Cardiac gated multidetector computed tomography (MDCT) to determine valvular leaflet thrombosis and leaflet restriction.

The evaluation of patients following aortic valve replacement has evolved, with multiple imaging modalities available that complement each other and permit better and prompt delineation of specific structural or functional valve complications. Multidetector computed tomography (MDCT) is one of the diagnostic modalities with significant technologic advancements that have made possible to evaluate high detail of the moving heart. The ability to deliver three-dimensional and multiplanar dynamic imaging with fine detail has demonstrated the technique is well suited to investigate valve complications. In this review article, we focus on some of the most contributing roles of MDCT in the diagnosis of complications associated with valvular pathology.

Comparison of the Quantra QPlus System With Thromboelastography in Cardiac Surgery.

OBJECTIVES: Use of viscoelastic testing, such as thromboelastography (TEG), is recommended in cardiac surgery to monitor coagulation and to guide the transfusion of blood products. The Quantra QPlus System is a novel point-of-care platform that uses ultrasonic pulses to characterize dynamic changes in viscoelastic properties of a blood sample during coagulation. Despite the ability to assess similar aspects of clot formation, limited studies addressing the interchangeability of viscoelastic testing parameters exist. The primary aim of the present study was to assess the correlation and agreement between Quantra and TEG5000 results using blood samples from cardiac surgery patients. DESIGN: Tertiary care, academic medical center. SETTING: Prospective observational study. PARTICIPANTS: Twenty-eight patients undergoing elective cardiac surgery undergoing cardiopulmonary bypass were evaluated. MEASUREMENTS AND MAIN RESULTS: Perioperative blood samples were collected and assessed using Quantra, and results were compared with TEG and conventional coagulation testing. Method comparison analysis demonstrated that Quantra parameters (Quantra clot time, clot stiffness, and fibrinogen contribution to clot stiffness) significantly correlated with TEG R and TEG G after induction of anesthesia, during cardiopulmonary bypass, and after rewarming (rs = 0.83, rs = 0.84, and rs = 0.73, respectively). However, Quantra parameters demonstrated poor agreement compared with equivalent TEG5000 parameters. CONCLUSIONS: The Quantra QPlus System significantly correlated with TEG5000, suggesting that this test may be used in a similar clinical context. Despite the strength of correlation between Quantra and TEG parameters, measurements are not interchangeable.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

OBJECTIVE: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. BACKGROUND: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. METHODS: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. RESULTS: Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. CONCLUSIONS: These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.

Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.

Put Me in Your Shoes: Does Perspective-Taking Inoculate Against the Appeal of Alternative Partners?

People commit to monogamous relationships with the intent of maintaining sexual exclusivity but often fail to do so. Existing research has focused on individual and relationship characteristics that render relationships more vulnerable to infidelity, paying less attention to strategies that decrease the likelihood of straying. Three experiments investigated the impact of one strategy that might encourage people to enact relationship-protective responses toward alternative partners, perspective-taking. In all studies, participants either adopted the perspective of their partner or not and then evaluated, encountered, or thought about attractive strangers, in Studies 1-3, respectively. Participants' pro-relationship orientation and reactions during these experiences (interest in alternative and current partners, commitment to current relationships, and fantasmatic themes) were recorded. Results showed that perspective-taking decreased sexual and romantic interest in alternatives, while increasing commitment and desire for current partners. These findings suggest that partner perspective-taking discourages engagement in behaviors that may hurt partners and damage the relationship with them.

Post-treatment bacterial endocarditis mimicking fungal organisms: a morphologic comparison and tips for avoiding this diagnostic pitfall.

