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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.
From peri-implant mucositis to peri-implantitis: Incidence and risk indicators in a university dental hospital sample with up to 10 years of follow-up
(Elsevier, 2026-01-06) Alahmari, Ahmad; Arsalan Askarizadeh, Amir; Barbosa de Figueiredo, Rui Pedro; García-García, Marta; Costa-Berenguer, Xavier; Sales Collado, Miquel; Valmaseda Castellón, Eduardo; Sánchez Torres, Alba
Objectives: To determine the proportion of patients with peri‑implant mucositis who develop peri‑implantitis over a 1- to 10-year follow-up period, and to identify the variables associated with this progression. Materials and Methods: A retrospective cohort study was conducted including 97 patients with 204 dental implants diagnosed with peri‑implant mucositis. Clinical and radiographic examinations were performed, and compliance with supportive peri‑implant care (SPIC) was recorded. A multilevel multinomial logistic regression model was developed to identify the predictors of disease progression. Results: After a mean follow-up of 49.8 months, 23.7% of patients initially diagnosed with peri‑implant mucositis became healthy, 57.7% showed no change and remained with peri‑implant mucositis, while 18.5% progressed to peri‑implantitis. A history of periodontitis significantly increased the odds of presenting peri‑implant disease at the last follow-up appointment (p < 0.001). Conversely, regular compliance with SPIC, prostheses with an adequate design, and single-unit restorations significantly reduced the risk of progression (p < 0.001). Conclusions: Almost one fifth of patients with dental implants with peri‑implant mucositis are likely to develop peri‑implantitis after a mean follow-up of 4 years. A history of periodontitis, irregular supportive peri‑implant care and inadequate prosthetic design increase the likelihood of bone loss and progression to peri‑implantitis. Clinical Significance: This study emphasizes the importance of regular supportive peri‑implant care and appropriate prosthetic design to prevent progression from peri‑implant mucositis to peri‑implantitis, especially in patients with a history of periodontitis
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.
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.
Neurological Symptoms and Cause of Death Among Young Children in Low- and Middle-Income Countries
(American Medical Association (AMA), 2024-09-03) Ajanovic, Sara; Mandomando, Inácio; Varo, Rosauro; Bassat Orellana, Quique; Child Health and Mortality Prevention Surveillance (CHAMPS) Consortium
IMPORTANCE The emergence of acute neurological symptoms in children necessitates immediate intervention. Although low- and middle-income countries (LMICs) bear the highest burden of neurological diseases, there is a scarcity of diagnostic and therapeutic resources. Therefore, current understanding of the etiology of neurological emergencies in LMICs relies mainly on clinical diagnoses and verbal autopsies. OBJECTIVE To characterize the association of premortem neurological symptoms and their management with postmortem-confirmed cause of death among children aged younger than 5 years in LMICs and to identify current gaps and improve strategies to enhance child survival. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study was conducted between December 3, 2016, and July 22, 2022, at the 7 participating sites in the Child Health and Mortality Prevention Surveillance (CHAMPS) network (Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa). Minimally invasive tissue sampling was performed at the CHAMPS sites with specimens from deceased children aged younger than 5 years. This study included deceased children who underwent a premortem neurological evaluation and had a postmortem-confirmed cause of death. Data analysis was performed between July 22, 2022, and January 15, 2023. MAIN OUTCOMES AND MEASURES Descriptive analysis was performed using neurological evaluations from premortem clinical records and from postmortem determination of cause of death (based on histopathology, microbiological testing, clinical records, and verbal autopsies). RESULTS Of the 2127 deaths of children codified during the study period, 1330 (62.5%) had neurological evaluations recorded and were included in this analysis. The 1330 children had a median age of 11 (IQR, 2-324) days; 745 (56.0%) were male and 727 (54.7%) presented with neurological symptoms during illness before death. The most common postmortem-confirmed neurological diagnoses related to death were hypoxic events (308 [23.2%]), meningoencephalitis (135 [10.2%]), and cerebral malaria (68 [5.1%]). There were 12 neonates with overlapping hypoxic events and meningoencephalitis, but there were no patients with overlapping meningoencephalitis and cerebral malaria. Neurological symptoms were similar among diagnoses, and no combination of symptoms was accurate in differentiating them without complementary tools. However, only 25 children (18.5%) with meningitis had a lumbar puncture performed before death. Nearly 90% of deaths (442 of 511 [86.5%]) with neurological diagnoses in the chain of events leading to deathwere considered preventable.
