Repositório RCAAP

Este artigo apresenta uma síntese da evolução geodinâmica e das variações eustáticas do nível do mar no Meso-Cenozóico e relaciona os acontecimentos globais com a formação da Ibéria e da Área Metropolitana de Lisboa (AML). Do regime tectónico distensivo resultou a desagregação da Pangeia, a separação entre as placas Norte-Americana e Euroasiática e a individualização da microplaca Ibérica no Cretácico Inferior. Até à formação de crusta oceânica no Atlântico desenvolveram-se bacias de rifting. A Bacia Lusitaniana está ligada à génese da Orla Mesocenozóica Ocidental, onde está incluída grande parte da AML Norte. O regime compressivo a partir do final do Cretácico deu origem a cadeias montanhosas na Península Ibérica e à reactivação de falhas tardi-hercínicas responsáveis pela formação e subsidência de uma depressão tectónica (Bacia Cenozóica do Tejo-Sado), onde se inclui a maioria da AML Sul. Neste quadro tectónico formaram-se o maciço subvulcânico de Sintra no final do Cretácico Superior ou a cadeia da Arrábida no Miocénico. A transição para o regime compressivo marcou o pico máximo do nível do mar no Meso-Cenozóico (170 a 250m acima do nível atual). As variações do nível do mar explicam a diversidade litológica da AML. As formações da AML Norte datam maioritariamente do Cretácico (predominância de calcários e margas), enquanto na AML Sul afloram sobretudo formações mais recentes (Pliocénico e Plistocénico), o que justifica o seu carácter detrítico

Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas importantes para a prática clínica, com base na melhor evidência científica disponível. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

A herança de mutações heterozigóticas nos genes BRCA predispõe as portadoras a formas clinicamente agressivas de cancro da mama, e muitas dessas mulheres são submetidas a mastectomia profilática bilateral para prevenção do cancro de mama. A análise detalhada de tecido mamário pré-maligno e normal de portadoras com mutações germinativa nos genes BRCA sugere que estes surgem a partir de uma população expandida de progenitores luminares aberrantes do epitélio mamário. Como as alterações no mRNA podem contribuir para a iniciação e progressão do cancro da mama, nós avaliámos as alterações transcriptómicas dos genes BRCA em fibroblastos, células pluripotentes induzidas e progenitores de epitélio mamário em desenvolvimento derivados de portadores de mutações germinativas BRCA e controlos normais. Nós utilizámos PCR digital para obter quantificações absolutas das moléculas de mRNA BRCA1 e BRCA2 nessas células e observamos que a expressão dos genes BRCA aumenta durante a reprogramação celular e diminui durante a diferenciação mamária. Nós mostramos que os genes BRCA têm uma expressão coordenada que é regulada em função proliferação celular, e ainda revelamos que esta regulação não é perturbada por variantes patogénicas presentes nesses genes. Utilizando células com uma mutação da linha germinativa BRCA2, fomos capazes de estudar a expressão específica de isoformas de mRNA geradas por splicing alternativo e demonstrar que as mutações da linha germinativa são heterozigóticas ao nível do RNA. Coletivamente, os nossos resultados apontam para um mecanismo biológico que regula a expressão dos genes BRCA em função da proliferação, possivelmente para manter a integridade genómica das células em divisão rápida. Ao revelar que a expressão da isoforma mutante BRCA2 é heterozigótica no nível do RNA em progenitores mamários, os nossos resultados suportam o modelo contínuo de supressão tumoral em que a haploinsuficiência resultante de variantes patogénicas heterozigóticas desencadeia oncogénese associada aos genes BRCA em progenitores mamários normais de portadores de mutação germinativa no gene BRCA2.

