"The truth should not be hidden": Experiences and recommendations of individuals making NPE discoveries through genetic genealogy databases.

PURPOSE: Fueled by direct-to-consumer (DTC) genetic testing and genetic-relative finder services, some participants in genetic genealogy databases are making "not parent expected" (NPE) discoveries. To better understand experiences of this phenomenon, we surveyed a large cohort of users of genetic relative finder (GRF) services concerning their experiences after an NPE discovery. METHODS: Using thematic analysis, we analyzed responses from a cohort of GRF users (n = 646) to open-ended survey items to understand these experiences and their recommendations for DTC genetic testing companies and other GRF users. RESULTS: We found that individuals had both positive and negative emotional experiences related to the NPE discovery. Positive aspects included deeper self-understanding, connecting with new family members, and uncovering answers to questions. Negative aspects included rejection by new genetic relatives, inability to seek answers from relatives who had already died, and impairment of family relationships, especially with mothers. For many participants, the challenges after the discovery nevertheless felt worthwhile because the truth was uncovered. Perhaps notably, some participants suggested enhanced warnings prediscovery and improved support after discovery from companies who provide DTC genetic testing services. CONCLUSION: GRF services are powerful tools for family research and genealogy. Despite some possible positive and worthwhile experiences arising from making an NPE discovery, GRF users risk dealing with this potentially life-altering experience without adequate support. Participants in this study recommended an increase in resources from DTC genetic testing companies that could help users anticipate and navigate an NPE discovery.

When Paying Attention Pays Back: Missense Mutation c.1006G>A p. (Val336Ile) in PRKAG2 Gene Causing Left Ventricular Hypertrophy and Conduction Abnormalities in a Caucasian Patient: Case Report and Literature Review.

PRKAG2 cardiomyopathy is a rare genetic disorder that manifests early in life with an autosomal dominant inheritance pattern. It harbors left ventricular hypertrophy (LVH), ventricular pre-excitation and progressively worsening conduction system defects. Its estimated prevalence among patients with LVH ranges from 0.23 to about 1%, but it is likely an underdiagnosed condition. We report the association of the PRKAG2 missense variant c.1006G>A p. (Val336Ile) with LVH, conduction abnormalities (short PR interval and incomplete right bundle branch bock) and early-onset arterial hypertension (AH) in a 44-year-old Caucasian patient. While cardiac magnetic resonance (CMR) showed a mild hypertrophic phenotype with maximal wall thickness of 17 mm in absence of tissue alterations, the electric phenotype was relevant including brady-tachy syndrome and recurrent syncope. The same variant has been detected in the patient's sister and daughter, with LVH + early-onset AH and electrocardiographic (ECG) alterations + lipothymic episodes, respectively. Paying close attention to the coexistence of LVH and ECG alterations in the proband has been helpful in directing genetic tests to exclude primary cardiomyopathy. Hence, identifying the genetic basis in the patient allowed for familial screening as well as a proper follow-up and therapeutic management of the affected members. A review of the PRKAG2 cardiomyopathy literature is provided alongside the case report.

Morphological and Genetic Aspects for Post-Mortem Diagnosis of Hypertrophic Cardiomyopathy: A Systematic Review.

Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.

Arrhythmogenic Right Ventricular Cardiomyopathy Post-Mortem Assessment: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.

Genetic Obesity Disorders: Body Mass Index Trajectories and Age of Onset of Obesity Compared with Children with Obesity from the General Population.

