To determine the incidence rate of neoplasms among the GPSD population and compare it with the Spanish general population, as well as to identify its role as a paraneoplastic syndrome in terms of temporal criteria.

An observational, single-center, longitudinal study on GPSD patients (2015-2023) was conducted. Demographic, clinical variables and neoplasms found after GPSD diagnosis (excluding metastatic events or recurrences and non-melanoma skin cancer) were collected. In order to adjust by age and sex, we performed an indirect standardization method and calculated the standardized neoplasm ratio (SNR) and standardized incidence ratio (SIR).

Among 334 patients, 16 (4.8%) developed neoplasms, with 11 diagnosed within the first two years (7 within the first year). The SNR was 4.03 (CI 95% 1.53-6.53) in women and 2.37 (CI 95% 0.47-4.27) in men. Considering the neoplasms diagnosed in the two first years, the SNR were 2.42 (CI 95% 0.484-4.356) in women and 2.11 (CI 95% 0.258-3.868) in men.

We observed a high incidence rate of neoplasms in our women GPSD patients. While no statistical significance was reached in men or in cases beyond two years post-diagnosis, a tendency toward higher rates was noted. These findings emphasize the need for further research on the potential oncologic implications of GPSD.

Natural killer (NK) cell neoplasms are a diverse group of entities with often nonspecific clinical presentations, making immunophenotyping essential for diagnosis. Immunophenotyping by flow cytometry can identify clonal NK cell populations by detecting restricted expression patterns of NK cell receptors such as killer cell immunoglobulin-like receptors (KIRs). However, reactive NK cells may also demonstrate KIR restriction through expansion of self-KIR-expressing NK cells, leading to identification of NK clones of uncertain significance (NK-CUS). A well-described reactive NK subset, termed "adaptive" NK cells, arises in response to cytomegalovirus (CMV) infection or reactivation, often appears KIR-restricted, and is defined by coexpression of CD57 and the activating receptor NKG2C. Because CMV reactivation is common among patients undergoing evaluation for hematolymphoid malignancy, we hypothesized that NK-CUS may frequently correspond to this non-neoplastic adaptive NK cell subset. Here, we describe a flow cytometry panel for immunophenotypic characterization of cytotoxic lymphocytes that includes NKG2C, enabling detection of non-neoplastic adaptive NK cells. We show that NK-CUS frequently represent reactive NKG2C⁺ adaptive NK cells. We describe several cases that meet diagnostic criteria for NK-large granular lymphocytic leukemia (NK-LGLL) and demonstrate that the NK cell clones are non-neoplastic NKG2C⁺ adaptive NK cells arising in the setting of CMV viremia. Further, we show that NKG2C expression is uncommon by neoplastic NK cell proliferations with recurrent molecular or cytogenetic abnormalities. Collectively, we demonstrate that NKG2C has a high specificity for reactive NK cell populations, and its inclusion in NK cell immunophenotyping panels is a useful strategy to more reliably distinguish between neoplastic and reactive NK cell populations.

To evaluate health-related quality of life and the psychosocial dimension in pediatric cancer patients and analyze their relationship with the clinical evolution parameters of the disease.

Prospective, observational, and analytical study with consecutive sampling of 53 patients aged 5 to 18 years, conducted between May 1, 2022, and May 1, 2023, in the pediatric oncohematology unit at Materno-Infantil Hospital of Miguel Servet University Hospital (Zaragoza, Aragón, Spain). Health-related quality of life was assessed using the Pediatric Quality of Life Inventory Cancer Module version 3.0, and PD was assessed using the Pediatric Quality of Life Inventory version 4.0. The study was approved by Comité de Ética de la Investigación de la Comunidad Autónoma de Aragón (C.P.-C.I. PI22/247). Statistical analyses were performed using Jamovi® version 1.2.

A total of 46 patients participated (N = 46), with a mean age of 12.08 ± 4.05 years. Girls accounted for 30.43% of the sample, and the most prevalent cancer type was acute lymphoblastic leukemia (39.13%). Health-related quality of life in patients with sarcoma was significantly lower than in those with acute lymphoblastic leukemia (mean 40.7 vs. 72.6; p = 0.037; Cohen's d = 1.2), suggesting a clinically relevant impact in this subgroup. No significant differences in perceived quality of life were found in relation to participants' laboratory parameters.