Galileo’s fateful confrontation with the Holy Office in 1633 is often taken to mark the start of the Scientific Revolution, the moment when a whole new approach to knowledge began to take over the western world. Amongst the many repercussions of this great epistemological shift was the development of a new ‘transparent’ type of discourse, felt to reflect reality more directly than the elaborate verbal edifices of the Scholastics. Today, the ‘authoritative plain style’, as Lawrence Venuti calls it, is so prevalent in English academic and factual writing that knowledge configured otherwise is rarely allowed past the cultural gatekeepers. There are countries, however, where, for historical and cultural reasons, the Scientific Revolution never really took place. In Spain and Portugal, for example, the anthropocentric paradigm favoured by the Christian humanist tradition has persisted well into the 21st century, and as a result, many of the academic texts produced in these countries operate according to an entirely different philosophy of language. This paper discusses some of the linguistic and ideological problems of translating such scholarship into a form that is publishable in English.

Varizes ectópicas são colaterais portossistémicos ingurgitados que se localizam em qualquer parte do abdómen, com exceção da região gastroesofágica. Representam até 5% de todos os episódios de hemorragia gastrointestinal por varizes. É fulcral a consciencialização desta entidade clínica uma vez que a hemorragia de varizes ectópicas pode atingir uma taxa de mortalidade de 70%, dependendo do tipo de varizes ectópicas. A hipertensão portal é a principal causa de varizes ectópicas, principalmente no contexto de cirrose hepática. Fatores que contribuem para o desenvolvimento de varizes ectópicas são: cirurgia abdominal prévia, procedimentos terapêuticos em varizes gastroesofágicas, malformações arteriovenosas, trombose vascular ou neoplasias intra-abdominais. As manifestações clínicas da hemorragia por varizes ectópicas variam desde formas assintomáticas, hemorragia gastrointestinal oculta ou evidente, hemoperitoneu ou mesmo choque hipovolémico. A marcha diagnóstica inclui endoscopia digestiva alta e colonoscopia. Caso a fonte de hemorragia não seja identificada, outras exames diagnósticos dependem do local de hemorragia mais provável: videocápsula endoscópica, ecoendoscopia, enteroscopia, TC abdominal ou cintigrafia com eritrócitos marcados. O manejo da hemorragia por varizes ectópicas deve ser individualizado para cada doente. As opções terapêuticas incluem abordagem 1) Médica, 2) Endoscópica, 3) Radiológica e 4) Cirúrgica, dependendo da experiência do centro clínico, da gravidade da hemorragia, do estado hemodinâmico do doente e da anatomia vascular das varizes ectópicas. Apresentamos um pequeno caso clínico ilustrativo, seguido de uma revisão da literatura com resumo dos casos clínicos publicados de hemorragia por varizes ectópicas.

Background: The relationship between restless legs syndrome (RLS) and peripheral neuropathy remains unclear. In order to clarify this relationship, we investigated if RLS is increased in familial amyloid polyneuropathy related to transthyretin (TTR-FAP) and investigated factors associated with RLS in this population. Methods: RLS frequency was compared between TTR-FAP patients and controls. Secondly, TTR-FAP patients with and without RLS were compared regarding demographic and clinical characteristics. Results: RLS frequency was significantly increased in TTR-FAP, with 18/98 (18.4%) cases contrasting with 5/104 (4.8%) controls (p-value 0.002). This difference remained significant after adjusting for confounders. In TTR-FAP patients, female sex (p-value 0.037), obesity (p-value 0.036) and weight excess (p-value 0.048) were associated with RLS, contrary to other classical RLS risk factors. Conclusions: RLS frequency is increased in TTR-FAP, thus supporting an association between RLS and neuropathy. This may represent a peripheral pathway in RLS pathogenesis. Furthermore, our results suggest that female sex and obesity/weight excess may be risk factors for RLS development among TTR-FAP patients.

Psychiatric disorders such as schizophrenia, bipolar disorder, and major depressive disorder are often accompanied by metabolic dysfunction symptoms, including obesity and diabetes. Since the circadian system controls important brain systems that regulate affective, cognitive, and metabolic functions, and neuropsychiatric and metabolic diseases are often correlated with disturbances of circadian rhythms, we hypothesize that dysregulation of circadian clocks plays a central role in metabolic comorbidity in psychiatric disorders. In this review paper, we highlight the role of circadian clocks in glucocorticoid, dopamine, and orexin/melanin-concentrating hormone systems and describe how a dysfunction of these clocks may contribute to the simultaneous development of psychiatric and metabolic symptoms.

