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Whole-exome sequencing of vulvar squamous cell carcinomas reveals an impaired prognosis in patients with TP53 mutations and concurrent CCND1 gains
(Nature Publishing Group, 2024-10-01) Ordi, Oriol ; Saco, Adela; Peñuelas, Núria; Blanco Irazuegui, Odei; Pino Saladrigues, Marta del; Carreras Dieguez, Núria ; Marimon, Lorena; Rodrigo Calvo, María Teresa; Morató, Alba; Sisuashvili, Lia; Bustamante Pineda, Mariona; Cruells, Adrià; Darecka, Katarzyna; Vega, Naiara; Alos, Silvia; Trias Puigsureda, Isabel; Fusté, Pere; Parra, Genís; Gut, Marta; Munmany, Meritxell; Torné Bladé, Aureli; Jares Gerboles, Pedro; Rakislova, Natalia
Very little information is available on the mutational landscape of vulvar squamous cell carcinoma (VSCC), a disease that mainly affects older women. Studies focusing on the mutational patterns of the currently recognized etiopathogenic types of this tumor (human papillomavirus [HPV]-associated [HPV-A], HPV-independent [HPV-I] with TP53 mutation [HPV-I/TP53mut], and HPV-I with wild-type TP53 [HPV-I/TP53wt]) are particularly rare, and there is almost no information on the prognostic implications of these abnormalities.Whole-exome DNA sequencing of 60 VSCC and matched normal tissues from each patient was performed. HPV detection, immunohistochemistry (IHC) for p16, p53, and mismatch repair proteins were also performed. Ten tumors (16.7%) were classified as HPV-A, 37 (61.7%) as HPV-I/TP53mut, and 13 (21.6%) as HPV-I/TP53wt. TP53 was the most frequently mutated gene (66.7%), followed by FAT1 (28.3%), CDKN2A (25.0%), RNF213 (23.3%), NFE2L2 (20%) and PIK3CA (20%). All the 60 tumors (100%) were DNA mismatch repair proficient. Seventeen tumors (28.3%) showed CCND1 gain. Bivariate analysis, adjusted for International Federation of Gynecology and Obstetrics stage, revealed that TP53 mutation, CCND1 gain, and the combination of the 2 alterations were strongly associated with impaired recurrence-free survival (hazard ratio, 4.4; P < .001) and disease-specific survival (hazard ratio, 6.1; P = .002). Similar results were obtained when p53 IHC status was used instead of TP53 status and when considering only HPV-I VSCC. However, in the latter category, p53 IHC maintained its prognostic impact only in combination with CCND1 gains. All tumors carried at least one potentially actionable genomic alteration. In conclusion, VSCCs with CCND1 gain represent a prognostically adverse category among HPV-I/TP53mut tumors. All patients with VSCCs are potential candidates for targeted therapy.
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.
TB as a risk factor for severe COVID-19 mortality
(International Union Against Tuberculosis and Lung Disease, 2025-04-01) Carmo Borges, Igor; Molina Lino, Fernando ; Luna Muschi, Alessandra; Nobrega Litvoc, Marcelo; Banks Lopes, Max Igor; Ryoiti Higashino, Hermes; Furtado Da Costa, Álvaro; Moraes Pereira, Rafael Henrique; Takashi Nakaya, Helder; Alves de Araújo, José Deney; Orlandi, Giovanna Mariah; Penón Rújula, Maria Josefa; Marques Pinto Carvalhanas, Telma Regina; Nielsen, Lucca; Martínez Minto, Cátia; Cerdeira Sabino, Ester; Figueiredo Costa, Silvia; Ranzani, Otavio T.
[No abstract available]
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.).
Unveiling a hidden phenotype of early tuberculosis
(2025-05-01) Ehrlich, Joanna Lynn Buikema; Suñer Navarro, Clara; Churchyard, Gavin; Cobelens, Frank ; Hatherill, Mark; Mendelsohn, Simon; Nelson, Kristin; Scriba, Tom; Theron, Grant ; Martinez, Leopoldo ; García-Basteiro, Alberto L.
[No abstract available]
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.
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.
