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BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with COVID-19, but uncertainty remains about the determinants of in-hospital mortality and data on post-discharge outcomes are scarce. The aims of this study were to investigate the variables associated with in-hospital outcomes in patients who received ECMO during the first wave of COVID-19 and to describe the status of patients 6 months after ECMO initiation.METHODS: EuroECMO-COVID is a prospective, multicentre, observational study developed by the European Extracorporeal Life Support Organization. This study was based on data from patients aged 16 years or older who received ECMO support for refractory COVID-19 during the first wave of the pandemic-from March 1 to Sept 13, 2020-at 133 centres in 21 countries. In-hospital mortality and mortality 6 months after ECMO initiation were the primary outcomes. Mixed-Cox proportional hazards models were used to investigate associations between patient and management-related variables (eg, patient demographics, comorbidities, pre-ECMO status, and ECMO characteristics and complications) and in-hospital deaths. Survival status at 6 months was established through patient contact or institutional charts review. This study is registered with ClinicalTrials.gov, NCT04366921, and is ongoing.FINDINGS: Between March 1 and Sept 13, 2020, 1215 patients (942 [78%] men and 267 [22%] women; median age 53 years [IQR 46-60]) were included in the study. Median ECMO duration was 15 days (IQR 8-27). 602 (50%) of 1215 patients died in hospital, and 852 (74%) patients had at least one complication. Multiorgan failure was the leading cause of death (192 [36%] of 528 patients who died with available data). In mixed-Cox analyses, age of 60 years or older, use of inotropes and vasopressors before ECMO initiation, chronic renal failure, and time from intubation to ECMO initiation of 4 days or more were associated with higher in-hospital mortality. 613 patients did not die in hospital, and 547 (95%) of 577 patients for whom data were available were alive at 6 months. 102 (24%) of 431 patients had returned to full-time work at 6 months, and 57 (13%) of 428 patients had returned to part-time work. At 6 months, respiratory rehabilitation was required in 88 (17%) of 522 patients with available data, and the most common residual symptoms included dyspnoea (185 [35%] of 523 patients) and cardiac (52 [10%] of 514 patients) or neurocognitive (66 [13%] of 512 patients) symptoms.INTERPRETATION: Patient's age, timing of cannulation (FUNDING: None.

Populations from different countries may present different cellular modifications among themselves, and the Buccal Micronucleus Cytome (BMCyt) assay in human buccal mucosal tissue may be a marker to evaluate these modifications. This study evaluated and compared DNA damage and other nuclear anomalies between Brazilian and Spanish gym users. This is a cross-sectional study carried out with gym users of Santa Cruz do Sul/Brazil and Madrid/Spain. The BMCyt assay was performed for biomarkers of DNA damage (micronuclei and/or nuclear buds), cytokinetic defects (binucleated cells), proliferative potential (basal cell frequency) and/or cell death (condensed chromatin, karyorrhexis, pyknotic and karyolytic cells) in human buccal mucosal. Of the 228 individuals evaluated, 163 were Brazilian, and 65 were Spanish. Gym users of both countries differed between weight, body mass index, body fat, and muscle mass. The Brazilians presented a significantly higher frequency of micronuclei, nuclear buds, cells with condensed chromatin and karyorrhexis. Spaniards, however presented a significantly higher frequency of karyolytic cells. In conclusion, Brazilian gym users presented significantly higher rates of DNA damage and cell death, while the Spanish presented a higher frequency of advanced stage cell death.

Estrone (E1) is a common environmental contaminant found in rivers and streams due to the farming of animals, such as swine and cattle. Our study evaluated the effects of chronic E1 exposure at environmentally relevant concentrations on spermatogenesis and the semen quality of zebrafish (Danio rerio). We exposed the fish to E1 at concentrations of 20, 200, and 2000 ng/L diluted in 0.001% ethanol (v/v) for 49 days. There were two control groups: one was exposed to water only and the other to ethanol at the same concentration used in the E1 groups. Following exposure, we analyzed the proportion of testicular cell types and other components (%), rate of cell proliferation and death, and sex steroid concentrations. Furthermore, we analyzed the expression of insulin-like growth factor 1 (IGF1), IGF2, IGF1 receptor (IGF1R), and inducible nitric oxide synthase and assessed the semen quality. E1 exposure increased spermatogonia, spermatids, Sertoli cells, Leydig cells, and the proportion of inflammatory infiltrate but decreased the spermatozoa amount. These changes were reflected by reductions in the gonadosomatic index and levels of 11-ketotestosterone in the testes. On the other hand, E1 exposure increased testicular estradiol, IGF1R expression, and nitric oxide production. After an evaluation using a computer-assisted sperm analysis (CASA) system, we observed reduced progressive motility, curvilinear velocity, and beat cross frequency of 20 and 2000 ng/L E1 groups. Our findings support that E1 causes deleterious effects on the testicular function and semen quality of D. rerio even at environmental concentrations. Thus, E1 concentrations should be monitored in surface waters for the purposes of fish conservation.

