Availability Of Genetic Testing Research Articles

"Antibody of Unknown Significance" (AUS): The Issue of Interpreting Antibody Test Results.

"Antibody of Unknown Significance" (AUS): The Issue of Interpreting Antibody Test Results.

Association of NOS3 and TNF Genetic Polymorphisms With the Predisposition to Elevated Cholesterol, Retrospective Study

Background: Endothelial nitric oxide synthetase (eNOS) encoded by NOS3 gene has an important role in modulating vascular endothelial function. TNFα gene is responsible for coding TNFα protein that plays a significant role in regulating body inflammation and lipid metabolism. Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated total cholesterol (TC) level, low-density lipoprotein (LDL), triglyceride (TG). In this study, we investigated the association of NOS3 (G>T) rs1799983 and TNFα -308G>A rs1800629 genetic polymorphisms with TC level. Methods: A random sample of 250 subjects with an elevated TC level (defined by TC level ≥ 200mg/dL) compared with 500 healthy subjects. Sample obtained from Palestinian adults who consented to genetic and biochemical testing. Subjects genotyped for NOS3 SNP (G > T) rs1799983 and TNFα -308G>A rs1800629 using ARMS PCR. TC level was obtained for all subjects. Logistic regression analysis adjusted for age and body mass index (BMI) was performed to test for association between NOS3 and TNFα genetic polymorphisms and TC level. Results: NOS3 T allele was significantly more frequent in the elevated TC group, (odds ratio = 1.8, 95% CI =1.02–3.18) with likelihood ratio statistically significant (P = 0.004). Homozygous TNFα variant was more frequent in the elevated cholesterol group without a statistically significant association (P = 0.54). Discussion: Many studies reported an association between NOS3 and TNFα genetic polymorphisms and elevated TC levels. Homozygous NOS3 variant was associated with a 1.8-fold increase in the risk of high TC after adjustment for age and BMI. TNFα polymorphism didn’t show a statisticallysignificant association with having elevated TC levels. With the increasing popularity and availability of genetic testing, NOS3 can serve as a screening tool to identify people with high risk for elevated TC. Further studies are required to understand the exact role of NOS3 genetic polymorphism in cholesterol metabolism. Conclusion: NOS3 genetic polymorphism had a statistically significant relationship with TC levels. These results support the association between NOS3 polymorphism and elevated TC.

Association of NOS3 Genetic Polymorphism With the Predisposition to Diabetes and Pre-Diabetes, Retrospective Study

Background: Endothelial nitric oxide synthetase (eNOS) encoded by NOS3 gene has an important role in modulating vascular endothelial function. Many studies reported a possible role of NOS3 in the pathogenesis of diabetes mellitus (DM). This study investigated the association of NOS3 (G>T) rs1799983 genetic polymorphism with DM, pre-diabetes (pre-DM), and insulin resistance (IR). Methods: A random sample of 220 subjects (DM & pre-DM) compared with 220 healthy subjects. Sample obtained from Palestinian adults who consented to genetic and biochemical testing. All subjects genotyped for NOS3 (G > T) rs1799983 SNP using ARMS PCR. Fasting blood sugar (FBS) and triglyceride (TGA) levels were obtained for all subjects. Triglyceride glucose index (TyG) was used as a surrogate marker for IR. Regression analysis adjusted for age and body mass index (BMI) was performed to investigate the association between DM & Pre-DM status, FBS, and TyG with NOS3 genetic polymorphism. Results: NOS3 minor allele frequency positively correlated with FBS levels after controlling for age and BMI (P-value 0.006). DM & pre-DM were more frequent in homozygous NOS3 subjects with an odds ratio of 2.04 (P = 0.05). NOS3 minor allele frequency positively correlated with TyG but not statistically significant association (P = 0.061). Discussion: Many studies reported a potential role of NOS3 genetic polymorphism in DM and IR pathogenesis. In this study, NOS3 minor allele frequency positivity correlated with FBS levels. Homozygous NOS3 was associated with a 2-fold increase in the prevalence of DM & pre-DM. NOS3 genetic polymorphism didn’t show a statistically significant correlation with TyG (P = 0.061). With the increasing availability of genetic testing, NOS3 may serve as an early screening tool to identify subjects with a high risk for elevated FBS. Further studies are required to understand the exact role of NOS3 genetic polymorphism in the pathogenesis of DM, and to evaluate the clinical efficacy and cost-effectiveness of genetic testing. Conclusion: NOS3 genetic polymorphism has a statistically significant relationship with the FBS level. Further studies are required to confirm the association between NOS3 and DM.