OBJECTIVE: We sought to assess body mass index trajectories of children with genetic obesity to identify optimal early age of onset of obesity (AoO) cut-offs for genetic screening. STUDY DESIGN: This longitudinal, observational study included growth measurements from birth onward of children with nonsyndromic and syndromic genetic obesity and control children with obesity from a population-based cohort. Diagnostic performance of AoO was evaluated. RESULTS: We describe the body mass index trajectories of 62 children with genetic obesity (29 nonsyndromic, 33 syndromic) and 298 controls. Median AoO was 1.2 years in nonsyndromic genetic obesity (0.4 and 0.6 years in biallelic LEPR and MC4R; 1.7 in heterozygous MC4R); 2.0 years in syndromic genetic obesity (0.9, 2.3, 4.3, and 6.8 years in pseudohypoparathyroidism, Bardet-Biedl syndrome, 16p11.2del syndrome, and Temple syndrome, respectively); and 3.8 years in controls. The optimal AoO cut-off was ≤3.9 years (sensitivity, 0.83; specificity, 0.49; area under the curve, 0.79; P < .001) for nonsyndromic and ≤4.7 years (sensitivity, 0.82; specificity, 0.37; area under the curve, 0.68; P = .001) for syndromic genetic obesity. CONCLUSIONS: Optimal AoO cut-off as single parameter to determine which children should undergo genetic testing was ≤3.9 years. In case of older AoO, additional features indicative of genetic obesity should be present to warrant genetic testing. Optimal cut-offs might differ across different races and ethnicities.

Direct-to-consumer genetic tests providing health risk information: A systematic review of consequences for consumers and health services.

Direct-to-consumer genetic tests (DTC-GT) offer a variety of genetic health risk information. Understanding evidence of impacts is required for effective policy to protect consumers and healthcare services. We undertook a systematic review according to PRISMA guidelines, searching five literature databases for articles assessing analytic or clinical validity, or reporting consumer or healthcare professional experience with health risk information derived from DTC-GT, published between November 2014 and July 2020. We performed a thematic synthesis to identify descriptive and analytical themes. Forty-three papers met inclusion criteria. Many consumers submit raw DTC-GT data for third-party interpretation (TPI). DTC-GT sometimes report 'false positive' or incorrectly interpreted rare variants, or that such information can result from TPI. Consumers have high expectations of DTC-GT and TPI, and are broadly satisfied, although many do not act on results. A minority of consumers experience adverse psychological impacts. Healthcare consultations can be complex, and professionals have reservations about the validity and utility of DTC-GT-derived information. The contrast between consumer and health professional perceptions can result in mutual dissatisfaction with consultations. Health risk information from DTC-GT and TPI is broadly valued by consumers but presents complex challenges for healthcare services and some consumers.

Preimplantation genetic testing for aneuploidy is not related to adverse obstetric and neonatal outcomes in singleton pregnancies.

STUDY QUESTION: What is the potential impact of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes? SUMMARY ANSWER: PGT-A is not associated with increased rates of adverse maternal and neonatal outcomes in singleton pregnancies following IVF/ICSI cycles. WHAT IS KNOWN ALREADY: PGT-A pregnancies may be associated with increased risks of lower birthweight, preterm delivery, and hypertensive disorders compared with natural pregnancies. In a recent meta-analysis, the overall obstetric and neonatal outcomes of PGT-A pregnancies were favorable compared with those of IVF/ICSI pregnancies, although PGT-A pregnancies were associated with a higher risk of hypertensive disorders. STUDY DESIGN, SIZE, DURATION: A multicenter retrospective cohort study was performed in University-affiliated infertility centers. Single live births following IVF/ICSI between October 2016 and January 2021 were included in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 7146 live births after single embryo transfers with (n = 3296) or without (n = 3850) PGT-A were included. The primary outcome was pre-eclampsia and secondary outcomes included gestational diabetes, low birthweight and very low birthweight, cesarean section delivery, emergency cesarean section, as well as preterm birth, birthweight, congenital abnormalities, neonatal sex, Apgar score at 5 min, and neonatal intensive care unit admission. In a subgroup analysis, were included only blastocysts screened with next-generation sequencing (NGS). MAIN RESULTS AND THE ROLE OF CHANCE: Univariate analysis showed that pre-eclampsia, cesarean section incidence, and low Apgar score were higher in women undergoing PGT-A. However, after performing multivariate logistic and linear regression models accounting for many possible confounders, pregnancies that had been conceived after embryo biopsy showed no increase in adverse obstetric and neonatal outcomes. The subgroup analysis including patients with blastocysts screened by NGS showed a decreased risk of preterm birth in the group undergoing PGT-A. LIMITATIONS, REASONS FOR CAUTION: Caution should be used when interpreting the data because of its limitations, mainly related to its retrospective design. Although this is a large multicenter study, data acquisition included self-reporting questionnaires, and the deliveries occurred in different institutions with distinct protocols. WIDER IMPLICATIONS OF THE FINDINGS: The current study does not show any major adverse clinical outcomes after PGT-A. Efforts should be made to promote good quality research on embryo biopsy in terms of neonatal and obstetric outcomes, as well as its long-term consequences. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was obtained for this study. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Medroxyprogesterone acetate: an alternative to GnRH-antagonist in oocyte vitrification for social fertility preservation and preimplantation genetic testing for aneuploidy.

