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- Advancing Vaccination Strategies for Older AdultsPublication . Del Riccio, Marco; Maggi, Stefania; Wieczorowska-Tobis, Katarzyna; Newell, Katherine; Czech, Marcin; Botelho-Nevers, Elisabeth; Michel, Jean Pierre; Hummers, Eva; Duque, Sofia; Lundgren, Jens; Barrat, Jane; Tan, Litjen; Wysocki, Jacek; Boccalini, Sara; Bechini, Angela; Jindal, Sakshi; Hendrickx, Greet; Van Damme, Pierre; Bonanni, Paolo; Pattyn, Jade; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Adis International LtdAs Europe’s population ages, optimizing vaccination strategies for older adults is an increasing public health priority. Vaccine-preventable infections pose significant risks, including increased morbidity and mortality, reduced quality of life, and substantial healthcare costs. Prevention, particularly adult vaccination, plays a vital role in mitigating these outcomes and supporting healthy ageing. While childhood immunization remains essential, a life-course approach including routine older adult vaccination is needed. Coverage among older adults across Europe remains suboptimal owing to factors such as heterogeneous (sub)national policies, health literacy issues, financial barriers, access issues, and persistent structural and societal barriers. To meet these challenges, the Adult Immunization Board (AIB) convened a technical meeting in May 2025, to discuss strategies for improving vaccination in older adults. The meeting explored how older adults are defined in immunization policies (for the meeting, an operational threshold of ≥ 50 years was used, while acknowledging that many national age-based programs commonly start around 60–65 years) and reviewed current adult vaccines and programmatic implementation across six vaccines. Discussions highlighted the need for a life-course approach with coordinated (inter)national policies, clear adult vaccination schedules, dedicated infrastructure and programs, stronger surveillance, and structured follow-up. Key recommendations included shifting from fragmented efforts to cohesive, system-wide approaches. This approach requires addressing organizational challenges with programmatic strategies such as integrating adult vaccination into routine healthcare, providing co-administration guidance, and adapting successful pediatric models for adult programs. This summary presents insights shared during the AIB meeting, highlighting gaps and promising solutions for advancing older adult immunization in Europe. Vaccination must be recognized as an investment in healthy ageing, which is also able to generate a return in economic terms, as part of a holistic health package for older adults, not as an optional add-on to treatment. With older adults now outnumbering children under 5 years globally, it is time to invest equally in their vaccination.
- Reproducibility of the Amsterdam consensus criteria for maternal vascular malperfusion (MVM)Publication . Rocha, Maria Linda; Menter, Thomas; Tomas, Sandra Zekic; Ciolka, Barbara; Castro, Eumenia; Coelho, Helder Oliveira; Keir, Heather; Neumayer, Bettina; Nogueira, Rosete; Orsaria, Maria; Trzeszcz, Martyna; Ewald, Jo Anne; Severens-Rijvers, Carmen; Turowski, Gitta; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Walter de Gruyter & CoObjectives: Maternal vascular malperfusion (MVM) refers to dysfunctional uteroplacental circulation and is associated with increased risk of adverse maternal and fetal outcomes. The diagnosis of MVM is one of the most common pathological diagnoses in term placentas. The aim of the study was to test the interrater reliability of the MVM Amsterdam criteria. Methods: A group of 12 international perinatal pathologists reviewed digital histological sections of placentas (n=29; 20 MVM/ 9 non-MVM controls), applying published Amsterdam workshop consensus criteria. Kappa statistics were used for interobserver agreement analysis. Results: Agreement levels on final MVM diagnosis according to Amsterdam consensus were calculated as slight to fair (K-values of 0.187 and 0.260, p<0.001). Substantial agreement was reached one time for infarcts (K-value of 0.707, p<0.001). Complementary tested criteria achieved none to moderate agreement. Conclusions: Our results highlight the need to refine current MVM criteria to support consistent international diagnosis.
