Management Of Family Members Research Articles

Familial polycystic kidneys with no genetic confirmation: Are we sure it isADPKD?

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable multifocal cystic disease encountered in clinical practice, and it is usually diagnosed in patients with family history by the evidence of markedly enlarged kidneys with multiple bilateral cysts at ultrasound (U.S.), computed tomography (CT) scan, or magnetic resonance imaging (MRI). In most cases, genetic testing is not required. Though ADPKD diagnosis is often straightforward, misdiagnosis is possible. Here we present a case of ADPKD misdiagnosis, followed by a review of the most important kidney heritable multifocal cystic diseases. Our case report demonstrates that ADPKD can be erroneously diagnosed when other kidney heritable multifocal cystic diseases occur without their distinguishing manifestations and when there is no genetic characterization among the relatives. A proper diagnosis of heritable diseases is crucial, as it allows an appropriate management of family members who carry disease allele, apart from patient management. Therefore, we suggest a careful differential diagnosis with possible molecular genetic analysis in presentations with familial cystic kidneys and suspicious clinical and radiological features.

The role of F-18 FDG PET/CT in the prognosis of patients with hypoxic/anoxic brain injury after cardio-circulatory arrest.

Advances in resuscitation techniques have resulted in more patients surviving cardio-circulatory arrest (CA) and consequently developing hypoxic/anoxic brain damage. The aim of this study is to evaluate the role of PET/CT (Positron Emission Tomography/Computerized Tomography scan) with F-18 FDG (F-18 fluorodeoxyglucose) during the early rehabilitative hospitalization phase in determining the V/C (Vermis/Cerebellar) ratio as a prognostic index to predict patient outcome, as defined by clinical evaluation scales. This is a single-center retrospective study of 37 consecutive adult patients admitted to the neurorehabilitation center between January 2011 and June 2019. Functional status was measured by the following clinical scales: FIM (Functional Indipendence Measure), LCFS (Levels of Cognitive Functioning Scale), GOS (Glasgow Outcome Scale) and CRS-R (Coma Recovery Scale-Revised). PET/CT with F-18 FDG as a functional imaging technique was used to calculate the V/C ratio as a ratio between the metabolism of the vermis and of the Cerebellar Hemisphere. A statistically significant correlation was observed between the V/C ratio and the delta values (difference between discharge and admission value) for each clinical evaluation scale (Delta FIM: P=0.0014; Delta LCFS P=0.0003). A statistically significant difference was observed between the V/C ratio of patients with LCFS ≥4 that showed an improved outcome (defined as an improvement of at least two points in LCFS), and that of patients with LCFS <4 that did not improve (P=0.0011). A V/C ratio cut-off of 1.5 corresponded with a positive predictive power of 80% and a negative predictive power of 82%; a value <1.5 predicted a better outcome. Clinical evaluation scales when associated with F-18 FDG PET/CT measurement of metabolism, provide a more reliable prognosis. This allows for more focused rehabilitation treatment and better management of family members' expectation.

Scialorrea e tappi di muco: consigli pratici di gestione nei pazienti eleggibili alle cure palliative pediatriche

Pediatric palliative care is a multidisciplinary area of pediatrics that aims to ensure a quality of life for children suffering from incurable diseases with high care complexity and also respond to their needs and those of their families. At the clinical level, there are many disturbing symptoms with a wide impact on the quality of life, which must be managed and treated. In particular some of them represent a major challenge for caregivers and health professionals looking after children eligible for PPC. This work aims to present, with a practical and immediately useful cut for the pediatrician, the management strategies of frequent symptoms, starting with drooling and mucus plugs; the latter are very frequent in children with non-oncological disease, followed by PPC. If not treated, they limit the child’s quality of life and have a significant impact on the concerns and management of family members / caregivers.

Pengaruh Promosi Kesehatan Keluarga Terhadap Peran Keluarga Dalam Pengelolaan Anggota Keluarga Dengan Diabetes Mellitus Di Puskesmas Kebakkrmat I

There are 90% diabetes mellitus sufferers in the world. Diabetes mellitus (DM) is a degenerative disease that has increased every year in countries. Diabetes Mellitus if not handled properly will lead to complications. Cooperation between patients and families is expected to prevent chronic complications of DM, by providing information through health promotion. In this study using "pre post test non control group design" where a group before a certain treatment (x) is given a pretest, then given treatment and after the treatment is carried out a post test or a measurement to determine the consequences of the treatment. The independent variable is family health promotion, while the dependent variable is the management of patients with Diabetes Mellitus. This study uses "purposive sampling". In this sampling, families that meet the criteria and can represent the characteristics of the population are selected, namely a family with one of the family members suffering from Diabetes Mellitus. Family health promotion significantly provides a change for the better towards improving the role of the family in the management of family members with DM as shown from the pre-test and post-test data which is then tested with the Kendal tau test on all components of the management of family members with DM. There is a significant influence between family health promotion on improving the role of the family in the management of family members with DM at the Kebakramat 1 Health Center where there is an improvement in the role of the family in the management of family members with DM.

