Applications of genome sequencing as a single platform for clinical constitutional genetic testing.

The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including the utilization of exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing.

Edge-to-edge repair for tricuspid regurgitation: 1-year follow-up and clinical implications from the TR-Interventional Study.

Aims: Tricuspid regurgitation affects 7% of the population, with moderate-to-severe tricuspid regurgitation contributing to up to 12% of heart failure-related hospitalizations. Traditional treatments have several limitations, prompting the exploration of innovative interventions. Our study aims to investigate the efficacy and clinical outcomes following transcatheter edge-to-edge repair (TEER) in patients with severe, symptomatic tricuspid regurgitation through a 1-year follow-up.

Cardiac Surgery and Transcatheter Intervention for Valvular Heart Disease in Carcinoid Syndrome: Risk Factors, Outcomes, and Evolving Therapeutic Strategies.

Carcinoid heart disease (CHD) affects right-sided valves and causes significant mortality and morbidity. Even though the pathophysiology of the disease is not entirely understood, it is known that chronic exposure to high levels of circulating serotonin is the main factor responsible for developing valvular heart disease. Cardiac imaging plays a critical role in the management of CHD, so the final diagnosis can be performed through multimodal imaging techniques and the measurement of biomarkers.

3D transesophageal echocardiographic assessment of acute reverse remodeling of the tricuspid annulus after transcatheter edge-to-edge repair.

Aims: Our study aims to evaluate the acute remodeling of the tricuspid valve annulus immediately after the T-TEER by using intraprocedural transesophageal three-dimensional (3D) echocardiography.

Methods And Results: We prospectively enrolled 62 consecutive symptomatic patients with at least severe TR, who underwent T-TEER with the TriClip System between March 2021 and June 2024. The following parameters were assessed using a multiplanar reconstruction analysis performed off-line using a 3D dataset: septal-lateral (SL) and antero-posterior (AP) annulus diameters; annulus area; annulus perimeter and eccentricity index.

A case study on the endeavour to identify the "unidentifiable" fallen soldiers of WWI on the Italian front.

If there is a category of war victims for whom the identification process has been and still remains an extremely challenging issue, it is the soldiers of World War One. There are various reasons for this, including unreliable identity tags, the unprecedented number of casualties, and the level of destruction caused by the massive use of "new" weapons. In Italy, this phenomenon was so severe and well-known that a monument was erected in Rome specifically in memory of those unknown soldiers ("Tomba del Milite Ignoto").

The challenges and opportunities of offering and integrating training in clinical molecular genetics and clinical cytogenetics: A survey of LGG Fellowship Program Directors.

Purpose: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model.

Methods: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time.

Controlled mitral valvuloplasty using steerable catheter- waist- formed balloon system: A clinical case series.

As the general population ages, the incidence of degenerative mitral stenosis (MS) among patients has increased. Percutaneous mitral valvuloplasty (PMV) has emerged as a well-established option for mitral rheumatic stenosis with specific characteristics. However, a blank therapeutic space must be filled with the treatment options for degenerative or rheumatic mitral stenosis in patients with many comorbidities and contraindication for valvuloplasty.

The safety of transesophageal echocardiography to guide transcatheter tricuspid valve edge-to-edge repair.

Background: Transesophageal echocardiography (TEE) is primarily used to guide transcatheter structural heart interventions, such as tricuspid transcatheter edge-to-edge repair (TEER). Although TEE has a good safety profile, it is still an invasive imaging technique that may be associated with complications, especially when performed during long transcatheter procedures or on frail patients. The aim of this study was to assess TEE-related complications during tricuspid TEER.

The vehicle of administration, feed or water, and prandial state influence the oral bioavailability of amoxicillin in piglets.

Feed and water components may interact with drugs and affect their dissolution and bioavailability. The impact of the vehicle of administration (feed and water) and the prandial condition of weaner piglets on amoxicillin´s oral bioavailability was evaluated. First, amoxicillin's in vitro dissolution and stability in purified, soft, and hard water, as well as release kinetics from feed in simulated gastric and intestinal media were assessed.

A novel telomere biology disease-associated gastritis identified through a whole exome sequencing-driven approach.

A whole exome sequencing (WES)-driven approach to uncover the etiology of unexplained inflammatory gastritides has been underutilized by surgical pathologists. Here, we discovered the pathobiology of an unusual chronic atrophic gastritis in two unrelated patients using this approach. The gastric biopsies were notable for an unusual pattern of gastritis with persistent dense inflammation, loss of both parietal and neuroendocrine cells in the oxyntic mucosa, and sparing of the antral mucosa.

Germline Variants Incidentally Detected via Tumor-Only Genomic Profiling of Patients With Mesothelioma.

Importance: Patients with mesothelioma often have next-generation sequencing (NGS) of their tumor performed; tumor-only NGS may incidentally identify germline pathogenic or likely pathogenic (P/LP) variants despite not being designed for this purpose. It is unknown how frequently patients with mesothelioma have germline P/LP variants incidentally detected via tumor-only NGS.

Objective: To determine the prevalence of incidental germline P/LP variants detected via tumor-only NGS of mesothelioma.

Exome sequencing identifies PD-L2 as a potential predisposition gene for lymphoma.