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.
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.).
Steady-state versus burst lasing techniques for thulium fiber laser
(Springer Verlag, 2024-12-01) Sierra, Alba; Solano, Catalina; Corrales, Mariela; Ventimiglia, Eugenio; Panthier, Frederic; Kwok, Jia Lun; Chicaud, Marie; Keller, Etienne Xavier; Traxer, Olivier
Objective To evaluate the stone ablation rate and direct thermal damage from thulium fiber laser (TFL) lithotripsy using continuous (C) and burst (B) lasing techniques on an in vitro ureteral model. Methods The TFL Drive (Coloplast, Humlebaek, Denmark) was used in an in vitro saline-submerged ureteral model. Ten participants, including five junior and five experienced urologists, conducted the experimental setup with 7 different settings comparing two lasing techniques: steady-state lasing (0.5 J/10 Hz = 5W for 300 s and 0.5 J/20 Hz = 10W for 150 s) and burst, intermittent 5 s on/off lasing (0.5 J/20 Hz, 0.5 J/30 Hz, 0.5 J/60 Hz, 0.1 J/200 Hz, and 0.05 J/400 Hz) with a target cumulative energy of 1500 J using cubic 125 mm3 phantom BegoStonesTM. Ureteral damage was graded 1–3 based on the severity of burns and holes observed on the surface of the ureteral model. Results The were no significant differences in stone ablation mass neither between C and B lasing techniques, nor between expertise levels. At C lasing technique had only mild ureteral lesions with no significant differences between expertise levels (p: 0.97) or laser settings (p: 0.71). At B lasing technique, different types of thermal lesions were found with no expertise (p: 0.11) or setting (p: 0.83) differences. However, B laser setting had higher grade direct thermal lesions than C (p: 0.048). Conclusion Regarding efficacy, C and B lasing techniques achieve comparable stone ablation rates. Safety-wise, B lasing mode showed higher grade of direct thermal lesions. These results should be further investigated to verify which of the lasing mode is the safest in vivo. Until then and unless proven otherwise, a C mode with low frequency should be recommended to avoid ureteral wall lesions.
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.
DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions
(Springer Verlag, 2024-08-01) Pons Escoda, Albert; Naval Baudin, Pablo; Viveros, Mildred; Flores-Casaperalta, Susanie; Martínez Zalacaín, Ignacio; Plans, Gerard; Vidal Sarró, Noemí; Cos Domingo, Mònica; Majós Torró, Carlos
Purpose The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values. Methods This retrospective study, spanning 2016–2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC. Results The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values. Conclusion Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma’s pure edema.