BACKGROUND: Histopathologic differentiation of bacterial endocarditis from yeast-like fungal endocarditis is usually straightforward; however, an underappreciated phenomenon is the effect of antimicrobial therapy on bacterial size, shape and septa (cross-wall) formation resulting in bacterial forms that mimic yeast-like fungi. In this article we illustrate the alterations that occur in antibiotic-treated Staphylococcus aureus endocarditis and compare these changes to histopathologic findings in unaltered S. aureus and Histoplasma endocarditis, respectively. METHODS: Resected valves from three cases of endocarditis were compared based on the type ofinflammatory reaction, organism morphology and culture results. Case 1 was S. aureus endocarditis initially misclassified as Histoplasma due to its atypical morphologic and histopathologic features. The two cases included for comparison were an S. aureus endocarditis with more classic features and an Histoplasma capsulatum endocarditis. Hematoxylin and eosin (H&E), Gram, periodic acid Schiff (PAS), Gomori-Grocott methenamine silver stains (GMS), and culture results were compared in all cases. Molecular and immunohistochemistry tests were used for confirmation of first case. High power oil-immersion was used to visualize organisms' characteristics in all three cases. RESULTS: Case 1 and Case 3 (Histoplasma-infected valves) had fibrinous exudates with scattered macrophages. The microorganisms observed in the first case of methicillin-sensitive S. aureus (MSSA) were ∼ 2-3 µm by GMS stain and had prominent septations. Histoplasma yeast were round to oval, ∼ 3-4 µm in size and demonstrated budding. S. aureus without alterations were round, ∼ 1 µm in size, and lacked prominent septations. Necrotizing purulent inflammation was present in the unaltered case of MSSA. The MSSA case with alterations from antibiotic treatment did not stain well with the Gram stain and organisms were best visualized with the PAS and GMS stains. CONCLUSIONS: Antibiotic therapy for bacterial endocarditis can alter the inflammatory reaction to infection, bacterial size, septa formation, and staining characteristics. Knowledge of these therapy-related effects and use of high-power magnification helps to avoid misclassification as yeast-like fungi.

Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells.

Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells.

Effect of environmental temperature on growth- and reproduction-related hormones gene expression in the female blue gourami (Trichogaster trichopterus).

Fish are ectothermic vertebrates, and their gonadal development and spawning are affected by changes in environmental temperature. Recent global temperature changes have increased the importance of studying the effect of temperature on reproduction. The aim of this paper was to study the effect of temperature on oogenesis and hormone gene expression related to reproduction and growth in the blue gourami female maintained under non-reproductive and reproductive conditions. In females under non-reproductive conditions, vitellogenic oocytes, gonadotropin-releasing hormone 3 (GnRH3), ß luteinizing hormone (ßLH) and growth hormone (GH) mRNA levels were affected by temperature changes. In females maintained under reproductive conditions with non-reproductively active males, a percentage of females in the final oocyte maturation (FOM) stage, pituitary adenylyl cyclase activating polypeptide (PACAP and PRP-PACAP), gonadotropins and GH mRNA levels were affected due to temperature changes. In females maintained under reproductive conditions with reproductively active males, also GnRH3 and insulin-like growth factor 1 (IGF-1) were affected by temperature changes. In conclusion, in blue gourami females, changes in environmental temperature affect oogenesis through changes in brain and pituitary hormone mRNA levels.

Simple and Effective Blood Salvage Technique for Extracorporeal Membrane Oxygenation Circuit.

Return of circuit blood after discontinuing extracorporeal membrane oxygenation (ECMO) is an important blood conservation strategy for reducing the need for blood transfusion. This follows the current standard of circuit blood salvaging after cardiopulmonary bypass (CPB). There is a variety of strategies and techniques of blood salvage described associated with CPB but not with ECMO. We describe a simplified technique to salvage the blood in the ECMO circuit that requires no special equipment, is safe, and maximizes blood salvage.

Surgical Management of Non-Small Cell Lung Cancer Invading the Fissure: Less Is More?

BACKGROUND: When a resectable lung cancer that invades across the fissure into an adjacent lobe is encountered, options include a bilobectomy on the right or a pneumonectomy on the left vs a parenchymal-sparing resection combined with a lobectomy. Although parenchymal-sparing combinations are technically possible, the available literature reporting on the related oncologic outcomes is limited. We sought to examine the influence of resection extent on overall survival and recurrence patterns in this scenario. METHODS: A single-center retrospective medical record review from 2006 to 2018 was performed on all preoperative computed tomography and operative reports of resections greater than a lobectomy. Patients were grouped into maximal resection: bilobectomy or pneumonectomy, and parenchymal-sparing resection: lobectomy with en bloc segment or nonanatomic wedge. Overall survival and cumulative incidence of recurrence were calculated. RESULTS: The size of our cohort was 54 patients; 19 maximal and 35 parenchymal-sparing resections. All resections were reported as complete (R0). The parenchymal-sparing group had lower odds of immediate surgical morbidity (odds ratio, 0.13; 95% confidence interval, 0.02-0.74; P = .02). Parenchymal-sparing resection was not associated with an increased cumulative incidence of recurrence (P = .98). Postresection estimated overall survival between the 2 cohorts was not significantly different (P = .30). CONCLUSIONS: When technically feasible, a parenchymal-sparing resection is a good option for the resection of tumors that invade across the fissure. R0 parenchymal-sparing resections do not appear to compromise the oncologic outcomes of overall survival or cumulative incidence of recurrence and also seem to carry less morbidity.

