The detrimental role of galectin-3 and endoplasmic reticulum stress in the cardiac consequences of myocardial ischemia in the context of obesity.

The association between cardiac fibrosis and galectin-3 was evaluated in patients with acute myocardial infarction (MI). The role of galectin-3 and its association with endoplasmic reticulum (ER) stress activation in the progression of cardiovascular fibrosis was also evaluated in obese-infarcted rats. The inhibitor of galectin-3 activity, modified citrus pectin (MCP; 100 mg/kg/day), and the inhibitor of the ER stress activation, 4-phenylbutyric acid (4-PBA; 500 mg/kg/day), were administered for 4 weeks after MI in obese rats. Overweight-obese patients who suffered a first MI showed higher circulating galectin-3 levels, higher extracellular volume, and LV infarcted size, as well as lower E/e'ratio and LVEF compared with normal-weight patients. A correlation was observed between galectin-3 levels and extracellular volume. Obese-infarcted animals presented cardiac hypertrophy and reduction in LVEF, and E/A ratio as compared with control animals. They also showed an increase in galectin-3 gene expression, as well as cardiac fibrosis and reduced autophagic flux. These alterations were associated with ER stress activation characterized by enhanced cardiac levels of binding immunoglobulin protein, which were correlated with those of galectin-3. Both MCP and 4-PBA not only reduced cardiac fibrosis, oxidative stress, galectin-3 levels, and ER stress activation, but also prevented cardiac functional alterations and ameliorated autophagic flux. These results show the relevant role of galectin-3 in the development of diffuse fibrosis associated with MI in the context of obesity in both the animal model and patients. Galectin-3 in tandem with ER stress activation could modulate different downstream mechanisms, including inflammation, oxidative stress, and autophagy.

Imaging modalities for confirming pulmonary embolism during pregnancy: results from a multicenter international study.

OBJECTIVES: We explored the variations in use of imaging modalities for confirming pulmonary embolism (PE) according to the trimester of pregnancy. METHODS: We included all pregnant patients with confirmed acute PE from RIETE, a prospective registry of patients with PE (03/2001-02/2020). Imaging modalities included computed tomography pulmonary angiography (CTPA), ventilation-perfusion (V/Q) scan, or presence of signs of acute PE along with imaging-confirmed proximal deep vein thrombosis (pDVT) without pulmonary vascular imaging. We compared the imaging modalities to postpartum patients with PE, and other non-pregnant women with PE. RESULTS: There were 157 pregnant patients (age: 32.7 ± 0.5), 228 postpartum patients (age: 33.9 ± 0.5), and 23,937 non-pregnant non-postpartum women (age: 69.5 ± 0.1). CTPA was the most common modality for confirming PE, from 55.7% in first trimester to 58.3% in second trimester, and 70.0% in third trimester. From first trimester to third trimester, V/Q scanning was used in 21.3%, 16.7%, and 18.3% of cases, respectively. Confirmed pDVT along with the presence of signs/symptoms of PE was the confirmatory modality for PE in 21.3% of patients in first trimester, 19.4% in second trimester, and 6.7% in third trimester. The proportion of postpartum patients confirmed with CTPA (85.5%) was comparable to that of non-pregnant non-postpartum women (83.2%). From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with PE diagnosed with CTPA (p = 0.039). CONCLUSION: CTPA was the primary modality for confirming PE in all trimesters of pregnancy, although its proportional use was higher in later stages of pregnancy. KEY POINTS: • Computed tomography pulmonary angiography (CTPA) was the primary modality of diagnosis in all trimesters of pregnancy among patients with confirmed pulmonary embolism, even in the first trimester. • From the first trimester of pregnancy to postpartum period, there was a linear increase in the proportion of patients with pulmonary embolism who were diagnosed based on CTPA. • In the postpartum period, use of CTPA as the modality to confirm pulmonary embolism was comparable to non-pregnant patients.

Bacteraemia and quick Sepsis Related Organ Failure Assessment (qSOFA) are independent risk factors for long-term mortality in very elderly patients with suspected infection: retrospective cohort study.