Universal access to genetic counseling for women with epithelial ovarian cancer in Nova Scotia: Evaluating a new collaborative care model.

Women with pathogenic variants in BRCA1/2 have a significantly increased lifetime risk of breast and ovarian cancers. The availability of genetic testing to identify BRCA1/2 carriers is imperative to disease prevention and treatment. We evaluated the effectiveness of a new collaborative care model in Nova Scotia, involving the integration of genetic counselors into tumor board rounds, reduction in time allotted for initial genetic counseling appointments from 60 to 45min, and a standardized dictation template, to increase referral rate for genetic counseling. We also assessed the study cohorts' preferences on timing for genetic testing. A retrospective chart review was performed on all women diagnosed with epithelial ovarian cancer (EOC) from 2012 to 2017 (N=386). Pertinent clinical outcomes were categorized and wait times to different nodes of the clinical pathway assessed. A questionnaire was sent to this same cohort of women to identify preference for the timing of genetic testing (n=103). The chi-square and Wilcoxon's rank-sum tests were used to compare demographic and clinical variables pre- and post-care model implementation. We identified a 48.2% (95% CI: 39.4-56.7, p<.001) increase in referral for genetic counseling following implementation of the new care model. Median time from diagnosis to referral decreased by 74.0days (p<.001) and median time from referral to first appointment by 54.0days (p<.001). 56.3% of women desired referral at the time of diagnosis. This care model for women newly diagnosed with EOC in Nova Scotia was successful in increasing referral rates for genetic counseling. Majority of women pursued genetic testing following and favored that referral for genetic counseling be made at the time of diagnosis, highlighting the importance for timely access.

Worldwide barriers to genetic testing for movement disorders.

Despite enormous advances in identifying genetic variants responsible for many neurological diseases, access to genetic testing may be limited in clinical practice. The objective of this study was to assess worldwide access to genetic tests for movement disorders and factors impacting their utilization. The Rare Movement Disorders Study Group of the International Parkinson and Movement Disorder Society designed an online survey electronically mailed to all 7815 members. Survey data completed by 1269 participants from 109 countries were analysed. Limited access to geneticists and genetic counsellors was reported in many world regions compared to Europe and North America. Availability of genetic testing was limited, with rates of access lower than 50%. Genetic testing for chorea was the most commonly available. For parkinsonism, dystonia, ataxia, hereditary spastic paraplegias and metabolic disorders, there was limited access to genetic testing in all countries compared to Europe and North America, with significant differences found for Africa, Central/South America, Asia. In many regions, genetic testing was supported by either private or public funding. Genetic testing was free of charge in Europe according to 63.5% of respondents. In North America, Africa, Central/South America, Asia and the Middle East access to free of charge genetic testing was by far significantly lower compared to Europe. This survey highlights difficulties in accessing genetic testing and individuals with expertise in genetics at the worldwide level. In addition, major disparities in genetic testing amongst world regions are highlighted, probably due to a variety of factors including financial barriers.

Public attitudes towards the genetic testing in Georgia.