- A 17-year-old boy with hemifacial flushing and anhidrosisPublication . Farinha, Pedro Simões; Ferreirinha, Ana; Vilela, Beatriz; Duarte, Bruno; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Elsevier
- Perinatal outcomes of twin pregnancies complicated by early twin-to-twin transfusion syndrome treated with fetoscopic laser surgeryPublication . Sileo, F. G.; Khalil, A.; Binder, J.; Brunelli, E.; Chianchiano, N.; Coutinho, C. M.; D'Antonio, F.; Döbert, M.; Fichera, A.; Gielchinsky, Y.; Hecher, K.; Iacovella, C.; Malone, S.; Martinez-Varea, A.; Nørgaard, L. N.; Rodo, C.; Simões, T.; Slaghekke, F.; Yinon, Y.; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); John Wiley and Sons LtdOBJECTIVE: The aim of this study was to evaluate the perinatal outcomes of monochorionic diamniotic (MCDA) twin pregnancies complicated by early twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser surgery (FLS), and to compare rates of fetal survival across Quintero stages. METHODS: This was a multicenter retrospective cohort study of MCDA pregnancies complicated by TTTS diagnosed ≤ 18 weeks' gestation (early TTTS) that underwent FLS from January 2007 to August 2023. Monoamniotic twins, triplets or higher-order multiple gestations, and pregnancies complicated by genetic or structural anomalies were excluded. Demographic data, gestational age at diagnosis and at FLS, Quintero stage at diagnosis and details of management of the pregnancy, including complications and perinatal outcomes, were obtained from patient records at each participating center. The primary outcome was survival at 28 days after birth. RESULTS: In total, 678 MCDA pregnancies with early TTTS were identified, of which 550 underwent FLS. Of these, 485 cases had a known pregnancy outcome and were therefore included. The median gestational age at diagnosis was 17 + 0 (interquartile range (IQR), 16 + 3 to 17 + 4) weeks, and median gestational age at FLS was 17 + 4 (IQR, 17 + 0 to 17 + 6) weeks. The most common Quintero stage at diagnosis was Stage III (46.0% (223/485)). At least one postoperative complication occurred in 36.5% (177/485) of cases, including preterm prelabor rupture of membranes, intrauterine fetal demise of the cotwin, vaginal bleeding, septostomy and pregnancy loss. Dual-twin survival was reported in 51.5% (250/485) of cases, while survival of at least one twin was reported in 76.7% (372/485). There were no surviving fetuses in 23.3% (113/485) of pregnancies. When considering cases diagnosed ≤ 16 weeks, the rate of survival of at least one twin was 87.5% for cases diagnosed at Quintero Stages I-II vs 59.5% for Stages III-IV (P = 0.019). CONCLUSIONS: The diagnosis and management of TTTS ≤ 18 weeks are more complex than those of TTTS diagnosed > 18 weeks. More early-TTTS cases were diagnosed at Quintero Stage III, but the overall survival rate was not significantly different between cases diagnosed at Quintero Stages I-II vs Stages III-IV, except when the diagnosis was made ≤ 16 weeks, in which case the survival rate was higher among cases diagnosed at Stages I-II. Revisions to the diagnostic criteria for early TTTS should be considered.
- The protocol for a patient-driven online prospective European observational cohort aiming to determine risk factors for the development of psoriatic arthritis among people living with psoriasisPublication . Grohmann, Teresa; Mtenga, Timeo; Kerr, David; Barrett, Joe; Gray, Nathanael; Bertheussen, Heidi; Cañete, Juan D.; de Vlam, Kurt; de Wit, Maarten; Dimitroulas, Theodoros; Groothuizen, Sam; Haugeberg, Glenn; Hoff, Mari; Horváth, Rudolf; Hurnakova, Jana; Koehm, Michaela; Kotyla, Przemyslaw; Letarouilly, Jean Guillaume; Lories, Rik; Løset, Mari; Möser, Christine; Möller, Burkhard; Mytilinaiou, Maria; Østergaard, Mikkel; Rodrigues, Ana; Ryan, Caitriona; Selmi, Carlo; Eidsmo, Liv; Svedbom, Axel; Torres, Tiago; Vreju, Florentin Ananu; van de Sande, Marleen G.H.; Werner, Lars; Pennington, Stephen R.; FitzGerald, Oliver; Coates, Laura C.; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); SAGE PublicationsBackground: Up