Severity of Primary and Secondary Dengue Virus 1 Infections: A Hospital-Based Study in Puerto Rico, 2012–2014
(American Society of Tropical Medicine and Hygiene, 2025-08-01) Camprubí Ferrer, Daniel; Torres Velásquez, Brenda; Pérez Padilla, Janice; Wong, Joshua; Sánchez González, Liliana; Munoz Jordan, Jorge L.; Rodriguez Vargas, Dania M.; Rivera Amill, Vanesa; Adams, Laura E.; Paz Bailey, Gabriela
ABSTRACT. Dengue is the most common mosquito-borne viral disease in humans. Although many dengue virus (DENV) infections are asymptomatic or produce only mild illness, DENV can occasionally cause severe and fatal disease. In this study, we compared the severity of primary and secondary DENV-1 infections among patients enrolled in a prospective, hospital-based, acute febrile illnesses surveillance system in Puerto Rico (2012–2014). Serum samples collected <7 days after symptom onset were tested for DENV-serotypes by a real time-polymerase chain reaction assay. The positive samples that were collected ≤5 days after onset were then tested by a DENV IgG antibody ELISA to classify primary (IgG negative) and secondary (IgG positive) infections. Overall, 720 dengue infections (679 DENV-1, 3 DENV-2, and 38 DENV-4) were diagnosed during the study period. Of the 679 DENV-1 patients, 595 were included in the study, 445 (75%) were classified as secondary infections, and 150 (25%) as primary infections. Among these patients, 150 (25%) were classified as severe dengue. Severe dengue occurred in 28% of secondary DENV-1 infections. Severe disease was also common among primary DENV-1 infections, including 27% with plasma leakage, 15% with severe dengue, and 9% requiring admission to the intensive care unit. Even though DENV-1 has caused thousands of cases in Puerto Rico, this is the first report describing DENV-1 as the cause of severe primary infection in this country. Although secondary DENV-1 infections have an increased risk for severe disease, it is important for clinicians to be aware that any individual with dengue should be considered at risk for severe dengue.
Etiologies and comorbidities of meningitis deaths in children under 5 years in high-mortality settings: Insights from the CHAMPS Network in the post-pneumococcal vaccine era
(Elsevier, 2024-11-08) Mahtab, Sana ; Ajanovic, Sara; Mandomando, Inácio; Bassat Orellana, Quique; CHAMPSconsortium
Background: The role of meningitis in causing deaths and in children under 5 is unclear, especially since widespread use of vaccines to prevent common causes of meningitis. Child Health and Mortality Prevention Surveillance (CHAMPS) uses post-mortem minimally invasive tissue sampling (MITS) and ante-mortem data to explore death causes. We aimed to assess meningitis’s contribution to mortality and identify causative pathogens in children under 5 within CHAMPS Network sites. Method: In this observational study, we analyzed deaths in live-born children < 5 years of age that occurred between December 16, 2016, and December 31, 2023, in CHAMPS catchments in six sub-Saharan African countries (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, South Africa) and Bangladesh. MITS was conducted within 24–72 h of death, including blood and cerebrospinal fluid (CSF) culture, multi-organism targeted nucleic acid amplification tests on blood, CSF and lung tissue, and histopathology of lung, liver and brain. Expert panels at each site reviewed data to attribute causes of death following ICD-10 standards. Result: Meningitis was in the causal pathway for 7.0% (270/3857) of deaths; in 4.8% (13/270) meningitis was considered the underlying condition. Neonates accounted for 65.9% (178/270) and infants or children 34.1% (92/270). Among neonatal meningitis deaths, 55.6% (99/178) occurred ≥72 h post-hospital admission; and common pathogens were Acinetobacter baumannii (49.5%, 49/99; mainly from South Africa) and Klebsiella pneumoniae (40.4%, 40/99). Forty-four percent (79/178) of neonatal meningitis deaths were community- associated, primarily due to K. pneumoniae (35.4%, 28/79) and Escherichia coli (13.9%, 11/79). Among infant and child meningitis deaths, 43.5% (40/92) occurred ≥72 h post-admission; and common pathogens were K. pneumoniae (42.5%,17/40) and A. baumannii (17.5%, 7/40). Among community-associated meningitis deaths in infants and children (56.5%, 52/92), Streptococcus pneumoniae (34.6%, 18/52) and K. pneumoniae (19.2%, 10/52) were common pathogens. Pathogen prevalence varied by region. Conclusion: Our study highlights meningitis as a significant contributor to under-5 mortality in low- middle-income countries. The prominent role of K. pneumoniae and A. baumannii, particularly in healthcare settings and specific regions, highlights the need for better infection control, targeted interventions, and more effective treatment strategies.
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.