BACKGROUND: In older adult patients, bloodstream infections cause significant mortality. However, data on long-term prognosis in very elderly patients are scarce. This study aims to assess 1-year mortality from bacteraemia in very elderly patients. METHODS: Retrospective cohort study in inpatients aged 80 years or older and suspected of having sepsis. Patients with (n = 336) and without (n = 336) confirmed bacteraemia were matched for age, sex, and date of culture, and their characteristics were compared. All-cause mortality and risk of death were assessed using the adjusted hazard ratio (aHR). RESULTS: Compared to controls, cases showed a higher 1-year mortality (34.8% vs. 45.2%) and mortality rate (0.46 vs. 0.69 deaths per person-year). Multivariable analysis showed significant risk of 1-year mortality in patients with bacteraemia (aHR: 1.31, 95% confidence interval [CI] 1.03-1.67), quick Sepsis Related Organ Failure Assessment (qSOFA) score of 2 or more (aHR: 2.71, 95% CI 2.05-3.57), and age of 90 years or older (aHR 1.53, 95% CI 1.17-1.99). CONCLUSIONS: In elderly patients suspected of sepsis, bacteraemia is associated with a poor prognosis and higher long-term mortality. Other factors related to excess mortality were age over 90 years and a qSOFA score of 2 or more.

Medium-term serostatus in Spanish case series recovered from SARS-CoV-2 infection.

The medium-term serologic response of SARS-CoV-2 infection recovered individuals is not well known. The aims were to quantify the incidence of seropositive failure in the medium term in a cohort of patients with different COVID-19 severity and to analyze its associated factors. Patients who had recovered from mild and severe forms of SARS-CoV-2 infection in an Academic Spanish hospital (March 12-May 2, 2020), were tested for total anti-SARS-CoV-2 antibodies by electrochemiluminescence immunoassay (Elecsys Anti-SARS-CoV-2 test; Roche Diagnostics GmbH). The non-seropositive status (seropositive failure) incidence (95% CI) was determined. Associations were tested by multiple logistic regression in a global cohort and severe pneumonia subpopulation. Of 435 patients with PCR-confirmed SARS-CoV-2, a serological test was carried out in 325: 210 (64.6%) had severe pneumonia (hospitalized patients), 51 (15.7%) non-severe pneumonia (managed as outpatients), and 64 (19.7%) mild cases without pneumonia. After a median (IQR) of 76 days (70-83) from symptom onset, antibody responses may not consistently develop or reach levels sufficient to be detectable by antibody tests (non-seropositive incidence) in 6.9% (95% CI, 4.4-10.6) and 20.3% (95% CI, 12.2-31.7) of patients with and without pneumonia, respectively. Baseline independent predictors of seropositive failure were higher leukocytes and fewer days of symptoms before admission, while low glomerular filtrate and fever seem associated with serologic response. Age, comorbidity or immunosuppressive therapies (corticosteroids, tocilizumab) did not influence antibody response. In the medium-term, SARS-CoV-2 seropositive failure is not infrequent in COVID-19 recovered patients. Age, comorbidity or immunosuppressive therapies did not influence antibody response.

Role of endoplasmic reticulum stress in renal damage after myocardial infarction.

