Glucose instability and outcomes of neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia.

BACKGROUND: To investigate the prevalence and associated outcomes of glucose abnormalities in infants with hypoxic ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). METHODS: Glucose values were reviewed in all HIE infants. Pearson's correlation was used to assess the association of hypo- and hyperglycemic episodes with neonatal brain MRI and neurodevelopmental outcomes (NDO) at 12 & 24 months. RESULTS: Of 153 infants included, 31, 56 and 43 had episodes of hypo-, hyperglycemia and combined, respectively. Hyperglycemia and combined hypo/hyper had higher mortality (p = 0.035), seizures (p = 0.009), and longer hospitalization (p = 0.023). Hypo- and hyperglycemia were associated with parenchymal hemorrhages (p = 0.028 & p = 0.027, respectively). Hypoglycemia was associated with restricted diffusion (p = 0.014), while hyperglycemia was associated with cortical injuries (p = 0.045). Each hour of hyper- or hypoglycemia was associated with 5.2-5.8 times unfavorable outcomes (p < 0.001). CONCLUSION: Blood glucose aberrations were detrimental in HIE infants treated with TH. Optimizing glucose management is crucial in this setting.

Comparative studies of four cumin landraces grown in Egypt.

One of the significant aromatic plants applied in food and pharma is cumin. Despite its massive trading in Egypt, there are no comprehensive reports on cumin landraces profile screening. This study aimed to investigate the variation in seeds' physical and biochemical profiles and genetic diversity as well as assess the efficiency of seeds' germination under salinity stress. Consequently, during the 2020/2021 growing season, four common cumin seed landraces were gathered from various agro-climatic regions: El Gharbia, El Menia, Assiut, and Qena. Results showed a significant variation in physical profile among the four seeds of landraces. In addition, Assiut had the highest percentage of essential oil at 8.04%, whilst Qena had the largest amount of cumin aldehyde, the primary essential oil component, at 25.19%. Lauric acid was found to be the predominant fatty acid (54.78 to 62.73%). According to ISSR amplification, El Menia presented a negative unique band, whereas other landraces offered a positive band. Additionally, the cumin genotypes were separated into two clusters by the dendrogram, with El Gharbia being located in an entirely separate cluster. There were two sub-clusters within the other cluster: El Menia in one and Assiut and Qena in the other. Moreover, the germination sensitivity to the diverse salinity concentrations (control, 4, 8, 12, and 16 dS/m) findings showed that landraces exhibited varying responses to increased salinity when El Gharbia and El Menia showed a moderate response at four dS/m. Whilst, Qena landraces showed supreme values among other landraces under 12 and 16 dS/m. The majority of the examined features had strong positive associations over a range of salinity levels, according to phenotypic correlation coefficient analysis. To accomplish the aims of sustainable agriculture in Egypt, it would be imperative that the potential breeding program for cumin landraces consider this screening study.

Pre-Medications for Non-Emergency Tracheal Intubation in the United States Neonatal Intensive Care Units.

BACKGROUND: Premedication in neonates undergoing elective intubation effectively minimizes the negative physiological events of bradycardia, systemic hypertension, intracranial hypertension, and hypoxia. Premedication decreases procedure-related pain and discomfort. This study aimed to evaluate the current practice of pre-intubation medications for non-emergent intubations in preterm and term neonates in the United States. STUDY DESIGN: A cross-sectional survey (Appendix) was sent via e-mail to all level 3 and 4 Neonatal Intensive Care Units (NICUs) of the Organization of Neonatal Perinatal Medicine Training Program Directors (ONTPD), NICU directors with pediatric residency only, and Baylor Scott and White Health, Mednax, and Envision health services systems. RESULTS: Of 170 responses, 41% (69/168) routinely premedicate, 38% (64/168) premedicate under specific circumstances, and 21% (35/168) do not administer any routine pre-intubation medications. Only 46% (77/168) of units had a written policy. The most frequently used drugs were fentanyl (68%, 116/170), atropine (39%, 66/170), midazolam (38%, 64/170), and morphine (26%, 45/170). 21% (36/170) used a two-drug combination, and 38% (64/170) used a three-drug combination. The most commonly used two-drug combination was atropine and fentanyl, and the most common three-drug combination was atropine, fentanyl, and a paralytic agent. CONCLUSION:  Despite the well-documented benefits of premedication for NICU intubations, as aligned with AAP recommendations, the US lags behind other nations, with stagnant rates since 2006. This disparity persists despite a rise in written policies, which exhibit significant content variations. The authors advocate for the adoption of standardized, AAP-aligned policies across all NICUs in the US. Continued research is vital to monitor the progress of this crucial practice and address any underlying barriers to implementation.

