Citations

ABSTRACT Genital lymphedema presents significant challenges in surgical management, with limited effective interventions. This case report explores the use of contrast‐enhanced ultrasound (CEUS) with microbubble injection as an alternative adjunct technique for lymphatic mapping in lymphaticovenous anastomosis (LVA) surgery for genital lymphedema. A retrospective chart review approved by our institutional review board was performed for patients with genital lymphedema undergoing LVA surgery between 2020 and 2024. Intraoperative CEUS for lymphatic mapping was used with intradermal injection of microbubble suspension Lumason (Bracco Suisse, Monroe Township, NJ, USA). Data regarding demographics, comorbidities, clinical and operative characteristics, complications, and surgical outcomes were retrieved. Three patients with genital lymphedema who underwent LVA were identified. The first patient was a 34‐year‐old female with recurrent lymphangioma circumscriptum and vesicular drainage. She successfully underwent CEUS‐guided LVA followed by two debulking procedures. The second patient was a 16‐year‐old male with congenital scrotal and lower extremity lymphedema. He had two CEUS‐guided LVAs and subsequent debulking for anterior scrotal swelling, with long‐term reduction in edema. The third patient was a 31‐year‐old female with primary lymphedema of the right lower extremity and genital region. She underwent seven CEUS and indocyanine green lymphography (ICG) guided anastomoses targeting the mons and lower abdomen, resulting in substantial symptomatic and volumetric improvement. CEUS detected target lymphatic vessels in all cases, including cases where ICG imaging failed to identify candidate lymphatic vessels. CEUS with intradermal microbubble injection successfully identified target lymphatic vessels in the preoperative planning for LVA surgery in patients with genital lymphedema.

ABSTRACT Objective Sacrifice of pterygopalatine fossa (PPF) neurovascular structures during endoscopic endonasal transpterygoid approach (EETPA) may impact a patient's comorbidity. We present anatomical and surgical techniques for maximizing PPF transposition while preserving its neurovascular structures through orbito‐pterygo‐sphenoidal (OPS) ligament release and descending palatine canal (DPC) decompression. Methods The EETPA was performed on six specimens. Two measurements were obtained to assess PPF transposition: (1) Inferior transposition (distance between the superior margins of the base of the pterygoid process and PPF); (2) lateral transposition (distance from Eustachian tube lateral margin to PPF medial margin). Results After incising the OPS ligament, a mean gain of PPF inferior transposition of 7 mm (4–11 mm, p = 0.03) was observed, with a total inferior transposition of 12 mm (6–15 mm). Subsequently, the posterior half of the inferior turbinate was removed and the DPC was decompressed, with a mean gain of PPF lateral transposition of 12 mm (range 8–15 mm, p = 0.01). Conclusion The OPS ligament release offers a significant advantage for the PPF inferior transposition, allowing access to the inferolateral recess of the sphenoid sinus, cavernous sinus, and paramedian middle cranial fossa, while the DPC decompression provides a significant advantage for the PPF lateral transposition, granting access to the Eustachian tube and ITF. Level of Evidence N/A.

Abstract Deconvolution models are a powerful tool for extracting cell-type-specific information from bulk gene expression profiles. Current methods leverage advanced machine learning models and high-resolution sequencing, like single-cell RNA-sequencing, showing promising results across diverse tissues and conditions. However, they still present important limitations: First, many depend on selecting a robust reference, which can strongly affect the deconvolution. Second, pseudobulk data used for training and real bulk RNA-seq samples often exhibit strong distribution shifts, which are currently unaccounted for. Finally, most deconvolution approaches behave as black boxes, which can compromise the reliability of the results. Here, we present Sweetwater, an adaptive and interpretable autoencoder that efficiently deconvolves bulk samples leveraging multiple classes of reference data. Moreover, we propose an improved way of generating training data from a mixture of FACS-sorted FASTQ files, reducing platform-specific biases and outperforming current single-cell-based references. Furthermore, we introduce a gold standard dataset to facilitate fair and accurate evaluation of deconvolution approaches. Finally, we demonstrate that Sweetwater adapts effectively to deconvolved samples during training, uncovering biologically meaningful patterns and enhancing result’s reliability. Sweetwater is available at https://doi.org/10.6084/m9.figshare.29609180, and we anticipate it will expedite the accurate examination of high-throughput clinical data across diverse applications.

