI), body weight, waist and hip circumferences, and waist-to-hip ratio and metabolic (levels of insulin, glucose, H1Ac, total, HDL, and LDL cholesterol, triglycerides, and the homeostasis model assessment score HOMA) parameters in 433 pre- and post-menopausal women with EBC at diagnosis and 3, 6, 9, 12, and 24 months thereafter. At diagnosis, compared with post-menopausal women, pre-menopausal patients were more likely to be leaner and to have a lower BMI, smaller waist and hip circumferences, and waist-to-hip ratio. They had also lower glucose, HbA1c, and triglyceride levels and a lower HOMA score. Furthermore, they were more likely to have an estrogen- and/or progesterone-positive tumor and a higher proliferating breast cancer. During the first two post-diagnosis years, all women showed a significant increase of weight (+0.72 kg/year,
P
< 0.001), waist circumference (+1.53 cm/year,
P
< 0.001), and plasma levels of LDL cholesterol (+5.4 mg/dl per year,
P
= 0.045) and triglycerides (+10.73 mg/dl per year,
P
= 0.017). In patients receiving chemotherapy only, there was a significant increase in hip circumference (+3.16 cm/year,
P
< 0.001) and plasma cholesterol levels (+21.26 mg/dl per year,
P
< 0.001). We showed that weight, body fat distribution, and lipid profile changed in EBC patients receiving adjuvant therapy. These changes occurred during the first 2 years after diagnosis and were not specifically related to chemotherapy, menopausal status, or initial body weight.
Background:
In more than 90% of chronic viral hepatitis C (HCV) patients treated with direct-acting antiviral agents (DAAs), a sustained viral response (SVR) was observed. Unfortunately, there are ...subgroups of subjects who display enduring liver fibrosis and are at high risk of developing hepatocellular carcinoma (HCC). Thus, liver fibrosis evaluation during the follow-up of these patients plays a pivotal role. The gold standard to evaluate hepatic fibrosis is liver biopsy, which is an invasive procedure. Imaging techniques and serum biomarkers have been proposed as safer and cheaper procedures.
Objectives:
In this study, we evaluated the concordance of transient elastography (TE) with ELF score ( enhanced liver fibrosis) in a cohort of patients with HCV before and after direct-acting antiviral (DAAs) treatment. ELF score has been validated in other chronic liver diseases; the evidence is not available in HCV patients treated with DAAs.
Study design:
We prospectively recruited all consecutive HCV patient candidates for DAAs therapy at the University of Naples “Federico II” between April 2015 and July 2016. TE and ELF scores were assessed at baseline, at SVR24, and at SVR48.
Results:
One-hundred-nineteen patients were treated with DAAs, and 94.1% of them reached SVR. A total of 55.5% of patients were males with a mean age of 64.7 ± 9.6 years. TE results revealed that 12 patients (10%) had F1-2 mild/moderate fibrosis, and 107 (90%) had F3-4 advanced fibrosis. At baseline, SVR24, and SVR48, the concordance between ELF test and TE was poor: 0.11 (
p
= 0.086), 0.15 (
p
= 0.124), and 0.034 (
p
= 0.002), respectively. However, at SVR24 and SVR48, both methods showed a significant amelioration of liver fibrosis compared to baseline (
p
< 0.001). In addition, both ELF index and TE were significantly associated with portal hypertension at baseline, but not with varices and ascites.
Conclusions:
Our findings suggested that ELF test could predict changes in liver fibrosis, independently of TE. In case of TE unavailability, ELF score could represent an appropriate tool. Notably, in the context of the COVID-19 pandemic, ELF testing should be encouraged to reduce unnecessary access to the hospital and prolonged physical contact.
Objectives
We designed a multicentre open prospective randomized trial to evaluate the risk-benefit profile of two different initial treatment schemes with levothyroxine (L-T4), 10-12.5 μg/kg/day vs ...12.6-15 μg/kg/day, on growth and neurodevelopmental outcomes in children with congenital hypothyroidism (CH) detected by neonatal screening to identify the best range dose to achieve optimal neurocognitive development.