Characteristics of fecal calprotectin as an early marker for suspected necrotizing enterocolitis in newborns exclusively fed maternal breast milk: a case-control study.

Objective: Numerous studies have proposed using fecal calprotectin among many biomarkers associated with necrotizing enterocolitis (NEC) diagnosis. This study aimed to evaluate fecal calprotectin as an early marker for suspected NEC (stage 1) in infants fed exclusively breast milk. Methods: We collected 20 stool samples from newborns admitted to the neonatal intensive care unit at Aswan University Hospital diagnosed with stage I NEC. We compared them with 20 samples from matched healthy newborns. Fecal calprotectin level was measured by enzyme-linked immunosorbent assay. Results: Fecal calprotectin level was higher in cases than in the control group (P < 0.001). Also, there was a positive correlation between fecal calprotectin and C-reactive protein in the studied cases (P = 0.001). However, there were no correlations between fecal calprotectin and sex or postnatal age. Conclusion: Fecal calprotectin levels increase in newborns with stage I NEC. Although not specific, its sensitivity suggests a role as a potential biomarker in the evaluation of suspected NEC.

Effects of long-term dehydration on stress markers, blood parameters, and tissue morphology in the dromedary camel (Camelus dromedarius).

Introduction: Dromedary camels robustly withstand dehydration, and the rough desert environment but the adaptation mechanisms are not well understood. One of these mechanisms is that the dromedary camel increases its body temperature to reduce the process of evaporative cooling during the hot weather. Stress in general, has deleterious effects in the body. In this study, we sought to determine the effects of dehydration and rehydration on stress parameters in the dromedary camels and how it pacifies these effects. Methods: Nineteen male camels were randomly divided into control, dehydrated and rehydrated groups, and fed alfalfa hay ad-libitum. The dehydrated and rehydrated groups were water-restricted for 20 days after which the rehydrated camels were provided with water for 72 h. The control and dehydrated camels were slaughtered at day 20 from the start of experiment whereas the rehydrated group was killed 72 h later. Many biochemical, hematological histopathological parameters and gene analysis were performed in relevant tissues collected including blood, plasma, and tissues. Results and discussion: It was observed that severely dehydrated camels lost body weight, passed very hard feces, few drops of concentrated urine, and were slightly stressed as reflected behaviorally by loss of appetite. Physiologically, the stress of dehydration elicited modulation of plasma stress hormones for water preservation and energy supply. Our results showed significant increase in cortisol, norepinephrine and dopamine, and significant decrease in epinephrine and serotonin. The significant increase in malondialdehyde was accompanied with significant increase in antioxidants (glutathione, retinol, thiamin, tocopherol) to provide tissue protection from oxidative stress. The physiological blood changes observed during dehydration serve different purposes and were quickly restored to normality by rehydration. The dehydrated/rehydrated camels showed reduced hump size and serous atrophy of perirenal and epicardial fat. The latter changes were accompanied by significantly increased expression of genes encoding proteins for energy production (ANGPTL4, ACSBG1) from fat and significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure. This process is vital for camel survival in the desert. Dehydration induced no major effects in the vital organs. Only minor degenerative changes were observed in hepatic and renal cells, physiological cardiomyocyte hypertrophy in heart and follicular hyperplasia in splenic but lipidosis was not depicted in liver hepatocytes. Ketone bodies were not smelled in urine, sweat and breathing of dehydrated animals supporting the previous finding that the ß hydroxybutyrate dehydrogenase, a key enzyme in ketone body formation, is low in the camel liver and rumen. Rehydration restored most of blood and tissues to normal or near normal. In conclusion, camels are adapted to combat dehydration stress and anorexia by increasing anti-stressors and modulating genes involved in fat metabolism.

Intracranial hemorrhages in infants of diabetic mothers: A national cohort study.

OBJECTIVE: To assess the association of maternal diabetes mellitus (DM) with intraventricular hemorrhage (IVH) and other intracranial hemorrhages (ICH) in newborns. STUDY DESIGN: We analyzed the National Inpatient Sample dataset and compared prevalence of IVH and other subtypes of ICH in infants of diabetic mothers (IDMs) vs. those born to mothers without DM. Regression models were used to control for demographic and clinical confounding variables. RESULT: A total of 11,318,691 infants were included. Compared to controls, IDMs had increased prevalence of IVH (aOR = 1.18, CI: 1.12-1.23, p < 0.001) and other ICH (aOR = 1.18, CI: 1.07-1.31, p = 0.001). Severe IVH (grades 3 & 4) was encountered less frequently in IDMs (aOR = 0.75, CI: 0.66-0.85, p < 0.001) than controls. Gestational DM was not associated with increased IVH after controlling for the demographic, clinical and perinatal confounders in the logistic regression model (aOR = 1.04, CI: 0.98-1.11, p = 0.22). CONCLUSION: Chronic maternal DM is associated with increased neonatal IVH and other ICH but not severe IVH. This association needs to be confirmed in further studies.