BMI as a predictor of progression from TB infection to active TB in PLHIV
(International Union Against Tuberculosis and Lung Disease, 2025-02-01) Nguenha, Dinis ; Ndebele, Felex; Saavedra, Belén ; Mambuque, Edson; Acácio, Sozinho ; Cardenas, Vicky; Chihota, Violet; Grant, Alison; Yimer, Getnet; Fielding, Katherine; Cobelens, Frank ; Churchyard, Gavin; García-Basteiro, Alberto L.
BACKGROUND: Low body mass index (BMI) is a globally important risk factor for TB progression. Little is known about this association in people living with HIV (PLHIV) and the functional form of the BMI-TB incidence curve. METHODS: Secondary analysis of a randomised controlled trial of TB preventive therapy among PLHIV in South Africa, Mozambique, and Ethiopia. Participants received 3 months of weekly high-dose rifapentine-isoniazid given once or twice over a period of 2 years. Multivariable fractional polynomials (MFPs) were used to investigate functional forms of BMI. Time to incident TB was modelled using Cox's proportional hazard regression. RESULTS: A total of 76 TB events were documented, giving an overall TB incidence rate of 1.2 per 100 person-years (95%CI 1.0-1.6). Baseline BMI = 30 kg/m(2) was associated with a lower hazard of TB (aHR 0.5, 95% CI 0.2-1.0). Continuous and categorical BMI showed weak evidence of quadratic dose-response relationships (P = 0.08 and P = 0.09, respectively). MFP analysis was consistent with a decline in TB incidence for increasing BMI to around 25 kg/m(2), followed by a less steep decline in TB incidence for increasing BMI >25 kg/m(2). CONCLUSIONS: In PLHIV, BMI showed an inverse log-linear association with TB incidence. The MFP approach showed that the relationship is more complex than a simple log-linear association.
Commentary: Navigating symptom and diagnostic overlap in pneumonia and malaria: insights from the field from the PERCH Study
(Oxford University Press, 2025-05-29) Torres Fernandez, David ; Bassat Orellana, Quique
Every year, severe pneumonia and malaria still cause an unacceptably high burden of disease and mortality globally. These illnesses predominantly affect children <5 years of age in low- and middle-income countries (LMICs), particularly in Southeast Asia and sub-Saharan Africa. In malaria-endemic regions, distinguishing severe pneumonia from malaria with respiratory symptoms is an almost impossible task for clinicians in the absence of accurate diagnostic tools, which are often scarcely available in these settings. The symptom overlap is frequent; in hospital-admitted paediatric patients, >40% of malaria cases have severe respiratory findings and 24% of paediatric patients fulfil World Health Organization (WHO) criteria for both diseases]. The true coinfection (or dual diagnosis) proportion of severe pneumonia among paediatric patients with malaria is estimated at about one-fifth of patients [1]. Understanding this overlapping clinical epidemiology and performing a reliable differential diagnosis between the two entities has arisen as a public health priority.
The Effect of Night Shift Work on the Gut Microbiome Diversity: The EXPONIT Study
(SAGE, 2026-01-25) Galán, Raquel ; Castaño Vinyals, Gemma ; Rubio García, Elisa ; López Aladid, Rubén ; Espinosa, Ana ; Papantoniou, Kyriaki ; Bustamante Pineda, Mariona ; Bhatti, Parveen; Lassale, Camille Melodie; Marquez, Cristina; Alfaro, Ana; Casals Pascual, Climent ; Kogevinas, Manolis ; Harding, Barbara N.