Non-invasive meningitis screening in neonates and infants: multicentre international study
(Nature Publishing Group, 2025-07-23) Ajanovic, Sara ; Petrone, Paula; Sial, Hassan; Muñoz, David; Agut, Thais; Salas, Barbara; Carreras Dieguez, Núria ; Alarcón Allen, Ana; Iriondo Sanz, Martín; Luaces Cubells, Carles; Arias, Sara; Bassat Orellana, Quique; The UNITED study group
BACKGROUND AND OBJECTIVES: Meningitis diagnosis requires a lumbar puncture (LP) to obtain cerebrospinal fluid (CSF) for a laboratory-based analysis. In high-income settings, LPs are part of the systematic approach to screen for meningitis, and most yield negative results. In low- and middle-income settings, LPs are seldom performed, and suspected cases are often treated empirically. The aim of this study was to validate a non-invasive transfontanellar white blood cell (WBC) counter in CSF to screen for meningitis. METHODS:: We conducted a prospective study across three Spanish hospitals, one Mozambican and one Moroccan hospital (2020–2023). We included patients under 24 months with suspected meningitis, an open fontanelle, and a LP performed within 24 h from recruitment. High-resolution-ultrasound (HRUS) images of the CSF were obtained using a customized probe. A deeplearning model was trained to classify CSF patterns based on LPs WBC counts, using a 30cells/mm3 threshold. RESULTS:: The algorithm was applied to 3782 images from 76 patients. It correctly classified 17/18 CSFs with 30 WBC, and 55/58 controls (sensitivity 94.4%, specificity 94.8%). The only false negative was paired to a traumatic LP with 40 corrected WBC/mm3. CONCLUSIONS:: This non-invasive device could be an accurate tool for screening meningitis in neonates and young infants, modulating LP indications. Pediatric Research (2026) 99:1040–1050; https://doi.org/10.1038/s41390-025-04179-7 IMPACT: ● Our non-invasive, high-resolution ultrasound device achieved 94% accuracy in detecting elevated leukocyte counts in neonates and infants with suspected meningitis, compared to the gold standard (lumbar punctures and laboratory analysis). ● This first-in-class screening device introduces the first non-invasive method for neonatal and infant meningitis screening, potentially modulating lumbar puncture indications. ● This technology could substantially reduce lumbar punctures in low-suspicion cases and provides a viable alternative critically ill patients worldwide or in settings where lumbar punctures are unfeasible, especially in low-income countries).
Ivermectin resistance mechanisms in ectoparasites: a scoping review
(Springer Verlag, 2024-05-01) Furnival-Adams, Joanna Elena Claire; Kiuru, Caroline; Sagna, André Barembaye; Mouline, Karine; Maia, Marta F.; Chaccour, Carlos
Ivermectin mass drug administration has been used for decades to target human and veterinary ectoparasites, and is currently being considered for use against malaria vectors. Although there have been few reports of resistance to date in human ectoparasites, we must anticipate the development of resistance in mosquitoes in the future. Hence, through this review, we mapped the existing evidence on ivermectin resistance mechanisms in human ectoparasites. A search was conducted on the 8th November 2023 through databases, PubMed, Web of Science, and Google Scholar, using terms related to ivermectin, human and veterinary ectoparasites, and resistance. Abstracts (5893) were screened by JFA and CK. Data on the study organism, the type of resistance, the analysis methods, and, where applicable, the gene loci of interest were extracted from the studies. Details of the methodology and results of each study were summarised narratively and in a table. Eighteen studies were identified describing ivermectin resistance in ectoparasites. Two studies described target site resistance; and 16 studies reported metabolic resistance and/or changes in efflux pump expression. The studies investigated genetic mutations in resistant organisms, detoxification, and efflux pump expression in resistant versus susceptible organisms, and the effect of synergists on mortality or detoxification enzyme/efflux pump transcription. To date, very few studies have been conducted examining the mechanisms of ivermectin resistance in ectoparasites, with only two on Anopheles spp. Of the existing studies, most examined detoxification and efflux pump gene expression, and only two studies in lice investigated target-site resistance. Further research in this field should be encouraged, to allow for close monitoring in ivermectin MDA programmes, and the development of resistance mitigation strategies.