Impact of postnatal steroids on peripheral avascular retina and severity of retinopathy of prematurity.

BACKGROUND: We investigated the role of postnatal steroids on the severity of retinopathy of prematurity (ROP) and its impact on peripheral avascular retina (PAR). METHODS: A retrospective cohort study of infants born at ≤32 weeks gestation and/or birth weight ≤1500 g. Demographics, the dose and duration of steroid treatment, and age when full retinal vascularization occurred were collected. The primary outcomes were the severity of ROP and time to full vascularization of the retina. RESULTS: A total of 1695 patients were enrolled, 67% of whom received steroid therapy. Their birth weight was 1142 ± 396 g and gestational age was 28.6 ± 2.7 weeks. The total hydrocortisone-equivalent dose prescribed was 28.5 ± 74.3 mg/kg. The total days of steroid treatment were 8.9 ± 35.1 days. After correction for major demographic differences, infants who received a higher cumulative dose of steroids for a longer duration had a significantly increased incidence of severe ROP and PAR (P < 0.001). For each day of steroid treatment, there was a 3.2% increase in the hazard of the severe form of ROP (95% CI: 1.022-1.043) along with 5.7% delay in achieving full retinal vascularization (95% CI: 1.04-1.08) (P < 0.001). CONCLUSION: Cumulative dose and duration of postnatal steroid use were independently associated with the severity of ROP and PAR. Thus, postnatal steroids should be used very prudently. IMPACT: We report ROP outcomes in a large cohort of infants from two major healthcare systems where we have studied the impact of postnatal steroids on the severity of ROP, growth, and development of retinal vessels. After correcting our data for three major outcome measures, we show that high-dose postnatal steroids used for a prolonged duration of time are independently associated with severe ROP and delay in retinal vascularization. Postnatal steroids impact the visual outcomes of VLBW infants significantly, so their clinical use needs to be moderated.

Investigation of a herpesvirus outbreak in mixed breeds of adult domestic ducks using next generation sequencing.

This report characterizes the first lethal outbreak of Marek's disease on a large farm of mixed-breed adult ducks (>18,000) and identifies the pathogen that resulted in high mortality (35%). Clinical signs included inappetence, respiratory distress, depression, muscle weakness, and ataxia. Post mortem revealed enlarged fragile liver mottled with miliary whitish spots and an enlarged spleen. Histopathology revealed hepatocellular necrosis with eosinophilic intra-nuclear inclusion bodies, necrosis of splenic follicles and degeneration/necrosis of renal tubules. The disease was tentatively diagnosed as a herpesvirus infection, confirmed by virus isolation from the liver. DNA was isolated from 15-year-old archival formalin-fixed tissues from infected ducks and subjected to next generation sequencing (NGS). Despite highly degraded DNA, short stretches of G- and C-rich repeats (TTAGGG and TAACCC) were identified as telomeric repeats frequently found in herpesviruses. Megablast and further investigative bioinformatics identified presence of Marek's disease virus (MDV), a Gallid alphaherpesvirus type 2 (GAHV-2), as the cause of the acute fatal infection. The source of infection may be attributed to a dead migratory flamingo found close to the duck enclosures three days prior to the outbreak; hence, GAHV-2 may also be responsible for the fatal infection of the flamingo accentuated by heat stress. Considering the possible spread of this highly contagious and lethal virus from a flamingo to the ducks, and the increasing zoonosis of animal viruses into humans, such as monkey B alphaherpesvirus transmission from macaques to humans with ~80% fatality, this observation has important ramifications for human health and safety of the poultry industry.

Association between IRS-1, PPAR-γ and LEP genes polymorphisms and growth traits in rabbits.