Night shift work may alter the gut microbiome through mechanisms involving circadian misalignment, sleep disturbance, and changes in dietary behavior. However, existing studies on this topic have been limited in sample size and scope. We analyzed stool samples from 240 participants (mean age 42 years, 80% women), of whom 53% were night shift workers. Gut microbiota composition was assessed using 16S rRNA gene sequencing to derive measures of relative abundance, alpha diversity, and beta diversity. Associations between night shift work and microbial composition and alpha diversity were examined using generalized linear models with a Gamma distribution and log link for alpha diversity and Aitchison distance for beta diversity. The effect of night shift work on microbiome genera abundance was evaluated using MaAsLin2 analysis. Models were adjusted for age, sex, and educational level. We also explored potential interactions by sleep quality, diet, and chronotype. There were no overall significant differences in alpha or beta diversity between day and night shift workers, but participants with less than 15 years of night work showed slightly higher Abundance-based Coverage Estimator than non-night workers. Interaction with sleep quality was observed (p-value: 0.01). Among participants with poor sleep quality, night shift work was significantly associated with lower alpha diversity (exp(beta): 0.93, 95% CI: 0.87-0.99, p-value: 0.02). Day shift workers showed high relative abundance of Ruminococcus, while night shift workers had increased Escherichia-Shigella at descriptive level, none of which remain statistically significant after false discovery rate. Our findings indicate that night shift work may influence gut microbiome diversity, especially in individuals with poor sleep quality. Future research should explore the long-term health consequences of these microbial changes.
Development of High-Level Daptomycin Resistance in Abiotrophia and Granulicatella Species Isolates from Patients with Infective Endocarditis
(American Society for Microbiology, 2021-09-17) Cañas, María Alexandra; Téllez, Adrián; García de la Mària, Cristina; Dahl, Anders; García González, Javier; Hernández Meneses, Marta; Almela, M. (Manel); Ambrosioni, Juan; Falces Salvador, Carles; Quintana, Eduard; Vidal, Bàrbara; Perissinotti, Andrés; Tolosana, José M. (José María); Sandoval, Elena; Pericàs, Juan M.; Moreno Camacho, Ma. Asunción; Miró Meda, José M. (José María), 1956- ; Hospital Clínic Endocarditis Team Investigator
Abiotrophia and Granulicatella species are fastidious organisms, representing the causative agents of ∼1% to 3% of cases of infective endocarditis (IE). Little is known about the optimal antibiotic treatment for these species, and daptomycin has been suggested as a therapeutic option. We describe the antimicrobial profiles of Abiotrophia and Granulicatella IE isolates, investigate high-level daptomycin resistance (HLDR) development, and evaluate daptomycin activity in combination therapy. In vitro studies with 16 IE strains (6 Abiotrophia defectiva strains, 9 Granulicatella adiacens strains, and 1 G. elegans strain) were performed using microdilution to determine MICs and time-kill methodology to evaluate combination therapy. Daptomycin nonsusceptibility (DNS) (MIC ≥ 2 mg/liter) and HLDR (MIC ≥ 256 mg/liter) were based on existing Clinical and Laboratory Standards Institute (CLSI) breakpoints for viridans group streptococci. All isolates were susceptible to vancomycin: G. adiacens was more susceptible to penicillin and ampicillin than A. defectiva (22% versus 0% and 67% versus 33%) but less susceptible to ceftriaxone and daptomycin (56% versus 83% and 11% versus 50%). HLDR developed in both A. defectiva (33%) and G. adiacens (78%) after 24 h of exposure to daptomycin. Combination therapy did not prevent the development of daptomycin resistance with ampicillin (2/3 strains), gentamicin (2/3 strains), ceftriaxone (2/3 strains), or ceftaroline (2/3 strains). Once developed, HLDR was stable for a prolonged time (>3 weeks) in G. adiacens, whereas in A. defectiva, HLDR reversed to the baseline MIC at day 10. This study is the first to demonstrate rapid HLDR development in Abiotrophia and Granulicatella species in vitro. Resistance was stable, and most combination therapies did not prevent it.
In Vitro Activity of Ampicillin Plus Ceftriaxone Against Non-faecalis and Non-faecium Enterococcal Isolates With/Without VanC Phenotype: Clinical Implications for Infective Endocarditis.