RESEARCH QUESTION: Can medroxyprogesterone acetate (MPA) be used as a pituitary suppressor instead of a gonadotrophin releasing hormone (GnRH) antagonist during ovarian stimulation in elective fertility preservation and preimplantation genetic testing for aneuploidy (PGT-A) cycles? DESIGN: A multicentre, retrospective, observational, cohort study conducted in 11 IVIRMA centres affiliated to private universities. Of a total of 1652 cycles of social fertility preservation, 267 patients were stimulated using a progestin-primed ovarian stimulation protocol (PPOS), and 1385 patients received a GnRH antagonist. In the PGT-A cycles, 5661 treatments were analysed: 635 patients received MPA and 5026 patients received GnRH antagonist. A further 66 fertility preservation and 1299 PGT-A cycles were cancelled. All cycles took place between June 2019 and December 2021. RESULTS: In the social fertility preservation cycles, the number of mature oocytes vitrified in MPA was similar to the number of those treated with an antagonist, a trend that was seen regardless of age (≤35 or >35 years). In the PGT-A cycles, no differences were found in number of metaphase II, two pronuclei, number of biopsied embryos (4.4 ± 3.1 versus 4.5 ± 3.1), rate of euploidy (57.9% versus 56.4%) or ongoing pregnancy rate (50.4% versus 47.1%, P = 0.119) between the group receiving MPA versus a GnRH antagonist, whereas the clinical miscarriage rate was higher in the antagonist group (10.4% versus 14.8%, P = 0.019). CONCLUSIONS: Administration of PPOS yields similar results to GnRH antagonists in oocytes retrieved, rate of euploid embryos and clinical outcome. Hence, PPOS can be recommended for ovarian stimulation in social fertility preservation and PGT-A cycles, as it allows greater patient comfort.

Evaluating the Value for Money of Precision Medicine from Early Cycle to Market Access: A Comprehensive Review of Approaches and Challenges.

OBJECTIVES: This study aimed to perform a comprehensive review of modeling approaches and methodological and policy challenges in the economic evaluation (EE) of precision medicine (PM) across clinical stages. METHODS: First, a systematic review was performed to assess the approaches of EEs in the past 10 years. Next, a targeted review of methodological articles was conducted for methodological and policy challenges in performing EEs of PM. All findings were synthesized into a structured framework that focused on patient population, Intervention, Comparator, Outcome, Time, Equity and ethics, Adaptability and Modeling aspects, named the "PICOTEAM" framework. Finally, a stakeholder consultation was conducted to understand the major determinants of decision making in PM investment. RESULTS: In 39 methodological articles, we identified major challenges to the EE of PM. These challenges include that PM applications involve complex and evolving clinical decision space, that clinical evidence is sparse because of small subgroups and complex pathways in PM settings, a one-time PM application may have lifetime or intergenerational impacts but long-term evidence is often unavailable, and that equity and ethics concerns are exceptional. In 275 EEs of PM, current approaches did not sufficiently capture the value of PM compared with targeted therapies, nor did they differentiate Early EEs from Conventional EEs. Finally, policy makers perceived the budget impact, cost savings, and cost-effectiveness of PM as the most important determinants in decision making. CONCLUSIONS: There is an urgent need to modify existing guidelines or develop a new reference case that fits into the new healthcare paradigm of PM to guide decision making in research and development and market access.

Impact of trophoectoderm biopsy for preimplantation genetic testing on serum ß-hCG levels, time of delivery and birthweight following frozen embryo transfer cycles.

