Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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Real-world use of terlipressin in cirrhosis and acute kidney injury: frequent use beyond hepatorenal syndrome
(Elsevier, 2026-04) Ma, Ann T.; Juanola Mayos, Adrià; Patidar, Kavish R.; Barone, Anna; Incicco, Simone; Kulkarni, Anand V.; Verma, Nipun; Lange, Christian Markus; Xie, Qing; Alessandria, Carlo; Cerda, Eira; Maiwall, Rakhi; Kim, Jeong Han; Marciano, Sebastián; Queiroz Farias, Alberto; Toledo, Claudio; Nardelli, Silvia; Vorobioff, Julio D.; Roblero, Juan Pablo; Thevenot, Thierry; Papp, Maria; Maan, Raoel; Solé, Cristina; Cordova Gallardo, Jacqueline; Simonetto, Douglas A.; Fouad, Yasser; Balcar, Lorenz; Raevens, Sarah; Nabilou, Puria; Merli, Manuela; Presa, José; Laleman, Wim; Krag, Aleksander; Bruns, Tony; Pereira, Gustavo; Mattos, Angelo Z.; Arab, Juan Pablo; Wentworth, Brian; Abdelaaty Abdelkader, Nadia; Wong, Yu Jun; Kim, Sung Eun; Roux, Olivier; Takkenberg, R. Bart; Galante, Antonio; Lofego Goncalves, Luciana; Pyrsopoulos, Nikolaos; Caraceni, Paolo; Pérez Hernández, José Luís; Asrani, Sumeet K.; Torre, Aldo; Díaz Ferrer, Javier; Orman, Eric S.; Perricone, Giovanni; Gadano, Adrian; Ivashkin, Vladimir; Fassio, Eduardo; Marino, Mónica; Vargas, Víctor; Rabinowich, Liane; Montes, Pedro; Mohammed, Abdulsemed; Carrera, Enrique; Cabrera, María Cecilia; Girala, Marcos; Samant, Hrishikesh; Madaleno, Joao; Kim, W. Ray; Ferreira, Carlos Noronha; Allegretti, Andrew S.; Sarin, Shiv K.; Ginès i Gibert, Pere; Angeli, Paolo; Solà, Elsa; Piano, Salvatore; International Club of Ascites GLOBAL AKI team
Background & Aims Terlipressin is indicated to treat hepatorenal syndrome (HRS)-acute kidney injury (AKI) but is likely used outside this primary indication in clinical practice. We aimed to investigate real-world practice patterns on the use of terlipressin in AKI in cirrhosis. Methods International prospective study including patients hospitalized for decompensated cirrhosis. This was a subgroup analysis of patients who received terlipressin to treat AKI. Primary outcome was AKI resolution. Secondary outcomes were respiratory failure and 28-day mortality. Results Among 1456 patients with AKI, 243 (17%) received terlipressin. Terlipressin was predominantly administered as a continuous infusion (75%). The AKI phenotype was HRS-AKI in 50%, acute tubular necrosis (ATN) in 17%, hypovolemic in 25%, and other in 8%. AKI resolution occurred in 49% of the patients, and was lowest in ATN (29%), followed by HRS-AKI (51%) and hypovolemic (63%). ATN was independently associated with lack of AKI resolution (odds ratio, 2.77; 95% confidence interval, 1.24–6.54; P = .02). De novo respiratory failure occurred in 20% of patients. There were no significant differences in the amount of albumin received nor acute-on-chronic liver failure grade between those who did and did not develop respiratory failure. The presence of pneumonia independently predicted respiratory failure (odds ratio, 7.80; 95% confidence interval, 2.43–26.95; P < .001). Mortality rate at 28 days was 36%; ATN and hospital-acquired AKI independently predicted 28-day mortality. Conclusions Terlipressin is often used for treatment of AKI outside its primary indication of HRS-AKI. Compared with patients with HRS-AKI, response to terlipressin is significantly lower in patients with ATN, in whom the risks may outweigh the benefits. Respiratory failure is common but does not seem to be driven by the amount of albumin received nor acute-on-chronic liver failure grade.
Palmaris longus muscle and its variations: Ultrasound anatomical and histological study with clinical and surgical applications
(MDPI, 2026-01-13) Miguel Pérez, Ma. Isabel; Muñiz Delgado, Ángel; Ortiz Miguel, Sara; López Prades, Sandra; Ortiz Sagristà, Juan Carlos; Miralles, Cristina; Ruiz Roig, Núria; Möller, Ingrid; Pérez Bellmunt, Albert
Background/objective: The palmaris longus muscle is a variable and often inconsistent muscle in the anterior compartment of the forearm. This fusiform-shaped muscle originates at the medial epicondyle of the humerus bone following a long and narrow tendon that inserts at the palmar aponeurosis. That tendon is used in reconstructive surgery, and for this reason, detailed information from an ultrasound is used to detect the tendon and the possible variations in the muscle. The present study aimed to investigate the palmaris longus muscle and its variations through ultrasound, anatomical, and histological analysis with clinical and surgical applications. Methods: A total of 72 upper limbs from 33 females and 39 males, 32 right and 40 left, were evaluated in ultrasound, anatomical, and histological studies. The main objective was to prove the existence of the palmaris longus muscle and its variations, as well as to measure the tendon for surgical applications. Results: Ultrasound analysis showed that it is possible to determine the existence of the muscle (76.4%) and its variations (23.6%), as well as its absence (15.3%). The anatomical results proved the ultrasound results. The width of the tendon was between 0.4 and 0.38 mm. by ultrasound and anatomical analysis. Also, normal palmaris longus tendons were not a direct cause of compression of the median nerve. Conclusions: It is important to confirm the existence and possible variations in the palmaris longus muscle and tendon through ultrasound before surgical reconstruction and for clinical diagnostics.
