Complement activation induces excessive T cell cytotoxicity in severe COVID-19.

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. Proportions of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19.

Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats?

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.

Driveline infections in left ventricular assist devices-Incidence, epidemiology, and staging proposal.

BACKGROUND: Driveline infections (DLI) are a serious complication in patients with left ventricular assist devices (LVAD). Apart from the differentiation between superficial and deep DLI, there is no consensus on the classification of the severity of DLI. Little is known about risk factors and typical bacteria causing DLI in centrifugal-flow LVADs. METHODS: In this single-center study with 245 patients, DLI were classified by their local appearance using a modification of a score suggested by the Sharp Memorial group. The driveline exit site was inspected routinely every 6 months. RESULTS: Severe DLI were detected in 34 patients (15%) after 6 months and in 24 patients (22%) after 24 months. The proportion of patients with DLI increased significantly during the follow-up (p = 0.0096). The most common bacteria in local smears were Corynebacterium, coagulase-negative Staphylococcus, and Staphylococcus aureus. Fifty-nine patients were hospitalized more than once for DLI. In these patients, S. aureus was the most common bacterium. It was also the most common bacterium in blood cultures. Higher BMI, no partnership, and a HeartMate 3 device were identified as risk factors for DLI in a multivariable cause-specific Cox regression. CONCLUSION: This study is a standardized analysis of DLI in a large cohort with centrifugal-flow LVADs.

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Acute Kidney Injury After Heart Transplantation: Risk Factors and Clinical Outcomes.

OBJECTIVE: Acute kidney injury (AKI) requiring renal-replacement therapy (RRT) after heart transplantation (OHT) is common and impairs outcomes. This study aimed to identify independent donor and recipient risk factors associated with RRT after OHT. DESIGN: A retrospective data analysis. SETTING: Data were collected from clinical routines in a maximum-care university hospital. PARTICIPANTS: Patients who underwent OHT. INTERVENTIONS: The authors retrospectively analyzed data from 264 patients who underwent OHT between 2012 and 2021; 189 patients were eligible and included in the final analysis. MEASUREMENTS AND MAIN RESULTS: The mean age was 48.0 ± 12.3 years, and 71.4% of patients were male. Ninety (47.6%) patients were on long-term mechanical circulatory support (lt-MCS). Posttransplant AKI with RRT occurred in 123 (65.1%) patients. In a multivariate analysis, preoperative body mass index >25 kg/m² (odds ratio [OR] 4.74, p < 0.001), elevated preoperative creatinine levels (OR for each mg/dL increase 3.44, p = 0.004), administration of red blood cell units during transplantation procedure (OR 2.31, p = 0.041) and ischemia time (OR for each hour increase 1.77, p = 0.004) were associated with a higher incidence of RRT. The use of renin-angiotensin-aldosterone system blockers before transplantation was associated with a reduced risk of RRT (OR 0.36, p = 0.013). The risk of mortality was 6.9-fold higher in patients who required RRT (hazard ratio 6.9, 95% CI: 2.1-22.6 p = 0.001). Previous lt-MCS, as well as donor parameters, were not associated with RRT after OHT. CONCLUSIONS: The implementation of guideline-directed medical therapy, weight reduction, minimizing ischemia time (ie, organ perfusion systems, workflow optimization), and comprehensive patient blood management potentially influences renal function and outcomes after OHT.

A mixture of glyphosate and 2,4-D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice.