Congeneric species often coexist in sympatry using behavioral and morphological adaptations to reduce competition and interspecific interference, but reproductive patterns behind coexistence remain unknown. We analyzed the gonadal morphology and development, reproductive cycle, and population structure of two sympatric congeneric fishes to evaluate the degree of overlap and differentiation of the reproductive biology between species in a Neotropical river. Development of testes and ovaries were similar between species, both showing asynchronous gonadal development, large diameter of gametes and synthesis of mucosubstances by follicle cells to form adhesive eggs. Although the morphometry of germ cells did not present differences, the zona radiata of mature eggs in Hypostomus garmani was markedly thicker than H. francisci, which suggests different spawning habitats. Both species have greater reproductive activity in the rainy season, concomitant with increase in water temperature, however H. garmani initiates and ends its reproduction earlier than H. francisci, indicating a differentiation of reproductive periods. Sexually mature males and females of H. francisci reproduced at a larger mean size then H. garmani. The two congeneric species had a similar abundance and sex ratios in the study area. Results show that although the species exhibited broad overlap of reproductive traits, a spatial and temporal differentiation of the reproductive biology was present. This study contributes to understanding reproductive mechanisms that may facilitate coexistence between congeneric sympatric species.

Although herbicides have been developed to act on the physiological processes of plants, they are responsible for causing deleterious effects on animals. These chemical compounds are widely used throughout the world, but especially in countries that export agricultural products such as Central and South America, their use has increased in recent years. Aquatic environments are natural reservoirs of herbicides, which after being applied on crops, run off through the soil reaching rivers, lakes, and oceans. Fish are among the many organisms affected by the contamination of aquatic environments caused by herbicides. These animals play an important ecological role and are a major source of food for humans. However, few studies address the effects of herbicides on fish in this region. Thus, in the present review we discuss the morphophysiological and molecular consequences of herbicide exposure in Neotropical fish systems as well as how the environmental and land use characteristics in this region can influence the toxicity of these pollutants. A toxicity pathway framework was developed summarizing the mechanisms by which herbicides act and endpoints that need to be further investigated.

OBJECTIVES Our goal was to analyse the implantation and outcome of thoracoscopic epicardial leads after a failed endovascular approach or follow-up (FU) complications after endovascular implantation. METHODS We reviewed the records of patients with failed endovascular left ventricular (LV) lead placement or complications during FU, who were subsequently referred to cardiac surgeons for treatment with thoracoscopic LV lead implantation. We analysed the reasons for endovascular failure; the indications for the surgical procedures; and the clinical, echocardiographic and device FU results. RESULTS Between 2010 and 2013, a total of 23 patients were included. Among them, 17 of the patients had no previous cardiothoracic surgery, 13 (76%) had successful video-assisted thoracoscopy (VAT) LV lead implantation, 3 (18%) had a conversion to thoracotomy and 1 (6%) failed. Of the 6 patients with prior cardiothoracic surgery, 2 (33%) had VAT only, 3 (50%) had primary thoracotomies and 1 (17%) had a conversion. Two major complications occurred. The reasons for LV endovascular lead failure were subclavian vein occlusion (n = 2), implant failure (n = 13) and complications during the FU period (n = 8). FU information was available for 20 patients: 17 (85%) had improved symptoms. The median FU period was 33 months. A total of 78% of patients were in New York Heart Association (NYHA) functional class III–IV before the operation; 30% were in NYHA functional class III–IV at the last FU examination. The left ventricular ejection fraction increased from 25% before surgery to 31% at the last FU examination. Overall, sensing and pacing threshold values remained stable over time. In 1 patient, lead revision was necessary due to an increase in the pacing threshold. CONCLUSIONS VAT implantation of LV leads had an excellent response rate with an improvement in NYHA functional class and left ventricular ejection fraction. The lead measurements were mainly stable over time.

Discharge of municipal wastewater promotes the entry of diverse oestrogenic compounds into the water bodies. This complex mixture of substances interferes in the steroidogenic pathway, being able to promote severe reproductive impairment in freshwater fish populations. The purpose of the present study was to evaluate the effects of oestrogenic endocrine disruptors (EDCs) mixture on gonadal sex steroids (testosterone, T; 11-ketotestosterone, 11-KT; 17β-oestradiol, E2; 17-hydroxyprogesterone, 17-OHP) in the peak of the reproductive season of Astyanax rivularis, correlating the results obtained with the proportion of germ cells and gonadal histopathology. Three sampling sites were chosen to conduct the study, one reference site (S1), without contamination by municipal wastewater and two sites (S2 and S3) receiving discharge of municipal wastewater. Males of A. rivularis presented higher concentrations of E2, lower androgens (T and 11-KT) in gonads when compared to males from site S1. Concentrations of 17-OHP did not present significant difference among sites. In sites S2 and S3, the proportion of early spermatocytes, spermatids and Leydig cells increased while spermatozoa decreased compared to fish from S1. The following gonadal histopathologies were detected in the male fishes: intersex gonads (28% in S3) and testicular degeneration with germinal epithelium exhibiting agglutinated germ cells masses and empty cysts (57% in S2 and 71% in S3). In females, concentrations of T, E2 and 17-OHP did not present significant difference among the sites, however higher 11-KT concentrations were detected in females from sites S2 and S3. A lower proportion of perinucleolar follicles and a higher incidence of vitellogenic follicles, besides, aged oocytes and the presence of eosinophilic proteinaceous fluid in the interstitial compartment were also found in females from impacted sites. These results indicate that the urbanization and consequent release of municipal wastewater containing oestrogenic compounds in the headwater creeks are altering the levels of sex hormones and gametogenesis of A. rivularis. Further studies should be performed to determine whether oestrogenic endocrine disrupters are disrupting the reproduction of A. rivularis.