Trusting the forces of our cell lines
(Elsevier, 2024-09-01) Moro López, Marina; Farré Ventura, Ramon; Otero Diaz, Jorge; Sunyer Borrell, Raimon
Cells isolated from their native tissues and cultured in vitro face different selection pressures than those cultured in vivo. These pressures induce a profound transformation that reshapes the cell, alters its genome, and transforms the way it senses and generates forces. In this perspective, we focus on the evidence that cells cultured on conventional polystyrene substrates display a fundamentally different mechanobiology than their in vivo counterparts. We explore the role of adhesion reinforcement in this transformation and to what extent it is reversible. We argue that this mechanoadaptation is often understood as a mechanical memory. We propose some strategies to mitigate the effects of on-plastic culture on mechanobiology, such as organoid-inspired protocols or mechanical priming. While isolating cells from their native tissues and culturing them on artificial substrates has revolutionized biomedical research, it has also transformed cellular forces. Only by understanding and controlling them, we can improve their truthfulness and validity.
Antibody and Cellular Immune Responses in Old α1,3-Galactosyltransferase-Knockout Mice Implanted with Bioprosthetic Heart Valve Tissues
(MDPI AG, 2025-12-31) Casós, Kelly; Llatjós, Roger ; Blasco Lucas, Arnau; Kuguel, Sebastián G.; Sbraga, Fabrizio; Galli, Cesare; Padler-Karavani, Vered; Le Tourneau, Thierry; Vadori, Marta; Roussel, Jean-Christian; Bottio, Tomaso; Cozzi, Emanuele; Soulillou, Jean Paul; Galiñanes, Manuel ; Mañez, Rafael ; Costa, Cristina
Structural valve deterioration (SVD) remains a key limitation in bioprosthetic heart valve (BHV) usage influenced by patient age. A deeper understanding of SVD pathogenesis, particularly of the immune-mediated processes altering current BHV materials, is therefore critical. To this end, commercially available BHV tissues of bovine, porcine, and equine origin were investigated following subcutaneous implantation into alpha 1,3-galactosyltransferase-knockout (Gal KO) mice. We compared the immune responses between adult and aged animals via histological assessments of explants and measurement of serum anti-galactose alpha 1,3-galactose (Gal) and anti-non-Gal antibodies at 2 months post-implantation. In contrast to adult mice, old Gal KO mice did not show increased levels of serum anti-Gal or -non-Gal antibodies after receiving specific BHV tissue (i.e., Freedom-Solo). Instead, a significant decrease in serum anti-Gal IgM was found in old recipients of Freedom-Solo. Furthermore, the overall cellular immune response was attenuated in explants from old mice compared with adults (i.e., ATS 3f and Crown). Nevertheless, the Freedom-Solo (bovine) and the Hancock-II (porcine) tissues still elicited strong cellular immune infiltration in the old cohorts. Therefore, the Gal KO mouse model offers a valuable platform to investigate age-related differences regarding cellular and humoral immune responses to various BHV tissues, contributing to our understanding of SVD.
Venetoclax as a possible chemopreventive agent in adenomatous polyposis: A case report
(Elsevier, 2025-03) Maimouni, Cautar el; Daca-Alvarez, Maria ; Delgado, Julio (Delgado González); Pellisé Urquiza, Maria; Balaguer Prunés, Francesc
Familial adenomatous polyposis (FAP) is a hereditary colorectal cancer (CRC) syndrome caused by a germline pathogenic variant in the Adenomatous Polyposis Coli (APC) gene. However, a pathogenic mutation in this gene is not identified in 20% of patients.
Bladder EpiCheck clinical utility to predict BCG response in non-muscle-invasive bladder cancer
(Wiley, 2025-10-01) Roldán, Fiorella L.; Ingelmo-Torres, Mercedes; Mercader Barrull, Clàudia; Figueras Torras, Marcel; Padullés, Bernat; Durán González, María Angeles; Carrasco Jordan, Josep Lluís; Ribal, María José; Franco de Castro, Agustín; Izquierdo Reyes, Laura; Alcaraz Asensio, Antonio; Mengual Brichs, Lourdes
Objective: To evaluate the performance of Bladder Epicheck® (BE; Nucleix Ltd., Rehovot, Israel) in predicting tumour recurrence and bacillus Calmette-Guérin (BCG) failure during the first year after induction treatment. Patients and methods: Prospective study including 65 patients with non-muscle-invasive bladder cancer treated with BCG between 2018 and 2021. Urine samples analysed with BE were collected before and after BCG induction. Logistic binary regression was used to assess the association between clinical and pathological variables and BE results with tumour recurrence and BCG failure during the first year after induction treatment. Results: During follow-up, 16 (24.6%) patients experienced a bladder cancer event, 11 (68.8%) of which were BCG failure (high-grade recurrence) and five (31.2%) were low-grade recurrences. The median (range) time to overall recurrence was 7.3 (3.8-17.4) months. A significant association was found between the risk of tumour recurrence/BCG failure and post-BCG cystoscopy (odds ratio [OR] 10.0; P < 0.001 and OR 13.1; P < 0.001, respectively), post-BCG BE result (OR 16.9; P < 0.001 and OR 33.1; P < 0.001, respectively) and pre/post-BCG EpiScore value variation (OR 14.4; P = 0.001 and OR 7.1; P = 0.018, respectively). A nomogram including these three variables outperformed the Club Urológico Español de Tratamiento Oncológico (CUETO) risk tables to predict any bladder cancer event after BCG induction (area under the curve 95.1% vs 67.1%). Result validation in a larger and independent series is needed. Conclusions: The BE post-BCG status and variations in EpiScore values can help us identify patients at higher risk of any bladder cancer event and BCG failure promptly. These data can have an impact on disease management.