Myocardial infarction (MI) is associated with renal alterations resulting in poor outcomes in patients with MI. Renal fibrosis is a potent predictor of progression in patients and is often accompanied by inflammation and oxidative stress; however, the mechanisms involved in these alterations are not well established. Endoplasmic reticulum (ER) plays a central role in protein processing and folding. An accumulation of unfolded proteins leads to ER dysfunction, termed ER stress. Since the kidney is the organ with highest protein synthesis fractional rate, we herein investigated the effects of MI on ER stress at renal level, as well as the possible role of ER stress on renal alterations after MI. Patients and MI male Wistar rats showed an increase in the kidney injury marker neutrophil gelatinase-associated lipocalin (NGAL) at circulating level or renal level respectively. Four weeks post-MI rats presented renal fibrosis, oxidative stress and inflammation accompanied by ER stress activation characterized by enhanced immunoglobin binding protein (BiP), protein disulfide-isomerase A6 (PDIA6) and activating transcription factor 6-alpha (ATF6α) protein levels. In renal fibroblasts, palmitic acid (PA; 50-200 µM) and angiotensin II (Ang II; 10-8 to 10-6M) promoted extracellular matrix, superoxide anion production and inflammatory markers up-regulation. The presence of the ER stress inhibitor, 4-phenylbutyric acid (4-PBA; 4 µM), was able to prevent all of these modifications in renal cells. Therefore, the data show that ER stress mediates the deleterious effects of PA and Ang II in renal cells and support the potential role of ER stress on renal alterations associated with MI.

"Are changes in breast density during the menstrual cycle relevant? To what?"

PURPOSE: Cancers can be hidden by high breast density (BDen)- the masking effect (ME). BDen is also a modifiable and highly prevalent breast cancer risk (BCR) factor. The purposes of this study were to determine how much glandular volume (GVol), breast volume (BVol) and their ratio: BDen change during the menstrual cycle, and if these changes could affect ME or be relevant to results of interventional studies aiming to diminish BCR using these parameters as surrogates. METHODS: We retrieved GVol, BVol and BDen data values obtained from 39,997 right mammograms performed with photon counting technique of 19,904 premenopausal women who reported their first day of last menses (FDLM). Many women had more than one study included over the years (with a different FDLM) but were not studied longitudinally. We segregated women by age (yearly), divided the menstrual cycle in 4 weeks, and assigned results with respect to the FDLM. RESULTS: All parameters vary cyclically, with higher values in week 4 (GVol and BDen) or week 1 (BVol). Mean inter-week differences were very small for the three parameters, and diminished with age. However, especially in the youngest women, inter-week differences could be more than 10% for BDen, 15% for GVol, and 50% for BVol. CONCLUSION: Small inter-week mean differences almost certainly rule out relevant changes to ME directly attributable to BDen. However, the possibility of large differences during the menstrual cycle in younger women, who are the ideal targets of interventional studies to diminish BCR, might distort results and should be accounted for.

Form of presentation, natural history and course of postoperative venous thromboembolism in patients operated on for pelvic and abdominal cancer. Analysis of the RIETE registry. / Forma de presentación, historia natural y evolución de la enfermedad tromboembólica venosa postoperatoria en pacientes operados por cáncer abdominal y pélvico. Análisis del registro RIETE.

INTRODUCTION: Venous thromboembolism (VTE) represents a serious complication after oncologic surgery. Recent studies have shown that the risk of VTE persists several weeks after surgery. This study assesses the form of presentation and time course of VTE after abdominal and pelvic cancer surgery. METHODS: Prospective, multicenter, observational study that analyzes data from an international registry (RIETE) that includes consecutive patients with symptomatic VTE. Our study assesses the form and time of presentation of postoperative VTE, as well as main outcomes, in patients operated for abdominopelvic cancer 8 weeks prior to VTE diagnosis. Variables related to the presentation of VTE after hospital discharge are identified. RESULTS: Out of the 766 analyzed patients with VTE, 395 (52%) presented pulmonary embolism (PE). Most VTE cases (84%) were detected after the first postoperative week, and 38% after one month. Among patients with VTE in the first postoperative week, 70% presented PE. VTE presented after hospital discharge in 54% of cases. Colorectal, urologic, and gynecologic tumors, the use of radiotherapy, and blood hemoglobin levels were independently associated with VTE diagnosis after hospital discharge. Complications (thrombosis recurrence, bleeding, and death) occurred in 34% of patients with VTE detected before hospital discharge, compared to 24% in VTE after hospital discharge (P<0.01). CONCLUSIONS: VTE occurs after hospital discharge in most patients, particularly in those operated for colorectal, urologic, and gynecologic cancer. Pulmonary embolism is more frequent in patients who develop early VTE, who also have worse prognosis.

