Citations

Background: Acute heart failure affects ~9% of patients with hematological malignancies. This study aimed to evaluate the impact of acute heart failure on in-hospital mortality among patients with hematological malignancies and to identify independent predictors of mortality in this population. Methods: The National Inpatient Sample (2016–2021) was queried for adults (⩾18 years of age) with hematological malignancies and those who experienced in-hospital mortality. Among these, we identified patients who were hospitalized with a diagnosis of acute heart failure. Univariate analysis and multivariate regression were employed to analyze the mortality risk. A p ⩽ 0.05 was considered significant. Results: Among 40,246 patients with hematological malignancies who died in the hospital, the univariate analysis showed a higher in-hospital mortality in the acute heart failure cohort compared to the non-acute heart failure group (8.08% versus 4.52%, p < 0.001). However, after adjusting for sociodemographic factors and comorbidities, acute heart failure was associated with a lower risk of in-hospital mortality (OR 0.87, 95% CI 0.84–0.9, p < 0.001). Predictors of mortality in the acute heart failure cohort were age >60 years, hematopoietic stem cell transplant, severe sepsis, arrhythmias, infective endocarditis, bleeding from any source, acute respiratory failure, hepatic dysfunction, metabolic encephalopathy, and invasive ventilation (all p < 0.01). On subgroup analysis, acute myeloid leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma had a higher in-hospital mortality in the acute heart failure cohort compared to the non-acute heart failure group ( p < 0.001). Conclusion: Acute heart failure in patients with hematological malignancies was associated with poor outcomes in the presence of severe sepsis, organ dysfunction, and the need for mechanical ventilation. Close monitoring and a multidisciplinary team approach are recommended to optimize the treatment plan for this population.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) often present with associated mild hyperprolactinemia, described in literature as "stalk effect." The presence of preoperative hyperprolactinemia caused by tumor compression of the pituitary stalk and endocrinological outcomes has been noted; however, a detailed investigation on the impact on perioperative endocrinological outcome is lacking. The authors aimed to determine whether elevated preoperative serum prolactin concentrations are associated with increased risk of perioperative pituitary dysfunction in patients with NFPAs undergoing endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a single-center retrospective cohort study of patients who underwent ETS for NFPAs between January 2013 and April 2023. Patients were divided into two groups based on preoperative prolactin concentrations: normal or hyperprolactinemic (prolactin values above upper limit of reference range, adjusted for sex). Outcomes included perioperative endocrinological function and surgical outcomes. Multivariable analysis was conducted to identify factors associated with perioperative endocrinological function outcomes. RESULTS Of 244 patients (140 [57%] males; median age 59 years) with a median follow-up of 65 months, 131 (54%) had hyperprolactinemia. Compared with patients with normal preoperative prolactin levels (n = 113), the hyperprolactinemia group had similar tumor size (median diameter 2.5 cm vs 2.3 cm, p = 0.102) but higher rates of cavernous sinus invasion (99% vs 91%, p = 0.035), pituitary stalk deviation (95% vs 74%, p = 0.001), stalk bending (14% vs 1%, p = 0.001), preoperative secondary hypothyroidism (39% vs 22%, p = 0.005), and adrenal insufficiency (AI; 34% vs 22%, p = 0.048). Postoperatively, the hyperprolactinemia group showed higher rates of new secondary hypothyroidism (16% vs 7%, p = 0.048) and new permanent AI (16% vs 6%, p = 0.046). Multivariable analysis revealed preoperative high prolactin as an independent predictor of preoperative secondary hypothyroidism (OR 1.83, 95% CI 1.17–3.44; p = 0.046) and its postoperative deterioration (OR 2.65, 95% CI 1.02–7.69; p = 0.042). Maximum tumor diameter was also a significant predictor of various endocrinological dysfunctions both pre- and postoperatively. CONCLUSIONS Preoperative hyperprolactinemia in patients with NFPA is associated with higher risks of specific perioperative endocrinological dysfunction and pronounced pituitary stalk deviation. These findings highlight the utility of preoperative prolactin levels as a biomarker for predicting postoperative endocrinological outcomes, potentially enhancing risk assessment and guiding personalized perioperative management.