The aim of this study is to assess attitudes towards genetic testing in Georgian public. We used a Likert-scale written questionnaire. The survey was completed by 480 respondents. A majority of respondents (75.3%) curious about predictive genetic testing and 40.6% of participants preferred to be tested only for disorders that are treatable or preventable. Approximately 65% of the participants would like to test their newborn children for late-onset disorders and undergo preconception carrier screening (73%). In addition, the majority (59%) of our respondents were not worried that genetic testing would further stigmatize people with disabilities. These results indicate that the respondents surveyed in our study may have placed particularly high importance on the availability of genetic testing and greatly valued access to genomic information.

Scaling Genetic Counseling in the Genomics Era

The development of massively parallel sequencing-based genomic sequencing tests has increased genetic test availability and access. The field and practice of genetic counseling have adapted in response to this paradigm-shifting technology and the subsequent transition to practicing genomic medicine. While the key elements defining genetic counseling remain relevant, genetic counseling service delivery models and practice settings have evolved. Genetic counselors are addressing the challenges of direct-to-consumer and consumer-driven genetic testing, and genetic counseling training programs are responding to the ongoing increased demand for genetic counseling services across a broadening range of contexts. The need to diversify both the patient and participant groups with access to genetic information, as well as the field of genetic counseling, is at the forefront of research and training program initiatives. Genetic counselors are key stakeholders in the genomics era, and their contributions are essential to effectively and equitably deliver precision medicine.

Clinical approach to genetic testing in amyloid cardiomyopathy: from mechanism to effective therapies.

To highlight the evolving understanding of genetic variants, utility of genetic testing, and the selection of novel therapies for cardiac amyloidosis. The last decade has seen considerable progress in cardiac amyloidosis recognition given the advancement in cardiac imaging techniques and widespread availability of genetic testing. A significant shift in the understanding of a genetic basis for amyloidosis has led to the development of disease-modifying therapeutic strategies that improve survival. The systemic amyloidoses are disorders caused by extracellular deposition of misfolded amyloid fibrils in various organs. Immunoglobulin light-chain or transthyretin amyloidosis are the most common types associated with cardiac manifestations. Genetic testing plays a central role in the identification of genotypes that are associated with different clinical phenotypes and influence prognosis. Given the emergence of effective therapies, a systematic approach to the diagnosis of cardiac amyloidosis, with the elucidation of genotype when indicated, is essential to select the appropriate treatment.

Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups

BackgroundTransthyretin amyloidosis, or ATTR, is a progressive and debilitating rare proteopathy generally manifested as either transthyretin amyloid polyneuropathy (ATTR-PN) or transthyretin amyloid cardiomyopathy (ATTR-CM). Irrespective of the clinical presentation, affected patients manage a chronic and life-threatening condition that severely impacts their quality of life. Although the primary symptoms and diagnostic criteria for ATTR are increasingly being discussed in the medical literature, due in large part by continual advances in uncovering disease pathophysiology, there exists a surprising paucity of published data on the patient journey and family experience. In order to address this disparity, two focus groups, one for ATTR-CM and one for ATTR-PN, were convened and asked to describe the diagnostic process, symptoms, and impact on their own quality of life that was experienced from these rare and typically misdiagnosed illnesses.ResultsPatients in both ATTR groups often underwent a long and difficult diagnostic odyssey characterized by seemingly nonspecific physical manifestations resulting in mismanagement and suboptimal care, inadequate interventions, and delays in establishing the correct diagnosis, which was integral to determining the specialized treatment they needed. Collectively, patients with ATTR-CM and patients with ATTR-PN reported a similar number of symptoms, but the type of symptoms varied. The ATTR-CM group identified intolerance to activity, inability to exercise, insomnia and fatigue as the most challenging symptoms. The ATTR-PN group identified fatigue, diarrhea/constipation and sensory deficits as the most difficult symptoms. In general, ATTR was reported to be highly stressful for both patients and their families. Spouses of patients with ATTR-CM were often in a caregiver role and reported experiencing considerable anxiety. Patients with ATTR-PN were stressed not only by the physical consequences of their illness, but also by its effects on their parents and other relatives, as well as concerns about children and grandchildren inheriting the disease-causing mutations associated with ATTR. Despite such challenges, family members are identified as an important resource of coping, motivation, inspiration and support.ConclusionsSeveral steps can be taken to reduce the challenges and burdens of living with ATTR, including increased education for primary care physicians and specialists who unknowingly encounter ATTR, increased access to and ready availability of mental health services and support, and increased engagement with support groups and advocacy organizations. Input from patients and their representatives should guide clinical trials, increase the availability of genetic testing, and generate natural history and qualitative studies detailing patients’ experience. Although each recommendation is impactful in itself, taken together they would jointly facilitate a shortened and ameliorated patient journey through more timely diagnosis and greater access to personalized medical care.