Bisphenol A (BPA) is an organic synthetic compound used in the plastic industry with endocrine disrupting activity. Although it is frequently found in surface waters, few studies have investigated its impact on fish gametogenesis, particularly when associated with natural stressors. In this regard, the present study evaluated BPA toxicity on spermatogenesis in the lambari Astyanax bimaculatus under controlled conditions and its interactive effects with water temperature. Adult specimens were exposed in duplicate to 40 μg/L and 400 μg/L BPA at 23 °C and 28 °C for 21 days; the control group did not receive BPA. Testicular samples were collected and analyzed using different cellular and molecular techniques. The results showed a significant reduction in the gonadosomatic index in the BPA-treated groups at both temperatures. A decrease in the testicular levels of 11-ketotestosterone was observed in the 400 μg/L BPA group at 23 °C, 17β-estradiol increased significantly in the treated groups at 28 °C, and vitellogenin showed no difference between the treatments. The morphometric analysis of spermatogenesis revealed a significant increase in the proportion of spermatogonia, spermatocytes, and Sertoli cells in the treated groups, with a higher proportion at 23 °C than at 28 °C. Otherwise, the proportion of spermatozoa was significantly lower in the BPA-treated groups, with a greater reduction at 23 °C. In addition, BPA also stimulated spermatogonial proliferation in the treated groups, but apoptosis was significantly increased in spermatids at 23 °C. Testis-ova, cell degeneration, and chromatin alterations in spermatids and Sertoli cells were observed in the germinal epithelium of the BPA-treated groups. The integrated biomarker response (IBR) index revealed that the analyzed endpoints are suitable for assessing estrogenic contamination. Taken together, our results indicate that the interactive effects of BPA and temperature contribute to the impairment of spermatogenesis in A. bimaculatus with more severe effects observed on sperm production at 23 °C than at 28 °C.

The field of mitral valve disease diagnosis and management is rapidly evolving. New understanding of pathophysiology and improvements in the adoption of sophisticated multimodality imaging modalities have led to early diagnosis and to more complex treatment. The most common cause of mitral regurgitation (MR) in the western world is in the primary alteration of the valve, which leads to degenerative leaflet prolapse due to chordal elongation or rupture and annular dilatation. Untreated, significant MR has a negative impact prognosis, leading to reduction of survival. In the setting of degenerative MR, surgical repair currently represents the standard of care. Treatment of asymptomatic patients with severe MR in the Valve Center of Excellence, in which successful repair reaches more than 95% and surgical mortality less than 1%, symbolizes the direction for the next years. Transcatheter mitral valve repair with different devices, more recently the chordal replacement ones, is providing good outcomes and became a therapeutic option in high-risk patients with degenerative MR. In the future, more advances are expected from further development of interventional techniques, careful evaluation and better patient selection. This review will focus on long-term surgical outcomes of mitral valve repair with artificial chordae and on the emerging transcatheter chordal repair devices as therapeutic options for degenerative MR patients.

The insulin-like growth factor (IGF) system plays important roles in fish reproduction, but the expression pattern and cellular location of IGF-I and IGF-II during gonadal maturation are uncertain. The present study reports a stage-specific assessment of gonadal expression levels and immunolocalisation of IGF-I and IGF-II in Astyanax fasciatus, a characid fish from South America. Adult fish in different maturity stages were caught in the Furnas Reservoir, Grande River, Brazil. Gonad samples were processed for histology, immunohistochemistry, and ELISA for IGF-I and IGF-II. Ovarian levels of IGF-I were low during ripening and ripe stages, higher in totally spent, and then decreased in resting. Levels of IGF-II increased during ovarian maturation, reaching significantly higher values at stage totally spent. In males, IGF-I levels followed gonadal maturation, with higher values in ripening and ripe stages, whereas IGF-II levels showed higher values in stage ripening and partially spent. A positive correlation was found between IGF-I and gonadosomatic index (GSI) for males (r = 0.59), while females showed a negative correlation (r = - 0.43), but IGF-II showed no correlation to GSI. IGF-I was expressed mainly in oogonia nests whereas IGF-II stained the follicular cells in the perinucleolar follicles, cortical vesicles in the previtellogenic follicles, and oogonia nests. In males, IGF-I was evident in spermatogonia and spermatocytes while IGF-II stained Sertoli cells surrounding spermatids cysts and spermatogonia in late stages. Together, these findings support a hypothesis that the balance between IGF-I and IGF-II levels is important in the regulation of gonad maturation in Astyanax fasciatus.

Robotically assisted mitral valve repair has proven its efficacy during the last decade. The most suitable approach for patients with difficult anatomies, such as morbid obesity, sternal deformities, cardiac rotation, or vascular anomalies, represents a current challenge in cardiac surgery. Herein, we present the case of a 71-year-old patient affected by severe degenerative mitral valve regurgitation with pectus excavatum and a right aortic arch with an anomalous course of the left subclavian artery who was successfully treated using a Da Vinci–assisted approach.