Lymphotoxin-mediated activation of the lymphotoxin-β receptor (LTβR; LTBR) has been implicated in cancer, but its role in T-cell acute lymphoblastic leukaemia (T-ALL) has remained elusive. Here we show that the genes encoding lymphotoxin (LT)-α and LTβ (LTA, LTB) are expressed in T-ALL patient samples, mostly of the TAL/LMO molecular subtype, and in the TEL-JAK2 transgenic mouse model of cortical/mature T-ALL (Lta, Ltb). In these mice, expression of Lta and Ltb is elevated in early stage T-ALL. Surface LTα1 β2 protein is expressed in primary mouse T-ALL cells, but only in the absence of microenvironmental LTβR interaction. Indeed, surface LT expression is suppressed in leukaemic cells contacting Ltbr-expressing but not Ltbr-deficient stromal cells, both in vitro and in vivo, thus indicating that dynamic surface LT expression in leukaemic cells depends on interaction with its receptor. Supporting the notion that LT signalling plays a role in T-ALL, inactivation of Ltbr results in a significant delay in TEL-JAK2-induced leukaemia onset. Moreover, young asymptomatic TEL-JAK2;Ltbr(-/-) mice present markedly less leukaemic thymocytes than age-matched TEL-JAK2;Ltbr(+/+) mice and interference with LTβR function at this early stage delayed T-ALL development. We conclude that LT expression by T-ALL cells activates LTβR signalling in thymic stromal cells, thus promoting leukaemogenesis.

Amyotrophic Lateral Sclerosis (ALS) is a devastating disease and the most common neurodegenerative disorder of young adults. ALS patients present a rapidly progressive motor weakness. This usually leads to death in a few years by respiratory failure. The correct prediction of respiratory insufficiency is thus key for patient management. In this context, we propose an innovative approach for prognostic prediction based on patient snapshots and time windows. We first cluster temporally-related tests to obtain snapshots of the patient's condition at a given time (patient snapshots). Then we use the snapshots to predict the probability of an ALS patient to require assisted ventilation after k days from the time of clinical evaluation (time window). This probability is based on the patient's current condition, evaluated using clinical features, including functional impairment assessments and a complete set of respiratory tests. The prognostic models include three temporal windows allowing to perform short, medium and long term prognosis regarding progression to assisted ventilation. Experimental results show an area under the receiver operating characteristics curve (AUC) in the test set of approximately 79% for time windows of 90, 180 and 365 days. Creating patient snapshots using hierarchical clustering with constraints outperforms the state of the art, and the proposed prognostic model becomes the first non population-based approach for prognostic prediction in ALS. The results are promising and should enhance the current clinical practice, largely supported by non-standardized tests and clinicians' experience.

Adenosine, through A(2A) receptor (A(2A)R) activation, can act as a metamodulator, controlling the actions of other modulators, as brain-derived neurotrophic factor (BDNF). Most of the metamodulatory actions of adenosine in the hippocampus have been evaluated in excitatory synapses. However, adenosine and BDNF can also influence GABAergic transmission. We thus evaluated the role of A(2A)R on the modulatory effect of BDNF upon glutamate and GABA release from isolated hippocampal nerve terminals (synaptosomes). BDNF (30 ng/ml) enhanced K(+)-evoked [(3)H]glutamate release and inhibited the K(+)-evoked [(3)H]GABA release from synaptosomes. The effect of BDNF on both glutamate and GABA release requires tonic activation of adenosine A(2A)R since for both neurotransmitters, the BDNF action was blocked by the A(2A)R antagonist SCH 58261 (50 nM). In the presence of the A(2A)R agonist, CGS21680 (30 nM), the effect of BDNF on either glutamate or GABA release was, however, not potentiated. It is concluded that both the inhibitory actions of BDNF on GABA release as well as the facilitatory action of the neurotrophin on glutamate release are dependent on the activation of adenosine A(2A)R by endogenous adenosine. However, these actions could not be further enhanced by exogenous activation of A(2A)R.

