Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients.

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.

Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature.

With the development of next generation sequencing, beyond identifying the cause of manifestations that justified prescription of the test, other information with potential interest for patients and their families, defined as secondary findings (SF), can be provided once patients have given informed consent, in particular when therapeutic and preventive options are available. The disclosure of such findings has caused much debate. The aim of this work was to summarize all opinion-based studies focusing on SF, so as to shed light on the concerns that this question generate. A review of the literature was performed, focusing on all PubMed articles reporting qualitative, quantitative or mixed studies that interviewed healthcare providers, participants, or society regarding this subject. The methodology was carefully analysed, in particular whether or not studies made the distinction between actionable and non-actionable SF, in a clinical or research context. From 2010 to 2016, 39 articles were compiled. A total of 14,868 people were interviewed (1259 participants, 6104 healthcare providers, 7505 representatives of society). When actionable and non-actionable SF were distinguished (20 articles), 92% of respondents were keen to have results regarding actionable SF (participants: 88%, healthcare providers: 86%, society: 97%), against 70% (participants: 83%, healthcare providers: 62%, society: 73%) for non-actionable SF. These percentages were slightly lower in the specific situation of children probands. For respondents, the notion of the «patient's choice¼ is crucial. For healthcare providers, the importance of defining policies for SF among diagnostic lab, learning societies and/or countries is outlined, in particular regarding the content and extension of the list of actionable genes to propose, the modalities of information, and the access to information about adult-onset diseases in minors. However, the existing literature should be taken with caution, since most articles lack a clear definition of SF and actionability, and referred to hypothetical scenarios with limited information to respondents. Studies conducted by multidisciplinary teams involving patients with access to results are sadly lacking, in particular in the medium term after the results have been given. Such studies would feed the debate and make it possible to measure the impact of such findings and their benefit-risk ratio.

Comparison between three mathematical models of KT/V.

In thirty anuric patients undergoing chronic hemodialysis the KT/V values obtained with the formula: (formula; see text) were compared with the values obtained with the following two formulae: (formula; see text) The results given by formulae B and C differed from those with formula A respectively by 12.81 +/- 11.98% and 10.38 +/- 3.64%. For routine determination of KT/V we suggest the use of formulae A and C as a means of establishing rapidly, in one step, whether the hemodialytic treatment examined is adequate.

[A case of Plasmodium vivax malaria]. / Considerazioni su di un caso di malaria da Plasmodium vivax.

A case of malaria caused by Plasmodium vivax is reported in order to underline the importance of correct pharmacological prophylaxis and meticulous anamnestic and epidemiological investigations.

Mortality from respiratory and digestive cancers among asbestos cement workers in Italy.

A cohort study is presented on the mortality of blue-collar workers in an asbestos-cement production plant that has been operating since 1907. Use of both crocidolite and chrysotile is reported. The cohort includes 2608 men and 759 women who were employed in the plant on Jan. 1, 1950 and those who started to work between 1950 and 1980. Follow-up was terminated on April 15, 1986 with 97.9% traced. Expected deaths were estimated from the age- and sex-specific regional mortality rates for the years 1969 to 1981. The data have been analyzed for the period 1964 to 1986 based on person-years at risk: 43,000 for men and 14,494 for women. A statistically significant increase was found in both sexes for mortality from all causes. From 1964 to 1986, 728 men died from all causes (608 expected), 275 with cancer at any site (158 expected) 110 with lung cancer (41 expected), 28 with pleural tumors (1 expected) and 85 with asbestosis (less than 1 expected). Corresponding figures for women were--all causes: 136 deaths versus 102 expected; all cancers: 79 verses 32 expected; lung cancer: 7 versus 2 expected; pleural tumor: 15 versus 0 expected and asbestosis: 4 versus 0 expected. Deaths from digestive tract cancer were in excess only among women (18 observed versus 10 expected, p less than 0.01). No excess was found for deaths from laryngeal cancer. Standardized mortality rates (SMR) for lung cancer among males showed a clear increase in direct relationship with length of follow-up. SMR according to length of employment were 234 for length 10 to 19 years, 363 for 20 to 29 years, and 256 for 30 years or longer (p less than 0.05 and lower).

Dynamics of bone aluminum over one year of functioning renal graft.

The concentration of aluminum (Al) in serum, urine, and bone, as well as bone histomorphometry parameters were studied before and 1 year after kidney transplantation (Tx) in 20 dialyzed patients. One year after Tx, serum Al fell significantly from 50.3 +/- 8.8 to 23.9 +/- 2.7 micrograms/l, (53% fall). Bone Al content also decreased significantly from 62.9 +/- 9.0 to 36.5 +/- 7.0 micrograms/kg bone weight, but urine Al excretion was still above normal. The repeat bone histomorphometric examination showed a good recovery of bone resorption which correlated well with serum parathyroid hormone levels, but poorer recovery of indices of bone formation and of the extent of Al deposits in the bone as shown by aluminum staining.