Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections.

Bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA), have high rates of antimicrobial tolerance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeutics that act synergistically can overcome antimicrobial tolerance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a nanoscale drug carrier for antimicrobial codelivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs outperforming negatively charged formulations. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic codelivery to treat recalcitrant bacterial infections.

Surgical Valve Choices for Pulmonary Valve Replacement.

The range of valve choices available to the cardiac surgeon for placement in the pulmonary position continues to expand. This article will provide a brief compendium of the most clinically relevant among these choices and review the contemporary literature regarding their relative durability as well as risk factors for structural valve deterioration and reintervention. The unique advantages and disadvantages of each of these valve choices will be discussed as they pertain to unique patient-specific factors, including patient size and the anatomy of the right ventricular outflow tract, that inform the choice of one prosthesis over another. Finally, general principles regarding the approach to valve choice, and future directions will be discussed.

Distinguishing Intrathyroid Parathyroid Adenoma from Colloid Nodules and Papillary Thyroid Carcinomas Using Multiphasic Multidetector Computed Tomography.

OBJECTIVE: The aim of the study is to determine whether multiphase multidetector computed tomography (4D-MDCT) can differentiate between intrathyroid parathyroid adenomas (ITPAs), colloid nodules, and papillary thyroid carcinoma (PTC). METHODS: We studied 22 ITPAs, 22 colloid nodules, and 11 PTCs in 55 patients. Hounsfield unit (HU) values of the nodules were measured on 4D-MDCT in the precontrast, arterial, venous, and delayed phases. Raw HU values, phase with peak enhancement, and washout percentages between the phases were evaluated. RESULTS: Regardless of size, all ITPAs (22/22) showed peak enhancement in the arterial phase, which was significantly greater than both colloid nodules (15/22) and PTC (6/11, P = 0.002); thus, nodules with peak enhancement in the venous or delayed phase were not ITPAs (specificity = 1). For nodules with peak enhancement in the arterial phase, the percentage washout in the arterial-to-venous phases separated ITPAs from PTC and colloid nodules (P < 0.001) with greater than or equal to 23.95% loss of HU value implying IPTA (area under curve, 0.79). This left a subset of colloid nodules or PTC that either peaked in the venous or delayed phase or had an arterial-to-venous phase washout of less than 23.95%. From this subset, PTC measuring 1 cm or greater could be separated from colloid based on HU values in the arterial phase with a cutoff HU value less than 81.4 for PTC (area under curve, 0.72) and an HU value greater than 164.5 suggested colloid. CONCLUSIONS: Intrathyroid parathyroid adenomas can be distinguished from colloid nodules and PTC by peak enhancement in the arterial phase and rapid washout. A subset of colloid and PTC measuring 1 cm or greater can be separated using arterial phase HU values.

Complete atrioventricular septal defect with absent or diminutive primum component: Incidence, anatomic characteristics, and outcomes.

BACKGROUND: Repair of complete atrioventricular septal defect with absent or diminutive primum defect is challenging because of atrial septal malposition and abnormal anatomy of the left atrioventricular valve. We sought to define the incidence, anatomy, and surgical outcomes of this entity. METHODS: We identified all patients in our institutional database presenting for complete atrioventricular septal defect repair from 2006 to 2018. Operative reports and echocardiograms were reviewed to determine the presence and size of the primum defect, atrioventricular valve anatomy, degree of atrioventricular valve regurgitation, repair method, and complications, including reoperation for atrioventricular valve regurgitation. Functionally univentricular patients and those receiving repair at an outside institution were excluded. RESULTS: Of 183 patients with complete atrioventricular septal defect, absent/diminutive primum defect occurred in 16 patients (8.7%; 10 absent, 6 diminutive). Six patients (38%) had leftward malposition of the atrium septum on the common atrioventricular valve. The rate of reoperation for left atrioventricular valve regurgitation was 31% (3 early, 2 late), for which preoperative predictors included leftward malposition of the atrial septum onto the common atrioventricular valve (4/6 patients with malposition required reoperation, P = .036, Fisher exact test). One patient exhibiting this risk factor died. The overall rate of moderate or greater left atrioventricular valve regurgitation on the most recent postoperative echocardiogram was 13% (2/16 patients; median follow-up, 141 days; range, 3-2236 days). CONCLUSIONS: Complete atrioventricular septal defect with absent or diminutive primum defect is a unique variant of complete atrioventricular septal defect for which the risk of reoperation for left atrioventricular valve regurgitation after complete repair is high and risk factors include leftward malposition of the atrial septum on the common atrioventricular valve.