A clinical case of the X-linked moesin deficiency

With the increasing availability of genetic testing, the population of patients diagnosed with CVID breaks down into groups depending on monogenic defects. There is more and more evidence that adults can have combined immunodeficiencies with a late onset.&#x0D; This article discusses a clinical case of X-linked moesin-associated immunodeficiency (X-MAID). This is a recently described immunodeficiency, which mostly manifests itself at an early age with severe lymphopenia and hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a weak immune response to vaccine antigens, and increased susceptibility to bacteria and type 3 human herpesvirus.&#x0D; X-MAID, X-linked immunodeficiency with a recessive mode of inheritance, is caused by genetic defects in the MOESIN gene (membrane organizing spike elongation protein, MSN). Until recently, there were records of 10 people with this mutation, 9 of which have the phenotype of severe combined immunodeficiency (SCID). The patient described in this article has been under observation since the age of 12 and diagnosed with SCID due to an IgG decrease accompanied by infectious-purulent processes of the respiratory tract and diarrheal syndrome.&#x0D; However, the patient did not entirely fit into the typical clinical picture of CVID due to a severe therapy-torpid papillomavirus infection, the increased number of switched memory B-cells, IgG isolated decrease, persistent severe leukopenia and lymphopenia of CD4+ cells. In accordance with the clinical picture and the results of the immunological examination, combined immunodeficiency was surmised. After a full exome DNA sequencing chrX: g.64951012C T missense type mutation was found in exon 5 of the MSN gene (change in the ENSP00000353408.5:p.Arg171Trp protein). X-MAID was therefore confirmed.&#x0D; Of the 9 described patients with a similar mutation, 8 had a clinical picture of severe combined immune deficiency. This clinical case confirms the possibility of a milder clinical phenotype development with a late onset under the guise of CVID and shows the need for molecular genetic examination of the adult population of patients with impaired antibody synthesis. The verification of the diagnosis allows not only to determine the prognosis and tactics of the therapy, but also to carry out genetic family counseling and to offer a possibility of giving birth to healthy offspring.

The Problems with Patchwork: State Approaches to Regulating Insurer Use of Genetic Information

The growing availability of genetic testing in the clinical, research, and direct-to-consumer realms has caused people to fear that they will be discriminated against for their genes. In response, Congress passed the Genetic Information Nondiscrimination Act (GINA), which prohibits the use of genetic information in much of health insurance and employment. Importantly, this prohibition does not apply to life, long-term care, and disability insurance. While these lines of insurance are not federally prohibited from using an individual’s genetic information, several states do regulate use of genetic information in these insurance lines. This paper presents a comprehensive 50-state survey on regulation of how life, long-term care, and disability insurers can use genetic information. Overall, it shows that the use of genetic information in these lines of insurance is still relatively unregulated and that the divergent strategies adopted across states are both weak and problematic. Consistent and even regulation, whether from the federal government or through model legislation, is needed to adequately protect insurers and families alike.

The ethical implications of genetic testing in neurodegenerative diseases: A systematic review.