ABSTRACT Aims The impact of treatment for tricuspid regurgitation (TR) across different levels of left ventricular ejection fraction (LVEF) remains uncertain. This study aimed to compare the outcomes of surgical and transcatheter tricuspid valve interventions (TTVI) to conservative (medical) management across LVEF categories. Methods and results Patients with severe isolated TR from the TRIGISTRY, a multicentre international registry, were categorized based on LVEF (preserved ejection fraction [pEF]: ≥50%, mildly reduced ejection fraction [mrEF]: 41–49%, and reduced ejection fraction [rEF]: ≤40%). We assessed the impact of treatment modality and procedural success (mild-to-moderate or lower residual TR) on 2-year survival within each LVEF category. Among 2384 patients, 1383 had pEF, 400 had mrEF, and 601 had rEF. Compared to conservative management, surgery (p < 0.0005) and TTVI (p < 0.0001) were associated with a survival benefit in patients with pEF. No significant survival advantage was observed in patients with mrEF (p = 0.28 for both), nor in those with rEF (p = 0.76 and p = 0.22, respectively). Similar results were obtained when surgical and transcatheter interventions were grouped (p < 0.0001, p = 0.17 and p = 0.29 in patients with pEF, mrEF and rEF, respectively). Patients with residual TR after TTVI exhibited a trend toward worse survival compared to those managed conservatively across all LVEF categories (p = 0.47, p = 0.33 and p = 0.008 in pEF, mrEF and rEF, respectively). Conclusions Transcatheter tricuspid valve intervention, whether surgical or transcatheter-based, was associated with improved survival in patients with pEF but not in those with mrEF or rEF. Residual TR remained a significant prognostic factor across the entire LVEF spectrum. These findings highlight the need for careful patient selection when considering TTVI in individuals with rEF.

IMPORTANCE: Accurate and reliable sedation assessment is crucial to improving patient outcomes in the ICU. OBJECTIVE: To evaluate the inter-rater agreement and reliability of Richmond Agitation Sedation Scale (RASS) assessments between bedside nurses and trained investigators in patients receiving mechanical ventilation in the ICU. DESIGN, SETTING, AND PARTICIPANTS: An assessor triad, comprising an ICU nurse providing direct patient care and two trained investigators, simultaneously performed RASS assessments during 79 encounters with 62 unique patients receiving mechanical ventilation at two ICUs at a tertiary care academic hospital in Colorado. A total of 58 nurses participated in the study. MAIN OUTCOMES AND MEASURES: The inter-rater reliability of RASS assessments was evaluated with the intraclass correlation coefficient (ICC) and weighted kappa (κ), and inter-rater agreement was evaluated with percentage agreement and Bland-Altman analysis. RESULTS: Acute respiratory failure (55%) and altered mental status (21%) were the most common reasons for mechanical ventilation. Most patients were receiving one (interquartile range, 0.5–2) continuous sedative during the assessment. The inter-rater reliability of RASS assessments between the nurses and investigators (ICC, 0.728–0.779; weighted κ, 0.62–0.63) was lower than between the two investigators (ICC, 0.891; weighted κ, 0.80). The assessor triad agreed on the same RASS values in only 35% of observations. The average differences in RASS were greater between the investigators and nurses, ranging from –0.658 to –0.544, compared with 0.114 between the two investigators. Compared with the mean of the two investigators, RASS values recorded by nurses were more likely to be higher (52% of observations), indicating a lighter sedation level. In 16% of observations, at least one assessor commented on uncertainty or ambiguity with the RASS. CONCLUSIONS AND RELEVANCE: The inter-rater reliability of RASS assessments was high. However, we observed variations in the degree of agreement by assessor category. Further studies are necessary to explore how factors such as assessor characteristics, ICU environment, and patient conditions influence the inter-rater agreement of the RASS in contemporary ICU practices.

Importance Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a substantial burden. Standardized global prevalence estimates and data on associated sociodemographic and risk factors are lacking. Objective To estimate the global prevalence of HS and study differences in prevalence by age, sex, geographical location, body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), smoking status, gross domestic product (GDP), and Human Development Index (HDI). Data Sources and Study Selection Included studies were conducted using the standardized Global Hidradenitis Suppurativa Atlas methodology with finalized data collection before May 19, 2023. Studies were required to use a population-based sampling method and conduct clinical confirmation of HS diagnosis following a screening questionnaire. Data Extraction and Synthesis Data were independently extracted from relevant studies by 2 reviewers (D.B. and C.E.M.) using a standardized form. Extracted variables included geographic location, age, sex, BMI (median and BMI >30), smoking status, HS prevalence estimates (with 95% CIs), GDP, and HDI. A proportional meta-analysis using a random-effects model was conducted on the included studies. Main Outcomes and Measures The primary outcome was the point prevalence of HS, confirmed by clinical examination. Secondary outcomes included differences in HS prevalence by sex, age, BMI category, smoking status, and country-level socioeconomic indicators (GDP and HDI). All outcomes were prespecified before data analysis. Results The sample included 22 743 participants, identifying 247 patients with HS, across 25 studies in 23 countries spanning 6 continents. The median proportion of female patients with HS was 55.6%, and the median age was 34.5 years. While the prevalence estimates showed considerable inconsistency ( I 2 > 75%; τ 2 = 0.747), the overall random-effects global prevalence of HS was 0.99% (95% CI, 0.67%-1.46%). Female sex was the only factor observed to be associated with the prevalence estimates (β = 1.02; 95% CI, 1.01-1.03). Conclusions and Relevance In this meta-analysis, an estimated global prevalence of HS between 0.67% and 1.46% surpassed previous global estimates. Substantial global variations in HS prevalence were also observed. Female sex was the only factor associated with prevalence in this sample. Future studies assessing genetic, environmental, and etiological factors are warranted to explain the heterogeneity in prevalence.