Screening for HPV-related oropharyngeal, anal, and penile cancers in middle-aged men: Initial report from the HOUSTON clinical trial.

BACKGROUND: The Human papillomavirus (HPV)-related Oropharyngeal and Uncommon Cancers Screening Trial of Men (HOUSTON) was designed to determine the prevalence of IgG antibodies to HPV type 16 E proteins (HPV16EAbs), to screen for persistence of HPV and/or detect HPV-related premalignancies and cancers, and to assess acceptance of screening among middle-aged men. METHODS: HOUSTON consists of a cross-sectional study and a longitudinal cohort study of men aged 50-64 years. Serologic HPV16EAb status and oral rinse HPV16 status were determined. All HPV16EAb-positive (HPV16EAb+) men and a matched cohort of HPV16EAb-negative (HPV16EAb-) men as well as all oral rinse HPV16-positive (HPV16+) men were included in the longitudinal study (blinded to their results) and underwent oropharyngeal screening every 6 months as well as one-time anal and penile screening. RESULTS: Of 553 men enrolled in the cross-sectional study, six (1.1%) were HPV16EAb+ (two were also oral rinse HPV16+), and 41 (7.4%) were HPV16EAb- but oral rinse HPV16+. These 47 men, along with five matched controls, were invited to participate in the longitudinal study, and 42 (81%) agreed and completed baseline in-person screening, with 93% and 90% completeing 6-month and 12-month follow-up visits. One HPV16EAb+ (also oral rinse HPV16+) man, who declined participation in the longitudinal study, presented 4 months after enrollment with an early-stage HPV16-related pharyngeal cancer. Additionally, one HPV16EAb+ (oral rinse HPV16-) man and two oral rinse HPV16+ (HPV16EAb-) men were diagnosed with oncogenic HPV-associated anal dysplasia. CONCLUSIONS: This biomarker panel deserves further prospective study to explore potential utility for HPV-related cancer screening among men.

Neonatal venoarterial extracorporeal membrane oxygenation cannulation technique.

Peripheral cannulation for initiation of neonatal venoarterial extracorporeal membrane oxygenation is an essential technical skill in the armamentarium of every congenital cardiac surgeon and is necessary for the care of newborns with congenital heart disease and other conditions presenting with cardiopulmonary failure. With certain exceptions, it is usually performed via a right neck cut-down to expose the right internal jugular vein and common carotid artery.   A strong understanding of the fundamental techniques, as well as strategies for avoiding common pitfalls, is critical to the success of cardiopulmonary rescue afforded by cannulation, especially considering the emergent conditions under which cannulation must usually be performed. We review here the operative approach and technique for neck cannulation for peripheral neonatal venoarterial extracorporeal membrane oxygenation.

Ascending Aortoplasty in Pediatric Patients Undergoing Aortic Valve Procedures.

BACKGROUND: The risks of ascending aortic dilation and indications for intervention in pediatric patients are unclear. Given the concern for aortic size mismatch with growth, larger ascending aortic diameters have been accepted in pediatric patients. The purpose of this study was to evaluate the effectiveness of ascending aortic reduction at the time of aortic valve surgery and its effect on recurrent aortic regurgitation. METHODS: A retrospective 8-year observational review (2010-2018) was conducted in pediatric patients with dilated ascending aorta undergoing aortic valve surgery at a single institution. RESULTS: Forty-seven patients underwent ascending aortoplasty during aortic valve surgery, of which 39 patients with complete data points had preoperative mean ascending aortic Z-scores of 5.35 ± 1.52 reduced to 1.22 ± 1.63 (P < .001) postoperatively. Ascending aortic Z-scores remained similar at 1.37 ± 1.72 at latest follow-up (P = .306). In contrast our matched control group (n = 39) without ascending aortoplasty had preoperative mean ascending aortic Z-scores of 4.15 ± 1.65 reduced to 3.26 ± 2.0 at the midterm follow-up. This reduction was significantly larger in the aortoplasty group, with an average difference in these changes of 3.12 (95% confidence interval, 2.43-3.8; P < .001). Multivariable logistic regression (controlling for aortic valve intervention type and body surface area) showed a 6.84 odds of moderate to severe aortic regurgitation at follow-up in the control group compared with the aortoplasty group (95% confidence interval, 1.43-32.8; P = .016). There were no complications associated with ascending aortoplasty. CONCLUSIONS: Ascending aortoplasty is effective in reducing ascending aortic dimensions and recurrent aortic regurgitation in pediatric patients. Longer-term follow-up is necessary to determine continued rate of growth.