Availability of genetic testing in neurodegenerative disorders has developed rapidly. This growing ability is providing specific genetic information to individuals and, in turn, their families, raising ethical concerns. However, family members' perspective is a seldom-studied phenomenon. The aim of this systematic review was to describe the ethical aspect of genetic testing in neurodegenerative diseases from the perspective of at-risk family members. A systematic review of data was performed in accordance with the PRISMA statement. The data search was conducted using the CINAHL, PubMed and Scopus databases to identify original peer-reviewed studies published between January 2009 and April 2019. A total of 24 articles were selected. The data were analysed using inductive content analysis. On the basis of the analysis, four central ethical implications were identified: (i) decision-making in genetic testing as a dilemma: balance between autonomy and responsibility, (ii) the individual's right to make a voluntary and informed decision for genetic testing, (iii) conflicting emotions after knowing one's genetic status and (iv) privacy and confidentiality of genetic information: the fear of genetic discrimination and stigma. The findings of this review increase understanding about the central ethical implications of genetic testing in neurodegenerative diseases from the perspective of family members, and identify and underline outstanding needs for further research.

What Do Students in Pharmacy and Medicine Think About Pharmacogenomics and Personalized Medicine Education? Awareness, Attitudes, and Perceptions in Malaysian Health Sciences.

This study reports on the attitudes and perceptions toward pharmacogenomics (PGx) and personalized medicine (PM) education among pharmacy and medical students in Malaysian health sciences. Importantly, the survey was developed through a codesign approach, with field pretesting/design with users before the actual survey, and based on collaboration between institutions in Greece and Malaysia. The study addressed eight key areas of interest to education in health sciences: (1) General awareness about genetics and PGx, (2) Attitude toward genetic testing usefulness, (3) Benefits of direct-to-consumer personal genome testing as a "diagnostic" tool, (4) Concerns (risks) about genetics, (5) Effectiveness of genetic testing in PM, (6) Benefits of PGx on disease management, (7) Benefits of PGx on drug management, and (8) Attitudes toward genetic testing public endorsement. We observed that Malaysian students appear aware of the term PGx, but there are areas of critical knowledge gap such as the need for greater familiarity with the concept of PGx implementation science, and the availability of genetic testing in clinical practice. This is one of the first studies on perceptions and attitudes toward PGx testing in Southeast Asia. The present findings provide a map of the views and perspectives of medicine and pharmacy students regarding PGx and implementation of PM in Malaysia and should assist toward facilitating the integration of genomics into the medical decision-making process. To this end, it is necessary to enhance collaboration between universities, health care institutions, and governing bodies to incorporate further training and additional education topics related to PGx and genetic testing. This is the first study that assesses the level of PGx and genomics knowledge of pharmacy and medicine students in Southeast Asia, Malaysia in particular, and thus paves the way to guide future global PGx implementation science.

Knowledge, Attitudes, and Perceived Barriers toward Genetic Testing and Pharmacogenomics among Healthcare Workers in the United Arab Emirates: A Cross-Sectional Study.

In order to successfully translate the scientific models of genetic testing and pharmacogenomics into clinical practice, empowering healthcare workers with the right knowledge and functional understanding on the subject is essential. Limited research in the United Arab Emirates (UAE) have assessed healthcare worker stances towards genomics. This study aimed to assess healthcare workers’ knowledge and attitudes on genetic testing. A cross-sectional study was conducted among healthcare workers practicing in either public or private hospitals or clinics as pharmacists, nurses, physicians, managers, and allied health. Participants were recruited randomly and via snowball techniques. Surveys were collected between April and September 2019; out of 552 respondents, 63.4% were female, the mean age was 38 (±9.6) years old. The mean knowledge score was 5.2 (±2.3) out of nine, which shows a fair level of knowledge. The scores of respondents of pharmacy were 5.1 (±2.5), medicine 6.0 (±2.0), and nursing 4.8 (±2.1). All participants exhibited a fair knowledge level about genetic testing and pharmacogenomics. Of the respondents, 91.9% showed a positive attitude regarding availability of genetic testing. The top identified barrier to implementation was the cost of testing (62%), followed by lack of training or education and insurance coverage (57.8% and 57.2%, respectively). Building upon the positive attitudes and tackling the barriers and challenges will pave the road for full implementation of genetic testing and pharmacogenomics in the UAE. We recommend empowering healthcare workers by improving needed and tailored competencies related to their area of practice. We strongly urge the stakeholders to streamline and benchmark the workflow, algorithm, and guidelines to standardize the health and electronic system. Lastly, we advocate utilizing technology and electronic decision support as well as the translational report to back up healthcare workers in the UAE.