Infection as cause of immobility and occurrence of venous thromboembolism: analysis of 1635 medical cases from the RIETE registry.

Several risk assessment models include infection and immobility among the items to be considered for venous thromboembolism (VTE) prevention. However, information on patients with infection leading to immobility and developing VTE are limited, as well as on the role of specific types of infection. Data were collected from the worldwide RIETE registry, including patients with symptomatic objectively confirmed VTE, and followed-up for at least 3 months. The overall population of RIETE at June 2013 (n = 47,390) was considered. Acute infection leading to immobility was reported in 3.9 % of non-surgical patients. Compared with patients immobilized due to dementia, patients with infection had a shorter duration of immobilization prior to VTE (less than 4 weeks in 94.2 vs. 25.9 % of cases; p < 0.001). During the 3-month follow-up, VTE patients with infection versus those with dementia had a lower rate of fatal bleeding (0.5 vs. 1.1 %; p < 0.05) or fatal PE (1.7 vs. 3.5 %; p < 0.01). Patients with respiratory tract infections had more likely PE as initial VTE presentation than other types of infection (62.3 vs. 37.7 %; p < 0.001). Significantly more patients with pneumonia than those with other respiratory infections had received VTE prophylaxis (50.2 vs. 30.6 %; p < 0.001). Following VTE, patients with sepsis showed a significantly higher risk of fatal bleeding. Based on our real-world data, infection seems to contribute to the pathogenesis of VTE by accelerating the effects of immobility. Its role as VTE risk factor probably deserves further attention and specific assessment in order to optimize VTE prophylaxis and treatment.

AI: Can It Make a Difference to the Predictive Value of Ultrasound Breast Biopsy?

(1) Background: This study aims to compare the ground truth (pathology results) against the BI-RADS classification of images acquired while performing breast ultrasound diagnostic examinations that led to a biopsy and against the result of processing the same images through the AI algorithm KOIOS DS TM (KOIOS). (2) Methods: All results of biopsies performed with ultrasound guidance during 2019 were recovered from the pathology department. Readers selected the image which better represented the BI-RADS classification, confirmed correlation to the biopsied image, and submitted it to the KOIOS AI software. The results of the BI-RADS classification of the diagnostic study performed at our institution were set against the KOIOS classification and both were compared to the pathology reports. (3) Results: 403 cases were included in this study. Pathology rendered 197 malignant and 206 benign reports. Four biopsies on BI-RADS 0 and two images are included. Of fifty BI-RADS 3 cases biopsied, only seven rendered cancers. All but one had a positive or suspicious cytology; all were classified as suspicious by KOIOS. Using KOIOS, 17 B3 biopsies could have been avoided. Of 347 BI-RADS 4, 5, and 6 cases, 190 were malignant (54.7%). Because only KOIOS suspicious and probably malignant categories should be biopsied, 312 biopsies would have resulted in 187 malignant lesions (60%), but 10 cancers would have been missed. (4) Conclusions: KOIOS had a higher ratio of positive biopsies in this selected case study vis-à-vis the BI-RADS 4, 5 and 6 categories. A large number of biopsies in the BI-RADS 3 category could have been avoided.

How Frequently Benign Uterine Myomas Appear Suspicious for Sarcoma as Assessed by Transvaginal Ultrasound?

