All-in-one gene therapy alternative for DBAS.

Diamond-Blackfan anemia syndrome is a ribosomopathy classified among the bone marrow failure syndromes. This disease exhibits significant heterogeneity, with up to 24 genetic variants identified to date. Voit et al.

Right ventricular myocardial work: proof-of-concept for the assessment of pressure-strain loops of patients with pre-capillary pulmonary hypertension.

Background: Right ventricular myocardial work (RVMW) assessed by transthoracic echocardiography allows to study the right ventricular (RV) function using RV pressure-strain loops. The assessment of these novel indexes of RVMW has not yet been exten sively studied, namely in pre-capillary pulmonary hypertension (PH) population.

Objectives: to evaluate the relationship between RVMW and invasive indices of right heart catheterization (RHC) in a cohort of patients with group I and group IV PH and to compare with a control group without PH.

Outcomes of Patients with Heart Failure Hospitalized for COVID-19-A Study in a Tertiary Italian Center.

Coronavirus Disease 2019 (COVID-19), triggered by SARS-CoV-2, has represented a global pandemic associated with an elevated rate of mortality, mainly among older individuals. The extensive pulmonary involvement by the viral infection might have precipitated pre-existing chronic conditions in this vulnerable population, including heart failure (HF). The aim of this retrospective, observational study was to assess the impact of COVID-19 in patients with a prior diagnosis of HF referred to the Emergency Department of the Agostino Gemelli University Hospital between March 2020 and January 2023.

Collagen scaffold-seeded iTenocytes accelerate the healing and functional recovery of Achilles tendon defects in a rat model.

Introduction: Tendon injuries represent an ongoing challenge in clinical practice due to poor regenerative capacity, structure, and biomechanical function recovery of ruptured tendons. This study is focused on the assessment of a novel strategy to repair ruptured Achilles tendons in a Nude rat model using stem cell-seeded biomaterial.

Methods: Specifically, we have used induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) overexpressing the early tendon marker Scleraxis (SCX, iMSC, iTenocytes) in combination with an elastic collagen scaffold.

Should the Faecal Microbiota Composition Be Determined to Certify a Faecal Donor?

Background/objectives: Faecal microbiota transplantation (FMT) is considered a safe and effective therapy for recurrent infection. It is the only current clinical indication for this technique, although numerous clinical research studies and trials propose its potential usefulness for treating other pathologies. Donor selection is a very rigorous process, based on a personal lifestyle interview and the absence of known pathogens in faeces and serum, leading to only a few volunteers finally achieving the corresponding certification.

Beyond precision: evaluation of off-target clustered regularly interspaced short palindromic repeats/Cas9-mediated genome editing.

The gene editing field has advanced rapidly since the development of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system because of its applicability in precisely modifying the genome. Among its multiple applications, the correction of genetic diseases has emerged as a potential curative treatment for many disorders that have eluded a cure to date. Despite its efficiency in achieving therapeutic levels of correction, the unexpected adverse effects of editing due to CRISPR/Cas9 nuclease activity are a major concern when translating these new strategies to the clinic.

Haematopoietic gene therapy of non-conditioned patients with Fanconi anaemia-A: results from open-label phase 1/2 (FANCOLEN-1) and long-term clinical trials.

Background: Allogeneic haematopoietic stem-cell transplantation is the standard treatment for bone marrow failure (BMF) in patients with Fanconi anaemia, but transplantation-associated complications such as an increased incidence of subsequent cancer are frequent. The aim of this study was to evaluate the safety and efficacy of the infusion of autologous gene-corrected haematopoietic stem cells as an alternative therapy for these patients.

Methods: This was an open-label, investigator-initiated phase 1/2 clinical trial (FANCOLEN-1) and long-term follow-up trial (up to 7 years post-treatment) in Spain.

SARS-CoV-2 and Environmental Changes: The Perfect Storm.

The COVID-19 pandemic has had a significant impact on the global economy. It also provided insights into how the looming global climate crisis might be addressed, as there are several similarities between the challenges proposed by COVID-19 and those expected from the coming climate emergency. COVID-19 is an immediate health threat, but climate change represents a more gradual and insidious risk that will lead to long-term consequences for human health.

ASIA Syndrome: State-of-the-Art and Future Perspectives.

The expression "Autoimmune/inflammatory syndrome induced by adjuvants (ASIA)" was coined by Shoenfeld and colleagues in 2011. It defines a group of immune-mediated disorders that arise in people, with a genetic predisposition, following exposure to adjuvant agents. This syndrome has been reported after contact with silicone implants, medications, infections, metals, vaccines, and other substances.