A novel chordal system enables automated implantation of artificial mitral chords to treat mitral regurgitation (MR). This article summarizes the first-in-man initial clinical results.The CHAGALL (CHordArt system study for the treatment of mitral ReGurgitAtion due to leaflet proLapse or fLail) trial is a single arm, multicenter, prospective study to test the feasibility of this system for mitral repair. The interim clinical and echocardiographic results of the first 5 patients with a 12-month follow-up are presented.Five patients (mean age, 64 years) with severe MR received implantation of neochords with this device under cardiopulmonary bypass. Technical success was obtained in all patients. Transesophageal echocardiogram showed either no or trace residual MR (1+/4+) after repair. Survival at 30 days was 100%, and no device-related complication occurred. Reduction of MR was sustained up to 12 months.This novel chordal system is promising because it greatly facilitates the deployment of neochords to repair the mitral valve. Results at 12 months are encouraging. The device is currently under development for transcatheter approach.

Background Patients with mechanical heart valves are still not eligible for treatment with direct oral anticoagulants (DOAC). We aimed to conduct a proof-of-principle study investigating the anti-Xa inhibitor rivaroxaban as antithrombotic treatment in patients with recent mechanical aortic valve replacement. Materials and methods Low-risk patients scheduled for elective mechanical aortic valve replacement were treated with rivaroxaban 20 mg once daily (OD) in a prospective cohort study, started on day 3 postoperatively and given for 6 months. The study was registered at ClinicalTrials.gov (# NCT02128841 ). Results Ten patients were included (median age, 48; range 39 to 60). Indication was aortic valve stenosis in 6 patients, aortic root aneurysm with severe aortic valve regurgitation in 3 patients, and mixed stenosis/regurgitation in 1 patient. Neither thromboembolic nor bleeding events were observed, and no patient died. Absence of valve thrombosis was demonstrated in all patients. On day 7, median D-dimers were 2723 μg/L (inter-quartile range [IQR] 1672, 5695 μg/L), median TAT levels were 4.5 μg/L (IQR 4.1, 5.6 μg/L); and median peak thrombin generation was 150 nM (IQR 91, 183). On day 90, median D-dimers were 426 μg/L (IQR 278, 569), median TAT levels were 2.7 μg/L (IQR 2.2, 3.1), and median peak thrombin generation were 66 nM (IQR 62, 87). Conclusions Rivaroxaban 20 mg OD was safe and effective in a pilot study of 10 low risk patients with mechanical aortic heart valve. Our results justify larger studies investigating the application of anti-Xa inhibitors in patients with mechanical heart valves.

Aims of the study An extracorporeal membrane oxygenation system (ECMO), as a bridge to either recovery, a ventricular assist device (VAD), or heart or lung transplantation, may be the only lifesaving option for critically ill patients suffering from refractory cardiac, respiratory or combined cardiopulmonary failure. As peripheral hospitals may not offer ECMO treatment, tertiary care centres provide specialised ECMO teams for on-site implantation and subsequent patient transfer on ECMO to the tertiary hospital. This study reports the results of the largest ECMO transportation programme in Switzerland and describes its feasibility and safety. Methods Patients transported on ECMO by our mobile ECMO team to our tertiary centre between 1 September 2009 and 31 December, 2016 underwent retrospective analysis. Implantation was performed by our specialised ECMO team (primary transport) or by the medical staff of the referring hospital (secondary transport) with subsequent transfer to our institution. Type of ECMO, transport data, patient baseline characteristics, operative variables and postoperative outcomes including complications and mortality were collected from medical records. Results Fifty-eight patients were included (three patients excluded: one repatriation, two with incomplete medical records). Thirty-five patients (60%) received veno-venous, 22 (38%) veno-arterial and one patient (2%) veno-venoarterial ECMO. Forty-nine (84%) patients underwent primary and nine (16%) secondary transport. Thirty-five (60%) patients were transferred by helicopter and 23 (40%) by ambulance, with median distances of 38.1 (13n225) km and 21 (3-71) km respectively. No clinical or technical complications occurred during transportation. During hospitalisation, three patients had ECMO-associated complications (two compartment syndrome of lower limb, one haemothorax after central ECMO upgrade). Median days on ECMO was 8 (l1n49) and median days in hospital was 17 (l1n122). ECMO weaning was successful in 41 patients (71%), on-transport survival was 100%, 40 patients survived to discharge (69%), and overall survival was 67% (39 patients) at a median follow-up of 58 days (l1n1441). Cumulative survival was significantly affected by cardiogenic shock vs. ARDS (p = 0.001), veno-arterial and veno-venoarterial vs. veno-venous ECMO (p = 0.001) and after secondary vs. primary transport (p l0.001). The ECMO weaning rate was significantly lower after secondary transfer (22%, two patients, both vaECMO) vs. primary transfer (80%, p = 0.002, 39 patients of which 35 (71%) had vvECMO). Conclusions The first results of our ECMO transportation programme show its feasibility, safety and efficacy without on-site implant or on-transport complications or mortality. The favourable early survival may justify the large effort with respect to logistics, costs and manpower. With rising awareness, referring centres may increasingly consider this lifesaving option at an early stage, which may further improve outcomes.