BACKGROUND: Uterine myomas may resemble uterine sarcomas in some cases. However, the rate of benign myomas appearing as sarcomas at an ultrasound examination is not known. The objective of this study is to determine the percentage of benign myomas that appear suspicious for uterine sarcoma on ultrasound examination. This is a prospective observational multicenter study (June 2019-December 2021) comprising a consecutive series of patients with histologically proven uterine myoma after hysterectomy or myomectomy who underwent transvaginal and/or transabdominal ultrasound prior to surgery. All ultrasound examinations were performed by expert examiners. MUSA criteria were used to describe the lesions (1). Suspicion of sarcoma was established when three or more sonographic features, described by Ludovisi et al. as "frequently seen in uterine sarcoma", were present (2). These features are no visible myometrium, irregular cystic areas, non-uniform echogenicity, irregular contour, "cooked" appearance, and a Doppler color score of 3-4. In addition, the examiners had to classify the lesion as suspicious based on her/his impression, independent of the number of features present. Eight hundred and ten women were included. The median maximum diameter of the myomas was 58.7 mm (range: 10.0-263.0 mm). Three hundred and forty-nine (43.1%) of the patients had more than one myoma. Using the criterion of >3 suspicious features, 40 (4.9%) of the myomas had suspicious appearance. By subjective impression, the examiners considered 40 (4.9%) cases suspicious. The cases were not exactly the same. We conclude that approximately 5% of benign uterine myomas may exhibit sonographic suspicion of sarcoma. Although it is a small percentage, it is not negligible.

Extra-Gynecological Pelvic Pathology: A Challenge in the Differential Diagnosis of the Female Pelvis.

Ultrasound technology with or without color Doppler allows a real-time evaluation of the entire female pelvis including gynecologic and non-gynecological organs, as well as their pathology. As ultrasound is an accurate tool for gynecological diagnosis and is less invasive and less expensive than other techniques, it should be the first imaging modality used in the evaluation of the female pelvis. We present a miscellany of non-gynecological pelvic images observed during the realization of gynecological ultrasound. Transvaginal and transabdominal ultrasound is the first choice among diagnostic techniques for the study of the female pelvis, providing information about gynecological and extra-gynecological organs, allowing for an orientation toward the pathology of a specific organ or system as well as for additional tests to be performed that are necessary for definitive diagnosis.

Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism.

BACKGROUND: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. RESEARCH QUESTION: Does an association exist between baseline HR and PE outcome across the continuum of HR values? STUDY DESIGN AND METHODS: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. RESULTS: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. INTERPRETATION: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

Fibrosis, the Bad Actor in Cardiorenal Syndromes: Mechanisms Involved.

Cardiorenal syndrome is a term that defines the complex bidirectional nature of the interaction between cardiac and renal disease. It is well established that patients with kidney disease have higher incidence of cardiovascular comorbidities and that renal dysfunction is a significant threat to the prognosis of patients with cardiac disease. Fibrosis is a common characteristic of organ injury progression that has been proposed not only as a marker but also as an important driver of the pathophysiology of cardiorenal syndromes. Due to the relevance of fibrosis, its study might give insight into the mechanisms and targets that could potentially be modulated to prevent fibrosis development. The aim of this review was to summarize some of the pathophysiological pathways involved in the fibrotic damage seen in cardiorenal syndromes, such as inflammation, oxidative stress and endoplasmic reticulum stress, which are known to be triggers and mediators of fibrosis.

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats.

We have evaluated the role of mitochondrial oxidative stress and its association with endoplasmic reticulum (ER) stress activation in the progression of obesity-related cardiovascular fibrosis. MitoQ (200 µM) was orally administered for 7 weeks to male Wistar rats that were fed a high-fat diet (HFD, 35% fat) or a control diet (CT, 3.5% fat). Obese animals presented cardiovascular fibrosis accompanied by increased levels of extracellular matrix proteins and profibrotic mediators. These alterations were associated with ER stress activation characterized by enhanced levels (in heart and aorta vs. CT group, respectively) of immunoglobulin binding protein (BiP; 2.1-and 2.6-fold, respectively), protein disulfide-isomerase A6 (PDIA6; 1.9-fold) and CCAAT-enhancer-binding homologous protein (CHOP; 1.5- and 1.8-fold, respectively). MitoQ treatment was able to prevent (p < 0.05) these modifications at cardiac and aortic levels. MitoQ (5 nM) and the ER stress inhibitor, 4-phenyl butyric acid (4 µM), were able to block the prooxidant and profibrotic effects of angiotensin II (Ang II, 10-6 M) in cardiac and vascular cells. Therefore, the data show a crosstalk between mitochondrial oxidative stress and ER stress activation, which mediates the development of cardiovascular fibrosis in the context of obesity and in which Ang II can play a relevant role.