Humanitarian migration relates to the movement of people who feel somehow forced to move. Yet, distinguishing which migration forms fall under the label of humanitarian migration is not straightforward. Migration research has a history of separating between ‘forced’ and ‘voluntary’ migration flows, however, this distinction has been challenged since the 1990s. This chapter includes an overview of research in the broad area of ‘humanitarian migration’, and summarises key research trends concerning refugees, asylum seekers, internally displaced people, victims of trafficking and unaccompanied migrant minors.

Pyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M. tuberculosis, M. africanum, and M. microti) but not against M. bovis and M. avium. The latter two are mycobacterial species involved in human and cattle tuberculosis and in HIV coinfections, respectively. PZA is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to form the active metabolite pyrazinoic acid (POA). As a result of this mechanism, resistance to PZA, as is often found in tuberculosis patients, is caused by point mutations in pyrazinamidase. In previous work, we have shown that POA esters and amides synthesized in our laboratory were stable in plasma (M. F. Simões, E. Valente, M. J. Gómez, E. Anes, and L. Constantino, Eur J Pharm Sci 37:257-263, 2009, http://dx.doi.org/10.1016/j.ejps.2009.02.012). Although the amides did not present significant activity, the esters were active against sensitive mycobacteria at concentrations 5- to 10-fold lower than those of PZA. Here, we report that these POA derivatives possess antibacterial efficacy in vitro and ex vivo against several species and strains of Mycobacterium with natural or acquired resistance to PZA, including M. bovis and M. avium. Our results indicate that the resistance probably was overcome by cleavage of the prodrugs into POA and a long-chain alcohol. Although it is not possible to rule out that the esters have intrinsic activity per se, we bring evidence here that long-chain fatty alcohols possess a significant antimycobacterial effect against PZA-resistant species and strains and are not mere inactive promoieties. These findings may lead to candidate dual drugs having enhanced activity against both PZA-susceptible and PZA-resistant isolates and being suitable for clinical development.

Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated.

Amyotrophic lateral sclerosis (ALS) is a disease leading to neuromuscular transmission impairment. A2A adenosine receptor (A2AR) function changes with disease stage, but the role of the A(1) receptors (A1Rs) is unknown and may have a functional cross-talk with A2AR. The role of A1R in the SOD1(G93A) mouse model of ALS in presymptomatic (4-6 weeks old) and symptomatic (12-14 weeks old) phases was investigated by recording endplate potentials (EPPs), miniature endplate potentials (MEPPs), and quantal content (q.c.) of EPPs, from Mg(2+) paralyzed hemidiaphragm preparations. In presymptomatic mice, the A1R agonist, N (6)-cyclopentyladenosine (CPA) (50 nM), decreased mean EPP amplitude, MEPP frequency, and q.c. of EPPs, an effect quantitatively similar to that in age-matched wild-type (WT) mice. However, coactivation of A2AR with CGS 21680 (5 nM) prevented the effects of CPA in WT mice but not in presymptomatic SOD1(G93A) mice, suggestive of A1R/A2AR cross-talk disruption in this phase of ALS. DPCPX (50 nM) impaired CGS 21680 facilitatory action on neuromuscular transmission in WT but not in presymptomatic mice. In symptomatic animals, CPA only inhibited transmission if added in the presence of adenosine deaminase (ADA, 1 U/mL). ADA and DPCPX enhanced more transmission in symptomatic mice than in age-matched WT mice, suggestive of increase in extracellular adenosine during the symptomatic phase of ALS. The data documents that at the neuromuscular junction of presymptomatic SOD1(G93A) mice, there is a loss of A1R-A2AR functional cross-talk, while in symptomatic mice there is increased A1R tonic activation, and that with disease progression, changes in A1R-mediated adenosine modulation may act as aggravating factors during the symptomatic phase of ALS.