Background: Cardioplexol™ with its low volume (100 mL) was originally conceived as cardioplegic solution for MiECC procedures. Introduced in its current form in 2008 in our clinic, it has immediately demonstrated attractive advantages including the easy and rapid administration by the surgeon him/herself, the almost immediate cardiac arrest and a prolonged delay before a second dose is necessary. We report here the results of our initial experience with this simple solution. Methods: Single centre, retrospective observational analysis of prospectively collected data of isolated coronary artery bypass graft (CABG) procedures performed with a MiECC. Results: Of 7,447 adult cardiac surgical operations performed during a 76 months period, 2,416 were isolated CABG-MiECC procedures. Patients were 81.3% males, 66.2±9.7 years old and had a median logistic EuroSCORE of 3.2. In average 3.2±0.8 vessels were bypassed. Median cross-clamp time was 45 minutes and more than 75% of the patients received only one 100 mL dose of Cardioplexol™. At reperfusion more than 90% of the hearts spontaneously recovered a rhythmic activity. Maximal value of troponin T during the first hours following myocardial reperfusion was 0.9±4.5 ng/mL (median =0.4 ng/mL). Mortality at 30 days was 0.9%. Conclusions: Cardioplexol™ seems very promising. It appears especially efficient and safe when used for CABG procedures performed with a MiECC.

Environmental disasters such as the rupturing of mine tailings dams are a major concern worldwide. In the present study, we assess the effects of the release of mine waste due to the rupture of the Fundão dam on two native fish species (Hoplias intermedius and Hypostomus affinis) from the Doce River basin. Two sampling sites were chosen: S1, a reference site, and S2, contaminated by mining waste. Water and sediment were collected to evaluate metals concentration. Adult fish were caught to analyse biological parameters, hepatic histopathology, and biomarkers of metal contamination. Compared to site S1, the concentration of manganese was statistically higher in water while lead, nickel, and arsenic were statistically higher in the sediment from site S2, and iron had no significant difference between sites. At site S1, fish of both species presented hepatic tissue with normal architecture. At site S2, hepatic alterations, such as cytoplasmic vacuolization and necrosis were frequently found in both species. Regarding the histopathological index, higher values were found in both species from site S2. The positive antibody reactions for cytochrome P450 1A (CYP1A) and metallothionein (MT) were statistically greater in site S2 for both species. The oxidative stress biomarkers, superoxide dismutase (SOD) and catalase (CAT) were statistically higher in H. intermedius from site S2, but only CAT was statistically greater in H. affinis at site S2. These results demonstrate that the release of mineral residues from the rupture of the Samarco mine dam is provoking hepatic damage in the fish from the Doce River besides inducing the expression of proteins and enzymes related to metal contamination.

Objectives The HAART ring device has been introduced as a novel strategy to facilitate aortic valve repair. This rigid, elliptical device aims to restore normal leaflet configuration and to provide annular stabilization in the setting of aortic regurgitation. The goal of this preclinical study is to evaluate the in vivo feasibility of 'aortic valve-in-ring' transcatheter aortic valve replacement (TAVR). Methods Six animals {landrace pigs, 87.6 [standard deviation (SD) 4.5] kg} underwent HAART ring implantation (5 cases #19 mm and 1 case #21 mm) via full sternotomy with cardiopulmonary bypass. Seven transfemoral TAVR implantations were performed with the Medtronic EvolutR prosthesis to assess the sizing and outcome (5 cases #23 mm, 1 case #26 mm and 1 case #29 mm). Results TAVR implantation was successful in 6 of 7 attempts. Post-dilatation was performed in 1 case without damage of the ring or the valve. One embolization occurred due to oversizing (EvolutR valve 29 mm in HAART ring 19 mm). No clinically relevant postimplantation gradient [7.6 (SD 4.0) mmHg] or regurgitation was detected by invasive and echocardiographic measurements. Postoperative computed tomography scans revealed good device configuration. Conclusions Transcatheter aortic valve-in-ring implantation of a self-expandable TAVR into a rigid aortic annuloplasty ring after aortic valve repair appears feasible. Proper sizing and correct depth of implantation are crucial.

Recently, a novel rigid ring has been introduced into surgical practice. The authors present the initial experience in Switzerland with this promising approach.

Continental waters salinisation is a global threat that has grown because of climate change and human activities, but little is known about how and what biological tracts are affected. The aim of this study was to investigate the influence of different water salinities on the expression of HSP70, PCNA and caspase-3 during spermatogenesis of Nile tilapia. Adult males were submitted to four salinity treatments: (S0) fresh water, (S7) 7 g L−1, (S14) 14 g L−1, and (S21) 21 g L−1 for 1, 4, and 9 days. All specimens were in spermatogenic activity and the highest values of the gonadosomatic index (GSI) occurred in the S0 and S7. In the morphometric analysis, spermatocytes were the most frequent germ cell detected in all treatments (>50%) and spermatids achieved about 20% of the testicular proportion, with few variations among treatments. Spermatozoa were significantly reduced only in S14 compared to S7. Leydig cells were significantly increased in S14 when compared to S7 but plasma concentrations of 11-KT showed no significant difference among treatments. ELISA assay showed higher testicular expression of HSP70 at 1 day in all groups, followed by a significant decrease at days 4 and 9 in S14 and S21. The expression of PCNA was significantly lower while the activity of caspase-3 was higher in S14 and S21 when compared to S0 and S7. These results indicate that higher salinities in S14 and S21 interfere with the relationship between testicular HSP70, PCNA, and caspase-3, but with few effects over spermatogenesis dynamics of Nile tilapia.