Ten-fold increase in genetic testing in pancreatic and metastatic prostate cancer with implementation of point of care (POC) testing.

1506 Background: Germline genetic testing (GT) for cancer susceptibility is recommended for pancreatic and advanced prostate cancer patients, due to potential implications for targeted therapies and risk assessment of family members. Traditional cancer GT programs may create barriers for certain patient populations. To more effectively integrate testing into standard oncology care POC GT was introduced in early 2018 in a joint protocol with Memorial Sloan Kettering Cancer Center. Here we report pre and post POC referral and testing numbers at the University of Pennsylvania. Methods: Patients with metastatic prostate or pancreatic cancer were ascertained through their GU/GI oncologist onto an IRB approved protocol and shown an educational video about GT by research staff who obtained informed consent and facilitated biospecimen collection. Genetic counselors returned results and provided post-test counseling by phone. To evaluate the impact of this model on the uptake of GT services, the number of patients who were referred to and proceeded with GT was compared before and after study initiation. Results: In 2017, 77 patients were referred to genetics of which 45 underwent genetic counseling and testing. Twenty-nine (38%) did not complete genetic counseling or testing, and 3 later underwent testing through the POC study. Since the study launched in 2018, 407 patients were referred and underwent testing through the study. This represents a ten-fold increase in patients who underwent GT. Conclusions: Comparing uptake of GT services before and after study initiation suggests that a POC model with abbreviated pre-test education and post-test genetic counseling by phone is a possible solution to barriers of traditional genetic counseling, increasing physician referrals and uptake of testing by patients. This approach allows for more timely access to genetic information that may impact treatment strategies and medical management of family members. Clinical trial information: pending. [Table: see text]

Identification of a novel hypertrophic cardiomyopathy-associated mutation using targeted next-generation sequencing.

Hypertrophic cardiomyopathy (HCM), one of the most common forms of myocardial diseases, is the major cause of sudden cardiac death in young adults and competitive athletes. Analyses of gene mutations associated with HCM are valuable for its molecular diagnosis, genetic counseling, and management of familial HCM. To dissect the relationship between the clinical presentation and gene mutations of HCM, the genetic characterizations of 19 HCM-related genes in 18 patients (8 cases from 6 pedigrees with familial HCM and 10 cases without familial HCM) were detected using next-generation sequencing (NGS). As a result, 12 disease-related mutations were identified in the 18 subjects, including 6 single mutations and 3 double mutations [MYBPC3 (p.Gln998Glu) plus TNNI3 (p.Arg145Gly), PRKAG2 (p.Gly100Ser) plus MYBPC3 (p.Lys1209Serfs*28) and TNNI3 (p.Glu124Gln) plus GLA (p.Trp47*)]. The 3 heterozygous double mutations were discovered for the first time in the malignant familial HCM patients. Of the 6 single mutations, a novel mutation was found in tafazzin (TAZ, p.Ile208Val), and a mutation in β-myosin heavy chain gene (MYH7, p.Arg54Gln), which was reported as rare in the general population, was firstly found in one HCM patient. Identification of novel and rare mutations in HCM patients have added new data to the spectrum of gene mutations associated with this disease. These findings provide an essential basis for the molecular diagnosis and better management of family members at risk of familial HCM.

Detection of mutations in symptomatic patients with hypertrophic cardiomyopathy in Taiwan

BackgroundHypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder associated with sudden death, heart failure, and stroke. The aim of the present study was to evaluate the prevalence and types of mutations in symptomatic patients with HCM in Taiwan. MethodsThirty-eight HCM index patients (mean age 60±16 years) underwent systematic mutation screening of eight sarcomeric genes: β-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), troponin T (TNNT2), troponin I (TNNI3), myosin ventricular regulatory light chain 2 (MYL2), myosin ventricular essential light chain 1 (MYL3), α-tropomyosin (TPM1), and cardiac α-actin (ACTC), using direct DNA sequencing. In silico programs predicted damaging amino acids. In the positive families, genotype–phenotype correlation studies were done. ResultsOverall, 13 mutations were identified in 13 index patients (34.2%). The three most frequently mutated genes were MYH7, MYBPC3, and TNNT2. One patient carried double mutations. Five mutations (MYH7 R147S; MYBPC3 R597Q; MYBPC3 W1007R; TNNI3 E124Q; MYL3 R63C) were novel; all were missense mutations. Analysis using in silico tools showed near consensus to classify these five novel mutations as pathological. Family pedigree analysis showed the presence of cosegregation in at least two affected members in each proband family, but incomplete penetrance in young family members with a positive genotype. ConclusionsWe identified 13 HCM pedigrees, including 5 carrying novel mutations and 1 with a double mutation. The three most commonly mutated genes were MYH7, MYBPC3, and TNNT2. These results, together with genetic counseling, could lead to earlier diagnosis and better management of family members at risk of HCM.