Prospective validation of the EASL management algorithm for acute kidney injury in cirrhosis
(Elsevier, 2024-09) Ma, Ann T.; Solé, Cristina; Juanola Mayos, Adrià ; Escudé, Laia; Napoleone, Laura; Avitabile, Emma; Pérez-Guasch, Martina; Carol, Marta; Pompili, Enrico; Gratacós Ginès, Jordi; Soria, Anna; Rubio, Ana Belén; Cervera Carbonell, Marta; Moreta, Maria José; Morales Ruiz, Manuel; Solà, Elsa; Poch, Esteban; Fabrellas i Padrès, Núria; Graupera, Isabel; Pose Méndez, Elisa; Ginès i Gibert, Pere
Background & Aims The management of acute kidney injury (AKI) in cirrhosis is challenging. The EASL guidelines proposed an algorithm for the management of AKI, but this has never been validated. We aimed to prospectively evaluate this algorithm in clinical practice. Methods We performed a prospective cohort study in consecutive hospitalized patients with cirrhosis and AKI. The EASL management algorithm includes identification/treatment of precipitating factors, 2-day albumin infusion in patients with AKI ≥stage 1B, and treatment with terlipressin in patients with hepatorenal syndrome (HRS-AKI). The primary outcome was treatment response, which included both full and partial response. Secondary outcomes were survival and adverse events associated with terlipressin therapy. Results A total of 202 AKI episodes in 139 patients were included. Overall treatment response was 80%, while renal replacement therapy was required in only 8%. Response to albumin infusion was achieved in one-third of episodes. Of patients not responding to albumin, most (74%) did not meet the diagnostic criteria of HRS-AKI, with acute tubular necrosis (ATN) being the most common phenotype. The response rate in patients not meeting the criteria for HRS-AKI was 70%. Only 30 patients met the diagnostic criteria for HRS-AKI, and their response rate to terlipressin was 61%. Median time from AKI diagnosis to terlipressin initiation was only 2.5 days. While uNGAL (urinary neutrophil gelatinase-associated lipocalin) could differentiate ATN from other phenotypes (AUROC 0.78), it did not predict response to therapy in HRS-AKI. Ninety-day transplant-free survival was negatively associated with MELD-Na, ATN and HRS-AKI as well as uNGAL. Three patients treated with terlipressin developed pulmonary edema. Conclusions The application of the EASL AKI algorithm is associated with very good response rates and does not significantly delay initiation of terlipressin therapy. Impact and implications The occurrence of acute kidney injury (AKI) in patients with cirrhosis is associated with poor short-term mortality. Improving its rapid identification and prompt management was the focus of the recently proposed EASL AKI algorithm. This is the first prospective study demonstrating that high AKI response rates are achieved with the use of this algorithm, which includes identification of AKI, treatment of precipitating factors, a 2-day albumin challenge in patients with AKI ≥1B, and supportive therapy in patients with persistent AKI not meeting HRS-AKI criteria or terlipressin with albumin in those with HRS-AKI. These findings support the use of this algorithm in clinical practice.
Dual-energy computed tomography (CT) versus cone-beam computed tomography (CT) in chronic thromboembolic pulmonary hypertension: diagnostic accuracy compared with digital subtraction angiography
(Elsevier, 2026-01-01) Páez Carpio, Alfredo; Serrano, Elena; Domenech Ximenos, Blanca; Cornellas Escayola, Llúria; Barberà i Mir, Joan Albert; Vollmer Torrubiano, Ivan; Blanco Vich, Isabel; Gomez, F. M.
AIM The aim of this study was to compare the diagnostic accuracy and interobserver agreement of dual-energy computed tomography pulmonary angiography (DECT-PA) and cone-beam computed tomography pulmonary angiography (CBCT-PA) for the evaluation of chronic thromboembolic pulmonary hypertension (CTEPH), using digital subtraction angiography pulmonary angiography (DSA-PA) as the reference standard. MATERIALS AND METHODS This retrospective study included 109 patients with confirmed CTEPH who underwent DECT-PA, CBCT-PA, and DSA-PA within a three-month interval between January 2017 and June 2022. Pulmonary arteries were evaluated at main, lobar, segmental, and subsegmental levels. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. Interobserver agreement was assessed using Cohen's kappa (κ). RESULTS Overall diagnostic accuracy was comparable between DECT-PA (89.5%) and CBCT-PA (89.3%). DECT-PA demonstrated higher overall sensitivity (65.0% vs 53.5%, P = 0.019) but CBCT-PA achieved greater interobserver agreement (κ = 0.76 vs 0.74). Sensitivity declined in distal segments for both modalities, with CBCT-PA outperforming DECT-PA at the subsegmental level (51.9% vs 43.6%). Specificity remained high across modalities (>89%). The CBCT-PA showed superior agreement for lesion subtype classification, particularly for occlusions (κ = 0.839). CONCLUSION DECT-PA and CBCT-PA offer complementary strengths for the evaluation of CTEPH. DECT-PA provides high specificity for central and segmental lesions, supporting its role in initial assessment. CBCT-PA improves sensitivity and reproducibility in distal arteries, reinforcing its value for procedural planning and detailed vascular assessment. These findings support the use of DECT-PA as a first-line diagnostic tool and highlight the role of CBCT-PA as an adjunct in patients with distal or morphologically complex disease, potentially influencing diagnostic pathways and procedural planning in CTEPH.
Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations
(Springer Science + Business Media, 2024-04-01) Marin, Concepció; Alobid, Isam; López Chacón, Mauricio; Rodriguez-Van Strahlen, Camilo; Mullol i Miret, Joaquim
Purpose of review: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases. Recent findings: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.
Development of a blood-based lipidomic fat quality score for the risk of ischemic stroke
(Oxford University Press (OUP), 2026-01-01) Lázaro, Iolanda; Luján Barroso, Leila ; Soldevila Domenech, Natalia ; Amor, Antonio J.; Ortega, Emilio; Ros, Emilio; Sánchez, María José; Rodríguez Barranco, Miguel ; Guevara, Marcela; Moreno ribas, Conchi; Schröder, Helmut; Fitó, Montserrat; Tintle, Nathan L. ; Ryder, Nathan; Harris, William S. ; Agudo, Antonio; Sala Vila, Aleix
Introduction: Poor-quality diets promote ischemic stroke. Red blood cell fatty acids (RBC-FAs) are objective, longterm biomarkers of diet. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain, we developed a blood-based lipidomic fat quality (LFQ) score considering pre-defined RBC-FA diet-related biomarkers, and examined whether LFQ score relates to the risk of ischemic stroke. Patients and methods: We determined the RBC-FAs (n = 438 cases of incident ischemic stroke, n= 438 matched controls). For each participant, we scored 1 for each beneficial metric (C15:0+C17:0; C18:2n-6; C18:3n-3; C20:5n-3; C22:6n-3) >= the median of the control group; and 1 for each detrimental metric (C16:0; C16:1n-7; C18:0) < the median of the control group. LFQ score resulted from the 8-component sum (range = 0-8; higher values, higher fat quality). We explored the validity of findings in a different background (n = 2468 participants from the Framingham Offspring Study without ischemic stroke at baseline, 12-year median follow-up, n= 121 cases). Results: In a fully adjusted model, the Odds Ratio (OR) for ischemic stroke was 0.86 (95% confidence interval [CI] = 0.77-0.95) for each 1-unit increase of the LFQ score. Compared to individuals at the lowest category of LFQ score (0-3 points), those at the top category (5-8 points) had lower odds (OR = 0.64, 95% CI = 0.44-0.94). The findings were similar in the Framingham Offspring Study (Hazard Ratio [HR] for each 1-unit increase = 0.83; 95% CI = 0.70-0.99; HR for those at top category = 0.49; 95% CI = 0.29-0.84, compared to those at the lowest category). Conclusion: Low blood-based LFQ scores relate to a high risk of ischemic stroke.
Endocervical Brush Cytology After Cervical Conization as a Predictor of Treatment Failure: A Prospective Cohort Study
(Lippincott, Williams & Wilkins. Wolters Kluwer Health, 2025-01-01) Carreras Dieguez, Núria ; Torras, Ines; Martí Delgado, Cristina; Matas, Isabel; Glickman, Ariel; Fusté, Pere; Mula, Cristina; Alos, Silvia; Hoya, Sandra; Rakislova, Natalia; Saco, Adela; Marimon, Lorena; Ordi i Majà, Jaume; Torné Bladé, Aureli; Pino Saladrigues, Marta del
Objective Endocervical curettage (ECC) is the gold standard for predicting the persistence of high-grade squamous intraepithelial lesions (HSIL) after cervical conization. However, ECC has a high rate of unsatisfactory samples and may be uncomfortable for women. Endocervical sampling with brush (ECB) has been proposed as an alternative to ECC, which, in addition to the cytological evaluation, allows performing HPV testing using the same sample. The authors compared ECC and ECB performed immediately after conization to identify women with persistent HSIL. Materials and Methods This is a prospective single-center study, including 518 patients who underwent conization over a 10-year period (2012–2021). Immediately after treatment conization, the authors performed ECB sampling followed by ECC to all patients. They evaluated the accuracy of the 2 techniques for diagnosing persistent HSIL during follow-up. Results Persistent HSIL was identified in 8.9% of women. Eighteen percent of the ECC samples and only 7% of ECB cytology were unsatisfactory (p < .001). The accuracy of detecting persistent HSIL was similar for ECB and ECC (89.0%, 95% CI = 85.9–91.5 vs 90.8%, 95% CI = 87.7–93.2; p = .797). Adding HPV testing to ECB cytological evaluation increased the accuracy to 91.5% (95% CI = 88.8–93.6). Conclusions ECB can be reliably used to identify women with persistent HSIL after conization, as its accuracy is similar to ECC, with a lower rate of unsatisfactory results. The technique allows adding HPV testing to cytological evaluation, improving the accuracy of the test.