To investigate germline predisposition in lymphoma, we performed whole-exome sequencing and discovered a novel variant (c.817-1G>T) in programmed cell death 1 ligand 2 (PD-L2) in a family with early-onset lymphomas and other cancers. The variant was present in the proband with follicular lymphoma and his son with Hodgkin's lymphoma.

Feasibility and limitations of cultured skin fibroblasts for germline genetic testing in hematologic disorders.

To avoid acquired variants found in the blood, cultured skin fibroblasts are a recommended DNA source for germline genetic testing in patients with hematologic disorders, but data are lacking regarding practicality and limitations. We conducted a retrospective cohort study of 350 subjects with hematologic disorders who underwent skin fibroblast culture for germline genetic testing. We analyzed next-generation sequencing data from the targeted capture of 144 inherited cancer and bonemarrow failure genes to identify variants at heterozygous and subclonal variant allele frequencies.

Novel Kabuki Syndrome Mutation With Hyperinsulinemic Hypoglycemia and Pulmonary Hypertension Requiring ECMO.

Kabuki syndrome (KS) is a multisystem disorder estimated to occur in 1:32 000 newborns. Pathogenic mutations cause the majority but not all cases of KS in either or . KS can be suspected by phenotypic features, including infantile hypotonia, developmental delay, dysmorphic features, congenital heart defects, and others.

Novel compound heterozygous LRBA deletions in a 6-month-old with neonatal diabetes.

We report a 6-month-old boy with antibody-positive insulin-dependent diabetes mellitus. Sequencing identified compound heterozygous deletions of exon 5 and exons 36-37 in LRBA. At three years, he has yet to exhibit any other immune symptoms.

Are cranial peri-mortem fractures identifiable in cremated remains? A study on 38 known cases.

Accurate identification and analysis of signs of trauma on human bone is one of the mainstays of forensic pathology. However, when a forensic pathologist has to deal with charred remains, the task become extremely difficult, because tissues are subjected to severe morphological alterations and their assessment can be critically distorted. We analyzed 38 individuals with peri-mortem skull fractures due to falls from height (17 cases), traffic accidents (16 cases), gunshots wounds (5 cases), of which we had the demographic and clinical data and the autopsy report with the description and photographic records of the fracture lines.

Further delineation of a recognizable type of syndromic short stature caused by biallelic SEMA3A loss-of-function variants.

The semaphorin protein family is a diverse set of extracellular signaling proteins that perform fundamental roles in the development and operation of numerous biological systems, notably the nervous, musculoskeletal, cardiovascular, endocrine, and reproductive systems. Recently, recessive loss-of-function (LoF) variants in SEMA3A (semaphorin 3A) have been shown to result in a recognizable syndrome characterized by short stature, skeletal abnormalities, congenital heart defects, and variable additional anomalies. Here, we describe the clinical and molecular characterization of a female patient presenting with skeletal dysplasia, hypogonadotropic hypogonadism (HH), and anosmia who harbors a nonsense variant c.

Common and much less common scenarios in which botany is crucial for forensic pathologist and anthropologists: a series of eight case studies.

It is commonly accepted that crime scene recovery and recording are key moments of any judicial inspection in which investigators must decide on the correct strategies to put into place. Complex outdoor scenarios, presenting partially or entirely skeletonised remains, can benefit more than others by the intervention of environmental specialists (forensic anthropologists, archaeologists, entomologists and botanists). These experts are capable of singling out, correctly recording and recovering environmental evidence that can lead to a more comprehensive reconstruction of a given criminal episode.

Variants in the SK2 channel gene (KCNN2) lead to dominant neurodevelopmental movement disorders.

KCNN2 encodes the small conductance calcium-activated potassium channel 2 (SK2). Rodent models with spontaneous Kcnn2 mutations show abnormal gait and locomotor activity, tremor and memory deficits, but human disorders related to KCNN2 variants are largely unknown. Using exome sequencing, we identified a de novo KCNN2 frameshift deletion in a patient with learning disabilities, cerebellar ataxia and white matter abnormalities on brain MRI.

Men at war, recovery and analysis of soldiers' remains from the WWI and WWII Italian Front.

Italy was hit hard by the World Wars, still today the discovery of human remains dating back to 20th century is a common phenomenon, in particular on Alpine glaciers, due to climate changes. The authors will describe the Italian scenario in terms of legislation, scientific procedures and related disciplines involved, then the difficulties in the identification of human remains of soldiers, but also potential issues related to uncontrolled "scavenging" activities and consequent ethical aspects. The interdisciplinarity, used as systematic approach to deal with complex cases, allowed the presumptive identification of a WWI soldier recovered after one century from the glaciers of the Adamello mountain, as described.

Telomere biology disorder prevalence and phenotypes in adults with familial hematologic and/or pulmonary presentations.

Telomere biology disorders (TBDs) present heterogeneously, ranging from infantile bone marrow failure associated with very short telomeres to adult-onset interstitial lung disease (ILD) with normal telomere length. Yield of genetic testing and phenotypic spectra for TBDs caused by the expanding list of telomere genes in adults remain understudied. Thus, we screened adults aged ≥18 years with a personal and/or family history clustering hematologic disorders and/or ILD enrolled on The University of Chicago Inherited Hematologic Disorders Registry for causative variants in 13 TBD genes.