Design, patients and methods
Children detected by neonatal screening were randomly assigned to receive an initial L-T4 dose of 10-12.5 μg/kg/day (Low) or 12.6-15 μg/kg/day (High). All patients underwent periodical clinical examination with measurement of growth parameters and measurement of TSH and FT4. Neurocognitive development was evaluated at the age of 24 months using Griffiths Mental Development Scales (GMDS) and cognitive and behavioral assessment was performed at 48 months of age using Wechsler Preschool and Primary scale of Intelligence (WIPPSI-III). The study was registered with clinicaltrials.gov (NCT05371262).
Results
Treatment schemes below or above 12.5 μg/kg/day were both associated with rapid normalization of TSH and thyroid hormone levels in most patients with no differences in the risk of over- and under-treatment episodes in the first months of life. Growth parameters were normal and comparable between the two groups. Developmental quotients at 24 months of age were normal in both groups (Low 100.6 ± 15.5 vs High 96.9 ± 16.6). Likewise, at 4 years of age IQ and subtest scores were comparable between patients from Low and High (Total IQ 104.2 ± 11.4 vs 101.0 ± 20.3, Verbal IQ 103.9 ± 11.5 vs 98.7 ± 15.1, Performance IQ 105.3 ± 10.4 vs 100.3 ± 19.8). 6/45 CH patients (13.3%) showed a total IQ below 85 (73.7 ± 5.9) regardless of age at diagnosis, L-T4 starting dose, time of FT4 and TSH normalization and episodes of over and undertreatment. Worse socioeconomic status and delayed bone age at diagnosis were the only predictors of an increased risk of having suboptimal IQ at 24 and IQ at 48 months.
Conclusions
Our results indicate that initial treatment with L-T4, 10-12.5 μg/kg/day vs 12.6-15 μg/kg/day, are both associated with normal growth and neurodevelopmental outcomes in children with CH detected by neonatal screening. Further studies with a long-term follow-up on a larger number of patients are needed to confirm these results.
Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT05371262?term=NCT05371262&draw=2&rank=1
identifer NCT05371262.
The Children's Sleep Habits Questionnaire (CSHQ) is a parent-report questionnaire used to examine sleep behavior in children. Linguistic adaptation of CSHQ into several languages and/or psychometric ...analysis of reliability have been published.
Our aim was to translate the original 33-items CSHQ from English to Italian and to examine its reliability for use in 4-10 years-old children of Italy. After translation and back-translation procedure of the original CSHQ, the Italian CSHQ (CSHQ-IT) was administered to 69 mothers of healthy children. Reliability of CSHQ-IT was examined by the internal consistency of the scale (using the Cronbach's alpha coefficient), and by the test-retest analysis obtained by asking mothers who had completed the CSHQ-IT at baseline to re-complete it after a two-week interval (measured with the Lin's Concordance Correlation Coefficient, CCC). The CSHQ-IT showed adequate internal consistency (Cronbach's alpha = 0.81 for the total scale). The total CSHQ-IT score showed a strong correlation in retests (CCC 0.87; 95% Confidence Interval, 0.80; 0.92).
CSHQ-IT is a valuable tool for evaluating sleep behavior in children 4-10 years-old in Italy. Future research should be implemented to provide definitive validity of CSHQ-IT in children with sleep-disordered breathing.