Oestrogens participate in various biological processes such as oogenesis, vitellogenesis and testicular development, but studies regarding the distribution and protein levels of oestrogen receptors (ERα and ERβ) and aromatase (Cyp19) in testis are rarely investigated in fish species. The aim of the present study was to analyse the expression pattern of ERα, ERβ and Cyp19 in testis of Astyanax rivularis and, in addition, to verify if oestrogenic contamination interferes in the expression levels of these proteins. Quarterly, field samplings were carried out during a reproductive cycle in a stream of the Upper Velhas River with a good conservation status (site S1). In the gonadal maturation peak (June), when ripe stage was most abundant, fish collection was made in three streams: S1, reference site, and S2 and S3, sites contaminated by untreated sewage. The results of immunohistochemistry demonstrated labelling of Cyp19 in Leydig cells and acidophilic granulocytes, but spermatogonia, Sertoli cells, spermatids and spermatozoa were also labelled. ERα was more widely distributed than ERβ being found in all developmental germ cell phases. On the other hand, ERβ was found only in spermatogonia and spermatocytes. During testicular maturation, ELISA levels for Cyp19, ERα and ERβ followed the gonadosomatic index (GSI) with significant higher values in the ripe stage. Regarding to endocrine disruption, the males exposed to domestic sewage presented significant higher expression of Cyp19 and ERα when compared to the non-exposed fish. Together, our results demonstrate expression patterns of Cyp19, ERα and ERβ in the testis of A. rivularis. In addition, we indicate ERα and Cyp19 as sensitive biomarkers for monitoring of oestrogenic contamination in freshwater environments.

18F-FDG PET/CT (PET/CT) is a useful tool for the diagnosis of aortic graft infection (AGI), but has rarely been used to influence therapeutic decisions during follow-up. We aimed to study the role of PET/CT in the long-term monitoring of patients. Participants of the prospective Vascular Graft Infection Cohort Study (VASGRA) were included if they had microbiologically proven AGI. We quantified the metabolic activity in PET/CT by using maximum standardized uptake value (SUVmax) and further classified it as being focal or diffuse. Multivariable linear regression models were fit using generalized estimating equations to investigate factors associated with SUVmax over time. Sixty-eight participants with AGI contributed to 266 PET/CTs including 36 examinations performed after stop of antimicrobial therapy. Higher C-reactive protein (CRP) (adjusted coefficient per log10 mg/L 0.05 [95% C.I. 0.02–0.08]) was associated with higher SUVmax. CRP, metabolic and clinical findings informed the decision to either start (medians of SUVmax 7.1 and CRP 31.5 mg/L; 100% focal uptake), escalate (SUVmax 9.5; CRP 31.5; 100% focal uptake), continue (SUVmax 6.0; CRP 9.95 mg/L; 90% focal uptake), or stop (SUVmax 4.3; CRP 3.5 mg/L; 61% focal uptake) antibiotic treatment. Of note, decisions to escalate or continue antibiotic treatment were taken despite normal CRP values in 12.5 and 35.7% of PET/CTs, respectively. Consecutive PET/CTs could influence the clinical decision-making in patients with AGI in the near future. More studies on the use of PET/CT in case of aortic graft infection may offer the potential for individualized treatment approaches. NCT01821664.

Resection of the calcium bar and creation of a more compressible annulus with pericardium are necessary in case of extensive calcification of the mitral valve annulus in patients with advanced myxomatous degenerative disease. Such annular bar calcification is technically challenging and represents a risk factor for death following mitral valve operations, because of atrio-ventricular rupture or encroachment of the coronary arteries. We describe a safe limited segmental annular debridement away from the coronary arteries that allows enough flexibility of the remaining calcified annulus to perform reduction annuloplasty in a young female patient with severe mitral regurgitation and a highly dilated and severely calcified mitral annulus.