The consumption of Western diet (WD) - enriched in fats and sugars - is associated with overweight, obesity and male reproductive disorders. In addition to WD intake, crops and dairy products display residues of herbicides, including glyphosate and 2,4-D that are widely applied worldwide. The concomitant exposure to WD and herbicides - mimicking contemporary scenarios - is not fully investigated. Thus, we evaluated the effects of glyphosate and 2,4-D, alone or in mixture, on WD-induced alterations in the male genital system. Male C57BL6J mice were submitted to WD (chow containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 months. Concomitantly to WD, the animals received glyphosate (0.05, 5, or 50 mg/kg/day), 2,4-D (0.02, 2 or 20 mg/kg/day) or their mixture (0, 05 + 0.02, 5 + 2, or 50 + 20 mg/kg/day) by intragastrical administration (5×/week). Doses were based on Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) values. Herbicide exposure did not alter the WD-induced obesity, hypercholesterolemia and hyperglycemia. WD induced sperm cell abnormalities, reduced the number, volume and area of Leydig cells, enhanced the frequency of epididymal abnormalities, decreased the proliferation in both germinal and epididymal epithelia, and reduced the number of androgen receptor (AR) positive epididymal cells. Remarkably, the herbicide mixtures promoted such WD-induced effects: increased the frequency of sperm cell and epididymal abnormalities (absence of sperm, cytoplasmic vacuoles, and clear cell hypertrophy) (5 + 2 and 50 + 20 doses); decreased Leydig cell nuclei volume and area (5 + 2 and 50 + 20 doses), reduced epididymal cell proliferation (all mixtures), and AR expression (50 + 20 dose). In addition, herbicide mixtures reduced serum testosterone levels (5 + 2 and 50 + 20 doses). Our findings indicate that the mixture of glyphosate and 2,4-D herbicides, mimicking environmentally relevant scenarios, promotes WD-induced changes in the male genital system.

Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats.

Ondansetron is a 5HT3 receptor antagonist widely used to treat hyperemesis gravidarum, although its safety is still questionable. Since 5HT3 receptors, which are the target of this drug, can interfere with brain development through changes in neurotransmitter levels, this study evaluated whether the prenatal exposure to this drug could compromise reproductive and behavioral parameters in male offspring. Pregnant rats were treated with ondansetron (1.7 and 2.5 mg/kg/body weight; gavage), from gestational day 1-21. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Ondansetron exposure did not alter the anogenital distance or age of preputial separation in male offspring. Similarly, males exposed to therapeutic doses of ondansetron did not exhibit changes in play behavior. In adulthood, there were no changes in sperm parameters, as well as in testosterone level, sexual behavior and fertility. Furthermore, ondansetron did not interfere with testicular and epididymal histology, and with androgen receptor expression in hypothalamus. In conclusion, prenatal exposure to ondansetron did not cause maternal toxicity, as well as did not interfere with reproductive parameters of male offspring, indicating its safety after gestational exposure in rats.

Long-term reproductive effects of benzo(a)pyrene at environmentally relevant dose on juvenile female rats.

Since studies on the reproductive consequences after the exposure to environmentally relevant doses of Benzo(a)pyrene (BaP) during critical stages of development are scarce, this study evaluated female reproductive parameters of adult rats exposed to a low dose of BaP during the juvenile phase. Female rats (Post-natal 21) were treated with BaP (0 or 0.1 µg/kg/day; gavage) for 21 consecutive days. During the treatment, no clinical signs of toxicity were observed. Nevertheless, the ages of vaginal opening and first estrus were anticipated by the BaP-exposure. At the sexual maturity, the juvenile exposure compromised the sexual behavior, as well as the placental efficiency, follicle stimulating hormone levels, placenta histological analysis, and ovarian follicle count. A decrease in erythrocyte, platelet, and lymphocyte counts also was observed in the exposed-females. Moreover, the dose of BaP used in this study was not able to produce estrogenic activity in vivo. These data showed that juvenile BaP-exposure, at environmentally relevant dose, compromised the female reproductive system, possibly by an endocrine deregulation; however, this requires further investigation.

Impact of left ventricular inspection employing cardiopulmonary bypass on outcome after implantation of left ventricular assist device.