(MDPI, 2024-12-05) García González, Javier; Cañas, María Alexandra; Cuervo Requena, Guillermo; Hernández Meneses, Marta; Verdejo, Miguel Ángel; Bodro, Marta; Díez de los Ríos, Javier; Gasch, Oriol; Ribera, Alba; Falces Salvador, Carles; Perissinotti, Andrés; Vidal, Bàrbara; Quintana, Eduard; Moreno Camacho, Ma. Asunción; Piquet, Maria; Roca Subirà, Ignasi; Fernández Pittol, Mariana José; San José Villar, Sol María; García de la Mària, Cristina; Miró Meda, José M. (José María), 1956- ; Hospital Clínic Endocarditis Study Group
1) Background: Alternative antibiotics are needed to treat infective endocarditis (IE) caused by non-faecalis/non-faecium enterococci; we aimed to assess the in vitro activity of ampicillin plus ceftriaxone (AMP + CTR) against these enterococci and to describe its clinical efficacy in IE cases. (2) Methods: Time–kill curves with standard (ISI) and high (IHI) inocula were performed to test VanC isolates [3 E. casseliflavus (ECAS) and 1 E. gallinarum (EGALL)] and non-VanC isolates [1 E. durans (EDUR), 1 E. hirae (EHIR) and 1 E. raffinosus (ERAF)]. The narrative literature review of IE cases treated with AMP + CTR was analyzed alongside three study cases. Clinical outcomes were relapse and death. (3) Results: Ampicillin plus gentamicin (AMP + GEN) showed synergistic and bactericidal activity against most isolates. AMP + CTR was synergistic at ISI for EGALL, EDUR, and EHIR and bactericidal against EHIR. At IHI, indifferent activity was observed for all isolates. In IE cases treated with AMP + CTR, it was only effective for EDUR and EHIR. Clinical information for EGALL IE is lacking. For IE caused by ECAS and ERAF, AMP + CTR seems suboptimal or ineffective, respectively. (4) AMP + CTR cannot be recommended for treating IE due to ECAS/ERAF. In contrast, this combination was effective in IE caused by EDUR/EHIR and could be recommended.
Recognizing post-malaria neurological syndrome in travellers: insights from three cases
(Oxford University Press, 2025-05-21) Riera, Elisa; Almuedo Riera, Alex; Álvarez Martínez, Míriam J.; Camprubí, Daniel
Post-malaria neurological syndrome (PMNS) is infrequent but might be underdiagnosed in travellers. Following a previous publication in the Journal, we present three additional cases of PMNS to broaden the discussion and offer possible insights on when to suspect it and how to proceed.
Time to Reappraise the Antibiotic Treatment for Methicillin-Susceptible Staphylococcus aureus Infective Endocarditis: Data From the Experimental Model
(Oxford University Press, 2025-09-15) García de la Mària, Cristina; Gasch, Oriol; Cañas, María Alexandra; García González, Javier; Marco Reverté, Francesc; Hernández Meneses, Marta; Quintana, Eduard; Ambrosioni, Juan; Falces Salvador, Carles; Tolosana, José M. (José María); Vidal, Bàrbara; Pericàs, Juan M.; Perissinotti, Andrés; Llopis Pérez, Jaime; Moreno Camacho, Ma. Asunción; Cuervo Requena, Guillermo; Miró Meda, José M. (José María), 1956- ; Hospital Clinic Endocarditis Study Group
Background Traditional treatment of methicillin-susceptible Staphylococcus aureus (MSSA) native valve endocarditis is based on cloxacillin/cefazolin monotherapy. Antibiotics with high activity against MSSA, such as ceftaroline and daptomycin, have been marketed for years, but there are no clinical trials evaluating them as monotherapy or combination therapy in patients with MSSA endocarditis. The objective of this study was to compare the efficacy of cloxacillin, ceftaroline, and daptomycin monotherapies and daptomycin combinations with β-lactams in a rabbit model of MSSA endocarditis. Methods Endocarditis was induced in rabbits with 2 strains of MSSA. After 24 hours of infection, they received human-like doses of cloxacillin, ceftaroline, or daptomycin or combinations of daptomycin plus either cloxacillin or ceftaroline. Isolates recovered from vegetation, spleen, and kidney were retested for daptomycin nonsusceptibility (DNS) posttreatment. Results MSSA vancomycin minimum inhibitory concentration did not influence the efficacy of any antibiotic treatment. Cloxacillin, ceftaroline, and daptomycin had similar activity (25%–50%) in sterilizing vegetations. However, 13% of rabbits treated with daptomycin developed DNS. The addition of daptomycin to cloxacillin or ceftaroline was synergistic and bactericidal, showing significantly more activity and higher rates of sterile vegetations (≥90%) than any monotherapy. Combinations also showed better activity in spleens and kidneys as compared with daptomycin monotherapy and prevented the development of DNS in all tissues. There were no differences between the daptomycin combinations. Conclusions In the MSSA experimental endocarditis model, daptomycin combinations with β-lactams had significantly better activity than any of the monotherapies in sterilizing valve vegetations and preventing DNS development. These findings support their use in clinical practice and to perform clinical trials.