Rudolph Nureyev’s Romeo and Juliet, first staged in 1977 and filmed in 1995, is a work of intermediality par excellence. Like all ballet productions, its ‘meaning(s)’ emerge(s) from the interaction of multiple semiotic codes (kinesthetic, visual and audio), mediated further by the process of filming that resulted in the Warner Music Video upon which this study centres. Moreoever, it is also an interesting example of intersemiotic translation, based as it is upon both a verbal and a musical text, Shakespeare’s play and Prokofiev’s musical score respectively. This paper examines Nureyev’s version of the tale of the ‘star cross’d lovers’ as a comment upon the era in which he himself lived, the aftermath of the youth revolution when the exuberance and optimism of the sixties was beginning to wear a little thin. In the light of this, his use of gay iconography, images of pestilence and invocations of doom take on a new sinister significance.

Developed in the context of the 60th anniversary of the inauguration of Brasília, this project recaptures this central symbol to the Brazilian cultural imagination. This capture is guided by two main notions: that Brasília was already born as its own ruin and that the permanence of this ruined state, fractured between ideal and reality, is set up as a kind of insomnia. Through these guidelines of ruin and insomnia, this project, developed under the scope of communication design, appropriates Brasília in three aspects: ideological propaganda, affective memory and soundscape. To do so, it uses digital tools with which it reorganises and manipulates images, news pieces and musical productions that make up the imaginary created around the Brazilian capital, using the notion of appropriation as a cultural practice that is typical of the digital culture and of the modern and postmodern experience. This text accompanies, as an historical, theoretical and technical elucidation, an online publication (www.estesconstruirambrasilia.com) that also serves as a critical repository of materials regarding the construction of the city. The project is also composed of a set of postcards and a printed newspaper, both of which result from the appropriation and reinterpretation of historical documents. This set of items aims to constitute a sensitive means of access to the imaginary that composes the Brasília-symbol, keeping in evidence the disturbances that affect its idealization

Backgound: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia among older patients, associated with thromboembolic events. Direct Oral Anticoagulants (DOAC) are the treatment of choice for most patients, but its use may have risks on standard dose. However, it is still unclear the effects related with the use of a lower dose off labelled DOAC. Objectives: We conducted a systematic review and meta-analysis to assess the effects of off-label underdose use of DOAC in patients with AF. Methods: MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO databases and EMBASE were searched for observational longitudinal studies evaluating the outcomes on off label underdosed patients compared with standard dosed patients with AF. We performed a random-effects meta-analysis to estimate the pooled Hazard Ratios (HR) with 95%Cis. Results: Eighteen cohort studies evaluating 237,533 patients with AF were included. Off-label underdose DOAC use is associated with higher risk of all-cause mortality [HR = 1.27 (95%CI 1.09-1.48)] and cardiovascular composite outcomes [HR = 1.32 (95%CI 1.08-1.62)], when compared with standard dose DOAC use. The effects in thromboembolic events [HR = 1.14 (95%CI 1.00-1.31)], major bleeding [HR = 1.02 (95%CI 0.91-1.15)], and composite of ischemic and bleeding events [HR = 1.22 (95%CI 0.79-1.88)] were not statistically significant. The certainty in the evidence was low or very low. Conclusions: Off label underdose DOAC use is associated with higher risk of all-cause mortality and cardiovascular composite outcomes, compared with standard dose.

Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group. Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391. Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p<0·001; 95% CI -4·45 to -1·62) compared with controls, with a clinically relevant effect size (Cohen's d=0·39). Interpretation: The results of this study show that the NEVERMIND system is superior to standard care in reducing and preventing depressive symptoms among patients with the studied somatic conditions. Funding: The NEVERMIND project received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 689691.

Objective: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. Methods: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. Results: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. Significance/interpretation: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.

Background: Some patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs). Purpose: To determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis. Methods: In April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents. Results: 16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2-11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI - 1.10 to - 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24-71%; I2 = 96%) and 25% (95% CI 20-29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ). Conclusion: Sham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.