BACKGROUND: Cardiopulmonary bypass (CPB) during left ventricular assist device (LVAD) implantation provides circulatory support and allows for safe inspection of the left ventricle (LV), whereas circulatory support by veno-arterial extracorporeal life support (va-ECLS) or off-pump implantation may reduce postoperative bleeding and inflammatory response. METHODS: Retrospective analysis of 616 consecutive adult patients who received an LVAD via median sternotomy between January 1, 2015 and December 31, 2019. All patients undergoing concomitant intracardiac procedures other than closure of persistent foramen ovale or atrial septal defect and redo surgeries were excluded from the analysis. The remaining patients (n = 222) were divided into two groups and 1:1 propensity score-matched regarding preoperative parameters: patients who underwent LVAD implantation with LV inspection employing CPB (CPB group, n = 62) and without LV inspection on va-ECLS or off-pump (non-CPB group, n = 62). RESULTS: The groups were well balanced with regard to preoperative baseline characteristics (standard difference <0.1). Patients in the CPB group required more blood transfusions (median 2 vs. 0 units, p = 0.031) during surgery and in the first 24 h afterwards. The median intensive care unit stay was longer in the CPB group (18 vs. 11 days, p = 0.021). The CPB group showed an absence of perioperative stroke and a smaller number of events per patient-year for postoperative ischemic stroke (0.02 vs. 0.12, p = 0.003). 30-day survival (87% vs. 87.1%) and 1-year survival (80.3% vs. 74%) were similar in both groups (p = 0.78). CONCLUSION: Visual LV inspection on CPB may reduce the risk of postoperative ischemic stroke. Despite the negative effects of employing CPB in lieu of other intraoperative strategies, survival was similar in both groups.

Evaluation of the safety of ethanolic extract from Piper amalago L. (Piperaceae) leaves in vivo: Subacute toxicity and genotoxicity studies.

Piper amalago L. (Piperaceae) is traditionally used due to its anti-inflammatory, analgesic, diuretic, and antiparasitic properties. However, few studies have focused on its adverse effects, compromising its safe use. This study evaluated the toxicological safety of ethanolic extract from Piper amalago leaves (EEPA), through subacute toxicity and genotoxicity assays in rodents. In subacute toxicity, 100, 200 or 300 mg/kg of EEPA were tested in female Wistar rats, by gavage, for 28 days. For genotoxicity test, female Swiss mice were orally treated with 17.5, 175 or 1750 mg/kg of EEPA and the comet, micronucleus, and splenic phagocytic assays were evaluated. In subacute toxicity, the extract induced an increase in the food and water intakes, as well as in the liver absolute weight, and in the heart and kidney relative weights. EEPA also provoked alterations in histopathological analysis of liver and in hemato-biochemical parameters, evidenced by a decrease in hematocrit levels and albumin levels, and an increase in the number of platelets and in alkaline phosphatase and cholesterol levels. However, EEPA did not presented genotoxic nor mutagenic properties. EEPA showed hemato-biochemical toxicity profile in rats and should be used with caution, especially when for prolonged period.

Cardiac Surgery-Related Acute Kidney Injury _ Risk Factors, Clinical Course, Management Suggestions.

OBJECTIVE: Acute kidney injury (AKI) is a common complication after cardiac surgery (CS). Because a therapeutic regimen remains scarce, the early implementation of preventive strategies is crucial. The authors investigated risk factors and the typical clinical course of CS-associated AKI (CS-AKI) to derive strategies for perioperative clinical routines. DESIGN: Retrospective data analysis. SETTING: The data were collected from clinical routines in a maximum care university hospital. PARTICIPANTS: Patients. INTERVENTIONS: The authors retrospectively analyzed data from 538 patients who underwent CS. MEASUREMENTS AND MAIN RESULTS: The median age of the 466 patients included was 66.6 years; 65.7% were men. AKI occurred in 131 (28.1%) patients, mainly (89.0%) starting postoperatively within 72 hours p. Thirty-one (6.7%) patients showed Kidney Disease Improving Global Outcome AKI stage 3. AKI was significantly more frequent in patients with chronic kidney disease (p < 0.001), emergency admission (p < 0.001), heart failure (p < 0.001), and postoperative complications (p < 0.001). In a multivariate analysis, postoperative CS-AKI risk significantly decreased with each 1 or 10 mL/min preoperative glomerular filtration rate (GFR) (odds ratio, 0.962 and 0.677; 95% confidence interval, 0.947-0.977 and 0.577-0.793; p < 0.001 and p < 0.0001). Only in patients who developed Kidney Disease Improving Global Outcome AKI stage 3, an early postoperative trend to decreased GFR and increased creatinine levels was observed. CONCLUSIONS: Especially in patients with preexisting CKD and signs of CS-AKI occurring on the day of surgery, close monitoring of renal function should be performed for at least 72 hours after CS to detect an onset of AKI early and initiate renal protective strategies. Optimal preoperative fluid management might prevent postoperative AKI.