Association between pituitary adenylate cyclase-activating polypeptide and reproduction in the blue gourami.

In order to gain a better understanding of the roles of pituitary adenylate cyclase-activating polypeptide (PACAP) in reproduction and growth, the expression of the PACAP gene during the reproduction cycle and its potential role in regulating gonadotropin and growth hormone (GH) gene transcription in blue gourami were investigated. The cDNA sequences of the full-length blue gourami brain PACAP and that of its related peptide (PRP) were acquired. PACAP cDNA had two variants, obtainable by alternative splicing: a long form encoding for both PRP and PACAP and a short form encoding only for PACAP. In females, mRNA levels of PACAP were very high only in individuals with oocytes in the maturation stage, as compared to levels in unpaired vitellogenic and non-vitellogenic fish. The PACAP mRNA levels in males were high only in nest builders, as opposed to in non-nest building males and juveniles. In pituitary culture cells from high vitellogenic females, PACAP38 (the 38 amino acid form) only brought about an increase in betaFSH levels, without altering GH and betaLH mRNA levels. On the other hand, in adult non-reproductive male pituitary cells, PACAP38 decreased the GH mRNA level. Based on these results, we propose that in the blue gourami, PACAP is involved in the final oocyte maturation stage in females, whereas in males, it is associated with sexual behavior. In addition, the effect of PACAP38 on pituitary hormone gene expression is different in females and males, indicating that PACAP38 is potentially a hypophysiotropic regulator of reproduction, which mediates pituitary hormone expression.

Transversus Abdominis Plane Block Improves Perioperative Outcome After Esophagectomy Versus Epidural.

BACKGROUND: Pain control is challenging during esophagectomy. An epidural is commonly used, but the sympathetic blockade can have unintended consequences such as hypotension or delayed return of bowel function. A transversus abdominis plane (TAP) block has the potential to control upper abdominal pain without these adverse consequences. We aimed to compare bilateral TAP blocks with patient-controlled analgesia (PCA) for immediate management after esophagectomy with a cohort using a thoracic (T5 to T8) epidural. METHODS: This was a retrospective review of patients undergoing esophagectomy between 2012 and 2016. Primary outcomes were pain scores (0 to 10) assessed at 24, 48, and 72 hours for adequacy of pain control. Secondary outcomes were volume resuscitation at 72 hours, hypotension (systolic blood pressure <90 mm Hg), length of stay (LOS), return of bowel function, and complications. RESULTS: Sixty-one patients underwent esophagectomy using bilateral TAP block and PCA (n = 32) or thoracic (T5 to T8) epidural (n = 29). Overall pain scores were not statistically different between the TAP group and the epidural group averaged over 72 hours (4.98 versus 4.39, p = 0.09). During the initial 72 hours after operation, hypotension was less prevalent in the TAP group (25% versus 76%, p < 0.05) with lower crystalloid resuscitation needs. The LOS in the intensive care unit (3.2 days versus 4.6 days, p < 0.05) and return of bowel function (5 days versus 6.7 days, p < 0.05) were considerably shorter in the TAP group. Pulmonary complications were similar. CONCLUSIONS: TAP blocks with a PCA is an alternative option for pain control in patients undergoing esophagectomy and may reduce hypotension and need for volume resuscitation with similar pulmonary complications.

A Combined Nissen Plus Hill Hybrid Repair for Paraesophageal Hernia Improves Clinical Outcomes and Reduces Long-Term Recurrences Compared with Laparoscopic Nissen Alone.

