Functional states of prelimbic and related circuits during the acquisition of a GO/noGO task in rats.

GO/noGO tasks enable assessing decision-making processes and the ability to suppress a specific action according to the context. Here, rats had to discriminate between 2 visual stimuli (GO or noGO) shown on an iPad screen. The execution (for GO) or nonexecution (for noGO) of the selected action (to touch or not the visual display) were reinforced with food. The main goal was to record and to analyze local field potentials collected from cortical and subcortical structures when the visual stimuli were shown on the touch screen and during the subsequent activities. Rats were implanted with recording electrodes in the prelimbic cortex, primary motor cortex, nucleus accumbens septi, basolateral amygdala, dorsolateral and dorsomedial striatum, hippocampal CA1, and mediodorsal thalamic nucleus. Spectral analyses of the collected data demonstrate that the prelimbic cortex was selectively involved in the cognitive and motivational processing of the learning task but not in the execution of reward-directed behaviors. In addition, the other recorded structures presented specific tendencies to be involved in these 2 types of brain activity in response to the presentation of GO or noGO stimuli. Spectral analyses, spectrograms, and coherence between the recorded brain areas indicate their specific involvement in GO vs. noGO tasks.

Renin angiotensin system inhibitors and outcome in patients with takotsubo syndrome: A propensity score analysis of the GEIST registry.

BACKGROUND: Few data are available on long-term drug therapy and its potential prognostic impact after Takotsubo syndrome (TTS). Aim of the study is to evaluate clinical characteristics and long-term outcome of TTS patients on Renin Angiotensin system inhibitors (RASi). METHODS: TTS patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Median follow-up was 31 (Interquartile range 12-56) months. Comparison of RASi treated vs. untreated patients was performed within the overall population and after 1:1 propensity score matching for age, sex, comorbidities, type of trigger and in-hospital complications. REGISTRATION: clinicaltrials.gov, NCT04361994, https://clinicaltrials.gov/study/NCT04361994 RESULTS: Of the 2453 TTS patients discharged alive, 1683 (68%) received RASi therapy. Patients with RASi were older (age 71 ± 11 vs 69 ± 13 years, P = .01), with higher prevalence of hypertension (74% vs 53%, P < .01) and diabetes (19% v s15%, P = .01), higher admission left ventricular ejection fraction (LVEF) (41 ± 11% vs 39 ± 12%, P < .01) and lower rates of in-hospital complications (18.9% vs 29.6%, P < .01). At multivariable analysis, RASi therapy at discharge was independently associated with lower mortality (HR 0.63, 95% CI 0.45-0.87, P < .01). Survival analysis showed that at long term, patients treated with RASi had lower mortality rates in the overall cohort (log-rank P = .001). However, this benefit was not found among patients treated with RASi in the matched cohort (log-rank P = .168). Potential survival benefit of RASi were present, both in the overall and matched cohort, in 2 subgroups: patients with admission LVEF ≤ 40% (HR 0.54 95% CI 0.38-0.78, P = .001; HR 0.59, 95% CI 0.37-0.95, P = .030) and diabetes (HR 0.41, 95% CI 0.23-0.73, P = .002; HR 0.41, 95% CI 0.21-0.82, P = .011). CONCLUSIONS: Long-term therapy with RASi after a TTS episode was not associated with lower mortality rates at propensity score analysis. However, potential survival benefit can be found among patients with admission LVEF ≤ 40% or diabetes.

Pediatric takotsubo cardiomyopathy: A review and insights from a National Multicentric Registry.

Takotsubo syndrome (TTS) in the pediatric population is an infrequent but relevant cause of morbidity and mortality, with limited studies addressing its clinical course and prognosis. We aimed to analyze the clinical features and prognosis of pediatric TTS in a nation-wide multicenter registry and considering the published literature. We included a total of 54 patients from 4 different hospitals in Spain, as well as pediatric TTS patients from the published literature. Comparisons between groups were performed in order to assess for statistically and clinically relevant prognostic differences between pediatric and adult population features. Patients with pediatric TTS are more commonly male and exhibit a higher prevalence of physical triggers. The left ventricular ejection fraction (LVEF) was significantly lower in the pediatric population (30.5 + 10.4 vs 36.9 + 16.9, p < 0.05), resulting in more than fivefold rates of cardiogenic shock on admission compared to the general adult TTS population (Killip IV 74.1% vs 10.5%, p < 0.001) with similar rates of death and recurrence between groups. TTS in the pediatric population presents a distinctive clinical profile, with higher prevalence of atypical symptoms and physical triggers, as well as higher rates of cardiogenic shock on admission and similar mortality and recurrence rates than those of the adult population. This study provides valuable insights into understanding pediatric TTS and underscores the necessity for further research in this age group.