Immunohistochemistry (IHC) and polymerase chain reaction (PCR) and fragment separation by capillary electrophoresis represent the current clinical laboratory standard for the evaluation of ...microsatellite instability (MSI) status. The importance of reporting MSI status in colorectal cancer is based on its potential for guiding treatment and as a prognostic indicator. It is also used to identify patients for Lynch syndrome testing. Our aim was to evaluate pre-analytical factors, such as age of formalin-fixed and paraffin-embedded (FFPE) block, neoplastic cell percentage, mucinous component, and DNA integrity, that may influence the accuracy of MSI testing and assess the concordance between three different MSI evaluation approaches. We selected the mucinous colorectal cancer (CRC) histotype for this study as it may possibly represent an intrinsic diagnostic issue due to its low tumor cellularity. Seventy-five cases of mucinous CRC and corresponding normal colon tissue samples were retrospectively selected. MMR proteins were evaluated by IHC. After DNA quality and quantity evaluation, the Idylla™ and TapeStation 4200 platforms were adopted for the evaluation of MSI status. Seventy-three (97.3%) cases were successfully analyzed by the three methodologies. Overall, the Idylla™ platform showed a concordance rate with IHC of 98.0% for microsatellite stable (MSS)/proficient MMR (pMMR) cases and 81.8% for MSI/deficient MMR (dMMR) cases. The TapeStation 4200 system showed a concordance rate with IHC of 96.0% for MSS/pMMR cases and 45.4% for MSI/dMMR cases. The concordance rates of the TapeStation 4200 system with respect to the Idylla™ platform were 98.1% for MSS profile and 57.8% for MSI profile. Discordant cases were analyzed using the Titano MSI kit. Considering pre-analytical factors, no significant variation in concordance rate among IHC analyses and molecular systems was observed by considering the presence of an acellular mucus cut-off >50% of the tumor area, FFPE year preparation, and DNA concentration. Conversely, the Idylla™ platform showed a significant variation in concordance rate with the IHC approach by considering a neoplastic cell percentage >50% (
-value = 0.002), and the TapeStation 4200 system showed a significant variation in concordance rate with the IHC approach by considering a DNA integrity number (DIN) ≥4 as cut-off (
-value = 0.009). Our data pinpoint a central role of the pre-analytical phase in the diagnostic outcome of MSI testing in CRC.
E-learning is a candidate tool for clinical practice guidelines (CPG) implementation due to its versatility, universal access and low costs. We aimed to assess the impact of a five-module e-learning ...course about CPG for acute gastroenteritis (AGE) on physicians' knowledge and clinical practice.
This work was conceived as a pre/post single-arm intervention study. Physicians from 11 European countries registered for the online course. Personal data, pre- and post-course questionnaires and clinical data about 3 to 5 children with AGE managed by each physician before and after the course were collected. Primary outcome measures included the proportion of participants fully adherent to CPG and number of patients managed with full adherence.
Among the 149 physicians who signed up for the e-learning course, 59 took the course and reported on their case management of 519 children <5 years of age who were referred to their practice because of AGE (281 and 264 children seen before and after the course, respectively). The course improved knowledge scores (pre-course 8.6 ± 2.7 versus post-course 12.8 ± 2.1, P < 0.001), average adherence (from 87.0 ± 7.7% to 90.6 ± 7.1%, P = 0.001) and the number of patients managed in full adherence with the guidelines (from 33.6 ± 31.7% to 43.9 ± 36.1%, P = 0.037).
E-learning is effective in increasing knowledge and improving clinical practice in paediatric AGE and is an effective tool for implementing clinical practice guidelines.
The treatment of children with subclinical hypothyroidism (SH) is controversial for TSH values between 4.5 and 10 mU/l. The aim of this cross-sectional, controlled study was to evaluate growth and ...intellectual outcome in children with persistent SH who have never been treated with levothyroxine.
Clinical and auxological parameters, thyroid function, and intellectual outcome were evaluated in 36 children with persistent SH at the age of 9.7±0.6 (range 4-18.0) years. Children had been followed longitudinally for 3.3±0.3 (range 2.0-9.3) years, from first diagnosis of SH until enrollment in the study. Thirty-six age- and sex-matched children were enrolled in the study as controls.
At study entry, height (-0.8±0.2 SDS), bone age/chronological age (BA/CA ratio 0.92±0.6), and body mass index (BMI -0.1±0.2 SDS) in SH children were normal. Despite long-term duration of SH, none of these parameters showed a worsening with respect to height (-0.7±0.2 SDS), BA/CA (0.97±0.03), and BMI (-0.1±0.2) at the time of first SH detection. None of the children showed overt signs or symptoms of hypothyroidism during the follow-up. Verbal (99.1±2.2), performance (100.4±1.9), and full-scale (99.7±1.9) intelligence quotient (IQ) scores in SH children were normal and comparable to those of controls. No relationship was detected between IQ scores and the degree or duration of SH.
Persistent SH in children is not associated with alterations in growth, bone maturation, BMI, and cognitive function or other complaints that could be ascribed to SH even after several years without therapeutic intervention.