Left ventricular global longitudinal strain is associated with filling pressure and cardiac output in an outpatient setting: Insights from CardioMEMS™.

Introduction And Objectives: Left ventricular global longitudinal strain (LVGLS) is an indicator of myocardial function in patients with heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Nevertheless, it is not clear whether LVGLS correlates with filling pressures and cardiac output (CO) in an ambulatory setting. We aimed to assess whether LVGLS is associated with invasive pulmonary artery pressures (PAP) and CO in outpatients using the invasive remote monitoring CardioMEMS™ system.

Inflammaging: The Next Challenge-Exploring the Role of Gut Microbiota, Environmental Factors, and Sex Differences.

The term 'inflammaging' has been coined to describe the chronic state of inflammation derived from ongoing cycles of tissue damage and the subsequent immune responses. This inflammatory status contributes to the decline of organs and physiological functions, accelerates the aging process, and increases the risk of age-related illnesses and death. During aging, the gut microbiota (GM) undergoes significant changes, including a decreased diversity of species, a decline in beneficial bacteria, and a rise in proinflammatory ones, resulting in persistent low-grade inflammation.

MicroRNAomic Analysis of Spent Media from Slow- and Fast-Growing Bovine Embryos Reveal Distinct Differences.

In bovine embryos, the microRNA (miRNA) expression has been profiled at each stage of early development in vitro. The miRNAomic analysis of spent media has the potential to reveal characteristics of embryo health; however, applications are limited without categorizing miRNA profiles by embryo quality. Time-lapse imaging has shown the timing of embryo development in vitro may be indicative of their developmental potential.

The Controlling Nutritional Status (CONUT) Score Predicts Post-operatory Risks and Prognosis in Patients With Surgically Treated Colon Cancer: A Retrospective Study.

Background/aim: The Controlling Nutritional status (CONUT) score, a valuable tool evaluating the preoperative conditions of patients from a nutritional point of view, has been successfully adopted for a plethora of malignancies including colorectal cancer (CRC). However, since rectal cancer has characteristics that differ from colon cancer (CC) and because, as of 2024, investigations targeted to surgical CC patients are lacking in the pertinent literature, we decided to assess the predictive role of this scoring system in relation to postoperative course and survival of surgical patients affected only by this malignancy. However, as of 2024, the existing literature on CONUT has typically treated colorectal cancer (CRC) as a single homogeneous entity, often combining results for both colon cancer (CC) and rectal cancer (RC).

The Impact of Climate Change on Immunity and Gut Microbiota in the Development of Disease.

According to the definition provided by the United Nations, "climate change" describes the persistent alterations in temperatures and weather trends. These alterations may arise naturally, such as fluctuations in the solar cycle. Nonetheless, since the 19th century, human activities have emerged as the primary agent for climate change, primarily attributed to the combustion of fossil fuels such as coal, oil, and gas.

Pollutants, microbiota and immune system: frenemies within the gut.

Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses.

Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.

In recent years, there has been a growing interest in the concept of the "gut-brain axis". In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of "neuroinflammation".

Management of surgical diseases of Primary Hyperparathyroidism: indications of the United Italian Society of Endocrine Surgery (SIUEC).

A task force of the United Italian society of Endocrine Surgery (SIUEC) was commissioned to review the position statement on diagnostic, therapeutic and health‑care management protocol in parathyroid surgery published in 2014, at the light of new technologies, recent oncological concepts, and tailored approaches. The objective of this publication was to support surgeons with modern rational protocols of treatment that can be shared by health-care professionals, taking into account important clinical, healthcare and therapeutic aspects, as well as potential sequelae and complications. The task force consists of 12 members of the SIUEC highly trained and experienced in thyroid and parathyroid surgery.

Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective.

The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment.

Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo.

Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)-directed immunotherapy, including T cells bearing chimeric antigen receptors (CARs) and systemically injected bispecific T cell engagers (TCEs), has shown remarkable clinical activity, and several products have received market approval. However, despite promising results, most patients eventually become refractory and relapse, highlighting the need for alternative strategies.

Global left ventricular myocardial work index and medium-term adverse cardiovascular events after ST-elevation myocardial infarction.

Background: Left ventricular global longitudinal strain (GLS) has incremental prognostic value over ejection fraction (EF) in patients with ST-segment-elevation myocardial infarction (STEMI), but it is also load dependent. It has been recently demonstrated that Myocardial work (MW), integrating blood pressure with GLS, predicts long-term all-cause mortality. We aimed to further explore the prognostic value of MW for cardiovascular endpoints in patients with STEMI.