When a "Disease-Causing Mutation" Is Not a Pathogenic Variant

The clinical utility of molecular genetic testing relies on our accurate and comprehensive knowledge about the relationships between genes/variants and diseases/symptoms. Correctly interpreting the clinical significance of detected variants continues to be a constant challenge for molecular diagnostic practice. This challenge has become substantially magnified as testing based on next generation sequencing (NGS)3 becomes rapidly integrated in routine clinical practice. Whole exome sequencing for clinical diagnostics is a new practice. There are many challenges that lie ahead. One key issue out of many remains our ability to correctly interpret the clinical significance of gene variants, which lags far behind our ability to discover them. Consequently, many variants are currently categorized as variants of “unknown significance” in a clinical report. This certainly poses a challenge to physicians who receive the report, but we would argue that an even more pressing issue is the possibility of a false diagnosis: a non–disease-causing variant being interpreted as a pathogenic variant owing to our incorrect knowledge about gene/variant and disease/symptom associations. This possibility may be small for tests based on single genes or gene panels but markedly higher for tests based on whole exome sequencing/whole genome sequencing. Assigning a non–disease-causing variant as causative to a patient will deny the patient the future opportunity for identifying the real disease causation, and as a result the patient may never receive a truly correct disease diagnosis. Any such false diagnosis has the potential to have a huge impact on the care of the individual patient, on the diagnosis and management of family members who test negative or positive for the false-positive variant, and potentially on future family planning. DNA sequence variants can largely be grouped into 2 categories: truncating variants and nontruncating variants. Truncating variants consist of nonsense variants, out-of-frame indels, most splicing variants, and partial gene …

Hypertrophic cardiomyopathy and planned in vitro fertilization

Hypertrophic cardiomyopathy (HCM) is often transmitted to the offspring of affected individuals. This case report describes the role of genetic screening in a 39-year-old woman with a family history of sudden cardiac death. The patient wished to become pregnant and was seeking medical consultation. In addition to electro- and echocardiograms, genomic DNA was isolated and direct sequencing was employed to screen the patient for some of the most common genes that cause HCM. A pathogenic heterozygous mutation c.700 g > a p.Arg186Gln in TNNI3 was identified, which was not found in 200 normal control chromosomes. Mutation-specific genetic testing was also performed in four family members, and the same mutation was absent. Genetic screening appears cost effective in familiar members with a known mutation, provides important information about the affected individual, and can facilitate the future management of family members and offspring.

Hereditary gastric cancer

Gastric cancer is a heterogeneous and highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer associated death worldwide. Most cases are sporadic and familial clustering is observed in about 10% of the cases. Hereditary gastric cancer accounts for a very low percentage of cases (1-3%) and a single hereditary syndrome - Hereditary Diffuse Gastric Cancer (HDGC) - has been characterised. Among families that fulfil the clinical criteria for HDGC, about 40% carry CDH1 germline mutations, the genetic cause of the others being unknown. The management options for CDH1 asymptomatic germline carriers are intensive endoscopic surveillance and prophylactic gastrectomy. In this chapter we review the pathophysiology and clinicopathological features of HDGC and discuss issues related with genetic testing and management of family members.

Preventing suicide: a resource for the family

The family can play an important role in the prevention of suicide if it is capable of aiding the mental health care services in the early detection and management of family members at risk. In order to attain this goal, the whole family should be informed in how to prevent suicide.

Angiographic screening and elective surgery of familial cerebral aneurysms: a decision analysis.

Up to 6% of cerebral aneurysms may be familial. Because the pattern of inheritance and the prevalence of aneurysms within families are unknown, the management of family members at risk of harboring a cerebral aneurysm is currently empirical. We established the prevalence of aneurysms in the second generation of individuals with familial cerebral aneurysms and determined the possible benefit of angiographic screening and elective surgery of such individuals by using a simple decision analysis model. Four consecutive families were identified in whom the mother and a child had a ruptured cerebral aneurysm. A total of 19 siblings at risk in the second generation were identified. Fifteen underwent elective cerebral angiography: one had a cerebral aneurysm and two had an infundibulum at the origin of the posterior communicating artery. Including the previously known aneurysms, the prevalence of aneurysms in the second generation was thus established at 29.4%. A decision analysis was performed with 2% as the annual risk of rupture, 72.7% as the risk of death or disability with rupture, 0.1% as the risk of angiography, and 6.5% as the risk of surgery. The benefit in years of survival free of sequelae resulting from angiographic screening and elective surgery (intervention) over natural history was computed for life expectancy corresponding to each quinquennial age group from age 15 to 100 years. Intervention equaled natural history, in terms of years of survival expected with each choice, at a life expectancy of 10.6 years, corresponding to age 76.5 years for men and 80 years for women, and produced a net gain of at least 1 year for patients whose life expectancy was 32 years or more, corresponding to age 53.5 years for women and 49 years for men. Greater benefit was achieved with increasing life expectancy (younger age). The prevalence of aneurysms in the second generation when a mother and child have an aneurysm is 29.4%. Intervention produces a benefit of at least 1 year of survival free of sequelae over natural history in such individuals if their life expectancy is 32 years or more.