Background Myxomatous mitral valve disease (MMVD) is a degenerative disorder marked by excess tissue fibrosis and matrix remodeling, leading to leaflet prolapse. While recent studies linked transforming growth factor beta (TGF-β) activation to MMVD development and progression, upstream regulators of this and other modulatory/causal pathways remain largely unexplored. Objectives In this study, we utilized high-throughput sequencing to conduct unbiased analyses of mRNA and microRNA (miRNA) levels in myxomatous and healthy mitral valve tissues, aiming to uncover novel molecular mechanisms involved in MMVD. Methods We defined differentially expressed mRNAs and miRNAs transcripts displaying a fold-change > 1.5 and P < .05. Pathway analysis was performed using Ingenuity Pathway Analysis and DAVID, with key findings validated via qRT-PCR. A total of 2378 transcripts were differentially expressed between myxomatous and normal valves. Established pathways, including TGF-β signaling, were confirmed as major contributors to MMVD. Additionally, Random Forests with Boruta Feature Selection identified transcripts with a 95% likelihood of importance, and subsequent pathway analysis on this subset of genes revealed unique signaling pathways. Results Most notably, circadian rhythm disruption emerged as a novel, highly ranked pathway in MMVD. Key miRNAs, such as miR-1, miR-133a, and miR-217 were highlighted as highly relevant, with miRNA–mRNA interactions displaying distinct molecular signatures predictive of MMVD. Conclusions Collectively, this study represents the first comprehensive analysis of both miRNA and mRNA expression in MMVD, revealing both established and novel disease-associated pathways. The discovery of circadian rhythm disturbances and new regulatory miRNAs suggests promising directions for further research and potential therapeutic targets for nonsurgical treatment strategies in patients with MMVD.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of postthymic T cell neoplasms, with ~40% classified as PTCL–not otherwise specified (PTCL-NOS). PTCL-GATA3, a molecularly defined subtype, associated with T helper 2 (T H 2)–like differentiation and poor prognosis, has frequent co-occurrence of TP53 loss/mutation and heterozygous PTEN loss. CD4+ T cell conditional mouse models with Trp53 mutation/deletion and Pten loss demonstrated mature T cell lymphomas (mTCLs) with T H 2-like transcriptomic and immunophenotypic profiles. Molecular studies revealed that codeletion of Trp53/Pten induced T cell receptor and Janus kinase–signal transducer and activator of transcription signaling, promoting T H 2 differentiation while inhibiting T H 1 differentiation. These findings were validated by CRISPR editing of TP53/PTEN loss in human CD4+ T cells and mechanistically evaluated the p53 binding region in intron-3 of GATA3, resulting in transcriptional repression. Transcriptomic profiles of m-TCLs recapitulated human-PTCL-GATA3 transcriptome and distinguished PTCL-NOS subtypes. Preclinical assessment of m-TCLs with PI3Kγ/δ inhibitors significantly improved survival, supporting a therapeutic approach for the p53-aberrant PTCL-GATA3.

Abstract The Guardian table is widely utilized for combined hip arthroscopy and periacetabular osteotomy (PAO) due to its postless traction design and the ability to perform both procedures without the need for redraping. This retrospective cohort study reports one surgeon’s use of the Guardian table extension during combined hip arthroscopy and PAO and the occurrence of intraoperative posterior column fractures. Seventy-two consecutive PAO procedures performed at a single institution between February 2023 and January 2025 were analysed. Procedures involving concomitant hip arthroscopy (n = 26) utilized the Guardian table, whereas those without arthroscopy (n = 46) used a conventional radiolucent table. Patient demographics, clinical data, and complications were reviewed. Additionally, mechanical testing quantified table stability by measuring peak absolute acceleration (‘table bounce’) using accelerometry during simulated malleting. The incidence of intraoperative posterior column fractures was significantly higher with the Guardian table (4/26, 15.4%) compared to the conventional table (0/46, 0%; P = .0062). Mechanical testing demonstrated significantly greater table bounce for the Guardian table (69.1 ± 3.4 m/s2 versus 28.2 ± 4.4 m/s2, P &lt; .001). Patient characteristics and surgical complexity did not differ significantly between fracture and non-fracture cases. These findings suggested that the Guardian table extension system was associated with increased risk of posterior column fractures, likely due to lack of distal support and stability. Surgeons should consider alternative table setups or intraoperative support modifications to mitigate this risk during PAO procedures.