Adenoma detection rate and tolerability of 2 ultra-low-volume bowel preparations in screening: a noninferiority randomized controlled trial
(Elsevier, 2025-01-01) Serradesanferm, Anna; Torà Rocamora, Isabel; Pozo, Àngels; Ocaña, Teresa; Diaz, Mireia; Moreira de Abreu, Rebeca; Rivero Sánchez, Liseth; Ortiz, Oswaldo; Carballal, Sabela; Moreira. Leticia; Vaquero, Eva C.; Ordás, Ingrid; Bayarri, Carolina; Daca-Alvarez, Maria ; Torres, Sonia; Grau, Jaume; Balaguer Prunés, Francesc; Castells Garangou, Antoni; Pellisé Urquiza, Maria
Background and aims: The adenoma detection rate (ADR), recognized as a surrogate marker for colorectal cancer (CRC) incidence and mortality reduction, is closely linked to the efficacy of bowel cleansing. However, there is a dearth of evidence examining the impact on ADR when using 2 distinct very-low-dose bowel cleansing products. This study sought to compare ADR in an immunochemical fecal occult blood test (iFOBT)-based organized screening program by using 1 L of polyethylene glycol plus ascorbate (1L-PEGA) versus sodium picosulfate with magnesium citrate (SPMC), both administered in a split-dose regimen. Methods: We conducted a comparative, parallel, randomized, noninferiority, and low-intervention clinical trial targeting individuals from a population CRC screening program aged 50 to 69 years with a positive iFOBT result scheduled for a workup colonoscopy in the morning. Participants were randomized to either 1L-PEGA or SPMC for bowel cleansing. The main outcome was ADR, whereas secondary outcomes were bowel preparation quality, safety, tolerability, and satisfaction. Results: A total of 1002 subjects, 501 were included in each group. There were no differences between groups with respect to pooled ADR (SPMC, 56.5% [95% CI, 52.1-60.8]; 1L-PEGA, 53.7% [95% CI, 49.3-58.0]; relative risk, .95 [95% CI, .85-1.06]); therefore, SPMC demonstrated noninferiority in ADR compared with 1L-PEGA (difference, 2.8%; 2-sided 95% lower confidence limit, -3.4). In addition, there were no significant differences in mean lesions regardless of size and location between arms. Bowel preparation favored 1L-PEGA (96.2% vs 89.2%, P < .001), whereas SPMC exhibited significantly higher safety and tolerability, as shown by fewer nonserious treatment-emergent adverse events. Conclusions: SPMC emerged as a noninferior laxative compared with 1L-PEGA concerning ADR. Despite the superior bowel preparation quality associated with 1L-PEGA, the safety, tolerability, and overall satisfaction of participants were higher with SPMC. (Clinical trial registration number: EudraCT: 2019-003186-18.).
Clinical characterisation of patients diagnosed with cancer following emergency self-referral
(Elsevier, 2024-07-09) Bosch Genover, Xavier; Montori Palacín, Elisabet; Mota Gomes, Tiago; Naval Álvarez, José; Moreno Lozano, Pedro Juan; López-Soto, Alfonso
Background: Despite their frequency and potential impact on prognosis, cancers diagnosed via self-referral to the emergency department are poorly documented. We conducted a detailed analysis of cancer patients diagnosed following emergency self-referral and compared them with those diagnosed following emergency referral from primary care. Given the challenges associated with measuring intervals in the emergency self-referral pathway, we also aimed to provide a definition of the diagnostic interval for these cancers. Methods: A retrospective observational analysis was performed on patients diagnosed with 13 cancers, either following emergency self-referral or emergency referral from primary care. We analysed demographics, tumour stage, clinical data (including 28 presenting symptoms categorised by body systems), and diagnostic intervals by cancer site, then testing for differences between pathways. Results: Out of 3624 patients, 37 % were diagnosed following emergency self-referral and 63 % via emergency referral from primary care. Emergency self-referrals were associated with a higher likelihood of being diagnosed with cancers manifesting with localising symptoms (e.g., breast and endometrial cancer), whereas the likelihood of being diagnosed with cancers featuring nonspecific symptoms and abdominal pain (e.g., pancreatic and ovarian cancer) was higher among patients referred from primary care. Diagnostic intervals in self-referred patients were half as long as those in patients referred from primary care, with most significant differences for pancreatic cancer (28 [95 % CI − 34 to − 23] days shorter, respectively). Conclusion: These findings enrich the best available evidence on cancer diagnosis through emergency self-referral and showed that, compared with the emergency referral pathway from primary care, these patients had a significantly increased likelihood of presenting with symptoms that are strongly predictive of cancer. Since the starting point for the diagnostic interval in these patients is their emergency presentation, comparing it with that of those referred from primary care as an emergency is likely to result in biased data.