Aim: This study investigated whether trophoectoderm (TE) biopsy adversely impacts serum ß-human chorionic gonadotropin (hCG) level on the 15th day of embryo transfer (ET), delivery week and birthweight, between biopsied and unbiopsied embryo groups, in a cohort of women who delivered a singleton baby, following frozen-thawed ET.Methods: All women having had a live birth after blastocyst ETs following frozen ET cycles with preimplantation genetic testing (PGT) were included. A control group was selected among women who had a live birth following single frozen blastocyst transfer without PGT-A at the same period in our clinicResults: One hundred fifteen and 173 cycles with- and without-PGT, respectively, were included. Serum ß-hCG level on the 15th day after ET was comparable between the groups (p = .336). Average birthweight of the babies born following biopsied embryos were significantly lower (3200 vs. 3380; p = .027). Women who received trophectoderm biopsied embryos had a significantly higher probability of having a baby weighing ≤1500 g and 1500-2500 g (p = .022) or ≤2500 g (p = .008). Proportion of preterm delivery was significantly higher in the biopsy group (p = .023). However, after adjusting for potential covariates, trophectoderm biopsy did not seem to increase the risk of preterm birth (OR 1.525; 95% CI, 0,644-3.611; p = .338)Conclusions: TE biopsy does not seem to impact serum ß-hCG level on the 15th day after ET. Average birthweight is lower when a biopsied embryo was transferred. After adjusting for potential covariates, trophectoderm biopsy does not seem to increase the risk of preterm birth.

Are there differences in perceptions, preferences and attitudes towards disclosure of genetic testing for Stroke? A qualitative study among stroke-free SIREN-SIBS genomics study participants.

OBJECTIVE: This study explored perceptions, preferences and attitudes towards disclosure of genetic testing results for stroke among stroke-free controls (and their family members) in the SIREN-SIBS Genomics Study, healthcare providers and policymakers. MATERIALS AND METHODS: We conducted a qualitative thematic analysis of key informant interviews with 61 participants recruited from community advisory boards (30) and health care providers (31) across seven sites in Nigeria and Ghana. RESULTS: Major findings illustrate differences in the knowledge of genetic testing with superior knowledge among health care professionals. Relatives and religious leaders were opined as the best to receive the disclosure as they would be able to break the news to the patient in a culturally sensitive manner to reduce the likely resultant emotional outburst. Poor level of awareness of national guidelines for disclosing genetic results exist. Key facilitating factors for disclosure are education, enabling environment, involvement of religious and community leaders, campaigns, and possible treatment options. Disclosure inhibitors include inadequate information, fear of marital break-up or family displacement, fear of stigmatization, fear of isolation, religious beliefs, health worker attitude, and lack of preparedness to accept results. CONCLUSIONS: These necessitate culturally sensitive interventions for continuing education, increased awareness and sustained engagement to equip all stakeholders in genetic testing disclosure process.

Epidemiologic Study of Gene Distribution in Romanian and Brazilian Patients with Non-Cicatricial Alopecia.

Background: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patient quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. Materials and Methods: We performed a retrospective study regarding the associations between AA and AGA and 45 tag SNPs of 15 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were collected from oral mucosa using a swab. The SNPs were determined by the qPCR technique. Each genetic test displays the subject's genotype of the selected gene and the prediction of a successful treatment (e.g., genotype AA of the GR-alpha gene is related to a predisposition to normal sensibility to topical glucocorticoid, and, therefore, glucocorticoids should be effective). Results: The GR-alpha, GPR44-2, SULT1A1, and CRABP2 genes were statistically significantly different in Brazil compared to Romania. The SULT1A1 activity that predicts the response to minoxidil treatment showed in our analysis that minoxidil is recommended in half of the cases of AGA and AA. Patients with AGA and a high expression of SRD5A1 or PTGFR-2 may benefit from Dutasteride or Latanoprost treatment, respectively. Most of the studied genes showed no differences between the two populations. Conclusions: The DNA analysis of the patients with alopecia may contribute to a successful treatment.

Experiences, Perceptions, and Meanings of the Ultra-Orthodox in Israel Regarding Premarital Genetic Testing.