ABSTRACT Background The efficacy and safety of PolarX cryoballoon for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF) is unclear. Methods PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were systematically searched for studies comparing the PolarX vs. standard cryoballoon (CB‐2/CB‐4). Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs) were computed for binary and continuous outcomes, respectively. Results This systematic review and meta‐analysis included 2 randomized controlled trials and 18 observational studies with a total of 7107 patients, of whom 3.188 (44.8%) underwent ablation with PolarX. When compared to standard cryoablation, PolarX had similar incidence of atrial arrhythmias recurrence (OR 1.04; 95% CI 0.82–1.32; p = 0.73), acute PVI success (OR 0.91; 95% CI 0.31–2.68; p = 0.98), and procedural duration (MD 3.41; 95% CI ‐2.89 to 9.71; p = 0.29). However, PolarX was associated with higher persistent phrenic nerve palsy (OR 2.17; 95% CI 1.26–3.74; p = 0.005) and a lower nadir temperature in all veins. Additionally, in a subgroup analysis of randomized trials and propensity score matching studies, similar findings were noted for recurrence of atrial arrhythmias. Conclusion In patients with AF undergoing PVI, PolarX had similar acute PVI success, procedural duration, and recurrence of atrial arrhythmias as compared with standard cryoballoon technology, however, was associated with a lower nadir temperature, and higher rates of persistent nerve palsy.

Background This systematic review and meta-analysis synthesized migraine-related disability outcomes according to headache frequency subclassifications, including low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM) and chronic migraine (CM). Methods We searched the PubMed and Cochrane Library (CENTRAL) up to 16 October 2024 for peer-reviewed non-interventional studies reporting migraine-related disability outcomes in CM and subclassifications of episodic migraine (e.g. LFEM and HFEM). Eligible studies with an HFEM subgroup were grouped by headache frequency measure (monthly migraine days [MMD] or monthly headache days [MHD]), HFEM subgroup, disability parameter and study setting. Random-effects meta-analyses were conducted on groups with three or more studies, with the results presented in forest plots. Risk of bias was assessed using Joanna Briggs Institute tools. Results Of the 32 included studies, 27 were grouped, yielding five meta-analysis groups containing three or more studies. All five groups had an HFEM subgroup of 8–14 MHD. Accordingly, we classified LFEM as 0–7 MHD and CM as ≥15 MHD. Ten studies contributed data to the five meta-analysis groups. Estimated pooled values are reported by headache frequency subgroup for each meta-analysis group: LFEM (95% confidence interval [CI]), HFEM (95% CI) and CM (95% CI). For meta-analysis group 1, four population-based studies reported Migraine Disability Assessment (MIDAS) Grade IV proportions, with pooled values of 11.1% (7.1–17.1), 43.9% (31.8–56.9) and 57.5% (42.7–71.1), respectively. For meta-analysis group 2, five population-based studies documented Work Productivity and Activity Impairment (WPAI) outcomes. Pooled mean overall work productivity impairment (OWPI) scores were 36.9% (30.8–43.1), 44.7% (38.4–51.0) and 52.0% (47.7–56.3), respectively. Pooled mean activity impairment (AI) scores were 36.4% (33.7–39.1), 46.4% (42.8–50.0) and 53.5% (52.1–54.8), respectively. For meta-analysis group 3, three clinic-based studies presented MIDAS Grade IV proportions. Pooled values were 15.0% (4.4–40.5), 42.4% (17.1–72.4) and 65.7% (30.3–89.4), respectively. For meta-analysis group 4, three clinic-based studies reported WPAI outcomes. Pooled mean OWPI scores were 28.8% (21.6–35.9), 40.2% (36.2–44.2) and 49.6% (46.3–52.9), respectively. Pooled mean AI scores were 29.4% (21.9–36.9), 43.5% (39.0–48.1) and 51.6% (48.8–54.4), respectively. For meta-analysis group 5, three clinic-based studies detailed MIDAS scores. Pooled mean scores were 10.7 (3.9–17.5), 23.9 (9.4–38.4) and 49.6 (15.8–83.3), respectively. Conclusions This study showed a pattern of increasing migraine-related disability with rising headache frequency. Regardless of study setting, our meta-analyses also suggested a severe level of disability in many individuals (42%–44%) with HFEM, highlighting an unmet need for more effective migraine management. Disability burden and headache frequency should both be considered when determining treatment needs and therapy access, particularly for patients with HFEM. Study Registration: INPLASY2024120039.