Single nucleotide polymorphisms are commonly associated with changes in quantitative traits, and have been considered useful markers for improving different traits in livestock. The current study aimed to explore the effect of three SNPs located in Insulin receptor substrate (IRS-1), Peroxisome proliferator-activated receptor γ (PPAR-γ), and Leptin (LEP) genes on the growth traits of rabbits. Individuals from three rabbit breeds were genotyped using RFLP-PCR. The IRS-1 variant (c.189T > G) was associated with post-weaning body weight, and body weight gains, However, the effect on growth rates was insignificant in Baladi Red and V-line rabbits. The PPAR-γ variant (c.207A > C) was significantly associated with 8-wk body weights in V-line rabbits, 10-wk body weights, and growth rates from 8 to 10 weeks of age in New Zealand rabbits. However, the differences between genotypes were insignificant for body weight gains and average daily gain. The LEP gene mutation (g.16079636C > G) had significant effects on body weights at 6 and 8 weeks of age in New Zealand White rabbits and 8 weeks of age in Baladi Red rabbits were associated with the presence of the C allele. Concludingly, the results stressed the importance of the IRS-1 gene in post-weaning growth and suggested the existence of breed-specific effects for PPAR-γ and LEP.

Transcriptomic plasticity of the hypothalamic osmoregulatory control centre of the Arabian dromedary camel.

Water conservation is vital for life in the desert. The dromedary camel (Camelus dromedarius) produces low volumes of highly concentrated urine, more so when water is scarce, to conserve body water. Two hormones, arginine vasopressin and oxytocin, both produced in the supraoptic nucleus, the core hypothalamic osmoregulatory control centre, are vital for this adaptive process, but the mechanisms that enable the camel supraoptic nucleus to cope with osmotic stress are not known. To investigate the central control of water homeostasis in the camel, we first build three dimensional models of the camel supraoptic nucleus based on the expression of the vasopressin and oxytocin mRNAs in order to facilitate sampling. We then compare the transcriptomes of the supraoptic nucleus under control and water deprived conditions and identified genes that change in expression due to hyperosmotic stress. By comparing camel and rat datasets, we have identified common elements of the water deprivation transcriptomic response network, as well as elements, such as extracellular matrix remodelling and upregulation of angiotensinogen expression, that appear to be unique to the dromedary camel and that may be essential adaptations necessary for life in the desert.

Modulation of hepatic stellate cells by Mutaflor® probiotic in non-alcoholic fatty liver disease management.

BACKGROUND: NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was effective in sustaining remission in ulcerative colitis patients. OBJECTIVE: To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor® on this network. METHODS: First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor® treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-ß, were estimated by ELISA. RESULTS: Mutaflor® administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-ß effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression. CONCLUSION: Mutaflor® may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661-PTPN11 mRNA Axis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221-miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients' sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.

Co-localization of nociceptive markers in the lumbar dorsal root ganglion and spinal cord of dromedary camel.

Nociceptive markers in mice have been identified in two distinct peptidergic and nonpeptidergic neurons in the dorsal root ganglion (DRG) and distributed in different laminae of the dorsal horn of the spinal cord. Recently, however, a study in humans showed a significant overlapping in these two populations. In this study, we investigated the distribution of various nociceptive markers in the lumbar DRG and spinal cord of the dromedary camel. Immunohistochemical data showed a remarkable percentage of total neurons in the DRG expressed IB4 binding (54.5%), calcitonin gene-related peptide (CGRP; 49.5%), transient receptor potential vanilloid 1 (TRPV1; 48.2%), and nitric oxide synthase (NOS; 30.6%). The co-localization data showed that 89.6% and 74.0% of CGRP- and TRPV1-labeled neurons, respectively, were IB4 positive. In addition, 61.6% and 84.2% of TRPV1- and NOS-immunoreactive neurons, respectively, were also co-localized with CGRP. The distribution of IB4, CGRP, TRPV1, substance P, and NOS immunoreactivities in the spinal cord were observed in lamina I and outer lamina II (IIo). Quantitative data showed that 82.4% of IB4-positive nerve terminals in laminae I and IIo were co-localized with CGRP, and 86.0% of CGRP-labeled terminals were co-localized with IB4. Similarly, 85.1% of NOS-labeled nerve terminals were co-localized with CGRP. No neuropeptide Y (NPY) or cholecystokinin (CCK) immunoreactivities were detected in the DRG, and no co-localization between IB4, NPY, and CCK were observed in the spinal cord. Our results demonstrate marked convergence of nociceptive markers in the primary afferent neurons in camels, which is similar to humans rather than the mouse. The data also emphasizes the importance of interspecies differences when selecting ideal animal models for studying nociception and treating chronic pain.

Multiomic analysis of the Arabian camel (Camelus dromedarius) kidney reveals a role for cholesterol in water conservation.