The contribution of minimally invasive tissue sampling compared to antemortem-derived cause of death determination among inpatient child deaths: the minimally invasive tissue sampling in Malawi study.
(International Society of Global Health, 2025-08-04) Voskuijl, Wieger P.; Chasweka, Dennis; Lawrence, Sarah; Brals, Daniella; Kamiza, Steve; Bandsma, Robert; Berkley, James A.; Mbale, Emmie; Attipa, Charalampos; Eneya, Chisomo; Huwa, Cornelius; Khoswe, Stanley; Moxon, Christopher; Potani, Isabel; Waller, Jessica L.; Diaz, Maureen H.; Walson, Judd; Ordi i Majà, Jaume; Denno, Donna M.
Improved causes of death (CoD) understanding in low- and middle-income countries is needed to reduce child mortality. Compared to full autopsy, minimally invasive tissue sampling (MITS), using transcutaneous needle sampling, is a feasible, socially acceptable, and validated method. We aimed to quantify the additional contribution of MITS to CoD attribution based on clinical records and inpatient research data with intensive patient characterisation. Methods We enrolled children aged seven days to 59 months who died while on admission for acute illness and/or severe malnutrition to Queen Elizabeth Central Hospital in Blantyre, Malawi. Standard MITS procedures included histologic, immunohistochemical, and microbiologic testing. Phase 1 CoD determination was based on medical records alone, Phase 2 also included research data, and Phase 3 included all data, including from MITS. Results We enrolled 29 children. Based on clinical notes alone (Phase 1), we identified 60 causal and 39 contributing conditions. Of the 45 (45%) infectious conditions, pathogens were identified in 15 (33%). Only one patient’s (3%) CoD was unchanged compared to including all data (Phase 3). Further, we identified 69 new (n = 43) or adjusted (n = 26) diagnoses among 28 cases (97%); the majority were undernutrition-related (n = 22, 32%) or infectious (n = 41, 59%) conditions. Overall, the majority of final Phase 3 conditions were also undernutrition-related (n = 46, 32%) or infectious (n = 61, 43%) and a pathogen was identified in 54 (89%) of the infectious conditions. Klebsiella pneumoniae was the most prevalent aetiology in both pneumonia and sepsis. Conclusions The addition of MITS to clinical and inpatient research data led to almost all (97%) of cases receiving new and/or refined diagnoses, including microbe identification in infectious conditions. Pathogens not specifically addressed by current clinical guidelines, such as Klebisiella pneumoniae, were commonly identified. Our findings support the utility of MITS to understand CoD even after thorough clinical characterisation of children during hospitalisation.
