Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population

Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD.Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions).Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132).Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.

Factors affecting the recurrence in patients with venous thromboembolism: A retrospective cohort study

Background: The aim of the study was to evaluate the frequency of recurrence and the risk factors for recurrence in patients who were diagnosed with venous thromboembolism. Methods: Between January 2005 and January 2015, a total of 412 venous thromboembolism patients (164 males, 248 females; mean age: 53.5±16.6 years; range: 19 to 95 years) were retrospectively analyzed. The demographics, underlying risk factors, comorbidities, imaging findings, and treatment data of the patients were recorded. Results: At least one transient/permanent risk factor was found in 341 (82.7%) of the index events, and the other 71 (17.2%) were idiopathic. Recurrence developed in 76 (18.4%) of the patients. The duration of the treatment in the first event was significantly longer in recurrent cases (p=0.007). The recurrence rate in patients diagnosed with only deep vein thrombosis or patients diagnosed with pulmonary thromboembolism + deep vein thrombosis was significantly higher than the patients diagnosed with only pulmonary thromboembolism (24% vs. 14.2%, respectively; p=0.007). The rate of idiopathic venous thromboembolism was higher in recurrent cases than in non-recurrent cases (26.3% vs. 15.2%, respectively; p=0.028). At the end of the first year, the mean D-dimer levels were higher in recurrent cases (p=0.034). Hereditary risk factors were also higher in recurrent cases (39.5% vs. 19.3%, respectively; p=0.031). There was no significant correlation between recurrence and mortality. Conclusion: The presence of deep vein thrombosis, idiopathic events, high D-dimer levels at the end of the first year and hereditary risk factors seem to be associated with recurrence.

Oncologists’ (ONCs) perceptions of tumor genomic profiling (TGP) and barriers to communicating secondary hereditary risk to African American (AA) patients.

10592 Background: TGP identifies targets for precision cancer treatments. TGP may also identify secondary hereditary cancer risks, necessitating complex decision support during informed consent. ONCs are poorly trained in the communication of genetic information, particularly for patients with low health literacy, poor knowledge of genetics, and high medical mistrust. AA patients are especially vulnerable in this setting. Methods: We conducted semi-structured interviews with 10 ONCs to assess perceived barriers related to communication of secondary hereditary risks of TGP, probing barriers unique to AA patients. Informed by results, an Internet-based survey was developed/distributed to a convenience sample of 50 ONCs nationwide to assess TGP knowledge, genomics confidence, and perceptions related to communication of secondary hereditary risk. Results: Six themes emerged from interviews: risk/benefits of TGP, knowledge of genetics, discussing hereditary risk, value/harm of TGP, unique risks in AA, and training needs. Most ONCs felt uncomfortable discussing hereditary risks of TGP w/patients. Seven out of 10 identified socio-economic status, medical mistrust, discrimination, genetic counseling non-compliance, low health literacy and family relationships as factors important to consider with AA patients. Online survey participants were 52% White, 66% male, with median age of 42 years. Education in the interpretation/communication of TGP was largely informal (56% reported only informal training) and 46% reported perceived gaps in their education. Genomic confidence was associated w/higher use of TGP (p = 0.05), but was not associated w/knowledge or years in practice; however, low knowledge was associated w/more perceived barriers to TGP and w/negative attitudes toward the value of TGP and the challenge of communication of possible hereditary risks (p = 0.05). Early-career ONCs were more likely to endorse perceived barriers to communication of genetic risk information from TGP to AA patients. Overall 86% ONCs felt additional online training in communication of secondary hereditary risks of TGP would be useful. Conclusions: ONCs recognize unique needs and barriers for AAs related to communication of secondary hereditary genetic information from TGP. Many feel uncertain about how/whether to address barriers and recognize the need to improve their skillset to do so. Training is critical to ensure informed decision making in vulnerable populations.

Drug‑induced hemolytic anemia

One of the reasons for the development of hemolytic anemia (HA) can be drugs, including some antibacterial, non-steroidal anti-inflammatory, antitumor and antihypertensive drugs. It was found that the most common drug-induced hemolytic anemia (DIHA) develops against the background of taking antibacterial drugs. The true prevalence of DIHA is not known and is approximately one case per 1.0–1.2 million patients. The mechanisms of the occurrence of DIHA are divided into immune and metabolic (non-immune). The first mechanism is associated with the formation of haptens, the second option – with the formation of immune complexes, the third option is mediated by the formation of true autoantibodies to red blood cells, the fourth option of the immune mechanism of the occurrence of DIHA is non-immunological protein absorption on the membranes of red blood cells. The risk factors for the development of DIHA are not fully established. The most common hereditary risk factor for DIHA is glucose-6-phosphate dehydrogenase deficiency. The main method of diagnosing DIHA is a direct antiglobulin test (direct Coombs’ test). The temporal relationship between the use of the inducer drug and the development of HA symptoms is important. The treatment strategy of DIHA is determined by the severity of the disease. In all cases, treatment should be initiated with the identification and withdrawal of the drug that initiated the occurrence of HA. With the development of severe HA, hemodialysis may be required. Prevention of DIHA involves avoiding the use of drugs associated with a high risk of its development.