to one-third of people living with psoriasis develop psoriatic arthritis (PsA), and the majority have active psoriasis prior to the development of arthritis. Clinical risk factors, such as nail involvement, in conjunction with novel blood biomarkers, could improve PsA risk monitoring and early diagnosis. Objectives: The aim of the HIPPOCRATES Prospective Observational Study (HPOS—www.hpos.study) is to follow a cohort living with psoriasis and identify risk factors for the development of PsA. Design: HPOS is a patient-driven online prospective European observational cohort. Methods: Adult participants with psoriasis but with no prior diagnosis of PsA are eligible. Participants are invited to provide consent and join the study online. They complete a semi-structured questionnaire to collect data on demographics, psoriasis, comorbidities, risk factors for PsA, and the Psoriasis Epidemiology Screening Tool screening questionnaire. Follow-up is conducted through a questionnaire every 6 months. The primary outcome is the new onset of PsA confirmed by a diagnosis from their doctor. The study will also collect peripheral blood samples from a subset of participants for biomarker identification. Ethics: This study follows the principles of the Declaration of Helsinki. To date, ethical approval has been granted by independent ethical committees in 10 countries. Discussion: Studying a cohort of individuals with psoriasis will allow us to identify risk factors for arthritis development and to develop a risk calculator. This can support focused efforts on screening, patient education, and even studies looking to delay or prevent the onset of arthritis. This study, run via remote online data collection, provides an efficient way to recruit a large cohort (25,000) across multiple countries. However, challenges have had to be addressed with some key changes in study design, ethical review, and recruitment strategies required for each individual country. Trial registration: HPOS, Clinicaltrials.gov ID: NCT05858528, IRAS number 325080; https://clinicaltrials.gov/study/NCT05858528?locStr=United%20Kingdom&United%20Kingdom&cond=Psoriasis&term=HPOS&aggFilters=status%3Anot%20rec&rank=1.
- On-demand testosterone for the treatment of female sexual dysfunctionPublication . Yin, Leyi B.; Bernardino, Rui M.; Pace, Keiran; Mansouri, Sara; Kaushal, Sanchit; Cockburn, Jessica G.; Fleshner, Neil E.; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Oxford University PressINTRODUCTION: Female sexual dysfunction is common, distressing, and notoriously difficult to treat. In the last two decades, short-course ("on-demand") testosterone (T) regimens-delivered sublingually, intranasally, inhaled, topically, or intramuscularly-have been explored as rapid-acting prn enhancers of female libido. The objective of this study is to quantify efficacy, safety, and pharmacokinetics (PK) of short-term T therapy (prn) in women with sexual dysfunction. METHODS: PRISMA 2020 guidelines for systematic reviews were followed. Twelve RCTs and five PK studies (n = 940) were identified via Embase/MEDLINE/Web of Science (inception-March 2025). Outcomes included desire/arousal scores, satisfying sexual events (SSE), pharmacokinetics, and adverse events. Risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: Although absolute serum T excursions differ widely across formulations, most achieve supra-physiological free-T peaks within 15 min and return to baseline within 2-6 h. There is mixed evidence that this window coincides with maximal central arousal effects. However, when combined with phosphodiesterase-5 or 5-HT1A agonists, there tends to be improved genital vasocongestion and sexual satisfaction. Adverse events were mild but tended to be common. CONCLUSIONS: Short-term T therapy combined with phosphodiesterase-5 inhibitors or 5-HT1A agonists may be benefit select subgroups of women with sexual dysfunction with a favorable short-term safety, however, sample sizes remain small and further research is required.Registration: This study was registered in PROSPERO: CRD42024615106.
