Hospital Reina Sofía de Murcia

Whipple's disease (WD) is a rare infectious disease caused by Tropheryma whipplei , which primarily affects the gastrointestinal tract but may also involve the joints, central nervous system, and skin. Although cutaneous manifestations are often overlooked, they can provide valuable diagnostic clues. We report the case of a 54-year-old male with long-standing seronegative migratory polyarthritis refractory to conventional treatment, who subsequently developed multiple subcutaneous inflammatory nodules and systemic symptoms. Histopathological examination of these lesions revealed a non-vasculitic, septal-predominant panniculitis with foamy macrophages containing periodic acid-Schiff (PAS)-positive diastase-resistant intracytoplasmic inclusions, raising a strong suspicion of Whipple's disease. Subsequent duodenal biopsies confirmed the diagnosis by electron microscopy and polymerase chain reaction (PCR) for T. whipplei . Panniculitis in WD represents a highly specific but rarely reported finding, characterized by thickened subcutaneous septa with partial lobular involvement, foamy macrophage infiltration, and absence of vasculitis. A literature review identified 15 cases of histologically confirmed WD-associated panniculitis, suggesting that this manifestation may be under-recognized in clinical practice. This study underscores the importance of cutaneous pathology in WD and expands current knowledge on its dermatological manifestations by providing clinicopathologic, ultrastructural, and literature-based data.

BackgroundAccurate mediastinal restaging in patients with non-small cell lung cancer (NSCLC) following neoadjuvant therapy is crucial for treatment planning. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), the standard technique, has limitations such as low diagnostic yield and false negatives, often requiring invasive mediastinoscopy. This study evaluates the performance of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) as a potential alternative to EBUS-TBNA in mediastinal restaging following neoadjuvant therapy. This study compares the diagnostic accuracy of EBUS-TBNA and EBUS-TMC, specifically focusing on diagnostic yield, false-negative rates, sample adequacy for molecular and immunohistochemical analyses, as well as the potential need for mediastinoscopy.MethodsThis prospective study was conducted on 22 NSCLC patients undergoing mediastinal restaging after neoadjuvant therapy from September 2023 to October 2024. Each patient underwent both EBUS-TBNA and EBUS-TMC in the same procedure. Mediastinoscopy was performed only in cases where both EBUS-TBNA and EBUS-TMC results were negative or non-diagnostic, serving as the reference standard.ResultsEBUS-TMC demonstrated superior diagnostic sensitivity (95.45% vs. 63.63%) and achieved sample adequacy for molecular and immunohistochemical analysis in 94.11% of cases compared to 29.41% for EBUS-TBNA. EBUS-TMC identified six additional malignancy cases and had fewer non-diagnostic results (4.5% vs. 22.7%). No complications were reported for any procedure, and mediastinoscopy confirmed all negative EBUS-TMC cases as true negatives.ConclusionsEBUS-TMC significantly improves diagnostic accuracy and sample adequacy for restaging NSCLC following neoadjuvant therapy, reducing the need for mediastinoscopy. Its integration into clinical practice could enhance patient outcomes, lower healthcare costs, and support personalized treatment strategies. This is the first study to demonstrate EBUS-TMC’s transformative potential in thoracic oncology.