O rio das Velhas, importante afluente da bacia do rio São Francisco, é considerado o rio mais poluído do estado de Minas Gerais, devido à alta carga de contaminação aquática proveniente de esgoto doméstico e industrial. Os principais objetivos desse estudo foram avaliar os efeitos de estrógenos ambientais sobre a reprodução da espécie Astyanax rivularis, espécie de pequeno porte encontrada em riachos com altitudes elevadas no alto rio das Velhas e avaliar a imunomarcação de CYP19, ERá e ERâ nos testículos ao longo do desenvolvimento gonadal e entre sites com diferentes níveis de contaminação estrogênica. Foram realizadas quatro coletas de campo em três córregos: S1 (baixa interferência antrópica) S2 e S3 (submetidos a contaminação por esgoto doméstico sem tratamento). Foram avaliados, em machos e fêmeas dessa espécie, a expressão hepática de vários biomarcadores moleculares (Zrp, Vtg, IGF-I, CYP19, ERá e ERâ), histológicos (histopatologia de ovócitos e intersexo), endpoints reprodutivos (índices gonadossomático, hepatossomático, fator de condição de Fulton, fecundidade e proporção de células da linhagem gametogênica) e desvios na proporção sexual nos diferentes sites de coleta. Foram avaliados os parâmetros físico-químicos por sonda Horiba e os compostos estrogênicos através de cromatografia líquida acoplada a espectrometria de massas (LC-MS). Os sites expostos a esgoto doméstico apresentaram níveis elevados de estradiol, estriol, estrona, bisphenol A e nonilfenol quando comparado com S1. Os parâmetros físico-químicos (temperatura e oxigênio dissolvido) não tiveram diferenças entre os sites de coleta. Os resultados indicam desregulação endócrina nos sites expostos a esgotos domésticos (S2 e S3), com aumento na proporção de fêmeas, aumento dos níveis de Vtg, Zrp, CYP19, ERá e ERâ em machos e diminuição de Vtg em fêmeas. O IGF-I de machos em S2 apresentou-se baixo em relação ao site referência. Em S2 e S3 foi observado proporção alta de ovócitos deficientes em vitelo e em S3 houve aumento de ovócitos supermaturados. A proporção de atresia folicular foi baixa e não apresentou diferenças significativas entre as populações de fêmeas amostradas. A condição de intersexo foi encontrada apenas nos sites expostos a esgoto doméstico. Análises morfométricas da gametogênese demonstraram maior proporção de ovócitos vitelogênicos e espermatozoides em S1 do que os peixes capturados nos sites S2 e S3. Os resultados da imunohistoquímica demonstraram marcação de CYP19 em células de Leydig e granulócitos acidófilos, espermatogônia, células de Sertoli, espermátides e espermatozóides. ERá apresentou distribuição mais ampla do que ERâ sendo encontrado em todas as fases de desenvolvimento de células germinativas. Por outro lado, ERâ foi encontrado apenas em espermatogônia e espermatócitos. Ambos ERs foram expressos nas células Leydig e Sertoli. Durante a maturação testicular, os níveis de ELISA para CYP19, ERá e ERâ seguiram o índice gonadossomático (GSI) com valores significativamente maiores no estágio maduro. Os efeitos reprodutivos observados estão relacionados com o aumento da urbanização e liberação de esgoto doméstico diretamente nos corpos dágua sem nenhum tratamento e mesmo que as populações de A. rivularis estejam habitando ambientes lóticos e com alta renovação de água a liberação de contaminantes por esgoto doméstico é constante, promovendo assim uma exposição crônica de peixes a esses desreguladores endócrinos. The Velhas River, an important tributary of the São Francisco river basin, is considered the most polluted river in the state of Minas Gerais, due to the high amount of water contamination from domestic and industrial sewage. The main objectives of this study were to evaluate the effects of environmental estrogens on the reproduction of the species Astyanax rivularis, a small species found in streams with high altitudes in the upper Rio de Velhas and to evaluate the immunostaining of CYP19, ERá and ERâ in the testis along the gonadal development and among sites with different estrogenic contamination. Four field samples were collected in three streams: S1 (low anthropogenic interference) S2 and S3 (contaminated by domestic sewage without treatment). The hepatica expression of a number of molecular (Zrp, Vtg, IGF-I, CYP19, ERá and ERâ) and histological biomarkers (oocytes histopathology and intersex), reproductive endpoints (gonadossomatic, hepatossomatic, Fulton, fecundity and proportion of gametogenic lineage cells) and deviations in the sexual proportion were assessed in the different collection sites. The physicochemical parameters were evaluated by Horiba probe and estrogenic compounds by liquid chromatography coupled to mass spectrometry (LC-MS). Sites exposed to domestic sewage presented high levels of estradiol, estriol, estrone, bisphenol A and nonylphenol when compared to S1. The physical-chemical parameters (temperature and dissolved oxygen) had no differences between the collection sites. The results indicate endocrine disruption in sites exposed to domestic sewage (S2 and S3), such as increase in the proportion of females, increase of Vtg, Zrp, CYP19, ERá and ERâ levels in males and decrease of Vtg in females. Male IGF-I in S2 was low in relation to the reference site. In S2 and S3, a high proportion of yolk deficient oocytes was observed, and in S3 there was an increase in over-ripening oocytes. The proportion of follicular atresia was low and did not present significant differences among the populations of females sampled. The intersex condition was found only in sites exposed to domestic sewage. Morphometric analyzes of gametogenesis demonstrated a higher proportion of vitellogenic oocytes and spermatozoa in S1 than fish captured at sites S2 and S3. The results of immunohistochemistry demonstrated CYP19 labeling in Leydig cells and acidophilic granulocytes, spermatogonia, Sertoli cells, spermatids and spermatozoa. ERá showed a broader distribution than ERâ being found in all stages of germ cell development. On the other hand, ERâ was found only in spermatogonia and spermatocytes. Both ERs were expressed in Leydig and Sertoli cells. During testicular maturation, ELISA levels for CYP19, ERá and ERâ followed the gonadosomatic index (GSI) with significantly higher values at the mature stage. The observed reproductive effects are related to the increase of urbanization and release of domestic sewage directly into water bodies without any treatment and even if the populations of A. rivularis are inhabiting lotic environments and with high water renewal the release of pollutants through sewage is constant, thus promoting chronic exposure of fish to these endocrine disrupters.