Intraoperative imaging and navigated spinopelvic instrumentation: S2-alar-iliac screws combined with tricortical S1 pedicle screw fixation.

PURPOSE: The present study aimed to assess the feasibility, safety and accuracy of navigated spinopelvic fixation with focus on S2-alar-iliac screws (S2AIS) and tricortical S1 pedicle screw implantation with the use of high-resolution three-dimensional intraoperative imaging and real-time spinal navigation. METHODS: Patients undergoing navigated intraoperative CT-based spinopelvic stabilization between January 2016 and September 2019 were included. Pelvic fixation was achieved by implantation of S2AIS or iliac screws (IS). S1 screws were implanted with the goal of achieving tricortical purchase. In all cases, instrumentation was performed with real-time spinal navigation and intraoperative screw positioning was assessed using intraoperative computed tomography (iCT), cone-beam CT (CBCT) and robotic cone-beam CT (rCBCT). Screw accuracy was evaluated based on radiographic criteria. To identify predictors of complications, univariate analysis was performed. RESULTS: Overall, 52 patients (85%) received S2AIS and nine patients (15%) received IS instrumentation. Intraoperative imaging and spinal navigation were performed with iCT in 34 patients, CBCT in 21 patients and rCBCT in six patients. A total number of 10/128 (7.8%) iliac screws underwent successful intraoperative correction due to misalignment. Tricortical purchase was successfully accomplished in 58/110 (53%) of the S1 screws with a clear learning curve in the course of time. S2AIS implantation was associated with significantly fewer surgical side infection-associated surgeries. CONCLUSIONS: Real-time navigation facilitated spinopelvic instrumentation with increasing accuracy of S2AIS and tricortical S1 screws. Intraoperative imaging by iCT, CBCT or rCBCT permitted screw assessment with the chance of direct navigated revision of misplaced iliac screws to avoid secondary screw revision surgery.

Safety of Contemporary Heart Failure Therapy in Patients with Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Limited data are available concerning the safety, optimal administration and benefits of contemporary heart failure therapy in patients after left ventricular assist device (LVAD) implantation. METHODS: Between 2015 and 2019, 257 patients underwent LVAD implantation and were included in this observational study. Oral heart failure therapy was initiated and uptitrated during the further course. After propensity matching and excluding patients with immediate postoperative treatment in an affiliated center with different medical standards, hospitalization rates and mortality within 12 months after LVAD implantation were compared between 83 patients who received medical therapy including an angiotensin receptor neprilysin inhibitor (ARNI) and 83 patients who did not receive an ARNI. RESULTS: The overall use of heart-failure medications after 12 months was high: prescriptions: beta-blockers, 85%; angiotensin inhibiting drugs, 90% (angiotensin-converting-enzyme inhibitors 30%, angiotensin receptor blockers 23%, ARNI 37%); mineralocorticoid receptor antagonists, 80%. No serious drug-related adverse events occurred. The conditional 1-year survival in the group with ARNIs was 97% (95% CI: 94%-100%) compared to 88% in the group without an ARNI (95% CI: 80%-96%); P = 0.06. CONCLUSIONS: Contemporary heart failure therapy is safe in patients with LVADs. No increase in serious adverse events was seen in patients receiving ARNIs. No significant difference in the conditional 1-year survival was seen between the ARNI group and the nonARNI group.