ObjectivesIn 2020, the International Society for the Study of the Pleura and Peritoneum (ISSPP) launched a database monitoring real-world data on Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC)-directed therapy in patients with peritoneal metastases (PM). This study covers data from the third annual report on the ISSPP PIPAC database.MethodsSystematic analysis of all data reported to the ISSPP PIPAC database between June 15th, 2020, and November 1st, 2024. We hypothesize that ISSPP PIPAC data align with existing literature.ResultsSeventeen PIPAC centers reported 3224 PIPAC treatments in 1126 patients with PM (median number of treatments 2, range 1–33). The median peritoneal cancer index (PCI) at PIPAC 1 was 19 and remained unchanged during subsequent treatments. The number of patients with >500 mL ascites significantly decreased from the first three PIPAC treatments to PIPAC 4+ (p<0.01). Major complications (Dindo–Clavien ≥3b) occurred in 0.7 % of the treatments, while Common. Terminology Criteria for Adverse Events (CTCAE) grades ≥3 were reported in 5.2 %. Peritoneal regression grading score (PRGS) was performed in 2306 (72 %) of the treatments. At PIPAC 1, 2, and 3, complete or major response (mean PRGS ≤2) was achieved in 57 %, 72 %, and 75 % of the patients, respectively. Median overall survival from PIPAC 1 was 12.5 months. Patients with complete/major response (mean PRGS ≤2) at PIPAC 1-3 had a longer overall survival compared to patients with minimal/no response (mean PRGS >2).ConclusionsThis study from the ISSPP PIPAC database provides substantial real-world data demonstrating the feasibility, safety, and potential effect of PIPAC-directed therapy in patients with PM.

PurposeTo reach consensus among international experts on a structured framework for standardized 3D leg alignment analysis based on 3D bone models, ensuring consistency and improving clinical applicability.MethodsA Delphi study was performed in four rounds. Rounds 1 and 2 involved a steering and rating group that developed statements based on principles preserving the 3D complexity of anatomical structures, identified through a systematic review. These statements encompassed approaches for deriving joint centres and joint orientations, and defining coordinate systems using 3D bone models. In Rounds 3 and 4, a panel of 35 international experts, including clinicians (54%) and engineers (46%), with participants from Europe (80%), Oceania (9%), Asia (6%), and the Americas (6%), evaluated these statements. Consensus was defined as ≥80% agreement.ResultsRounds 1 and 2 resulted in 31 statements to be included in the survey. Of these, 26 achieved consensus in Round 3, with the five remaining statements refined and reaching consensus in Round 4. Experts agreed on utilising all available relevant surface data to define joint centres, joint orientations, and individual femoral and tibial coordinate systems alongside a combined leg coordinate system, and adopting central 3D axes for femoral version and tibial torsion.ConclusionsThis international Delphi consensus study provides a structured framework for a standardized 3D leg alignment analysis based on 3D bone models. This framework aims to enhance clinical applicability for preoperative planning and execution of uni‐ and multiplanar correction osteotomies around the knee, reduce the methodological variability in 3D leg alignment analysis literature, and improve cross‐study comparability.Level of EvidenceLevel V.

Population pharmacokinetic (popPK) models are essential tools for optimizing ustekinumab (UST) dosing for the treatment of inflammatory bowel disease (IBD) through therapeutic drug monitoring. The external validation of these models is necessary to ensure their predictive performance and clinical utility. The aim of the study was to externally validate 4 published popPK models of UST in a real-world cohort of patients with IBD using prediction-based and simulation-based diagnostics, as well as Bayesian forecasting. Four popPK models of UST, identified through a systematic literature review, were evaluated using data from 99 patients with IBD and 374 serum UST concentrations. Predictive performance and Bayesian forecasting were assessed using statistical metrics, including mean prediction error, median prediction error (MDPE), and median absolute prediction error (MADPE). The acceptability criteria (MDPE ±20%, MADPE ≤30%, F20 ≥35%, and F30 ≥50%) were applied. None of the models satisfied the predefined acceptability criteria. The Xu et al model demonstrated the best performance, achieving an MDPE of 19.55% and the lowest RMSPE (2.88 mcg/mL), but F20 (20.1%) and F30 (32.4%) values fell below thresholds. The model proposed by Adedokun et al showed strong results in simulation-based diagnostics, with only 5.6% of the observed concentrations outside the prediction interval. The models developed by Xu et al and Adedokun et al exhibited the most promising predictive performance and potential clinical applicability for model-informed precision dosing. Refinements to these models and further research are required to enhance their use in personalized UST therapies for IBD.