Background: Ischemia–reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI). While the precise mechanisms of AKI are still incompletely defined, extensive evidence highlights tubular cell injury and death as key factors in its development. Necroptosis has recently emerged as a critical pathway in the pathogenesis of ischemia–reperfusion-induced AKI (IR-AKI). Although sex differences in susceptibility to IR-AKI have been reported, it remains unclear whether there are sex differences in necroptosis dynamics and whether these differences underlie the observed sexual dimorphism in kidney IRI. This study aimed to address these questions. Methods: male and female C57BL/6 J mice were subjected to AKI via ischemia induced by bilateral renal pedicle clamping for 18 min at 37 °C. Plasma, urine, and kidney samples were collected at 0 h, 3 h, 6 h, 12 h, 24 h, 48 h, and 72 h post-reperfusion. Kidney injury and function were assessed by measuring plasma creatinine (PCr), blood urea nitrogen (BUN) levels, and histological damage (PAS and cleaved caspase3 staining). Necroptosis activation was assessed by quantifying phosphorylated forms of key markers: p-RIPK1 and p-MLKL. To explore the role of sex hormones in regulating necroptosis dynamics, ovariectomized female mice were subjected to the same IR-AKI protocol, and their kidney injury and functional outcomes were compared with those of intact counterparts. Results: The PCr was 0.35 ± 0.04 and 0.32 ± 0.06 mg/dL for males and females, respectively, at 3 h of IR. The levels exponentially increased to 2.05 ± 0.18 at 48 h post-reperfusion in the males but only gradually to 0.94 ± 0.13 mg/dL in females. Necroptosis activation began as early as 3 h post-IR in males but was delayed until ~6 h in females. Males exhibited stronger and more sustained necroptosis activation than females, showing elevated phosphorylation levels of pRIPK1 and pMLKL in Western blot. Female sex hormone deficiency exacerbated the female response to IR-induced injury, which reduced the sex difference in the dynamic of the necroptotic activation and subsequent kidney injury. To our knowledge, this is the first study to characterize sex differences in the initiation and progression of necroptosis and subsequent injury in a mouse model of IR-AKI. Conclusions: Our findings reveal distinct temporal patterns of programmed cell death between sexes. Necroptosis-targeted therapies require early intervention in males, which can be delayed in females after IR-AKI, highlighting the need for sex-specific therapeutic windows.

This cross-sectional study examines the lawsuits that followed national and international policies for pembrolizumab approval.

Background: Patients with end-stage heart failure-related cardiogenic shock (HF-CS) are conclusively associated with a poor health-related quality of life (HRQL). Axillary mechanical circulatory support (aMCS), such as the Impella 5.5, is increasingly used in this population and may improve HRQL during hospitalization by providing enhanced left ventricular unloading. We aimed to assess changes in HRQL between admission and two weeks after Impella 5.5 placement in patients with HF-CS, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: We conducted a prospective longitudinal analysis on patients with the Impella 5.5 between May 2023 and July 2023. Participants completed the condensed KCCQ-12 at admission and again two weeks post-implantation. Changes in the scores were evaluated using the Wilcoxon signed-rank test. Results: Fifteen patients were enrolled. The median age was 59 years (50–63), and the median ejection fraction at implantation was 20% (15–30). On admission, most patients reported an overall HRQL of poor-to-fair (46.7%) according to the summary KCCQ-12 score. The median overall summary score increased significantly after Impella 5.5 support (50.52 vs. 28.13, p = 0.005). Symptom frequency (70.83 vs. 43.75, p = 0.009) and quality-of-life (50.00 vs. 12.50, p = 0.023) domains improved significantly, while physical limitation showed a positive trend and social limitation remained unchanged. These HRQL improvements occurred alongside a significant shift toward lower SCAI shock stages, marked increases in cardiac output and cardiac index, and no escalation in vasoactive-inotropic requirements. Conclusions: Impella 5.5 support in HF-CS patients was associated with early and clinically meaningful improvements in HRQL, particularly in symptom frequency and quality of life, during the critical pre-transplant or recovery period. These findings suggest that the Impella 5.5 may provide both physiological and patient-perceived benefits in this high-risk population.