Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and ...poor prognosis. This review will present the substantial advances achieved in the understanding of IPF pathogenesis and in the therapeutic options that can be offered to patients, and will address the issues regarding diagnosis and management that are still open.
Over the last two decades much has been clarified about the pathogenic pathways underlying the development and progression of the lung scarring in IPF. Sustained alveolar epithelial micro-injury and activation has been recognised as the trigger of several biological events of disordered repair occurring in genetically susceptible ageing individuals. Despite multidisciplinary team discussion has demonstrated to increase diagnostic accuracy, patients can still remain unclassified when the current diagnostic criteria are strictly applied, requiring the identification of a Usual Interstitial Pattern either on high-resolution computed tomography scan or lung biopsy. Outstanding achievements have been made in the management of these patients, as nintedanib and pirfenidone consistently proved to reduce the rate of progression of the fibrotic process. However, many uncertainties still lie in the correct use of these drugs, ranging from the initial choice of the drug, the appropriate timing for treatment and the benefit-risk ratio of a combined treatment regimen. Several novel compounds are being developed in the perspective of a more targeted therapeutic approach; in the meantime, the supportive care of these patients and their carers should be appropriately prioritized, and greater efforts should be made toward the prompt identification and management of relevant comorbidities.
Building on the advances in the understanding of IPF pathobiology, the further investigation of the role of gene variants, epigenetic alterations and other molecular biomarkers reflecting disease activity and behaviour will hopefully enable earlier and more confident diagnosis, improve disease phenotyping and support the development of novel agents for personalized treatment of IPF.
This is a registered study protocol on a randomized controlled trial (RCT) testing an intervention aimed to improve men's adherence to evidence-based guidelines on BRCA1/2 germline genetic testing. ...BRCA1- and BRCA2-associated Hereditary Breast and Ovarian Cancer Syndrome (HBOC) increases the relative and absolute risk of developing breast and ovarian cancer and, to a lesser extent, prostate and pancreatic cancer. Men face BRCA-related cancer risks as women do, although with a different magnitude, and they may also transmit the mutations to their children. Notwithstanding, men are under-tested compared to women and the communication is not tailored on their needs. The present RCT applies principles of the Health Action Process Approach (HAPA) in testing the psychological determinants of the men's adherence to evidence based guidelines on BRCA1/2 germline genetic and testing the efficacy of two messages.
A total of 264 participants will be involved, among the men's relatives of women with verified germline mutations. The study entails a pre- post- evaluation with randomization of the participants in two conditions corresponding to the two messages.
The expected results provide answers related to the impact of action self-efficacy, outcome expectancy (personal or familiar), risk perception, health risk aversion, intolerance of uncertainty, perceived barriers, and coping self-efficacy on informed decision-making. Data gathered from this study may inform health care providers, policy makers, and public health managers about the communication strategy for men and about the psychological variables influencing decision-making.
Name of the Registry: Clinical Trials. Trial registration number: NCT04683068. Date of registration: 16/12/2020. URL of trial registry record: https://www.clinicaltrials.gov/.
This paper analyses elemental (EC), organic (OC) and total carbon (TC) concentration in PM2.5 and PM10 samples collected over the last few years within several national and European projects at 37 ...remote, rural, urban, and traffic sites across the Italian peninsula.
The purpose of the study is to obtain a picture of the spatial and seasonal variability of these aerosol species in Italy, and an insight into sources, processes and effects of meteorological conditions.
OC and EC showed winter maxima and summer minima at urban and rural locations and an opposite behaviour at remote high altitude sites, where they increase during the warm period due to the rising of the Planetary Boundary Layer (PBL). The seasonal averages of OC are higher during winter compared to summer at the rural sites in the Po Valley (from 1.4 to 3.5 times), opposite to what usually occurs at rural locations, where OC increases during the warm period. This denotes the marked influence of urban areas on the surrounding rural environment in this densely populated region.
The different types of sites exhibit marked differences in the average concentrations of carbonaceous aerosol and OC/EC ratio. This ratio is less sensitive to atmospheric processing than OC and EC concentrations, and hence more representative of different source types. Remote locations are characterised by the lowest levels of OC and especially EC, with OC/EC ratios ranging from 13 to 20, while the maximum OC and EC concentrations are observed at road-traffic influenced urban sites, where the OC/EC ratio ranges between 1 and 3. The highest urban impacts of OC and EC relative to remote and rural background sites occur in the Po Valley, especially in the city of Milan, which has the highest concentrations of PM and TC and low values of the OC/EC ratio.
•We compared OC and EC data from different sites across the Italian Peninsula.•OC and EC concentration maxima occur during winter and minima during summer at all except remote sites.•Higher OC levels characterize the Po Valley compared to the rest of Italy both during summer and winter.•Biomass burning for residential heating strongly affects winter OC concentrations in the Po Valley.•Carbonaceous matter contribution to PM2.5 ranges between 37% at rural and 47% at traffic sites, on an annual basis.