Determinants of Intention to Use HIV Pre-exposure Prophylaxis and Condom Use Among a Sample of Cisgender Female Sex Workers Working Mostly Outdoors in Madrid, Spain
(Springer Verlag, 2024-06-10) Vazquez Guillamet, Laia J.; Valencia, Jorge; Ryan, Pablo; Cuevas Tascón, Guillermo; Del Olmo Morales, Miguel Angel; Cobo, Inés; Lazarus, Jeffrey V.; Chevance, Guillaume
There is scant knowledge regarding pre-exposure prophylaxis (PrEP) use among female sex workers (FSWs) in Europe. Spain recognized FSWs as a population at high risk of acquiring HIV and granted them subsidized access to PrEP when the medication first became nationally available in 2019. Nevertheless, FSWs represented just 0.2% of PrEP users in 2022. A total of 102 HIV-negative FSWs reached through field activities of local NGOs located in Madrid were interviewed between January and March 2022. Participants were selected through convenience sampling over a fixed recruitment period. FSWs completed a 73-item survey with questions about individual, occupational, social, and structural determinants. The objective of this study was to identify (1) the prevalence of intention to use oral PrEP and its determinants, and (2) the prevalence of inconsistent condom use, which is the risk factor that qualifies FSWs for subsidized PrEP in the national health system, and its determinants. Importantly, the study sample overrepresented street-based FSWs (71.6%). A quarter (25.5%) of the study participants used condoms inconsistently. PrEP awareness was low (9.8%), but intention to use PrEP was high (72.5%). Intention to use oral PrEP was significantly associated with feeling protected against HIV by taking PrEP and perceiving insufficient protection by condom use alone. Inconsistent condom use was significantly associated with frequent heroin/cocaine use, having clients who inject drugs, and willingness to take PrEP despite it not protecting 100% against HIV infection. FSWs, in this specific sample, are likely to benefit from targeted PrEP awareness campaigns and implementation projects that prioritize those who use drugs and are more likely to engage in condomless sex.
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.
High-Fidelity Clinical Simulation to Improve a Pediatric Clinical Trial Design: Lessons Learned and Conceptualization of the Return on Investment (ROI) and Return on Engagement (ROE) Analysis
(Springer Nature, 2025-01-01) Quintillá, José Maria; Gala, Carmen de la; Berrueco Moreno, Rubén; Claverol, Joana; Figueres, Bibiana; Bergós, Anna; Rodríguez, Lourdes; Mora, Anna; DiBiaso, Victoria; Llanos, Cristina; Nafria Escalera, Begonya
Clinical trials entail complex processes that are more challenging when they are addressed to pediatric patients and include a decentralized design. High-realistic simulation allows for the testing and refining of procedures, organizational systems, and interactions between professionals and patients/families, narrowing the gap between work-as-imagined and work-as-done. Objectives The aim of this research was to analyze the impact of simulation in three key moments of a clinical trial: the baseline visit, home administration of the investigational drug by parents, and the drawing and processing of pharmacokinetics samples by a home nurse. Methods Multidisciplinary meetings were held between the team of Barcelona Children’s Hospital and the sponsor to define the simulation objectives. Three simulation scenarios were executed in 2 days. Subsequently, a post-process analysis was performed, including the assessment of the patient/family experience. Results In the baseline visit scenario, minimum duration was calculated, and main aspects related to task dynamics, materials, and training were identified. In the drug administration scenario, the family was able to carry out the infusion within the time established in the protocol, but with some difficulties. In the home nursing scenario, some recommendations for improving safety and patient experience were suggested. Conclusions High-realistic clinical simulation can contribute to anticipate risks, refine the design of activities, and to identify specific needs prior to the protocol finalization, a timepoint in the process when modifications can still be made that constitutes a significant return on investment and return on the engagement, in the experience of the patients that will participate in the study.
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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