Over the last few years, treatment of severe symptomatic aortic stenosis in high-risk patients has drastically changed to adopt a less-invasive approach. Transcatheter aortic valve implantation (TAVI) has been developed as a very reproducible and safe procedure, as shown in many trials. When compared to surgery, TAVI has produced superior, or at least comparable, results, and thus a trend to broaden treatment indications to lower-risk patients has erupted as a natural consequence, even though there is a lack of long-term evidence. In this review, we summarize and underline aspects that still remain unanswered that are compulsory if we want to enhance our understanding of this disease.

OBJECTIVES: Many surgical and interventional methods are available to restore patency for patients with degenerative severe mitral valve regurgitation. Leaflet resection and neochordoplasty, which both include ring annuloplasty, are the most frequently performed techniques for the repair of posterior mitral leaflet flail. It is unclear which technique results in the best haemodynamics. In this study, we investigated the effect of different mitral valve reconstruction techniques on mitral valve haemodynamics and diastolic transvalvular pressure gradient in an ex vivo porcine model. METHODS: Eight porcine mitral valves were tested under pulsatile flow conditions in an in vitro pulsatile flow loop for haemodynamic quantification. Severe acute posterior mitral leaflet flail was created by resecting the posterior marginal chorda. The acute mitral valve regurgitation was corrected using 4 different repair techniques, in each valve, in a strictly successive order: (i) neochordoplasty with polytetrafluoroethylene sutures alone and (ii) with ring annuloplasty, (iii) edge-to-edge repair and (iv) triangular leaflet resection, both with ring annuloplasty. Valve haemodynamics were measured and quantified for all valve configurations (native, rupture and each surgical reconstruction). The results were analysed using a validated statistical linear mixed model, and the P-values were calculated using a 2-sided Wald test. RESULTS: All surgical reconstruction techniques were able to sufficiently correct the acute mitral valve regurgitation. Neochordoplasty without ring annuloplasty was the only reconstruction technique that resulted in haemodynamic properties similar to the native mitral valve (P-values from 0.071 to 0.901). The diastolic transvalvular gradient remained within the physiological range for all reconstructions but was significantly higher than in the native valve for neochordoplasty with ring annuloplasty (P

Background Minimally invasive aortic valve surgery (MIAV) through a right anterior minithoracotomy evolved to an accepted procedure with favorable short- and mid-term outcomes, whereas long-term results lack. The aim of this study was to evaluate the long-term outcomes. Materials and Methods All our MIAV patients were included (n = 225). Mean age was 68 ± 12 years, 29% were older than 75 years, and median EuroSCORE was 5 (0–11). Baseline characteristics, inhospital outcomes, and follow-up information about survival, major adverse cardiac and cerebrovascular events (MACCE), and need for reoperation were collected and analyzed. Results In this study, 30-day mortality was 1.3%, and there was no permanent stroke. Mean follow-up time was 69.65 ± 24 months, being the longest so far reported in the literature. At 1 and 7 years, survival was 95.8 and 79%, freedom from MACCE 98.1 and 95.7%, and from reoperation 99.5 and 98.7%, respectively. Conclusion MIAV is safe and feasible with favorable long-term outcomes. In the future, it could serve as benchmark for interventional methods as soon as indications are expanded to young and low-risk patients. Randomized studies are needed to compare the long-term outcomes of these approaches.

Food restriction is part of the life cycle of many fish species; however, nutritional deficiency may negatively influence gametogenesis and gonadal maturation. The aim of this study was to evaluate the effects of food restriction on the spermatogenesis of Nile tilapia. For this, adult males were submitted to starvation and refeeding cycles (alternating periods of starvation and feeding) for 7, 14, 21, and 28 days. After 7 days of starvation, glycaemic and lipid levels were significantly reduced, followed by reduction of plasma testosterone (T) and 11-ketotestosterone (11-KT). In addition, reduced proliferation of spermatogonia and increased apoptosis of spermatocytes, spermatids, and spermatozoa was observed in starvation groups. In the refeeding groups, the sex steroids and the proportion of germ cells had no significant alterations compared to the control group, except for spermatozoa. In this sense, the present study suggests that starvation after 7 days progressively reduces T and 11-TK, resulting in damage to the production of spermatogenic cells, while refeeding may delay spermatogenesis but does not lead to testicular impairment.

To support sperm production, fish testes undergo intense tissue remodelling, with endocrine, paracrine and autocrine signals regulating gonad physiology. The aim of this study was to investigate the testicular expression of insulin-like growth factor (Igf) 1 and Igf2 during spermatogenesis, and their relationship with cell proliferation and apoptosis throughout the reproductive cycle. The study was performed in male Hypostomus garmani, a catfish living in headwater rivers of the São Francisco River basin, Brazil. Spermatogenesis was analysed using histology, morphometry, immunohistochemistry and terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL) analysis at different maturity stages. The results showed the proliferation of spermatogonia throughout the reproductive cycle, with a higher rate during the ripe stage. Germ and Sertoli cells expressed Igf1 at all stages of testicular maturity, Igf2 was predominant at the ripe stage and both Igf1 and Igf2 occurred at the spent stage. Caspase-3 and TUNEL analysis revealed a higher rate of apoptosis at the spent stage associated with reduced expression of Igf1 and Igf2. Sertoli cell proliferation was associated with spermatogonia and spermatocyte cysts at different stages of the reproductive cycle. Together, the data support a proliferative role for Igf1 and Igf2 in regulating testicular apoptosis in H. garmani, with cyclical variation in their expression during gonad maturation.