Patient-reported outcomes in patients with hematologic malignancies treated with CAR T-cell therapy in Europe
(American Society of Hematology, 2025-09-24) Pennings, Elise R. A.; Spanjaart, Anne M.; Thielen, Frederick W. ; Oerlemans, Simone; Fleischer, Anna; Sanges, Carmen; Gomes Da Silva, Maria; Cabrerizo, Yolanda; Lecot, Pacôme; Roux Opstaele, Lutgart; Dreuillet, Caroline; Gonzalez Marcano, Eglys; Millán, Olga; Jaeger, Ulrich; Delgado, Julio; Luu, Maik; Huber, Barbara; Lorrain, Margot; Pina, Mariana; Kremer, Andreas; Bolaños, Natacha; Clavreul, Solène; Nier, Samantha; Liu, Roberto D. K. ; Lissenberg Witte, Birgit I.; Anguille, Sébastien; Robin, Marie; Morris, Emma C. ; Sureda, Anna; Préau, Marie; Pannard, Myriam; De Bock, Geertruida H. ; Wagers, Scott S. ; Negre, Hélène; Maucort Boulch, Delphine; Hudecek, Michael; Uyl de Groot, Carin A.; José Kersten, Marie
Patient-reported outcomes (PROs) give direct insights into the treatment's impact on patient's life and complement clinical outcomes. However, since the advent of chimeric antigen receptor T-cell therapy (CAR-T), PROs have been underreported. Particularly, little is known about long-term health-related quality of life (HRQoL) and dimensions such as mental- and social well-being, working life, and financial burden. Therefore, we evaluated multidimensional PROs in a cross-sectional study among European patients who received CAR-T for hematologic malignancies. Patients completed validated questionnaires (EQ-5D-5L/EORTC-QLQ-C30/PCL-5/modified-iPCQ) and ad hoc items on treatment experiences, unmet care needs, and HRQoL. The survey was available online (January-October 2023) in 7 languages. Outcomes were compared with the European general population, a matched CAR-T-naive cohort with hematologic malignancies and across subgroups, using established thresholds for clinically important differences/problems and regression models. From 10 European countries, 389 patients participated (>1 year post-CAR-T: 56%). Mean EQ-VAS was 73.1 (standard deviation, 18.5). HRQoL was similar or better than reference cohorts, except for role-, social-, and cognitive-functioning. Physical-functioning problems were most frequently reported (41%), particularly by women, older individuals, and those who experienced neurotoxicity. The latter subgroup also reported more cognitive- and social-functioning problems. Anxiety regarding disease recurrence (76%), infections (66%) and long-term side effects (59%) was common. Among working-age patients, 72% could continue paid work after CAR-T. Younger patients (32%) reported more financial difficulties than older patients (9%). This study shows favorable general HRQoL after CAR-T compared with reference cohorts. However, a notable proportion of patients experienced problems in physical-, mental- and social well-being. We identified high-risk subgroups and care needs that should be addressed during follow-up.
Standard or Fin SIGN® nail? which option is better for the treatment of femoral fractures in low and middle-income countries?
(Springer Verlag, 2024-08-01) Perdomo Lizarraga, Juan Carlos; Andrade Arellano, Dennys J.; Necchi, Marco; Zavatta, Marcello; Ryan Coker, Marcella F. D.; Dixon Cole, Richmond; Muñoz Mahamud, Ernesto; Combalía Aleu, Andrés
Purpose Femoral fractures are common in low and middle-income countries (LMIC), predominantly caused by high-energy trauma. The surgical implant generation network (SIGN®) program offers two different intramedullary nails in LMIC which are designed to be used without image intensifier free of charge for the patients: the SIGN standard nail (SSN®) and the SIGN Fin nail (SFN®). This study aimed to compare the results of the SSN® and the SFN® for the treatment of middle and distal shaft femoral fractures through a retrograde approach. Material and Methods This was a retrospective, descriptive, and non-experimental study including all consecutive patients who underwent surgical management of middle or distal shaft femoral fracture between January 2017 and May 2022 in an NGO hospital located in Freetown, Sierra Leone. The duration of surgery, type of reduction, complications like screw loosening, implant migration, anterior knee pain and non-union rate at six months of follow up were evaluated. Results A total of 122 patients were included in the study. Group A: 60 patients were managed with SSN® and Group B: 62 patients with SFN®. The mean operative time was 104 min with SSN® and 78 with SFN® (p < 0.001). Open reduction of the fracture was necessary in ten (16.7%) patients with SSN® and 12 (19.4%) patients treated with SFN® (p = 0.69). Non-union was observed in one (1.7%) patient with SSN® and two (3.2%) patients with SFN® (p = 0.57). Conclusions Both options seem equally effective in treating midshaft and distal femoral shaft fractures. The SFN® reduces the surgical time, due to this fact, in polytraumatized patients, patients with bilateral femur fracture or patients with ipsilateral tibia fracture, it can be considered as the best option to be used. There was no statistical difference in the complications presented by the two groups.
White matter diffusion estimates in obsessive-compulsive disorder across 1653 individuals: machine learning findings from the ENIGMA OCD Working Group.