Validity of the 6-Minute Walk Test in Patients with End-Stage Lung Diseases Wearing an Oronasal Surgical Mask in Times of the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVES: The 6-minute walk test (6MWT), as a clinical assessment tool for functional exercise capacity, is an integral component of lung allocation scores (LASs). In times of the coronavirus disease (COVID-19) pandemic, patients underwent 6MWTs wearing a surgical mask in ambulatory care. We investigated the impact of wearing a mask on 6-minute walk distances (6MWDs). METHOD: 6MWDs of 64 patients with end-stage lung diseases wearing an oronasal surgical mask were retrospectively compared to previously investigated 6MWDs of the same cohort, in a pre-COVID-19 pandemic era, without wearing a mask. Four patients were excluded due to a primary vascular disease, 29 patients due to clinically unstable pulmonary functions, and 1 patient due to a psychiatric disorder. RESULTS: The median age of the patients included was 55 (46-58) years; 15 (48%) were male. Ten (32.2%) were on the Eurotransplant lung transplant waiting list with a median LAS of 34.3 (31.9-36.2). Twenty (64.5%) patients had chronic obstructive pulmonary diseases, 7 (22.6%) had interstitial lung diseases, and 4 (12.9%) had other end-stage lung diseases. The mean 6MWD without versus with wearing a mask was 306.9 (101.9) versus 305.7 (103.8) m, with a mean difference of -1.19 m (95% confidence interval -13.4 to 11.03). The observed difference is statistically equivalent to zero (p < 0.001). No significant differences in 6MWDs were observed between the clinical groups. CONCLUSION: Wearing an oronasal surgical mask did not affect the 6MWDs of patients with advanced lung diseases. Therefore, a masked 6MWT appears to provide a reliable examination of functional exercise capacity in this cohort.

Propensity score-based analysis of 30-day survival in cardiogenic shock patients supported with different microaxial left ventricular assist devices.

BACKGROUND AND METHODS: Microaxial left ventricular assist devices are used increasingly for treating cardiogenic shock. We compared the short-term outcome of patients supported with different microaxial devices for cardiogenic shock. A retrospective propensity score-adjusted analysis was performed in cardiogenic shock patients treated with either the Impella CP (n = 64) or the Impella 5.0/5.5 (n = 62) at two tertiary cardiac care centers between 1/14 and 12/19. RESULTS: Patients in the Impella CP group were significantly older (69.6 ± 10.7 vs. 58.7 ± 11.9 years, p = .001), more likely in INTERMACS profile 1 (76.6% vs. 50%, p = .003) and post-C-reactive protein (CPR) (36% vs. 13%, p = .006). The median support time was 2.0 days [0.0, 5.3] in the CP group vs. 8.5 days [4.3, 15.8] in the 5.0/5.5 group (p < .001). The unadjusted 30-day survival was significantly higher in the Impella 5.0/5.5 group (58% vs. 36%, p = .021, odds ratio [OR] for 30-day survival on Impella 5.0/5.5 was 3.68 [95% confidence interval [CI]: [1.46-9.90]], p = .0072). After adjustment, the 30-day survival was similar for both devices (OR: 1.23, 95% CI: [0.34-4.18], p = .744). Lactate levels above 8 mmol/L and preoperative CPR were associated with a significant mortality increase in both cohorts (OR: 10.7, 95% CI: [3.45-47.34], p < .001; OR: 13.2, 95% CI: [4.28-57.89], p < .001, respectively). CONCLUSION: Both Impella devices offer a similar effect with regard to survival in cardiogenic shock patients. Preoperative CPR or lactate levels exceeding 8 mmol/L immediately before implantation have a poor prognosis on Impella CP and Impella 5.0/5.5.

Impact of a surgical approach for implantation of durable left ventricular assist devices in patients on extracorporeal life support.

BACKGROUND: The aim of this study was to evaluate the impact of the surgical approach on the postoperative outcome in patients who underwent left ventricular assist device (LVAD) implantation after having received veno-arterial extracorporeal life support (va-ECLS) using data from a European registry (ECLS-VAD). Five hundred and thirty-one patients were included. METHODS: A propensity score-adjusted outcome analysis was performed, resulting in 324 patients in the full sternotomy (FS) group and 39 in the less invasive surgery (LIS) group. RESULTS: The surgery lasted in median 236 min in the FS group versus 263 min in the LIS group (p = 0.289). The median chest tube output during the first 24 h was similar in both groups. Patients who underwent implantation with an FS required more blood products during the first 24 postoperative hours (median 16 vs. 12, p = 0.033). The incidence of revision due to bleeding was also higher (35.5 vs. 15.4%, p = 0.016). A temporary postoperative right ventricular assist device was necessary in 45.1 (FS) versus 23.1% (LIS) of patients, respectively (p = 0.067). No stroke occurred in the LIS group during the first 30 days after surgery (7.4% in the FS group). The incidence of stroke and of renal, hepatic, and respiratory failure during the follow-up was similar in both groups. The 30-day and one-year survival were similar in both groups. CONCLUSION: LIS for implantation of a durable LVAD in patients on va-ECLS implanted for cardiogenic shock is associated with less revision due to bleeding, less administration of blood products and absence of perioperative stroke, with no impact on survival.

