Several recent papers have generated new hope about the use of white adipose tissue (WAT)-derived progenitor cells for soft tissue reconstruction in a variety of diseases including breast cancer ...(BC), a procedure that is increasingly used worldwide. We revised the available literature about WAT cells and BC. In the BC field, we believe that the hype for the exciting results in terms of WAT progenitor cell engraftment and tissue augmentation should be tempered when considering the recent and abundant preclinical studies, indicating that WAT progenitors may promote BC growth and metastasis. White adipose tissue progenitors can contribute to tumour vessels, pericytes and adipocytes, and were found to stimulate local and metastatic BC progression in several murine models. Moreover, there are clinical retrospective data showing a significant increase in the local recurrence frequency in patients with intraepithelial neoplasia who received a lipofilling procedure for breast reconstruction compared with controls. Retrospective and prospective clinical trials are warranted to investigate in depth the safety of this procedure in BC. Preclinical models should be used to find mechanisms able to inhibit the tumour-promoting activity of WAT progenitors while sparing their tissue reconstruction potential.
Single nucleotide polymorphism (SNP) genotyping tools, which can analyse thousands of SNPs covering the whole genome, have opened new opportunities to estimate the inbreeding level of animals ...directly using genome information. One of the most commonly used genomic inbreeding measures considers the proportion of the autosomal genome covered by runs of homozygosity (ROH), which are defined as continuous and uninterrupted chromosome portions showing homozygosity at all loci. In this study, we analysed the distribution of ROH in three commercial pig breeds (Italian Large White, n = 1968; Italian Duroc, n = 573; and Italian Landrace, n = 46) and four autochthonous breeds (Apulo-Calabrese, n = 90; Casertana, n = 90; Cinta Senese, n = 38; and Nero Siciliano, n = 48) raised in Italy, using SNP data generated from Illumina PorcineSNP60 BeadChip. We calculated ROH-based inbreeding coefficients (FROH) using ROH of different minimum length (1, 2, 4, 8, 16 Mbp) and compared them with several other genomic inbreeding coefficients (including the difference between observed and expected number of homozygous genotypes (FHOM)) and correlated all these genomic-based measures with the pedigree inbreeding coefficient (FPED) calculated for the pigs of some of these breeds. Autochthonous breeds had larger mean size of ROH than all three commercial breeds. FHOM was highly correlated (0.671 to 0.985) with FROH measures in all breeds. Apulo-Calabrese and Casertana had the highest FROH values considering all ROH minimum lengths (ranging from 0.273 to 0.189 and from 0.226 to 0.152, moving from ROH of minimum size of 1 Mbp (FROH1) to 16 Mbp (FROH16)), whereas the lowest FROH values were for Nero Siciliano (from 0.072 to 0.051) and Italian Large White (from 0.117 to 0.042). FROH decreased as the minimum length of ROH increased for all breeds. Italian Duroc had the highest correlations between all FROH measures and FPED (from 0.514 to 0.523) and between FHOM and FPED (0.485). Among all analysed breeds, Cinta Senese had the lowest correlation between FROH and FPED. This might be due to the imperfect measure of FPED, which, mainly in local breeds raised in extensive production systems, cannot consider a higher level of pedigree errors and a potential higher relatedness of the founder population. It appeared that ROH better captured inbreeding information in the analysed breeds and could complement pedigree-based inbreeding coefficients for the management of these genetic resources.
Single nucleotide polymorphisms (SNPs) able to describe population differences can be used for important applications in livestock, including breed assignment of individual animals, authentication of ...mono-breed products and parentage verification among several other applications. To identify the most discriminating SNPs among thousands of markers in the available commercial SNP chip tools, several methods have been used. Random forest (RF) is a machine learning technique that has been proposed for this purpose. In this study, we used RF to analyse PorcineSNP60 BeadChip array genotyping data obtained from a total of 2737 pigs of 7 Italian pig breeds (3 cosmopolitan-derived breeds: Italian Large White, Italian Duroc and Italian Landrace, and 4 autochthonous breeds: Apulo-Calabrese, Casertana, Cinta Senese and Nero Siciliano) to identify breed informative and reduced SNP panels using the mean decrease in the Gini Index and the Mean Decrease in Accuracy parameters with stability evaluation. Other reduced informative SNP panels were obtained using Delta, Fixation index and principal component analysis statistics, and their performances were compared with those obtained using the RF-defined panels using the RF classification method and its derived Out Of Bag rates and correct prediction proportions. Therefore, the performances of a total of six reduced panels were evaluated. The correct assignment of the animals to its breed was close to 100% for all tested approaches. Porcine chromosome 8 harboured the largest number of selected SNPs across all panels. Many SNPs were included in genomic regions in which previous studies identified signatures of selection or genes (e.g. ESR1, KITL and LCORL) that could contribute to explain, at least in part, phenotypically or economically relevant traits that might differentiate cosmopolitan and autochthonous pig breeds. Random forest used as preselection statistics highlighted informative SNPs that were not the same as those identified by other methods. This might be due to specific features of this machine learning methodology. It will be interesting to explore if the adaptation of RF methods for the identification of selection signature regions could be able to describe population-specific features that are not captured by other approaches.