Pulmonary Valve-Sparing Techniques for Tetralogy of Fallot: A Systematic Approach for Maximizing Success and Minimizing Risk.

Valve-sparing techniques for the treatment of Tetralogy of Fallot with pulmonary stenosis have evolved over the past few decades. This article will discuss the rationale for a more aggressive approach to sparing the pulmonary valve, the various techniques available (including commissurotomy, leaflet thinning and debridement, balloon dilation, and finally modified monocusp repair), as well as a systematic approach for employing these techniques based on individual patient anatomy in a manner that takes full advantages of the benefits of the valve-sparing approach while mitigating the risks involved.

Oblique Lateral Closing-Wedge Osteotomy for Cubitus Varus in Skeletally Immature Patients.

BACKGROUND: We perform an oblique lateral closing-wedge osteotomy of the distal end of the humerus to correct cubitus varus deformity in children. This deformity is often the consequence of undertreatment, malreduction, or malunion of supracondylar humeral fractures1. Although standard arcs of motion may be altered, cosmesis was traditionally considered a primary surgical indication. However, uncorrected cubitus varus leads to posterolateral rotatory instability of the elbow (PLRI)2, lateral condylar fractures3, snapping medial triceps, and ulnar nerve instability4. A contemporary understanding of these delayed sequelae has expanded our current indications. Detailed parameters predictive of late sequelae are needed to further specify surgical indications. DESCRIPTION: We remove an oblique lateral closing wedge from the distal end of the humerus via a standard lateral approach. The osteotomy is angled away from the varus joint line such that lateral cortices after reduction lack prominence. Kirschner wires provide adequate fixation in young patients. In older children, extension is simultaneously corrected, and fragments are stabilized via plate osteosynthesis. ALTERNATIVES: Patients who decline surgery are counseled regarding risks of delaying treatment until symptoms are present. PLRI manifests as lateral elbow pain or instability while rising from a chair. Once symptomatic, the lateral ulnar collateral ligament (LUCL) is irreversibly attenuated and morphologic changes in the ulnohumeral joint necessitate more extensive surgery to include distal humeral osteotomy, LUCL reconstruction, and possibly ulnar nerve transposition5. Alternative osteotomy techniques are described and categorized as simple lateral closing wedge, step-cut6-9, dome, 3-dimensional10, or distraction osteogenesis. Simple closing-wedge osteotomies include a distal cut parallel to the joint line and retain a problematic lateral prominence (if the medial cortex is intact or the distal end of the humerus is not translated medially)11,12. Step-cut osteotomies theoretically minimize this lateral prominence while enhancing inherent stability. However, these additional cuts mandate wide surgical exposure despite similar outcomes13. Three-dimensional planning employs computed tomography to create expensive anatomic cutting guides that address varus, extension, and internal rotation. However, residual internal rotation is generally well tolerated, derotation is associated with loss of fixation, and the extension deformity will successfully remodel in patients who are <10 years old14. We employ 3-dimensional planning in skeletally mature patients with complex deformity and no remodeling potential. RATIONALE: The oblique lateral closing wedge is ideal for skeletally immature patients because it is simple, reproducible, and efficient. It avoids the lateral prominence without increasing complexity or complications.

Early Distal Migration of a Self-Expanding Aortic Valve Prosthesis Causing Myocardial Infarction.

Early distal migration after transcatheter aortic valve replacement is a rare but potentially catastrophic complication that presents unique technical challenges for subsequent surgical management. This report describes a case of early distal migration of a Medtronic CoreValve Evolut R bioprosthesis (Minneapolis, MN) causing myocardial infarction from coronary ostial obstruction and provides a practical technique for open surgical device explantation and aortic valve re-replacement. Snaring the stent of the device using standard instruments is a simple but effective method for transcatheter aortic valve replacement explant that allows for optimal positioning of a single aortotomy at the standard anatomic site to facilitate subsequent surgical aortic valve replacement.

Molecular basis of flowering under natural long-day conditions in Arabidopsis.

Plants sense light and temperature changes to regulate flowering time. Here, we show that expression of the Arabidopsis florigen gene, FLOWERING LOCUS T (FT), peaks in the morning during spring, a different pattern than we observe in the laboratory. Providing our laboratory growth conditions with a red/far-red light ratio similar to open-field conditions and daily temperature oscillation is sufficient to mimic the FT expression and flowering time in natural long days. Under the adjusted growth conditions, key light signalling components, such as phytochrome A and EARLY FLOWERING 3, play important roles in morning FT expression. These conditions stabilize CONSTANS protein, a major FT activator, in the morning, which is probably a critical mechanism for photoperiodic flowering in nature. Refining the parameters of our standard growth conditions to more precisely mimic plant responses in nature can provide a powerful method for improving our understanding of seasonal response.