This article focuses on experiences and perceptions of the Jewish ultra-Orthodox population in Israel-a religious minority-regarding premarital genetic testing. Semistructured interviews with 38 ultra-Orthodox individuals revealed four major themes. These themes reflect strong awareness of testing importance among Ashkenazi ultra-Orthodox, along with a high frequency of testing, while low awareness of testing importance was evident among Sephardi ultra-Orthodox along with a very low frequency of testing. The study's findings also indicate the central role that the Ashkenazi rabbis have in the routinization of the premarital genetic testing among their communities. Study limitations are discussed, and future research recommendations are provided.

Identification of a novel mutation in the BMPR2 gene in a pulmonary arterial hypertension patient using next-generation sequencing.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a hemodynamic state that is characterized by pulmonary vasoconstriction and vascular remodeling, leading to a continuous increase in mean pulmonary arterial pressure, and eventually right heart failure. Mutations of the bone morphogenetic protein type II receptor (BMPR2) gene are the most common genetic cause of PAH. METHODS: A 52-year-old woman was admitted to Shaoxing People's Hospital after suffering from a cough for 2 months. In our hospital, the proband got a thorough medical examination and was diagnosed with PAH following genetic testing. RESULTS: Genetic test showed that the proband carried a novel heterozygous c.1481C>T (p.Ala494Val) mutation in the BMPR2 gene. The new mutation was initially discovered as a potential pathogenic variant by bioinformatics research, but it needed to be functionally verified. CONCLUSIONS: The novel mutation may be related to the development of the PAH. In addition to general examinations, clinicians must thoroughly examine molecular genetics to provide an accurate diagnosis in the clinic, particularly for rare disorders.

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential.

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

Clinical management among individuals with variant of uncertain significance in hereditary cancer: A systematic review and meta-analysis.

Improper medical use of variant of uncertain significance (VUS) remains a concern in hereditary cancer genetic testing. The goal of this study was to assess the association between pathogenic and likely pathogenic (P/LP), VUS, and benign and likely benign (B/LB) genetic test results and cancer-related surgical and screening management. Systematic searches of Medline, Embase, EBSCO CINAHL Plus, and PsycINFO were conducted from 1946 to August 26, 2020. Eligible studies included individuals with cancer genetic test result and surgical or screening management outcomes. We reviewed 885 abstracts and 22 studies that reported relevant surgical and screening outcomes were included. Meta-analysis revealed significantly higher surgical rates among individuals with P/LP than among those with VUS for therapeutic mastectomy with contralateral prophylactic mastectomy (OR = 7.35, 95% CI, 4.14-13.64), prophylactic mastectomy (OR = 3.05, 95% CI, 1.5-6.19), and oophorectomy (OR = 6.46, 95% CI, 3.64-11.44). There were no significant differences in therapeutic mastectomy, or breast conservation or lumpectomy rates between individuals with P/LP and VUS, or in any outcomes between patients with VUS and B/LB. Studies evaluating screening outcomes were limited, and results were conflicting. Comprehensive analysis do not indicate that a significant number of individuals with VUS results undergo inappropriate clinical management.

A preliminary study on the role of Bacteroides fragilis in stent encrustation.

OBJECTIVE: To preliminarily study the characteristics of bacterial flora distribution in the urine of ureteral stent encrustation patients as well as the relation between Bacteroides and stent encrustation. METHODS: Patients undergoing ureteral stenting were included in the study and divided into encrustation group and non-encrustation group based on the condition of stent encrustation. The urine of patients was collected to undergo 16s DNA test to compare the bacterial flora distribution characteristics of the two groups. The bacterial genus with highest abundance in the urine of encrustation group was used for animal experiment. A rat model with a foreign body in the bladder was created, in which the rats were injected with the aforesaid bacterial genus. A control group injected with normal saline was also formed. The incidence of foreign body tube encrustation between the two groups was compared. RESULTS: The urine collected from the patients in encrustation group contained a variety of bacteria, while dominant bacteria genera included g_Lactobacillus (23.1%), g_Bacteroides (18.8%) and g_norank_Bacteroides (17.1%). While the urine from the non-encrustation group was less diverse in bacteria flora, as the major bacteria genera were g_Escherichia-Shigella (32.2%), g_Enterococcus (24.9%) and g_Pseudomonas (18.2%). Bacteroidetes in the encrustation group were significantly higher, therefore Bacteroides fragilis in this genus was adopted for animal experiment, resulting in a higher incidence of foreign body tube encrustation in the bladder among rats. CONCLUSION: The present study enriches our knowledge about ureteral stent encrustation and reveals that the target regulation of urine bacteria is worth further research and clinical application.