Prevalence of adverse cardiovascular events in pediatric cardiomyopathies: an analysis of 110 patients followed at a long-standing tertiary care paediatric centre

Abstract Introduction Pediatric cardiomyopathies (CMP) are disorders of the morphology and function of the heart, with a greater heterogeneity concerning etiology and clinical presentation than adult CMP. The assessment of etiology and genetic status is of paramount importance for prognosis, family screening, and therapeutic choices. Purpose To report clinical presentation, etiology, and outcome of a cohort of children diagnosed with CMP followed at tertiary care pediatric referral centre. Methods We retrospectively reviewed clinical, laboratory and imaging data of all patients referred to our cardiomyopathy centre from May 2008 to May 2019 for pediatric CMP (&amp;lt;18 years). CMP due to arrhythmic disorders, toxic agents' exposure, rheumatic conditions and maternal disease (i.e. maternal diabetes) were excluded. Primary endpoint was a composite of major adverse cardiovascular events (MACE: cardiovascular death, heart failure [HF] hospitalization, arrhythmic events, need for surgery or heart transplant referral). Results We enrolled 110 patients (65 males, age at diagnosis 67±71 months). Hypertrophic cardiomyopathy (HCM, N=48, 44%) was most frequent, followed by dilated cardiomyopathy (DCM, N=35 32%) and left ventricular non-compaction phenotype (LVNC, N=12, 11%). Mixed phenotype (N=7, 6%) and restrictive cardiomyopathy (RCM, N=3, 3%) were less common. No cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) were detected. Five genotype-positive patients presented with negative clinical phenotype. A diagnosis was confirmed in all patients; the most common was sarcomere disease (30%, N=33) followed by metabolic (28%,N=31) disease, genetic syndromes (11%, N=12), neuromuscular (7,3%, N=8) diseases, and post-myocarditis cases (4,5%,N=5). Twenty-one patients (19%) were identified as idiopathic. At referral, 4,5% of children presented with NYHA class III/IV. At 35 [14–72] months, 4 (3.7%) patients required ICD implantation, 8 (7.4%) underwent cardiac surgery, and 1 (1%) underwent heart transplant. Furthermore, 28 (26%) patients required hospitalization due to acute HF, with DCM patients being at higher risk (p&amp;lt;0.01), 7 (6.8%) experienced arrhythmic events and 4 (3.9%) had syncope. Overall, 13 (12%) died (7 with metabolic disorders, 3 with genetic syndromes, 1 with a sarcomeric mutation, 1 post myocarditis, and 1 idiopathic). Conclusions In our cohort, HCM was the most common cause of pediatric CMP followed by DCM and non-compaction. MACE were present in 41% of patients. While HCM had a less severe phenotype (characterized by a higher arrhythmic burden), DCM was characterized by a higher prevalence of HF hospitalizations. DCM, inborn errors in metabolism and genetic syndromes had the worst outcome in terms mortality and heart failure long term. Widespread availability of genetic testing provides several benefits to the clinician, confirming diagnosis in ambiguous cases and defining etiology in order to guide management and identifying relatives at risk. Figure 1 Funding Acknowledgement Type of funding source: None

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

IntroductionAlpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States.MethodsUsing data from the 2012–2017 PharMetrics Plus Administrative Claims Database and 2011–2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD.ResultsA cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant.DiscussionSignificant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

Waiting times in renal transplant candidates with a history of malignancy: time for a change?