Background
Artificial genomic reference standards in a cytocentrifuge/cytospin format with well‐annotated genomic data are useful for validating next‐generation sequencing (NGS) on routine ...cytopreparations. Here, reference standards were optimized to be stained by different laboratories before DNA extraction and to contain a lower number of cells (2 × 105). This was done to better reflect the clinical challenge of working with insufficient cytological material.
Methods
A total of 17 worldwide laboratories analyzed customized reference standard slides (slides A‐D). Each laboratory applied its standard workflow. The sample slides were engineered to harbor epidermal growth factor receptor (EGFR) c.2235_2249del15 p.E746_A750delELREA, EGFR c.2369C>T p.T790M, Kirsten rat sarcoma viral oncogene homolog (KRAS) c.38G>A p.G13D, and B‐Raf proto‐oncogene, serine/threonine kinase (BRAF) c.1798_1799GT>AA p.V600K mutations at various allele frequencies (AFs).
Results
EGFR and KRAS mutation detection showed excellent interlaboratory reproducibility, especially on slides A and B (10% and 5% AFs). On slide C (1% AF), either the EGFR mutation or the KRAS mutation was undetected by 10 of the 17 laboratories (58.82%). A reassessment of the raw data in a second‐look analysis highlighted the mutations (n = 10) that had been missed in the first‐look analysis. BRAF c.1798_1799GT>AA p.V600K showed a lower concordance rate for mutation detection and AF quantification.
Conclusions
The data show that the detection of low‐abundance mutations is still clinically challenging and may require a visual inspection of sequencing reads to detect. Genomic reference standards in a cytocentrifuge/cytospin format are a valid tool for regular quality assessment of laboratories performing molecular studies on cytology with low‐AF mutations.
Cytological genomic reference standards are a valid educational and validation tool and show highly reproducible results. The detection of low‐abundance mutations is challenging and may require a visual inspection of sequencing reads.
: ischemic stroke (IS) is among the most frequent causes of death worldwide; thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk ...subjects.
:we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants.
: we did not observe significant differences between TIA and the GP for any of the variants, while the allele frequencies of methylene-tetrahydrofolate reductase (MTHFR) C677T, beta-fibrinogen -455G>A and factor (FXIII) V34L were significantly higher in patients with IS than in the subjects from the GP. No significant interaction was observed with sex.
: the present data argue that some gene variants have a role in IS and this appears to be an interesting possibility to be pursued in large population studies to help design specific strategies for IS prevention.
Indication for prostate biopsy is presently mainly based on prostate-specific antigen (PSA) serum levels and digital-rectal examination (DRE). In view of the unsatisfactory accuracy of these two ...diagnostic exams, research has focused on novel markers to improve pre-biopsy prostate cancer detection, such as phi and PCA3.
The purpose of this prospective study was to assess the diagnostic accuracy of phi and PCA3 for prostate cancer using biopsy as gold standard.
Phi index (Beckman coulter immunoassay), PCA3 score (Progensa PCA3 assay) and other established biomarkers (tPSA, fPSA and %fPSA) were assessed before a 18-core prostate biopsy in a group of 251 subjects at their first biopsy.
Values of %p2PSA and phi were significantly higher in patients with PCa compared with PCa-negative group (p<0.001) and also compared with high grade prostatic intraepithelial neoplasia (HGPIN) (p<0.001). PCA3 score values were significantly higher in PCa compared with PCa-negative subjects (p<0.001) and in HGPIN vs PCa-negative patients (p<0.001). ROC curve analysis showed that %p2PSA, phi and PCA3 are predictive of malignancy.
In conclusion, %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men undergoing their first prostate biopsy. PCA3 score is more useful in discriminating between HGPIN and non-cancer.
► Novel markers have been proposed to improve pre-biopsy detection of prostate cancer. ► We assessed the diagnostic accuracy of phi and PCA3 for prostate cancer. ► %p2PSA, phi and PCA3 may predict a diagnosis of PCa in men at their first biopsy. ► PCA3 score is more useful in discriminating between HGPIN and non-cancer.
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