Ancestry and genetic structure of resident and anadromous rainbow trout (Oncorhynchus mykiss) in Argentina.

Since the first introduction from North America more than a century ago, rainbow trout (Oncorhynchus mykiss) have rapidly established self-sustaining populations in major river basins of Patagonia. Many generations later, only the freshwater resident life history is expressed in the Chubut and Negro rivers of northern Argentinian Patagonia, whereas both the resident and anadromous life histories are found in the Santa Cruz River of southern Argentina. Despite previous studies that have tried to identify the sources of these introduced populations, uncertainty still exists. Here we combined data from many single-nucleotide polymorphisms and microsatellite loci in O. mykiss populations from Argentina and North America to evaluate putative source populations, gene flow between Argentinian river basins, and genetic diversity differences between Argentinian and North American populations. We found that populations from northern and southern Patagonia are highly differentiated and have limited gene flow between them. Phylogeographic analysis also confirmed that they have separate origins, with the northern populations most closely related to the domesticated rainbow trout strains that are raised worldwide and the Santa Cruz River populations most closely related to North American populations from California and Oregon that have an anadromous component. In addition, fish with different life histories in the Santa Cruz River were found to constitute a single interbreeding population. No evidence was found of reduced genetic variation in introduced rainbow trout, suggesting multiple contributing sources. In spite of these advances in understanding, significant questions remain regarding the origins and evolution of the introduced O. mykiss in Patagonia.

Donor selection for adoptive cell therapy with CD45RA- memory T cells for patients with coronavirus disease 2019, and dexamethasone and interleukin-15 effects on the phenotype, proliferation and interferon gamma release.

BACKGROUND AIMS: We have previously demonstrated the safety and feasibility of adoptive cell therapy with CD45RA- memory T cells containing severe acute respiratory syndrome coronavirus 2-specific T cells for patients with coronavirus disease 2019 from an unvaccinated donor who was chosen based on human leukocyte antigen compatibility and cellular response. In this study, we examined the durability of cellular and humoral immunity within CD45RA- memory T cells and the effect of dexamethasone, the current standard of care treatment, and interleukin-15, a cytokine critically involved in T-cell maintenance and survival. METHODS: We performed a longitudinal analysis from previously severe acute respiratory syndrome coronavirus 2-infected and infection-naïve individuals covering 21 months from infection and 10 months after full vaccination with the BNT162b2 Pfizer/BioNTech vaccine. RESULTS: We observed that cellular responses are maintained over time. Humoral responses increased after vaccination but were gradually lost. In addition, dexamethasone did not alter cell functionality or proliferation of CD45RA- T cells, and interleukin-15 increased the memory T-cell activation state, regulatory T cell expression, and interferon gamma release. CONCLUSIONS: Our results suggest that the best donors for adoptive cell therapy would be recovered individuals and 2 months after vaccination, although further studies with larger cohorts would be needed to confirm this finding. Dexamethasone did not affect the characteristics of the memory T cells at a concentration used in the clinical practice and IL-15 showed a positive effect on SARS-CoV-2-specific CD45RA- T cells.

Surfing the tide: Homeward migration of sea trout (Salmo trutta) in a Patagonian river.

This study evaluates the influence of marine and freshwater conditions on the timing of river entry and upstream migration of sea trout (Salmo trutta) in the Grande River of Tierra del Fuego, Patagonia. We analysed the in-river catch-and-release records from a group of fishing lodges that dominate the Grande River fishery during January-April 2008 (n = 5029 fish) as a function of environmental variables: tidal amplitude, stage in the lunar cycle, river discharge, and river water temperature along the homeward migration season. We discuss the value of the daily catch rate as an abundance index in the Grande river, then analyse the temporal structure of the tidal cycle in the Grande River estuary, a macro-tidal environment with a mean tidal amplitude of 5.7 m, and analyse the fit of a generalized additive model to trout catches on a daily basis in four sections along the river to identify the environmental variables that may affect trout abundance throughout the homeward migration. Fish catches in each section of the river were differentially affected by specific environmental variables: tidal amplitude had a positive and significant effect on catches in the lower river sections, whereas water temperature and river discharge significantly affected catches in upper sections (positive effect of temperature; negative effect of discharge). Catches in the lower section clearly reflect the river entry stage of the homeward migration, with a bi-modal shape significantly correlated with the tidal cycle. The first peak was composed mainly of larger multi-sea-winter trout that move upstream, whereas the second one had a wider range of fish lengths, including a large proportion of small and maybe nonreproductive trout that overwinter in the lower river. Based on our results, we conclude that the large tides in the Grande River estuary strongly affect the river entry timing of sea trout. The underlying mechanisms of this effect may be a combination of increased olfactory recognition and increased tidal transport modulated by the seasonal tidal cycle, which operates on trout during coastal migration to produce the pulses observed in the Grande River sea trout run. In the middle and upper sections of the river, where the tidal effect at river entry was dissipated as upstream migration progressed, trout catches increased with water temperature and decreased with river discharge, which may operate through their influence on in-river migration rate and abundance, but also through changes in catchability.

Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry.

BACKGROUND: The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. METHODS: HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. RESULTS: We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure. CONCLUSION: RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

Association between coffee consumption and total dietary caffeine intake with cognitive functioning: cross-sectional assessment in an elderly Mediterranean population.

PURPOSE: Coffee is rich in compounds such as polyphenols, caffeine, diterpenes, melanoidins and trigonelline, which can stimulate brain activity. Therefore, the possible association of coffee consumption with cognition is of considerable research interest. In this paper, we assess the association of coffee consumption and total dietary caffeine intake with the risk of poor cognitive functioning in a population of elderly overweight/obese adults with metabolic syndrome (MetS). METHODS: PREDIMED-plus study participants who completed the Mini-Mental State Examination test (MMSE) (n = 6427; mean age = 65 ± 5 years) or a battery of neuropsychological tests were included in this cross-sectional analysis. Coffee consumption and total dietary caffeine intake were assessed at baseline using a food frequency questionnaire. Logistic regression models were fitted to evaluate the association between total, caffeinated and decaffeinated coffee consumption or total dietary caffeine intake and cognitive impairment. RESULTS: Total coffee consumers and caffeinated coffee consumers had better cognitive functioning than non-consumers when measured by the MMSE and after adjusting for potential confounders (OR 0.63; 95% CI 0.44-0.90 and OR 0.56; 95% CI 0.38-0.83, respectively). Results were similar when cognitive performance was measured using the Clock Drawing Test (CDT) and Trail Making Test B (TMT-B). These associations were not observed for decaffeinated coffee consumption. Participants in the highest tertile of total dietary caffeine intake had lower odds of poor cognitive functioning than those in the reference tertile when screened by the MMSE (OR 0.64; 95% CI 0.47-0.87) or other neurophysiological tests evaluating a variety of cognitive domains (i.e., CDT and TMT-A). CONCLUSIONS: Coffee consumption and total dietary caffeine intake were associated with better cognitive functioning as measured by various neuropsychological tests in a Mediterranean cohort of elderly individuals with MetS. TRIAL REGISTRATION: ISRCTN89898870. Registration date: July 24, 2014.

Donor's graft ex vivo T-cell depletion with fludarabine reduces graft-versus-host disease signs and improves survival after intestinal transplantation - an experimental study.

Intestinal passenger T leukocytes are responsible for graft-versus-host disease (GvHD) in intestinal transplantation (ITx). We hypothesized that ex vivo fludarabine treatment of the bowel graft would diminish the risk of GvHD and improve overall survival post-transplant. We performed isolated heterotopic small bowel transplantations from Lewis (LEW) to Brown Norway (BN) rat strains, which generated GvHD signs from the fourth day post-transplant. These symptoms included rash, weight loss, piloerection, and diarrhea. The grafts of one of the experimental groups were immersed and sealed in cold Celsior preservation solution with 1000 µm fludarabine for 1 h, prior to its implantation into recipient animals. No histological signs of intestinal tissue alterations were observed after fludarabine treatment. Fludarabine-treated bowel recipients showed significantly later and milder clinical signs of GvHD and reduced total donor cell chimerism, as determined by flow cytometry using strain-specific anti-HLA antibodies. Additionally, fludarabine treatment prolonged recipients' overall survival (13.5 days ± 0.3 days vs. 9.2 days ± 0.5). We conclude that active modification of the intestinal leukocyte composition is advantageous in our ITx animal model. Immunosuppression with fludarabine during the surgical procedure, which could be translated directly to the clinic, protects bowel recipients from GvHD and improves overall post-transplant survival.

Maternal influence on early lipid content in an introduced partially anadromous population of Oncorhynchus mykiss.

This study evaluated how the maternal migratory tactic in a partially anadromous population of Oncorhynchus mykiss may influence the early energetic status of their offspring. Total lipid content variation (% dry mass) of recently emerged fry caught in the Santa Cruz River, Argentina, was evaluated as a function of their maternal origin (anadromous v. resident) and fork length (LF ). Lipid content of fry decreased with LF and was higher for offspring of anadromous mothers.