Survival comparison analysis between cervical squamous cell carcinoma and adenocarcinoma with a special focus on the HPV status
(Elsevier BV, 2026-01-22) Jain, Deepti; Marya Wahidib; Effendib, Judy; Hoangc, Lien ; Terinted, Cristina ; Pescie, Anna ; Kiyokawaf, Takako ; Alvarado Cabrero, Isabel ; Oliva, Esther; Rakislova, Natalia; Felix, Ana ; Allison, Douglas ; Guerrao, Esther ; Romap, Andres ; Fadare, Oluwole ; Turashvili, Gulisa ; Parra Herran, Carlos ; Kirs, Gozde ; Erbagci, Ahmet ; Mills, Anne; Regauer, Sigrid ; Ordi i Majà, Jaume; Jang, Hyejeong ; Kim, Seongho ; Gogoi, Radhika ; Zannoni, Gian Franco; Mateoiu, Claudia ; Lastra, Ricardo ; Devins, Kyle ; Horn, Lars-Christian ; McCluggage, W. Glenn ; Stolnicu, Simona ; Ali-Fehmi, Rouba
Background: Our study examines impact of HPV status and patient-specific characteristics on recurrence-free survival (RFS) and overall survival (OS) for SCC and ECA. Methods: This multi-continental retrospective study analyzed clinicopathologic data of 634 patients with microscopically confirmed cervical cancer (CC; only SCC and ECA) across Asia, Europe, and North America. HPV status was determined using PCR or HPV in situ hybridization (ISH) for both HR-HPV (SCC and ECA) and LR-HPV (SCC), using same platform. Descriptive analysis and Cox regression models were produced. Results: Out of total 634 patients, 533 (84.1%) were HPVA and 101 (15.9%) were HPVI. 65% had SCC morphology (88.1%: HPVA; 11.9%: HPVI) and 35% had ECA differentiation (76.6%: HPVA; 23.4%: HPVI). Compared to ECA, patients with SCC were older (median age: 51 vs. 45 years old; p < 0.001), had higher HPVA status (88.1% vs. 76.6%; p < 0.001), and a higher rate of lymph-vascular invasion (LVI; 64.8% vs. 56.8%; p = 0.004). However, patients with ECA had a higher rate of metastases to pelvic organs (13.5% vs. 2.4%; p < 0.001). In univariable analysis, HPV status, tumor type, higher FIGO stage, older age, LVI positive, lymph node metastasis (LNM), and adjuvant treatment were all associated with impaired RFS and OS (all p <= 0.007). In multivariable analysis, LVI, HPV status, institution, and tumor type remained significant for RFS, while age at diagnosis, FIGO stage, LVI, and tumor type remained significant for OS. Conclusion: Tumor type and HPV status play significant role in determining survival outcomes in CC.
A cross-sectional pilot study to define anal cancer risk factors in HIV-positive solid organ transplant recipients.
(Taylor & Francis, 2025-11-14) Fuertes, Irene; Chivite, Ivan; Cranston, R.D.; Sánchez, Emilia; Lazzari, Elisa de; Marimon, Lorena; Ordi i Majà, Jaume; Miró Meda, José M. (José María), 1956-; Blanco, José L.
Background HIV-positive organ transplant recipients are at high risk of anal cancer, but there are no data on the prevalence of high-risk human papillomavirus (hr-HPV) or anal dysplasia, in this population. Objective To assess the prevalence of anal hr-HPV, and anal cytological and histological abnormalities in this population. Design and setting Prospective single tertiary hospital. Results Twenty-five (53%) transplant recipients were recruited from 47 eligible individuals. Median (IQR) age was 56 years (52.5–60), 17 were male, 9 (36%) were men who have sex with men and 8 (32%) were active smokers. Twelve (48%) patients had abnormal anal cytology and 12 (48%) had detectable hr-HPV DNA. Six (50%) individuals with abnormal cytology had high-grade squamous intraepithelial lesions (HSIL) on biopsy. Abnormal anal cytology was significantly associated with current hr-HPV infection [crude prevalence rate ratio, cRR = 2.3, 95% CI (1.43–3.7); p = 0.001] and any previous history of HPV associated disease [cRR = 2.49, 95% CI (1.09–5.67); p = 0.030]. Anal HSIL on biopsy was associated with presence of condyloma [cRR = 3.00, 95% CI (1.31–6.88); p = 0.001] and any previous history of any HPV associated disease [cRR = 6.67, 95% CI (0.96–46.32); p = 0.055]. Anal hr-HPV infection was associated with any previous HPV disease (Crude risk ratios [cRR = 2.89, 95% CI (1.21–6.88); p = 0.017]) and presence of condyloma (Crude risk ratios [cRR = 2.00, 95% CI (1.28–3.13); p = 0.002]). No cases of invasive anal cancer were detected among study participants. Conclusions This highly medicalized population of HIV-positive organ transplant recipients have a high prevalence of HPV-associated anal dysplasia and screening to prevent anal cancer may need to be prioritised.

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