Fibrotic hypersensitivity pneumonitis is a complex interstitial lung disease that is not entirely understood. In its chronic and fibrotic form, hypersensitivity pneumonitis is one of the main ...mimickers of idiopathic pulmonary fibrosis (IPF). Distinguishing between these two conditions is challenging but is of particular clinical relevance. Two approved therapies are available for IPF, and a considerable number of clinical trials are now exploring newer pharmacological options. This impressive research effort is a consequence of new pathogenetic understanding, updated diagnostic criteria and a long history of pharmacological trials. Conversely, current knowledge gaps on pathogenesis of chronic hypersensitivity pneumonitis, coupled with lack of validated diagnostic criteria, make the management of this disease an unsolved clinical challenge. This also reflects the paucity of therapeutic clinical trials in this field. In this review, we describe the current evidence and the possible future options to approach this complex disease.
germline mutations predispose carriers to an increased risk of breast, ovarian, prostate, pancreatic, and skin cancer. Men and women are equally likely to pass on or inherit the pathogenic variant. ...However, there is evidence that male relatives are less involved in cascade screening than female ones. At the same time, little attention has been given to the research on psychological determinants of men's adherence to cascade screening in
-positive families. Applying some principles of the Health Action Process Approach model, the present research tested a model of relationships on the adherence to
cascade testing guidelines. The sample comprised 115 men's first-degree relatives of women with verified germline mutations (Mage = 41.93; SD = 17.27). A pre-post test design was applied. Significant associations emerged between the intention to uptake
genetic testing and age, parental status, breast cancer risk perception, self-referred outcome expectancies, perceived benefit, coping self-efficacy, and planning. Higher perceived benefit predicted increases in intention, and higher intention and coping self-efficacy predicted increases in planning. Intention was a positive total mediator of the relationship between benefit and planning. On a theoretical level, our findings partially supported the Health Action Process Approach as a valuable model based on which interventions could be developed in the context of cascade screening for
genetic testing. Those results supported the importance of integrated genetic counselling sessions with a strict collaboration between geneticists and psychologists together with interventions planned to increase men's self-monitoring ability to support their self-efficacy.
E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited ...predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as-(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC).
There appears to be a sex-specific association between obesity and colorectal neoplasia in patients with Lynch Syndrome (LS). We meta-analyzed studies reporting on obesity and colorectal cancer (CRC) ...risk in LS patients to test whether obese subjects were at increased risk of cancer compared to those of normal weight. We explored also a possible sex-specific relationship between adiposity and CRC risk among patients with LS. The summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We investigated the causes of between-study heterogeneity and assessed the presence of publication bias. We were able to retrieve suitable data from four independent studies. We found a twofold risk of CRC in obese men compared to nonobese men (SRR = 2.09; 95%CI: 1.23–3.55, I2 = 33%), and no indication of publication bias (p = 0.13). No significantly increased risk due to obesity was found for women. A 49% increased CRC risk for obesity was found for subjects with an MLH1 mutation (SRR = 1.49; 95%CI: 1.11–1.99, I2 = 0%). These results confirm the different effects of sex on obesity and CRC risk and also support the public measures to reduce overweight in people with LS, particularly for men.
The PARP inhibitor olaparib has been approved in the maintenance setting of platinum-sensitive epithelial ovarian cancer patients with germline or somatic
mutation. Therefore, the availability of a ...tumor BRCA test has become a clinical need. We report the results of the clinical implementation of a tumor BRCA test within the frame of an institutional workflow for the management of patients with nonmucinous and nonborderline epithelial ovarian cancer. In total, 223 patients with epithelial ovarian cancer were prospectively analyzed.
status was evaluated on formalin-fixed, paraffin-embedded tumor specimens using next-generation sequencing technology. The tumor BRCA test had a success rate of 99.1% (221 of 223 successfully analyzed cases) and a median turnaround time of 17 calendar days. Among the 221 cases,
or
pathogenic/likely pathogenic mutations were found in 62 (28.1%) cases and variants of uncertain significance in 25 (11.3%) cases. The concordance rate between tumor BRCA test results and germline
status was 87%, with five cases harboring pathogenic/likely pathogenic somatic-only mutations. The next-generation, sequencing-based tumor BRCA test showed a high success rate and a turnaround time compatible with clinical purposes. The tumor BRCA test could be implemented in a molecular diagnostic setting and it may guide the clinical management of patients with epithelial ovarian cancer.
Gastric cancer (GC) has long been a 'Cinderella' among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of ...multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in
(n = 3),
(n = 2),
(n = 1), and
(n = 1), while one patient (2%) carried two variants of unknown significance (VUSs).
and
emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (
,
,
) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (
-value: 0.045) or Lynch-related tumors (
-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results.
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