A Cognition-Related Neural Oscillation Pattern, Generated in the Prelimbic Cortex, Can Control Operant Learning in Rats.

The prelimbic (PrL) cortex constitutes one of the highest levels of cortical hierarchy dedicated to the execution of adaptive behaviors. We have identified a specific local field potential (LFP) pattern generated in the PrL cortex and associated with cognition-related behaviors. We used this pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected θ to ß-γ (θ/ß-γ) transition pattern across training sessions. The selected LFP pattern appeared to coincide with a significant decrease in the firing of PrL pyramidal neurons and did not seem to propagate to other cortical or subcortical areas. An indication of the PrL cortex's cognitive nature is that the experimental disruption of this θ/ß-γ transition pattern prevented the proper performance of the acquired task without affecting the generation of other motor responses. The use of this LFP pattern to trigger an operant task evoked only minor changes in its electrophysiological properties. Thus, the PrL cortex has the capability of generating an oscillatory pattern for dealing with environmental constraints. In addition, the selected θ/ß-γ transition pattern could be a useful tool to activate the presentation of external cues or to modify the current circumstances.SIGNIFICANCE STATEMENT Brain-machine interfaces represent a solution for physically impaired people to communicate with external devices. We have identified a specific local field potential pattern generated in the prelimbic cortex and associated with goal-directed behaviors. We used the pattern to trigger the activation of a visual display on a touch screen as part of an operant conditioning task. Rats learned to increase the presentation rate of the selected field potential pattern across training. The selected pattern was not modified when used to activate the touch screen. Electrical stimulation of the recording site prevented the proper performance of the task. Our findings show that the prelimbic cortex can generate oscillatory patterns that rats can use to control their environment for achieving specific goals.

Anterior intercostal artery perforator flap in immediate breast reconstruction: Anatomical study and clinical application.

BACKGROUND: Although the use of lateral intercostal artery perforator (ICAP) flaps for immediate breast reconstruction has been widely described, data on the use of the anterior ICAP (AICAP) flaps for this indication are limited. In this context, we describe the results of anatomical study and our clinical experience with AICAP flaps for breast reconstruction. METHODS: In this study, the location and characteristics of the AICAPs were dissected in 12 female adult formalin-preserved hemitrunks and two fresh-frozen cadavers. Fourteen patients (mean BMI 23) underwent partial breast resection for a quadrant breast cancer followed by breast reconstruction with an intercostal perforator flap. The mean resection size was 6 × 5 × 5.5 cm (range 3-8 × 3.5-7 × 4-8 cm).The main outcome measures were pre-operative and postradiotherapy health-related quality of life assessed with the BREAST-Q reconstruction survey. RESULTS: According to anatomical study, at least one perforator was found in each third of hemitrunks dissected. The mean of perforator size was in diameter 0.42 ± 0.05 mm and in length 3.1 ± 0.36 cm. In clinical outcomes, the mean of flap size was 16 × 5 × 3 cm (range 14-19 × 3-8 × 2-5 cm). The mean surgical time was 120 min (range 109-125 min). Only one partial flap failure was detected. No postoperative changes in breast size were observed, although soft tissue changes were observed in four patients after radiotherapy. The mean BREAST-Q scores changes were 0 in satisfaction with the breast, 5 in satisfaction with outcome, 0 in psychosocial well-being, 6.15 in sexual well being, and 34.69 in physical well-being. CONCLUSIONS: Based on this anatomical and clinical study, we found AICAP flap has a consistent vascularization with good perforators. And moreover, it is suitable for partial breast reconstruction (quadrantectomy) and does not appear to negatively impact patient satisfaction.

Synchronic gastric and pancreatic ductal adenocarcinoma. A case report.

Simultaneous gastric and pancreatic ductal adenocarcinoma is an exceptional situation with short literature review. The accumulated risk throughout life in women is 0.8% for gastric cancer and 0.6% for pancreas cancer. We report a case where both tumors are demonstrated. The patient was surgically intervened removing both tumors and achieving total recovery, with no signs of tumor recurrence after four months. This is to remind us that simultaneous tumors do exist, especially when suggestive images of neoplasia appear in a patient previously diagnosed of tumor in another location.

Ecological drivers of guanaco recruitment: variable carrying capacity and density dependence.

