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Microbiome and response to therapy in triple negative breast cancer: a systematic review
Publication . Lopes, Mariana; Vila Nova, Carlos; Oliveira, Rui Caetano; Schmitt, Fernando; Mendes, Fernando; Martins, Diana
Objectives: Triple-negative breast cancer (TNBC) accounts for approximately 15% of all invasive breast cancers and is characterized by aggressive behavior, limited therapeutic options, and poor clinical outcomes. Due to the absence of hormone receptors and HER2 expression, systemic treatment relies predominantly on chemotherapy, which is associated with high rates of early recurrence and mortality. Emerging evidence suggests that alterations in the microbiome can contribute to TNBC progression and influence therapeutic response, particularly affecting the efficacy of chemotherapy and immunotherapy through immune-mediated mechanisms; however, its role in TNBC remains incompletely understood. This systematic review aims to explore the role of the microbiome in TNBC. It specifically aims to understand if the microbiome influences complete pathological response in TNBC. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed in PubMed and Cochrane databases. Fourteen eligible studies were included, encompassing preclinical and clinical evidence. Results: The findings indicate that both gut and tumor-associated microbiota significantly influence therapeutic response in TNBC, especially in the context of neoadjuvant chemotherapy (NACT) and immune checkpoint blockade (ICB). Higher microbial diversity and the presence of specific commensal taxa were consistently associated with enhanced antitumor immune activation, increased immune cell infiltration, and improved treatment efficacy. Conversely, antibiotic-induced dysbiosis was linked to reduced pCR rates and poorer clinical outcomes. Microbiome-modulating interventions demonstrated potential in restoring eubiosis and enhancing therapeutic responsiveness. Conclusions: Overall, the available evidence supports the microbiome as a promising biomarker and therapeutic target for optimizing treatment strategies and improving outcomes in TNBC
Changes in hamstrings’ active stiffness during fatigue tasks are modulated by contraction duration rather than intensity
Publication . Martínez-Serrano, Antonio; Radaelli, Régis; Freitas, Tomás T.; Alcaraz, Pedro E.; Freitas, Sandro R.
Despite the increase in research of hamstring stiffness through the use of ultrasound-based shear wave elastography, the active stiffness of biceps femoris long head (BFlh) and semitendinosus (ST) muscles under fatigue conditions at various contraction intensities has not been sufficiently explored. This study aimed to compare the effects of knee flexor’s isometric contraction until exhaustion performed at 20% vs. 40% of maximal voluntary isometric contraction (MVIC), on the active stiffness responses of BFlh and ST. Eighteen recreationally active males performed two experimental sessions. The knee flexors’ MVIC was assessed before the fatiguing task, which involved a submaximal isometric contraction until failure at 20% or 40% of MVIC. Active muscle stiffness of the BFlh and ST was assessed using shear wave elastography. BFlh active stiffness remained relatively unaltered at 20% of MVIC, while ST active stiffness decreased from ≅ 91% contraction time (55.79 to 44.52 kPa; p < 0.001). No intramuscular stiffness changes were noted in BFlh (36.02 to 41.36 kPa; p > 0.05) or ST (63.62 to 53.54 kPa; p > 0.05) at 40% of MVIC session. Intermuscular active stiffness at 20% of MVIC differed until 64% contraction time (p < 0.05) whereas, at 40% of MVIC, differences were observed until 33% contraction time (p < 0.05). BFlh/ST ratios were not different between intensities (20%=0.75 ± 0.24 ratio vs. 40%=0.72 ± 0.32 ratio; p > 0.05), but a steeper increase in BFlh/ST ratio was found for 20% (0.004 ± 0.003 ratio/%) compared to 40% (0.001 ± 0.003 ratio/%) of MVIC (p = 0.003). These results suggest that contraction duration could play a major role in inducing changes in hamstrings’ mechanical properties during fatigue tasks compared to contraction intensity.
Case report : Wernicke–Korsakoff syndrome after bariatric surgery
Publication . Bento, Margarida Alves; Vieira, João Barriga; Silva, Maria Leonor; Camolas, José
Vitamin and mineral deficiencies are prevalent nutritional disorders following bariatric surgery. Although they are more prevalent after malabsorptive procedures such as bypass, they also occur in restrictive procedures such as gastric sleeve. The mechanisms that lead to the occurrence of these deficits are related to the presence of poor nutritional intake or poor adherence to multivitamins and multimineral supplementation. Wernicke–Korsakoff syndrome (WKS) is an acute neurological disorder resulting from thiamine deficiency. This syndrome is composed of two distinct phases: first, Wernicke Encephalopathy (WE), the acute phase of this syndrome, which is characterized by a triad of mental confusion, ocular signs, and ataxia, followed by the chronic phase of WKS, called Korsakoff’s syndrome (KS), which is known for the presence of anterograde amnesia and confabulation. We aimed to report a case of a patient with WKS after bariatric surgery. The patient’s retrospective chart review was performed in order to retrieve the relevant clinical data. The patient was a 24-year-old female student with a BMI of 48 kg/m2 who underwent sleeve gastrectomy surgery for morbid obesity. Over the following 2 months, recovery from surgery was complicated by non-specific symptoms such as nausea, recurrent vomiting, and a significant reduction in food intake, which led the patient to visit the emergency department six times with hospitalization on the last occasion for a definitive diagnosis. During the 15 days of hospitalization, the patient developed ocular diplopia, nystagmus, complaints of rotatory vertigo, and gait abnormalities. A magnetic resonance imaging of the head was performed but revealed no significant changes. After a formal neurological assessment, treatment with parenteral thiamine (100 mg, three times a day) was started without prior dosing. The observed clinical improvement confirmed the diagnosis of WKS. Bariatric surgery may contribute to thiamine deficiency and, consequently, to WKS. Education about the adverse consequences of malnourishment is mandatory before and after the surgery. Investigation of nutritional deficiencies both pre- and post-operatively is crucial in order to prevent complications such as WKS.
Caries experience before and after COVID-19 restrictions : an observational study
Publication . Guerreiro, Eduardo; Botelho, João; Machado, Vanessa; Proença, Luís; Mendes, José João; Manso, Ana Cristina
Background: The declaration of COVID-19 as a pandemic by the World Health Organization in 2020 led to the suspension of several clinical practices globally, including dentistry. This study investigates the impact of these restrictions on dental caries experience. Methods: A retrospective cross-sectional study was conducted at Egas Moniz University’s dental hospital in the Lisbon Metropolitan Area from June 2019 to June 2021. The study involved 3380 participants who were divided into two cohorts: after and before COVID-19 restrictions. Data collection included a questionnaire, full-mouth clinical examinations, and radiographs (panoramic X-rays, bitewings). Results: Before the COVID-19 restrictions, the prevalence of dental caries was 91.8%, with an average DMFT (decayed, missing, and filled teeth) index of 12.13. Post-restrictions, the prevalence decreased to 84.5%, with a DMFT index of 10.99. There was an increase in missing teeth and a decrease in decayed and filled teeth. Additionally, the frequency of toothbrushing declined among participants. Conclusions: The COVID-19 pandemic restrictions have significantly impacted dental caries experiences and oral health, highlighting a decrease in dental caries, but also a concerning reduction in oral hygiene practices. These results emphasize the importance of customized dental healthcare during public health emergencies to reduce impacts and maintain oral health.
Burden of disease scenarios for 204 countries and territories, 2022–2050 : a forecasting analysis for the Global Burden of Disease Study 2021
Publication . GBD 2021 Forecasting Collaborators
Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.
Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.
Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]).
Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.