INTRODUCTION: We compared clinical and objective outcomes of combined Nissen-Hill hybrid (HYB) to Nissen fundoplication (LNF) for repair of paraesophageal hernia (PEH). METHODS: This study is a single-institution retrospective chart review of prospectively collected data for consecutive patients undergoing PEH repair from 2006 to 2015 with at least 6 months of follow-up. Quality of life metrics (QOLRAD, HRQL, and dysphagia), manometry, radiographic imaging, and pH testing were administered pre- and postoperatively. RESULTS: With 319 repairs (HYB = 141, LNF = 178), the groups were comparable in age and gender, but HYB had a higher BMI (30.95 vs 29.27, p < 0.05), larger hernia (6 vs 5 cm, p < 0.05), and more Barrett's esophagus (42 vs 29, p < 0.05). At a median follow-up of 22 months, DeMeester scores were equivalent but PPI use was higher in the LNF group. All three quality of life scores were better for HYB: GERD-HRQL 3.75 vs 7.49, p = 0.01; QOLRAD 6.59 vs 6.23, p = 0.04; and swallowing 40.71 vs 36.47, p = 0.01. At a median follow-up of 60 months (HYB = 39, LNF = 31), anatomic recurrences and reoperations were lower for HYB: 5 vs 45 % (p < 0.05), 2.6 vs 9.7 % (p = 0.2). CONCLUSION: Combining Nissen and Hill for PEH repair appears to result in better quality of life and fewer recurrences compared to LNF.

Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways.

A standard therapy used today for prostate cancer is androgen ablation by gonadotropin-releasing hormone analogs (GnRH-a). Although most patients respond to androgen ablation as an initial systemic therapy, nearly all cases will develop androgen resistance, the management of which is still a major challenge. Here, we report that GnRH-a can directly induce apoptosis of the androgen-independent prostate cancer-derived DU145 and PC3 cell lines. Using specific inhibitors, we found that the apoptotic effect of GnRH-a is mediated by c-Jun NH2-terminal kinase (JNK) and inhibited by the phosphatidylinositol 3'-kinase (PI3K)-protein kinase B (PKB) pathway. Indeed, in DU145 cells, GnRH-a activates the JNK cascade in a c-Src- and MLK3-dependent manner but does not involve protein kinase C and epidermal growth factor receptor. Concomitantly, GnRH-a reduces the activity of the PI3K-PKB pathway, which results in the dephosphorylation of PKB mainly in the nucleus. The reduction of PKB activity releases PKB-induced inhibition of MLK3 and thus further stimulates JNK activity and accelerates the apoptotic effect of GnRH-a. Interestingly, extracellular signal-regulated kinase is also activated by GnRH-a, and this occurs via a pathway that involves matrix metalloproteinases and epidermal growth factor receptor, but its activation does not affect JNK activation and the GnRH-a-induced apoptosis. Our results support a potential use of GnRH-a for the treatment of advanced prostate cancer and suggest that the outcome of this treatment can be amplified by using PI3K-PKB inhibitors.

Genetic Analysis of the Rhodopsin Gene Identifies a Mosaic Dominant Retinitis Pigmentosa Mutation in a Healthy Individual.

PURPOSE: Retinitis pigmentosa (RP) is a group of clinically and genetically heterogeneous hereditary retinal diseases that result in blindness due to photoreceptor degeneration. Mutations in the rhodopsin (RHO) gene are the most common cause of autosomal dominant RP (adRP) and are responsible for 16% to 35% of adRP cases in the Western population. Our purpose was to investigate the contribution of RHO to adRP in the Israeli and Palestinian populations. METHODS: Thirty-two adRP families participated in the study. Mutation detection was performed by whole exome sequencing (WES) and Sanger sequencing of RHO exons. Fluorescence PCR reactions of serially diluted samples were used to predict the percentage of mosaic cells in blood samples. RESULTS: Eight RHO disease-causing mutations were identified in nine families, with only one novel mutation, c.548-638dup91bp, identified in a family where WES failed to detect any causal variant. Segregation analysis revealed that the origin of the mutation is in a mosaic healthy individual carrying the mutation in approximately 13% of blood cells. CONCLUSIONS: This is the first report of the mutation spectrum of a known adRP gene in the Israeli and Palestinian populations, leading to the identification of seven previously reported mutations and one novel mutation. Our study shows that RHO mutations are a major cause of adRP in this cohort and are responsible for 28% of adRP families. The novel mutation exhibits a unique phenomenon in which an unaffected individual is mosaic for an adRP-causing mutation.