Ungulates living in predator-free reserves offer the opportunity to study the influence of food limitation on population dynamics without the potentially confounding effects of top-down regulation or livestock competition. We assessed the influence of relative forage availability and population density on guanaco recruitment in two predator-free reserves in eastern Patagonia, with contrasting scenarios of population density. We also explored the relative contribution of the observed recruitment to population growth using a deterministic linear model to test the assumption that the studied populations were closed units. The observed densities increased twice as fast as our theoretical populations, indicating that marked immigration has taken place during the recovery phase experienced by both populations, thus we rejected the closed-population assumption. Regarding the factors driving variation in recruitment, in the low- to medium-density setting, we found a positive linear relationship between recruitment and surrogates of annual primary production, whereas no density dependence was detected. In contrast, in the high-density scenario, both annual primary production and population density showed marked effects, indicating a positive relationship between recruitment and per capita food availability above a food-limitation threshold. Our results support the idea that environmental carrying capacity fluctuates in response to climatic variation, and that these fluctuations have relevant consequences for herbivore dynamics, such as amplifying density dependence in drier years. We conclude that including the coupling between environmental variability in resources and density dependence is crucial to model ungulate population dynamics; to overlook temporal changes in carrying capacity may even mask density dependence as well as other important processes.

Differences in Mu rhythm when seeing grasping/motor actions in a real context versus on screens.

Mu rhythm (∼8-12 Hz) in the somatosensory cortex has traditionally been linked with doing and seeing motor activities. Here, we aimed to learn how the medium (physical or screened) in which motor actions are seen could impact on that specific brain rhythm. To do so, we presented to 40 participants the very same narrative content both in a one-shot movie with no cuts and in a real theatrical performance. We recorded subjects' brain activities with electroencephalographic (EEG) procedures, and analyzed Mu rhythm present in left (C3) and right (C4) somatosensory areas in relation to the 24 motor activities included in each visual stimulus (screen vs. reality) (24 motor and grasping actions x 40 participants x 2 conditions = 1920 trials). We found lower Mu spectral power in the somatosensory area after the onset of the motor actions in real performance than on-screened content, more pronounced in the left hemisphere. In our results, the sensorimotor Mu-ERD (event-related desynchronization) was stronger during the real-world observation compared to screen observation. This could be relevant in research areas where the somatosensory cortex is important, such as online learning, virtual reality, or brain-computer interfaces.

Efficacy and safety of bempedoic acid in acute coronary syndrome. Design of the clinical trial ES-BempeDACS.

INTRODUCTION AND OBJECTIVES: Only about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. METHODS: An independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. RESULTS: The results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. CONCLUSIONS: Early intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). IDENTIFICATION NUMBER: EudraCT 2021-006550-31.

Statin therapy and outcome in Takotsubo syndrome patients: Results from the multicenter international GEIST registry.

BACKGROUND AND AIMS: Several studies have shown that endothelial dysfunction plays a role in the pathogenesis of Takotsubo syndrome (TTS). Given the potential benefit of statin therapy on endothelial dysfunction, we hypothesized that such treatment could improve outcome. Aim of our study was to evaluate clinical characteristics and outcome of TTS patients treated with statin therapy. METHODS: Patients were enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry. Demographic data, clinical features and drug therapy at discharge were recorded. Primary study outcome was the occurrence of all-cause death at follow-up. RESULTS: Study population included 2429 consecutive TTS patients: 1293 (53.2%) discharged on statin and 1136 (46.8%) without statin. Patients with statin were older (age 72 ± 11 vs 69 ± 13 years, p < 0.001), with higher prevalence of hypertension (74.3% vs 60.3%, p < 0.001), diabetes (21.1% vs 14.7%, p < 0.001), dyslipidemia (56.1% vs 23.3%, p < 0.001), history of coronary artery disease (13.3% vs 6.3%, p < 0.001) and lower rates of in-hospital complications (14.7% vs 19.3%, p = 0.003). Survival analysis showed similar mortality rates between groups (log rank p = 0.803). At univariable analysis, statin therapy at discharge was not associated with lower mortality (HR: 0.97, 95% CI 0.74-1.26, p = 0.803). At multivariable analysis age (HR: 1.06 95% CI 1.04-1.08, p < 0.001), male sex (HR: 1.83, 95% CI 1.20-2.80, p = 0.005), diabetes (HR: 2.55, 95% CI 1.83-3.54 p < 0.001), malignancies (HR: 2.41, 95% CI 1.68-3.44, p < 0.001) and physical trigger (HR: 2.24, 95% CI 1.62-3.10, p < 0.001) were associated with increased mortality. CONCLUSIONS: Statin therapy after a TTS event was not associated with better prognosis at follow-up.