The quick Sepsis-related Organ Failure Assessment (qSOFA) is a good predictor of in-hospital mortality in very elderly patients with bloodstream infections: A retrospective observational study.

People over 80 years old are now the fastest-growing age group. Bloodstream infections (BSI) in these patients may present with specific characteristics. The objective of this study was to analyze independent factors affecting in-hospital mortality (IHM) due to BSI in very elderly patients (≥80 years of age) and to compare the clinical presentation of BSI in patients aged 80-89 years versus those aged 90 or more. Retrospective, cross-sectional and observational study of BSI in patients aged 80 years or older. The study used IHM as the primary outcome. Stepwise multiple logistic regression models were used to identify associations between potential predictors and IHM. Of the 336 included patients, 76.8% (n = 258) were in the 80-89-year age group and 23.2% (n = 78) in the 90+ age group; 17.3% (n = 58) of patients died during admission. This outcome was independently associated with quick Sepsis Related Organ Failure Assessment (qSOFA) of 2 or more (adjusted odds ratio [aOR] 4.7, 95% confidence interval [CI] 2.3-9.4; p < 0.001). Other predictors included an origin of BSI outside the urinary tract (aOR 5.5, 95% CI 2.4-12.6; p < 0.001), thrombocytopenia (aOR 4.9, 95% CI 1.8-13.4; p = 0.002), hospital-acquired infection (aOR 3.0, 95% CI 1.2-7.5; p = 0.015), and inappropriate empiric antibiotics (aOR 2.0, 95% CI 1.1-3.9; p = 0.04). IHM was 23.1% in the 90+ age group and 15.5% in patients aged 80 to 89 (p = 0.012). However, the 90+ age group was more likely to have a score of at least 2 on the qSOFA (29.9% vs. 19.1%, p = 0.043) and Pitt bacteremia scales (44.9% vs. 30.2%; p = 0.02), as well as chronic kidney disease (56.4% vs. 36.0%; p = 0.001) and altered mental state (40.3% vs. 25.7%; p = 0.013). In conclusion: A qSOFA score of 2 or more and a BSI originating outside the urinary tract were independent predictors of IHM. The 90+ age group was at higher risk than the 80-89-year age group of having a qSOFA score and Pitt bacteremia score of 2 or more as well as an altered mental state.

The Impact of Cardiac Lipotoxicity on Cardiac Function and Mirnas Signature in Obese and Non-Obese Rats with Myocardial Infarction.

Cardiac lipotoxicity is involved in the cardiac functional consequences associated with obesity. Therefore, the aim of this study was to explore whether changes in the mitochondrial lipid cardiac profile could reflect differences in cardiac function and structure in obese and non-obese rats with myocardial infarction (MI). Whether these changes can also be reflected in a specific plasma miRNA signature as markers of cardiac damage was also evaluated. Rats were fed with either standard (3.5% fat) or high fat diet (35% fat) for 6 weeks before the induction of MI and sacrificed 4 weeks later. MI showed cardiac lipotoxicity independently of the presence of obesity, although obese and non-obese rats did not present the same cardiac lipid profile at mitochondrial level. Several cardiac lipid species in mitochondria, including cardiolipins and triglycerides, were associated with myocardial fibrosis, with mitochondrial triglyceride levels being independently associated with it; this supports that lipotoxicity can affect cardiac function. MI down-regulated plasma levels of miRNA 15b-5p and 194-5p in obese and non-obese animals, which were associated with cardiac function, mitochondrial lipids and myocardial fibrosis, with miRNA 15b-5p levels being independently associated with cardiac fibrosis. This could support that lipotoxicity could affect heart function by modulating plasma miRNAs.

[Acute liver failure in a patient with hairy cell leukemia]. / Fallo hepático agudo en un paciente con tricoleucemia.