(Nature Publishing Group, 2024-02-07) Kim, Bo-Gyeom; Kim, Gakyung; Abe, Yoshinari; Alonso Ortega, María del Pino; Ameis, Stephanie H.; Anticevic, Alan; Arnold, Paul D.; Balachander, Srinivas; Banaj, Nerisa; Bargalló Alabart, Núria; Batistuzzo, Marcelo C.; Benedetti, Francesco; Bertolín Triquell, Sara; Beucke, Jan C.; Bollettini, Irene; Brem, Silvia; Brennan, Brian P.; Buitelaar, Jan K.; Calvo Escalona, Rosa; Castelo-Branco, Miguel; Cheng, Yuqi; Chhatkuli, Ritu Bhusal; Ciullo, Valentina; Coelho, Anna; Couto, Beatriz; Dallaspezia, Sara; Ely, Benjamin A.; Ferreira, Sónia; Fontaine, Martine; Fouche, Jean Paul; Grazioplene, Rachael G.; Gruner, Patricia; Hagen, Kristen; Hansen, Bjarne; Hanna, Gregory L.; Hirano, Yoshiyuki; Höxter, Marcelo Q.; Hough, Morgan; Hu, Hao; Huyser, Chaim; Ikuta, Toshikazu; Jahanshad, Neda; James, Anthony; Jaspers-Fayer, Fern; Kasprzak, Selina; Kathmann, Norbert; Kaufmann, Christian; Kim, Minah; Koch, Katharina; Kvale, Gerd; Kwon, Jun Soo; Lázaro García, Luisa; Lee, Junhee; Lochner, Christine; Lu, Jin; Rodriguez Manrique, Daniela; Martínez Zalacaín, Ignacio; Masuda, Yoshitada; Matsumoto, Koji; Maziero, Maria Paula; Menchón Magriñá, José Manuel; Minuzzi, Luciano; Moreira, Pedro Silva; Morgado, Pedro; Narayanaswamy, Janardhanan C.; Narumoto, Jin; Ortiz García, Ana Encarnación; Ota, Junko; Pariente, Jose Carlos; Perriello, Chris; Picó Pérez, Maria; Pittenger, Christopher; Poletti, Sara; Real, Eva; Reddy, Y. C. Janardhan; Rooij, Daan van; Sakai, Yuki; Sato, João R; Segalàs Cosi, Cinto; Shavitt, Roseli G.; Shen, Zonglin; Shimizu, Eiji; Shivakumar, Venkataram; Soriano Mas, Carles; Sousa, Nuno; Sousa, Mafalda Machado de; Spalletta, Gianfranco; Stern, Emily R.; Stewart, S. Evelyn; Szeszko, Philip R.; Thomas, Rajat; Thomopoulos, Sophia I.; Vecchio, Daniela; Venkatasubramanian, Ganesan; Vriend, Chris; Walitza, Susanne; Wang, Zhen; Watanabe, Anri; Wolters, Lidewij H.; Xu, Jian; Yamada, Kei; Yun, Je-Yeon; Zarei, Mojtaba; Zhao, Qin; Zhu, Xi; ENIGMA-OCD working group; Thompson, Paul M.; Bruin, Willem B.; Wingen, Guido van; Piras, Federica; Piras, Fabrizio; Stein, Dan J., 1962-; Heuvel, Odile A. van den; Simpson, Helen Blair; Marsh, Rachel; Cha, Jiook
White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) “OCD vs. healthy controls” (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) “unmedicated OCD vs. healthy controls” (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) “medicated OCD vs. unmedicated OCD” (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6–79.1 in adults; 35.9–63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.
Neuroaxonal Injury May Mediate the Association Between Hyperglycemia and Prognosis in Spontaneous Subarachnoid Hemorrhage
(Humana Press., 2025-02-01) Santana Moreno, Daniel; Llull Estrany, Laura; Mosteiro Cadaval, Alejandra; Pedrosa Eguílez, Leire; Pujol Fontrodona, Gabriel; Zattera, Luigi; Werner, Mariano; Martín, Abraham; Justicia Mercader, Carles; Chamorro, Ángel; Torné, Ramón; Amaro Delgado, Sergio
Hyperglycemia during early brain injury (EBI) period after spontaneous subarachnoid hemorrhage (SAH) is associated with poor outcome, but the underlying physiopathology is unknown. This study assessed if hyperglycemia during EBI is associated with markers of neuroaxonal injury and whether these biomarkers partially account for the association between hyperglycemia and poor clinical outcome. Ninety-two SAH patients admitted within 24 h of bleeding onset were prospectively included. Glucose levels were measured at arrival and every 6 h for 72 h. Serum neurofilament light chain (NFL) levels were measured at 72 h. Functional outcome was assessed with the modified Rankin Scale (mRS) at 90 days (poor outcome, mRS > 2). The association between glucose metrics, NFL levels, and clinical outcome was assessed with univariate and multivariate analyses. Mediation analysis was performed to examine the potential chain in which NFL may mediate the relationship between glucose and functional outcome. Higher glucose and NFL levels during EBI were associated with poor clinical outcome in adjusted analysis. NFL levels were associated with older age, higher initial severity, and higher glucose levels during EBI period. In adjusted mediation analyses, the association between glucose and clinical outcome was significantly mediated by NFL levels. The mediator NFL explained 25% of the association between glucose during EBI period and poor functional outcome at 90 days. In SAH, the association between glucose levels during EBI and poor clinical outcome might be significantly mediated by NFL levels. The link between hyperglycemia and poor clinical outcome might be explained in part through secondary neuroaxonal injury.