The Arabian camel (Camelus dromedarius) is the most important livestock animal in arid and semi-arid regions and provides basic necessities to millions of people. In the current context of climate change, there is renewed interest in the mechanisms that enable camelids to survive in arid conditions. Recent investigations described genomic signatures revealing evolutionary adaptations to desert environments. We now present a comprehensive catalogue of the transcriptomes and proteomes of the dromedary kidney and describe how gene expression is modulated as a consequence of chronic dehydration and acute rehydration. Our analyses suggested an enrichment of the cholesterol biosynthetic process and an overrepresentation of categories related to ion transport. Thus, we further validated differentially expressed genes with known roles in water conservation which are affected by changes in cholesterol levels. Our datasets suggest that suppression of cholesterol biosynthesis may facilitate water retention in the kidney by indirectly facilitating the AQP2-mediated water reabsorption.

Role of extracellular LncRNA-SNHG14/miRNA-3940-5p/NAP12 mRNA in colorectal cancer.

BACKGROUND: We aim to identify and analyze the expression of dyregulated RNAs in colorectal cancer (CRC). METHODS: We selected a panel of RNAs specific to CRC composed of Nucleosome Assembly Protein 1 Like 2 (NAP1L2) mRNA, LNCRNA SNHG14 small nucleolar RNA host gene 14 (LNCRNA SNHG14) and homo sapiens microRNA-3940-5p(hsa-miRNA-3940-5p) from genetic and epigenetic databases. Validation of the chosen RNAs was achieved by real time quantitative PCR in sera of patients with CRC, versus controls groups (benign lesions and healthy individual). RESULTS: We found that LLNCRNA SNHG14, hsa-miRNA-3940-5p and NAP1L2 mRNA had an excellent performance characteristics and more superior than CEA, and CA19.9 for differentiating CRC from controls. Combined expression of lncRNA SNHG14- hsa-miR-3940-5p and NAP1L2 mRNA had reached 100% sensitivity with accuracy 93%. Interestingly, serum hsa-miRNA-3940-5p could be an independent prognostic factor in CRC. CONCLUSION: The extracellular lncRNA SNHG14- hsa-miR-3940-5p - NAP1L2 mRNA may aid in CRC management.KEY MESSAGESThe extracellular RNAs provide a potential class of noninvasive biomarkers with high specificity, accuracy and stability for detection of CRC.We used insilico data analysis followed by qPCR for detection of differential NAP1L2 gene expression with the selected epigenetic regulators.Our data presented interesting biomarker panel (NAP1L2 gene, lncRNA-SNHG14 and hsa-miR-3940-5p) that may be potential for CRC diagnosis and prognosis.

The effect of long-term dehydration and subsequent rehydration on markers of inflammation, oxidative stress and apoptosis in the camel kidney.

BACKGROUND: Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression. RESULTS: The cytokines IL-1ß and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days. CONCLUSIONS: Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.

Incidence, Mechanisms, and Predictors of Mean Systolic Gradients ≥20 mm Hg after Transcatheter Aortic Valve Implantation.

There is a significant increase in transvalvular gradients after transcatheter aortic valve implantation (TAVI) in some patients; however, mechanisms underlying the greater than expected gradients are unknown. We sought to determine the incidence and mechanisms of greater than expected gradients post-TAVI. A total of 424 patients who underwent TAVI at our institution between November 2008 and August 2015 and had at least 1 follow-up echocardiogram were included in the study. Greater than expected gradients were defined as mean systolic Doppler gradients ≥20 mm Hg. The primary end-point was incidence and mechanisms of mean systolic Doppler gradients ≥20 mm Hg. A total of 36 (8%) patients had mean systolic Doppler gradients ≥20 mm Hg. The mechanisms of mean systolic Doppler gradients ≥20 mm Hg were: patient prosthesis mismatch in 15 (42%) patients, high cardiac output in 13 (36%), prosthetic and periprosthetic regurgitation in 11 (31%), stenosis in 5 (14%), and multiple mechanisms in 8 (22%). Patients with mean systolic Doppler gradients ≥20 mm Hg had higher cardiac re-hospitalization rate, but no difference in mortality or major cardiovascular events when compared with the normal gradient group. Smaller prosthetic valve size (p <0.0001) and larger body mass index (p = 0.02) were associated with mean systolic Doppler gradients ≥20 mm Hg; warfarin therapy at discharge had no effect on gradients. In conclusion, about 8% patients had mean systolic Doppler gradients ≥20 mm Hg following TAVI, and patient-prosthesis mismatch was the most common mechanism. The mean systolic Doppler gradients ≥20 mm Hg after TAVI are not benign and warrant careful surveillance.