Comparison of different algorithms in laboratory diagnosis of alpha1-antitrypsin deficiency.

OBJECTIVES: Alpha1-antitrypsin deficiency (AATD) is an inherited condition that predisposes individuals to an increased risk of developing lung and liver disease. Even though AATD is one of the most widespread inherited diseases in Caucasian populations, only a minority of affected individuals has been detected. Whereas methods have been validated for AATD testing, there is no universally-established algorithm for the detection and diagnosis of the disorder. In order to compare different methods for diagnosing AATD, we carried out a systematic review of the literature on AATD diagnostic algorithms. METHODS: Complete biochemical and molecular analyses of 5,352 samples processed in our laboratory were retrospectively studied using each of the selected algorithms. RESULTS: When applying the diagnostic algorithms to the same samples, the frequency of False Negatives varied from 1.94 to 12.9%, the frequency of True Negatives was 62.91% for each algorithm and the frequency of True Positives ranged from 24.19 to 35.15%. We, therefore, highlighted some differences among Negative Predictive Values, ranging from 0.83 to 0.97. Accordingly, the sensitivity of each algorithm ranged between 0.61 and 0.95. We also postulated 1.108 g/L as optimal AAT cut-off value, in absence of inflammatory status, which points to the possible presence of genetic AATD. CONCLUSIONS: The choice of the diagnostic algorithm has a significant impact on the correct diagnosis of AATD, which is essential for appropriate treatment and medical care. The fairly large number of possible false negative diagnoses revealed by the present paper should also warn clinicians of negative results in patients with clinically-suspected AATD.

Genomic considerations for FHIR®; eMERGE implementation lessons.

Structured representation of clinical genetic results is necessary for advancing precision medicine. The Electronic Medical Records and Genomics (eMERGE) Network's Phase III program initially used a commercially developed XML message format for standardized and structured representation of genetic results for electronic health record (EHR) integration. In a desire to move towards a standard representation, the network created a new standardized format based upon Health Level Seven Fast Healthcare Interoperability Resources (HL7® FHIR®), to represent clinical genomics results. These new standards improve the utility of HL7® FHIR® as an international healthcare interoperability standard for management of genetic data from patients. This work advances the establishment of standards that are being designed for broad adoption in the current health information technology landscape.

Performance evaluation of stool DNA methylation tests in colorectal cancer screening: a systematic review and meta-analysis.

AIM: There is not sufficient evidence about whether stool DNA methylation tests allow prioritizing patients to colonoscopy. Due to the COVID-19 pandemic, there will be a wait-list for rescheduling colonoscopies once the mitigation is lifted. The aim of this meta-analysis was to evaluate the accuracy of stool DNA methylation tests in detecting colorectal cancer. METHODS: The PubMed, Cochrane Library and MEDLINE via Ovid were searched. Studies reporting the accuracy (Sackett phase 2 or 3) of stool DNA methylation tests to detect sporadic colorectal cancer were included. The DerSimonian-Laird method with random-effects model was utilized for meta-analysis. RESULTS: Forty-six studies totaling 16 149 patients were included in the meta-analysis. The pooled sensitivity and specificity of all single genes and combinations was 62.7% (57.7%, 67.4%) and 91% (89.5%, 92.2%), respectively. Combinations of genes provided higher sensitivity compared to single genes (80.8% [75.1%, 85.4%] vs. 57.8% [52.3%, 63.1%]) with no significant decrease in specificity (87.8% [84.1%, 90.7%] vs. 92.1% [90.4%, 93.5%]). The most accurate single gene was found to be SDC2 with a sensitivity of 83.1% (72.6%, 90.2%) and a specificity of 91.2% (88.6%, 93.2%). CONCLUSIONS: Stool DNA methylation tests have high specificity (92%) with relatively lower sensitivity (81%). Combining genes increases sensitivity compared to single gene tests. The single most accurate gene is SDC2, which should be considered for further research.