Lipofilling has been indicated for postmastectomy and postlumpectomy breast reconstruction. The clinical literatures underline its technical efficacy but experimental studies raise important ...questions about the potential detrimental effect of adipocytes on the stimulation of cancer growth and reappearance.
We collected 321 consecutive patients operated for a primary breast cancer between 1997 and 2008 who subsequently underwent lipofilling for reconstructive purpose. For each patient, we selected two matched patients with similar characteristics who did not undergo a lipofilling.
Eighty-nine percent of the tumors were invasive. Median follow-up was 56 months from the primary surgery and 26 months from the lipofilling. Eight and 19 patients had a local event in the lipofilling and control group, respectively, leading to comparable cumulative incidence curves P = 0.792; Hazard RatioLipovs No lipo = 1.11 (95% confidence interval 0.47–2.64). These results were confirmed when patients undergoing quadrantectomy and mastectomy were analyzed separately and when the analysis was limited to invasive tumors. Based on 37 cases, the lipofilling group resulted at higher risk of local events when the analysis was limited to intraepithelial neoplasia.
Lipofilling seems to be a safe procedure in breast cancer patients. Longer follow-up and further experiences from oncological series are urgently required to confirm these findings.
Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)–resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory ...Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy.
The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data.
From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval CI, 7.7–12.6) and 23.8 months (95% CI, 19.7–25.0) respectively.
Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.
•Patients with metastatic differentiated thyroid cancer (DTC) have poor survival rate.•Lenvatinib improved clinical outcomes in patient with metastatic radioactive iodine-refractory DTC.•Lenvatinib is active and safe, even in a real-life patient population.•Older patients show survival benefit from lenvatinib, without safety concern.
Mitigating the COVID-19 related disruptions in mental health care services is crucial in a time of increased mental health disorders. Numerous reviews have been conducted on the process of ...implementing technology-based mental health care during the pandemic. The research question of this umbrella review was to examine what the impact of COVID-19 was on access and delivery of mental health services and how mental health services have changed during the pandemic. A systematic search for systematic reviews and meta-analyses was conducted up to August 12, 2022, and 38 systematic reviews were identified. Main disruptions during COVID-19 were reduced access to outpatient mental health care and reduced admissions and earlier discharge from inpatient care. In response, synchronous telemental health tools such as videoconferencing were used to provide remote care similar to pre-COVID care, and to a lesser extent asynchronous virtual mental health tools such as apps. Implementation of synchronous tools were facilitated by time-efficiency and flexibility during the pandemic but there was a lack of accessibility for specific vulnerable populations. Main barriers among practitioners and patients to use digital mental health tools were poor technological literacy, particularly when preexisting inequalities existed, and beliefs about reduced therapeutic alliance particularly in case of severe mental disorders. Absence of organizational support for technological implementation of digital mental health interventions due to inadequate IT infrastructure, lack of funding, as well as lack of privacy and safety, challenged implementation during COVID-19. Reviews were of low to moderate quality, covered heterogeneously designed primary studies and lacked findings of implementation in low- and middle-income countries. These gaps in the evidence were particularly prevalent in studies conducted early in the pandemic. This umbrella review shows that during the COVID-19 pandemic, practitioners and mental health care institutions mainly used synchronous telemental health tools, and to a lesser degree asynchronous tools to enable continued access to mental health care for patients. Numerous barriers to these tools were identified, and call for further improvements. In addition, more high quality research into comparative effectiveness and working mechanisms may improve scalability of mental health care in general and in future infectious disease outbreaks.
•Face-to-face outpatient consultations for mental health were severely disrupted.•Services mainly adapted by implementing synchronous telemental health tools.•Poor technological literacy and failed technological integration limited service adaptations.•Flexibility in scheduling remote mental health services facilitated continuity of care.•More virtual mental health programs and training of staff may facilitate sustainable adoption.
Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer ...development.
Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline.
Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy.
Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.
Data are limited regarding bone metastases from colorectal cancer (CRC). The objective of this study was to survey the natural history of bone metastasis in CRC.
This retrospective, multicenter, ...observational study of 264 patients with CRC involving bone examined cancer treatments, bone metastases characteristics, skeletal-related event (SRE) type and frequency, zoledronic acid therapy, and disease outcomes.
Most patients with bone metastases had pathologic T3/4 disease at CRC diagnosis. The spine was the most common site involved (65%), followed by hip/pelvis (34%), long bones (26%), and other sites (17%). Median time from CRC diagnosis to bone metastases was 11.00 months; median time to first SRE thereafter was 2.00 months. Radiation and pathologic fractures affected 45% and 10% of patients, respectively; 32% of patients had no reported SREs. Patients survived for a median of 7.00 months after bone metastases diagnosis; SREs did not significantly affect survival. Subgroup analyses revealed that zoledronic acid significantly prolonged median time to first SRE (2.00 months versus 1.00 month, respectively, P = 0.009) and produced a trend toward improved overall survival versus no zoledronic acid.
This study illustrates the burden of bone metastases from CRC and supports the use of zoledronic acid in this setting.
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