Pre-pubertal exposure to ibuprofen impairs sperm parameters in male adult rats and compromises the next generation.

Ibuprofen is one of the most commonly prescribed anti-inflammatory drugs in pediatric practice. This drug inhibits the cyclooxygenase enzyme, reducing the production of prostaglandin, an important mediator on male reproductive function. We examined if pre-pubertal treatment with ibuprofen in male rats can affect the reproductive parameters of these animals in adult life and on their descendants. Male rats (23 days old) received ibuprofen (0; 2.4; 7.2 or 14.3 mg/kg/day), per gavage, from postnatal day (PND) 23 to 53. At sexual maturity, treated males were placed with untreated females for obtaining the next generation (F1). The highest dose of ibuprofen interfered in sexual behavior and reduced the fertility potential of these animals in adulthood. Additionally, the ibuprofen treatment altered the sperm quantity and quality, as evidenced by a decrease in sperm motility and in the daily sperm production in the testis. Testosterone levels were also reduced by pre-pubertal treatment. The paternal treatment with this drug also influenced the reproductive outcomes of progeny. The male offspring from males treated exhibited acceleration in sperm transit time in the epididymis and the number and volume of Leydig cell nuclei were decreased, while the estrous cyclicity was displayed and the fertility potential reduced in the female offspring. The pre-pubertal ibuprofen-treatment caused negative reproductive impacts in adulthood, compromising sperm quality and quantity, as well as interfered in the reproductive outcomes of the next generation.

Global work index correlates with established prognostic parameters of heart failure.

AIM: Identification of patients with heart failure and a poor prognosis is paramount to ensure timely and adequate treatment. We investigated the relationship between the new measures of noninvasive pressure-strain analysis, such as the global work index (GWI), and established prognostic parameters of echocardiography, cardiopulmonary exercise test (CPX), and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP). METHODS AND RESULTS: We retrospectively analyzed data of 51 patients with heart failure. Echocardiography and CPX were performed, and NT-pro-BNP was determined. Patients with a GWI < 500 mm Hg% had a mean LVEDV of 286.1 ± 100.8 mL, an LVEF of 21.3 ± 5.7%, and a stroke volume (SV) of 45.9 ± 11.6 mL, and patients with a GWI > 1000 mm Hg% had an LVEDV of 147.9 ± 39.6 mL, an LVEF of 42.6 ± 4.8%, and a SV of 70.9 ± 14.3 mL. The GWI also showed a significant correlation with peak oxygen consumption (peak VO2 ) (r = .521; P < .001) and with NT-pro-BNP (r = .635; P < .001). Patients with a GWI of <500 mm Hg% had a significantly higher NT-pro-BNP (median 2415 pg/mL [IQR 1071, 5933]) and a lower peak VO2 (9.5 mL/min/kg ± 2.6) compared to patients with a GWI of >1000 mm Hg% (NT-pro-BNP median 253 pg/mL [IQR 150, 549]; peak VO2 15.6 ± 4.2 mL/min/kg). CONCLUSION: GWI correlates with known prognostic markers of heart failure. A GWI of <500 mm Hg% was a predictor of severely impaired ejection fraction, very low exercise capacity, and strongly elevated NT-pro-BNP, indicating a poor prognosis.

Template Removal via Boudouard Equilibrium Allows for Synthesis of Mesostructured Molybdenum Compounds.

Oxidative thermal removal of the polymeric templates is not trivial for molybdenum oxides and hampers mesostructuring of this material. At ambient oxygen fugacity, MoVI is the thermodynamically stable oxidation state and sublimation of MoO3 leads to a quick loss of the mesostructure through Oswald ripening. Taking advantage of the Boudouard equilibrium allows to fix the oxygen fugacity at a level where non-volatile MoO2-x is stable while carbonaceous material may be oxidized by CO2 . Mesostructured MoO2-x can be chemically converted into MoO3 or MoN under retention of the mesostructure.