Key Points Serum glycerol-3-phosphate (G3P) levels were significantly associated with higher fibroblast growth factor 23 levels in ESKD. Pathway and mediation analyses identified the pentose phosphate pathway as the top mediator of the relationship between serum G3P and fibroblast growth factor 23. The role of G3P in ESKD provides new insights into potential therapeutic targets for CKD-mineral and bone disorder. Background Fibroblast growth factor 23 (FGF23) is a key regulator of mineral metabolism that is independently associated with mortality in patients with ESKD. Glycerol-3-phosphate (G3P), a byproduct of glycolysis that can be derived from injured kidneys, stimulates FGF23 production. We aimed to determine if serum G3P is associated with FGF23 levels in patients with ESKD and identify potential molecular pathways that mediate their relationship. Methods We conducted a cross-sectional study of 99 nondiabetic patients with ESKD on hemodialysis. We used linear regression to examine the association between G3P terciles and log-transformed C-terminal FGF23 levels, adjusting for demographics, coronary artery disease, serum calcium, phosphorus, and parathyroid hormone. Mann–Whitney U tests compared 247 serum metabolite levels between the first and third FGF23 terciles; significant metabolites ( P < 0.01) were selected for pathway enrichment analyses. Top pathway scores were used in mediation analyses. Results The median age of participants was 54 years (interquartile range [IQR], 44–63), 38% were women, 71% self-identified as Black, and 27% had coronary artery disease. The median FGF23 level was 777 (interquartile range, 222–1310) RU/ml. In adjusted analyses, compared with participants with the lowest G3P tercile, those with the highest G3P tercile had a 95% higher FGF23 level (95% Confidence Interval, 6% to 260%; P = 0.04). Of the 27 metabolites significantly associated with FGF23 levels, pathway enrichment analysis identified the pentose phosphate pathway as the top hit (impact score=0.33, false discovery rate-adjusted P value = 0.01). The pentose phosphate pathway mediated the relationship between G3P and FGF23, resulting in a 62% change in the β coefficient. Conclusions In nondiabetic patients with ESKD on hemodialysis, serum G3P positively correlated with serum C-terminal FGF23, and this relationship was mediated by the pentose phosphate pathway. Exploring the pentose phosphate pathway could yield critical mechanistic insights into the regulation of FGF23, enhancing our understanding of its broader biologic functions.

Since Tanzer’s seminal work introducing costal cartilage for ear reconstruction, subsequent advances by Brent, Nagata, and Firmin have refined surgical techniques and aesthetic outcomes. However, fundamental aspects of the procedure—such as planning incisions, achieving accurate ear positioning, and guiding chest wall incisions for rib harvest—have seen limited innovation. The current standard practice of using projection paper or transparent templates to replicate the contralateral ear position remains imprecise. Similarly, autologous cartilage harvest can be particularly challenging in patients with higher BMI, due to difficulty in accurate rib palpation and visualization. Misplaced chest wall incisions can result in suboptimal rib harvest, longer operative times, and increased morbidity. In this study, we introduce patient-specific, three-dimensional (3D) printed masks, termed hEARo masks, as a novel and user-friendly tool for ear framework positioning. Furthermore, we present the integration of augmented reality (AR) technology to enhance preoperative planning and intraoperative guidance during microtia repair, enabling more precise incision placement for rib harvest. The combined use of 3D printing and AR facilitates complex ear reconstruction, offering increased surgical precision, reduced operative time, and potentially improved patient outcomes. These innovations represent a significant advancement in the personalization and accuracy of auricular reconstruction.