Acute liver failure as a manifestation of primary non-Hodkin's lymphoma is a rare phenomenon with a fatal prognosis. Hairy cell leukemia (HCL) is an uncommon chronic B-cell lymphoproliferative disorder, representing about 2 percent of all leukemies. We report a 78-year-old patient with a history of hairy cell leukemia since 10 years, presenting whith fulminant liver failure due to massive liver infiltration. He have reviewed several cases of infiltration of the liver by haematological malignancies, but we only have found after a review in MEDLINE between 1980 and 2006, one case of acute liver failure in a patient with hepatic invasion by hairy cell leukaemia.

Uterine bleeding during anticoagulation in women with venous thromboembolism.

BACKGROUND: Women presenting with uterine bleeding during the course of anticoagulant therapy for venous thromboembolism (VTE) present a difficult therapeutic dilemma due to the absence of evidence-based recommendations. METHODS: We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to assess the clinical characteristics of women presenting with uterine bleeding during anticoagulation for VTE, its frequency, time course, management and 30-day outcomes. RESULTS: As of October 2016, 31,951 women with VTE were recruited in RIETE. During the course of anticoagulant therapy, 53 (0.17%) developed major uterine bleeding, 118 (0.37%) non-major uterine bleeding and 948 (2.97%) had major bleeding in other sites. Median time elapsed from VTE to bleeding was: 32, 71 and 22 days, respectively. Mean age was: 56±17, 52±20 and 75±14 years, respectively. Women with major uterine bleeding more likely had cancer (51%), anemia (72%), raised platelet count (19%) or recent major bleeding (11%) at VTE presentation than those in the other subgroups. During the first 30 days after bleeding, 17%, 1.7% and 31% of women died, respectively. Of 11 women with uterine bleeding who died, 9 (82%) had cancer, two (18%) died of bleeding and one (9.1%) died of pulmonary embolism after discontinuing anticoagulation. CONCLUSIONS: Uterine bleeding during the course of anticoagulation for VTE is not uncommon and mostly affects young women. Those with cancer, anaemia, raised platelet count or recent bleeding at baseline are at an increased risk for uterine bleeding during anticoagulation.

Clinical outcomes during anticoagulant therapy in fragile patients with venous thromboembolism.

BACKGROUND: Subgroup analyses from randomized trials suggested favorable results for the direct oral anticoagulants in fragile patients with venous thromboembolism (VTE). The frequency and natural history of fragile patients with VTE have not been studied yet. OBJECTIVES: To compare the clinical characteristics, treatment and outcomes during the first 3 months of anticoagulation in fragile vs non-fragile patients with VTE. METHODS: Retrospective study using consecutive patients enrolled in the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry. Fragile patients were defined as those having age ≥75 years, creatinine clearance (CrCl) levels ≤50 mL/min, and/or body weight ≤50 kg. RESULTS: From January 2013 to October 2016, 15 079 patients were recruited. Of these, 6260 (42%) were fragile: 37% were aged ≥75 years, 20% had CrCl levels ≤50 mL/min, and 3.6% weighed ≤50 kg. During the first 3 months of anticoagulant therapy, fragile patients had a lower risk of VTE recurrences (0.78% vs 1.4%; adjusted odds ratio [OR]: 0.52; 95% confidence intervals [CI]: 0.37-0.74) and a higher risk of major bleeding (2.6% vs 1.4%; adjusted OR: 1.41; 95% CI: 1.10-1.80), gastrointestinal bleeding (0.86% vs 0.35%; adjusted OR: 1.84; 95% CI: 1.16-2.92), haematoma (0.51% vs 0.07%; adjusted OR: 5.05; 95% CI: 2.05-12.4), all-cause death (9.2% vs 3.5%; adjusted OR: 2.02; 95% CI: 1.75-2.33), or fatal PE (0.85% vs 0.35%; adjusted OR: 1.77; 95% CI: 1.10-2.85) than the non-fragile. CONCLUSIONS: In real life, 42% of VTE patients were fragile. During anticoagulation, they had fewer VTE recurrences and more major bleeding events than the non-fragile.