Age, treatment received and hospital stay influence the various dimensions of health-related quality of life, however, cancer and analytical parameters do not influence the perception of the psychosocial dimension of health-related quality of life. Sarcoma reflects a worse health-related quality of life compared to other more common tumours.

Lipomas are among the most common specimens encountered in surgical pathology. Beyond distinguishing a lipoma from an atypical lipomatous tumor or well-differentiated liposarcoma (ALT/WDLS), there are important clinical considerations to keep in mind, as lipomas and lipomatosis may occur in association with various syndromes. These syndromes can be inherited or sporadic, and some are linked to an increased risk of other malignancies. Moreover, several are associated with systemic findings that carry significant morbidity and mortality. Careful attention to specific clinicopathologic features-together with molecular testing when indicated-can facilitate early recognition of these syndromes, which is essential for appropriate counseling and long-term surveillance. Despite numerous case reports and isolated studies, a comprehensive synthesis of these syndromes remains lacking. In this review, we aim to summarize the Syndromes Associated with Lipomatous Tumors (SALT) and highlight key clinicopathologic features relevant to diagnosis and management. We also hope that this overview will stimulate further research by providing a succinct framework for exploring potential biologic networks underlying the origin and development of these common neoplasms.

Secondary myelofibrosis (SMF) represents a late stage of polycythemia vera and essential thrombocythemia, with overall survival (OS) currently defined by the MYelofibrosis SECondary to PV and ET (MYSEC) Prognostic Model (MYSEC-PM). To identify additional myeloid neoplasm-associated cancer gene variants (CGVs) associated with SMF outcome, we evaluated next-generation sequencing panel testing in 644 patients within the MYSEC cohort. Overall, 429 (66.6%) subjects reported at least one CGV, with ASXL1, TET2 and DNMT3A being the most frequently involved. Specific molecular profiles affected OS (p < .001): U2AF1, TP53 or SRSF2 variants (UTS, 9.3% of cases, median OS 4.1 years) and ASXL1 without UTS (25.3%, median OS 8.4 years). By integrating these genetic signatures within the MYSEC-PM through penalized Cox regressions, we identified the following independent predictors (p from < .0001 to .02) and weighted: hemoglobin <11 g/dl (1 point), circulating blasts ⩾3% (2), platelets <150 × 109/l (2), age (0.21 points/year), ASXL1 without UTS mutations (1) and any UTS mutations (3). Finally, we developed the MYSEC-molecular prognostic model (MYSEC-mPM) allocating 582 SMF patients into four categories with different OS (p < .001): low (median OS 18.0 years, 95%CI: 14.2-not reached; score <14), intermediate-1 (8.8. years, 95%CI: 7.7-9.7; score 14-16), intermediate-2 (4.6 years, 95%CI: 3.1-7.2; score 17-18), and high risk (1.9 years, 95%CI: 1.2-2.5; score ⩾19). Additionally, in 381 SMF with available cytogenetics, the MYSEC-mPM was implemented with complex/monosomal karyotype, generating the karyotype-enhanced MYSEC-kmPM. Our study shows that genomic and cytogenetic profiling improve survival prediction in SMF, outperforming the MYSEC-PM.

Despite Australia's overall health achievements, persistent health disparities exist among Aboriginal and Torres Strait Islander communities in rural Victoria, Australia.

This paper explores the importance of respectful community engagement and local co-design in addressing the challenges faced by rural Aboriginal and Torres Strait Islander communities in accessing healthcare, encompassing historical factors and systemic challenges.

The impact of community empowerment and collaboration in addressing the challenges faced by rural Aboriginal and Torres Strait Islander communities in accessing healthcare, including geographical barriers in rural Aboriginal and Torres Strait Islander communities, are explored. A community-led approach to overcome barriers and promote culturally sensitive healthcare, emphasising the importance of empowering Aboriginal and Torres Strait Islander leaders in program design and evaluation, is proposed. An excellent example of local co-design in action are Aboriginal Community Controlled Health Organisations (ACCHOs), as showcased by their effective response to the COVID‑19 pandemic. Examples of effective, yet simple, strategies for the mainstream general practitioner in providing culturally safe primary care for Indigenous patients are also discussed.