Systematic Review of Long Term Sinonasal Outcomes in CRSwNP after Endoscopic Sinus Surgery: A call for Unified and Standardized Criteria and Terms
(Springer Science + Business Media, 2024-06-24) Rodriguez-Van Strahlen, Camilo; Arancibia Verdugo, Claudio; Calvo Henriquez, Christian; Mullol i Miret, Joaquim; Alobid, Isam
Purpose of review: To present current evidence in long-term (> 5 years) results after endoscopic sinus surgery (ESS) focusing on Patients Reported Outcome Measures (PROMs) and other sinonasal outcomes while assessing the role of ESS in the treatment of CRSwNP, and identifying outcomes which affect the results of ESS and defining recommendations for future studies. Recent findings: Long-term results of ESS in CRSwNP can be branched in PROMs and other objective measurements. Despite the heterogeneity of reported outcomes make it difficult to perform comparisons and meta-analysis, ESS improves PROMs, including symptoms, QOL and olfaction. Objectives outcomes such as NPS, LMS, type of surgery, or recurrence and revision surgery don't have a clear role in long-term results. Clustering patients suggest asthma, N-ERD, allergy, eosinophil count and IL-5 could have a role in predicting recurrence and severe disease. Long-term studies of CRSwNP treated with ESS are scarce. There is a significant need to standardize the report of results. The use of tools as SNOT-22, NPS, validated smell tests, defined criteria for disease recurrence and control and ESS extension in a unified systematic way could allow better comparisons between treatments in the new era of biologics.
Genomic classification and outcomes of young patients with polycythemia vera and essential thrombocythemia according to the presence of splanchnic vein thrombosis and its chronology
(Springer Verlag, 2024-03-01) Garrote, Marta; López Guerra, Mónica; García Pagán, Juan Carlos; Arellano Rodrigo, Eduardo; Ferrer Marín, Francisca; Hernández Boluda, Juan Carlos; Bellosillo Paricio, Beatriz; Nomdedeu i Fàbrega, Meritxell; Hernández Gea, Virginia; Triguero, Ana; Guijarro Tomas, Francisca; Álamo Moreno, José Ramón; Baiges, Anna; Turon, Fanny; Colomer Pujol, Dolors; Cervantes Requena, F.; Alvarez Larrán, Alberto
To elucidate the role of splanchnic vein thrombosis (SVT) and genomic characteristics in prognosis and survival, we compared patients with polycythemia vera (PV) or essential thrombocythemia (ET) presenting SVT at diagnosis (n = 69, median age 43 years) or during follow-up (n = 21, median age 46 years) to a sex- and age-matched control group of PV/ET without SVT (n = 165, median age 48 years). The majority of patients presenting with SVT at diagnosis were classified as myeloproliferative neoplasm with heterozygous JAK2 mutation (87% of cases vs. 69% in PV/ET control group, p < 0.05), characterized by low JAK2 allele burden and no high-risk mutations. Despite this lower molecular complexity, patients presenting with SVT showed a higher risk of death (HR 3.0, 95% CI 1.5-6.0, p = 0.003) and lower event-free survival (HR 3.0, 95% CI 1.9–4.8, p < 0.001) than age- and sex-matched PV/ET controls. In patients presenting with SVT, molecular high-risk was associated with increased risk of venous re-thrombosis (HR 5.8, 95% CI 1.4–24.0, p = 0.01). Patients developing SVT during follow-up were more frequently allocated in molecular high-risk than those with SVT at diagnosis (52% versus 13%, p < 0.05). In the whole cohort of patients, molecular classification identified PV/ET patients at higher risk of disease progression whereas DNMT3A/TET2/ASXL1 mutations were associated with higher risk of arterial thrombosis. In conclusion, clinical and molecular characteristics are different in PV/ET patients with SVT, depending on whether it occurs at diagnosis or at follow-up. Molecular characterization by NGS is useful for assessing the risk of thrombosis and disease progression in young patients with PV/ET.
Clinical management of patients diagnosed with acute myeloid leukemia treated with venetoclax in combination with hypomethylating agents after achieving a response: a real-life study
(Springer Verlag, 2024-10-01) Jiménez Vicente, Carlos; Guardia Torrelles, Ares; Pérez Valencia, Amanda Isabel; Martínez-Roca, Alexandra; Castaño Díez, Sandra; Guijarro Tomas, Francisca; Cortés Bullich, Albert; Merchán, Beatriz; Triguero, Ana; Hernández, Isabel; Brillembourg, Helena; Munárriz, Daniel; Zugasti, Inés; Fernández Avilés, Francesc; Díaz Beyà, Marina; Esteve, Jordi
Although there is an approved indication for venetoclax and hypomethylating agents (VenHMA) and its use in different AML settings will be expanded in the following years, the management of the adverse events (AEs) lacks of harmonized algorithms during treatment of these patients. We have studied the incidence of relevant AEs of 43 patients who achieved a response to VenHMA and its management. Median overall survival of our cohort was 19 months. No patients discontinued treatment due to AEs after C3D1, Regarding severe AEs, high rates of grade 4 neutropenia (97.6%) and grade 4 thrombocytopenia (65.1%) were observed. Severe infectious AEs rate was 16%. Due to severe myelotoxicity, most patients required a progressive dose reduction of both venetoclax and hypomethylating agents during follow-up, being 87.8% at C6D1. Transfusional dependence rate was 91% and G-CSF was prescribed to 86% of the patients. Finally, there was not a significant difference in hemoglobin, platelets and absolute neutrophil count after achieving complete response comparing paired samples during follow-up, although cytopenia rate was high during initial follow-up. We conclude that dose reduction of VenHMA after achieving a response in patients diagnosed with AML is required in most patients and essential to avoid prolonged cytopenia-related adverse events and a rapid and standardized method on how to perform it might decrease the AEs rate.

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