- A Mathematical Model of Cysteine-Driven Metabolic Adaptation to Hypoxia in Ovarian CancerPublication . Rodrigues, José A.; Nunes, Sofia C.; Ramos, Cristiano; Gonçalves, Luis G.; Serpa, Jacinta; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Instituto de Tecnologia Química e Biológica António Xavier (ITQB); MDPI AGOvarian cancer progression is strongly influenced by tumour hypoxia and associated oxidative stress. Experimental evidence indicates that cysteine availability supports ovarian cancer cell fitness under hypoxic conditions, yet the quantitative integration of cysteine metabolism, redox control, and energetic maintenance remains incompletely understood. We present a reduced mechanistic mathematical model describing intracellular cysteine allocation between glutathione (GSH) synthesis and hydrogen sulfide production under experimentally imposed hypoxia. The model integrates extracellular cysteine uptake, GSH-dependent reactive oxygen species (ROS) detoxification, hypoxia-amplified ROS generation, and redox-modulated ATP maintenance. Parameter estimation was performed using experimentally derived extracellular metabolite fluxes measured over a 24 h interval. Uncertainty was assessed via bootstrap resampling, and variance-based sensitivity analysis was conducted within (patho)physiologically constrained parameter domains. The calibrated model reproduces extracellular fluxes with relative deviations below 7% and identifies GSH synthesis capacity as the dominant determinant of ATP maintenance within experimentally supported ranges. Hydrogen sulfide (H2S) production exerts a secondary stabilising influence, whereas hypoxia-driven ROS amplification negatively impacts energetic state. Numerical continuation across hypoxia levels reveals distinct qualitative response regions but does not imply a formal bifurcation structure. Importantly, intracellular metabolite dynamics are inferred as latent variables consistent with extracellular constraints and established biochemical knowledge; the model does not uniquely identify intracellular pool sizes or enzyme kinetics. The framework therefore provides flux-consistent mechanistic plausibility rather than direct intracellular validation. This systems-level analysis supports cysteine allocation as a quantitatively influential control point in hypoxic adaptation and establishes a constrained modelling framework for subsequent metabolic network expansions and experimental validation.
- Advancing Immunotherapy in Cervical CancerPublication . Antunes, Sofia Carralas; Nogueira, Joana; Pinto, Daniel Gomes; de Carvalho, Leda Viegas; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); MDPI - Multidisciplinary Digital Publishing InstituteCervical cancer is strongly associated with persistent infection by high-risk human papillomavirus (HPV). Recent advances in immunotherapy have redefined the therapeutic landscape of this disease. We aim to review the biological rationale, clinical evidence, and biomarker standardization supporting the use of immune checkpoint inhibitors (ICIs) in cervical cancer. A comprehensive review of recent literature and pivotal phase II–III clinical trials was performed, focusing on the PD-1/PD-L1 and CTLA-4 pathways, mechanisms of immune evasion, and predictive biomarkers. Persistent HPV infection leads to immune dysregulation and PD-L1 upregulation through E6/E7-mediated activation of the PI3K/AKT/mTOR and JAK/STAT pathways. ICIs have demonstrated significant improvements in overall survival, progression-free survival, and objective response rates in advanced and recurrent disease. PD-L1 immunohistochemistry using standardized assays such as 22C3 pharmDx and SP263 remains the key biomarker for treatment selection, while emerging molecular markers (TMB, MSI, HLA-I expression) are under investigation. Immunotherapy represents a major step forward in cervical cancer management, integrating molecular diagnostics and immune modulation into clinical practice. Continued efforts to refine biomarkers, optimize combination strategies, and expand global access will be essential to achieve equitable outcomes and disease elimination goals.
- Digital interventions for improving quality of life and physical function in adults aged 50 and over living with rheumatic and musculoskeletal diseasesPublication . Henriques, Ana Rita; Andrade, Carolina; Silvério Serra, Sofia; Costa, Teresa; Mateus, Elsa; Conde, Monserrat; Mendonça, Nuno; De Cock, Diederik; Rodrigues, Ana Maria; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); WileyOBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effectiveness of digital health interventions, compared with usual care, non-digital structured intervention, or no intervention, in improving quality of life and physical function among community-dwelling adults (i.e. people living in the community) aged 50 years or over, diagnosed with osteoarthritis, osteoporosis, low-back pain, rheumatoid arthritis, or polymyalgia rheumatica.
- Corrigendum to “The EUFOREA pocket guide on paediatric asthmaPublication . Jesenak, Milos; Diamant, Zuzana; Conti, Diego; Antolin-Amerigo, Dario; Backer, Vibeke; Bjermer, Leif; Feleszko, Wojciech; Hellings, Peter; Jauhola, Outi; Khaleva, Ekaterina; Mäkela, Mika; Papadopoulos, Nikolaos; Pite, Helena; Pohunek, Petr; Quirce, Santiago; Rennerova, Zuzana; Scadding, Glenis; Thio, Boony; Lau, Susanne; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Elsevier Science B.V., Amsterdam.The authors regret < that in the original version of this article, the name of Ekaterina Khaleva was misspelled as ‘Katerina Khaleva’. Additionally, a typographical error occurred in the title of Fig. 3; the correct title is ‘Asthma management in children’ instead of ‘Asthma managament in children'.>. The authors would like to apologise for any inconvenience caused.