Mycoplasma pneumoniae (MP) is a common pathogen responsible for diverse infections in children and adolescents, primarily affecting the respiratory tract. Besides causing atypical pneumonia, MP can also lead to extrapulmonary manifestations, including mucocutaneous, hematological, neurological, cardiac, and gastrointestinal symptoms. These extrapulmonary manifestations are often overlooked, complicating diagnosis and management. Here, we delineate the spectrum of cutaneous and non-cutaneous diseases caused by MP in children, focusing on the pathophysiology, clinical features, and treatment of mucocutaneous manifestations.

The regional enrollment of participants in pivotal randomized controlled trials (RCTs) often does not represent the regional distribution of cardiovascular diseases. Over the past four decades, trials have enrolled participants primarily from North America and Europe, limiting the global generalizability of findings. In this Perspective, we review the evolution of regional participation in RCTs, using heart failure as a case study to assess temporal trends, current gaps in representativeness and opportunities for improvement. We assess the regulatory, logistical and financial barriers to clinical trial enrollment in underrepresented regions. We examine the manner in which global regions have been classified in trials, and propose a standardized regional classification system for reporting and subgroup analysis. To improve regional representativeness, we suggest targeted strategies that address barriers faced at the national, regulatory, sponsor or funder, institution and patient level. We also recommend the use of a representativeness index during trial planning and site selection to enhance regional representativeness. Expanding trial participation beyond historically dominant regions could be a key step in improving trial efficiency, external validity and global health equity.

In natural settings, energy storage and mobilization maintain a dynamic balance in response to recurrent overfeeding and fasting. Imbalanced energy storage and mobilization lead to a variety of metabolic dysfunctions. However, whether the metabolic status directly couples with epigenetic modifications and transcriptional outputs remains unclear. Here, we aimed to investigate the epigenetic mechanism underlying this adaptive balance and observed that, in an overfeeding state, increased glucose availability is associated with enhanced histone acetylation coinciding with acetyl-CoA production in an acyl-CoA short-chain synthetase 2 (ACSS2)-dependent manner, contributing to energy storage (e.g., lipogenesis); in contrast, in the fasting state, elevated D-β-hydroxybutyrate levels are associated with altered histone acetylation distribution and transcriptional programs, supporting a metabolic shift from anabolism to catabolism, such as fatty acid oxidation. In both overfeeding and fasting states, acetylated lysines in the histone require BRD4 to recognize and initiate transcriptional regulation. Inhibition of BRD4 leads to context-dependent phenotypic effects: it ameliorates non-alcoholic fatty liver disease (NAFLD) pathology induced by a high-fat diet, while it exacerbates hepatic steatosis in fasted mice or mice fed a ketogenic diet. Thus, these findings highlights that epigenetic regulation of energy storage and mobilization is closely linked to the availability of glucose, and ketone bodies. Moreover, our study revealed that modulation of ACSS2-associated pathway may represent a potential strategy for treatment of metabolic diseases, such as NAFLD.

Hematopoietic stem cell transplantation (HSCT) is a cornerstone in the treatment of hematological disorders. However, its application is frequently complicated by acute and chronic graft-versus-host disease (aGVHD/cGVHD), pathological conditions in which donor-derived immune cells attack host tissues. With suboptimal survival rates and limited therapeutic options, GVHD remains a major clinical challenge. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic modality due to their immunomodulatory capabilities, yet standardized protocols for their use in preventing or treating GVHD have not been established.

We performed a comprehensive literature search of PubMed, Web of Science, EMBASE, and the Cochrane Library up to 10 February 2025 to identify eligible randomized controlled trials (RCTs). Study selection was based on the PICOS framework, and the risk of bias was assessed using appropriate quality appraisal tools. Outcome data were systematically extracted and synthesized via meta-analysis.

A total of 15 RCTs were included. The meta-analysis revealed that MSC administration significantly reduced the incidence of aGVHD (OR: 0.47; 95% CI 0.32-0.71; p = 0.00003) and cGVHD (OR: 0.50; 95% CI 0.34-0.74; p = 0.0005) compared with controls. MSC therapy was also associated with improved response rates in steroid-refractory aGVHD (SR-aGVHD) (OR: 1.50; 95% CI 1.04-2.17; p = 0.03).

MSCs demonstrate efficacy in preventing both aGVHD and cGVHD following HSCT, particularly in moderate to severe forms. A dose range of 1 × 10⁶ to < 4 × 10⁶ cells/kg was associated with optimal prophylactic outcomes. For SR-aGVHD, MSC infusion resulted in significantly higher remission rates compared to conventional treatments, especially in severe cases.