With the aging population of kidney transplant candidates, a history of malignancy is an increasingly prevalent finding. Tumors can constitute a contraindication for transplantation or can lead to a delay of acceptance to the waiting-list. Current waiting time guidelines mainly refer to early data collected nearly 30 years ago, when the knowledge on tumors was, by current standards, still limited. Today, cancers can usually be divided into many different biological subtypes, according to histological and molecular subclassification and the availability of genetic testing. A more precise stratification and targeted antitumor therapies have led to better therapy outcomes or even cures from certain malignancies and to a better appreciation of tumor risks for the patient. Even though transplant patients do have an increased risk for malignancies, it is often overlooked that patients, while on dialysis, are equally prone to develop a tumor. Competing risks (e.g. cardiovascular, mortality risks) through prolonged time on dialysis have to be equally considered, when the decision for acceptance of a patient to the waiting-list is made. Current waiting time suggestions should be critically reconsidered for every patient after a thorough discussion with an oncologist, including new diagnostic and therapeutic strategies, as well as novel risk stratifications.

Delayed diagnoses of mitochondrial cytopathies in patients presenting with end stage kidney disease: two case reports

BackgroundUp to one third of patients on renal replacement programmes have an unknown cause of kidney disease, and the diagnosis may only be established following renal transplantation when the disease recurs or if new extra-renal symptoms develop.Case presentationWe present two patients who presented with progressive chronic kidney disease of unknown cause. Both patients underwent successful renal transplantation but subsequently developed multisystem abnormalities, and were ultimately diagnosed with mitochondrial cytopathy 10–15 years following transplantation.ConclusionsMitochondrial cytopathies are rare inborn errors of metabolism that should be considered in adults with renal impairment, especially in those with a family history of kidney or other multisystem disease. The widespread availability of genetic testing provides the potential for earlier diagnoses, thereby enhancing management decisions, anticipation of complications, avoidance of mitotoxic drugs, and informed prognosis prediction.

Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines.

The outlook for transthyretin amyloidosis (ATTR) is changing with the availability of new and emerging treatments. ATTR now appears to be more common than previously thought and is no longer viewed as an obscure diagnosis with a grim prognosis. Now more than ever, there is growing emphasis on the need for early diagnosis because the treatments appear to be most effective if started in earlier stages of the disease. Diagnosing ATTR is a challenge as it may initially present with nonspecific symptoms and it is often thought of as a diagnosis of exclusion. Increased awareness is imperative as new treatments offer hope and have the potential to change the disease trajectory. ATTR commonly presents with neurological and cardiac features. Transthyretin (TTR) is a protein produced in the liver which misfolds either due to genetic mutations or due to aging and results in deposition of amyloid fibrils in organs and tissues. Apart from the traditional imaging modalities, newer techniques including echocardiographic strain imaging, magnetic resonance imaging (MRI), and nuclear scintigraphy, as well as the increased availability of genetic testing are aiding in making a timely diagnosis. In this review, we present the current understanding of the ATTR disease process, diagnostic and surveillance approaches, newer treatment modalities, and the future directions.

Interstitial Lung Disease in Rare Congenital Syndromes.

Diffuse or interstitial lung disease (DLD/ILD) comprises a diverse group of disorders that involve the pulmonary parenchyma. Its aetiology varies (which makes the diagnostic process difficult), but congenital diseases, including malformation syndromes or developmental disorders, constitute one of the causative factors. They are rare conditions, and thus their frequency is not high. However, considering the progress and increasing availability of genetic testing, detection of these rare syndromes may increase. The aim of this work is, therefore, to present the symptomatology of selected congenital syndromes with ILD, taking into account the genetic background.