How I Treat Metastatic Hormone-Sensitive Prostate Cancer?

Androgen deprivation therapy (ADT) combined with docetaxel or antiandrogens (abiraterone, enzalutamide, or apalutamide) improved the outcomes in men with metastatic hormone-sensitive prostate cancer (mHSPC). When multiple options are available, the dilemma remains how to choose among these options. Similarly, issues of bone health, long-term side effects of therapies, and hereditary risk need to be discussed for comprehensive care. In the present article, we reviewed the relevant evidence for the treatment of mHSPC. ADT alone is not the current standard of care for most patients. In these times of plenty and price crisis, it is imperative to find the best option for treating these patients.

Public support for healthcare-mediated disclosure of hereditary cancer risk information: Results from a population-based survey in Sweden

Background Targeted surveillance of at-risk individuals in families with increased risk of hereditary cancer is an effective prevention strategy if relatives are identified, informed and enrolled in screening programs. Despite the potential benefits, many eligible at-risk relatives remain uninformed of their cancer risk. This study describes the general public’s opinion on disclosure of hereditary colorectal cancer (CRC) risk information, as well as preferences on the source and the mode of information. Methods A random sample of the general public was assessed through a Swedish citizen web-panel. Respondents were presented with scenarios of being an at-risk relative in a family that had an estimated increased hereditary risk of CRC; either 10% (moderate) or 70% (high) lifetime risk. A colonoscopy was presented as a preventive measure. Results were analysed to identify significant differences between groups using the Pearson’s chi-square (χ2) test. Results Of 1800 invited participants, 977 completed the survey (54%). In the moderate and high-risk scenarios, 89.2 and 90.6% respectively, would like to receive information about a potential hereditary risk of CRC (χ2, p = .755). The desire to be informed was higher among women (91.5%) than men (87.0%, χ2, p = .044). No significant differences were found when comparing different age groups, educational levels, place of residence and having children or not. The preferred source of risk information was a healthcare professional in both moderate and high-risk scenarios (80.1 and 75.5%). However, 18.1 and 20.1% respectively would prefer to be informed by a family member. Assuming that healthcare professionals disclosed the information, the favoured mode of information was letter and phone (38.4 and 33.2%). Conclusions In this study a majority of respondents wanted to be informed about a potential hereditary risk of CRC and preferred healthcare professionals to communicate this information. The two presented levels of CRC lifetime risk did not significantly affect the interest in being informed. Our data offer insights into the needs and preferences of the Swedish population, providing a rationale for developing complementary healthcare-assisted communication pathways to realise the full potential of targeted prevention of hereditary CRC.

Determination Of Prevalence Of Thrombosis And Predisposing Factors In Patients Followed Up With A Central Venous Catheter In Pediatric Intensive Care Unit

Objective: Objective of this study is determination of prevalence of thrombosis and predisposing factors in critically ill patients with central venous catheter (CVC) placement in Pediatric Intensive Care Unit. Material and method: Of 76 cases with CVC placement aged between 1 month to 18 years; venous structures at the extremity where the CVC was placed and their symmetrical equivalents were prospectively examined by using Doppler ultrasonography (DUSG) at days 0, 3, 7, 14 and 28. Results: Median age of the cases included in the study was 19 (2-201) months. Of the cases; 49 (64.5%) was male and 27 (35.5%) was female, with a male/female ratio of 1.81:1. 55 (72.3%) of the cases had an underlying disease. Most common accompanying diseases were neurological and neuromuscular diseases (35.5%), followed by inborn errors of metabolism (14.4%). More than one catheters were placed for 26 (34.2%) of the cases. A total of 107 catheters were placed. Median catheter dwelling time was 12 (2-46) days. Most commonly placed catheters were of Seldinger type (90%). As an early complication, arterial embolism was observed in one (0.9%) case and pneumothorax in one (0.9%) case. As a late complication during the period with a catheter placed, six (7.8%) cases developed catheter infections and 11 (14.4%) cases developed catheter-induced thrombosis. Four (36.3%) of the cases which developed thrombosis were symptomatic. In six (54.4%) of the cases, thrombosis was determined to occur within first three days. When the cases were evaluated in regard to risk factors for thrombosis other than CVC placement, a significant association of CPR application (p= 0.004) and multiple catheter placement (p< 0.001) with thrombosis was determined in uni- and multivariate analyses. 72.7% of the cases with thrombosis were examined for hereditary risk factors and no significant evidence was determined. Conclusion: Our study reveals that multiple catheter placement and CPR application significantly increases risk of thrombosis. Even in absence of any clinical finding, routine evaluation with DSUG within first seven days following catheter placement is useful. Our results suggest that screening for hereditary risk factors which may cause predisposition to thrombosis in all patients with thrombosis in presence of acquired risk factors is unnecessary.