Primary synovial chondromatosis of the subtalar joint: case report and review of the literature.

Primary synovial chondromatosis is a rare benign condition of uncertain etiology manifested by synovial proliferation. In the radiology literature, there is only 1 prior case report of primary synovial chondromatosis involving the subtalar joint with only partial description of the imaging appearance. We present a 28-year-old female with primary synovial chondromatosis of the subtalar joint and conduct a literature review of the imaging features of primary synovial chondromatosis presenting in the feet.

Bicuspid Aortic Valvulopathy and Associated Aortopathy: a Review of Contemporary Studies Relevant to Clinical Decision-Making.

OPINION STATEMENT: The bicuspid aortic valve (BAV) phenotype is becoming increasingly recognized as a complex and heterogeneous clinical entity, with some but not all patients developing accelerated degrees of both aortic insufficiency (AI) and aortic stenosis (AS) in comparison to patients with tricuspid aortic valves (TAV). In addition, there remains a well-established association between the BAV phenotype and aortic enlargement independent of valve function as well as progression among some to ascending aortic aneurysm and the attendant concern over risk of aortic dissection. Because the understanding of the complexity of the BAV phenotype is evolving as quickly as are the options for medical, surgical, and interventional therapy, this review aims to provide an update on the most clinically relevant recent advances in the realm of BAV and associated aortopathy from a genetic, morphologic, and clinical outcomes perspective in order to give the practicing clinician a deeper understanding of how to approach both medical and surgical decision-making in the patient with BAV. The following major principles have emerged in recent years including (1) the importance of cusp anatomy and its implications on the long-term risk of AI, aortic dilation, and aortic dissection, (2) the role of post-valvular flow dynamics in the pathogenesis of aortic dilation in BAV patients, (3) the ability of aortic valve replacement to halt accelerated dilation rates, and (4) the finding that the risk of aortic dissection, while still overall intermediate is much more akin to the baseline risk present in TAV patients rather than the much higher rates observed in patients with Marfan's disease. Together, these data support the less aggressive approach to aortic replacement in BAV patients as reflected in the most recent ACC/AHA guidelines and provide a stronger basis upon which future studies, including those aimed at medical and transcatheter therapies, stand to make further impact on our ability to optimally treat this epidemiologically important and complex population of patients.

TCP4-dependent induction of CONSTANS transcription requires GIGANTEA in photoperiodic flowering in Arabidopsis.

Photoperiod is one of the most reliable environmental cues for plants to regulate flowering timing. In Arabidopsis thaliana, CONSTANS (CO) transcription factor plays a central role in regulating photoperiodic flowering. In contrast to posttranslational regulation of CO protein, still little was known about CO transcriptional regulation. Here we show that the CINCINNATA (CIN) clade of class II TEOSINTE BRANCHED 1/ CYCLOIDEA/ PROLIFERATING CELL NUCLEAR ANTIGEN FACTOR (TCP) proteins act as CO activators. Our yeast one-hybrid analysis revealed that class II CIN-TCPs, including TCP4, bind to the CO promoter. TCP4 induces CO expression around dusk by directly associating with the CO promoter in vivo. In addition, TCP4 binds to another flowering regulator, GIGANTEA (GI), in the nucleus, and induces CO expression in a GI-dependent manner. The physical association of TCP4 with the CO promoter was reduced in the gi mutant, suggesting that GI may enhance the DNA-binding ability of TCP4. Our tandem affinity purification coupled with mass spectrometry (TAP-MS) analysis identified all class II CIN-TCPs as the components of the in vivo TCP4 complex, and the gi mutant did not alter the composition of the TCP4 complex. Taken together, our results demonstrate a novel function of CIN-TCPs as photoperiodic flowering regulators, which may contribute to coordinating plant development with flowering regulation.

18F-PET/CT imaging of metastasis to the thyroid gland: Imaging findings and effect on patient management.

PURPOSE: While metastasis to the thyroid from a primary cancer remote to the thyroid is uncommon, current imaging techniques have improved detection of these intrathyroid metastases. The purpose of this study was to evaluate the 18F-PET/CT appearance of intrathyroid metastases and assess the impact of detection on patient management. METHODS: The 18F-PET/CT appearance of intrathyroid metastasis, including standardized uptake value (SUV), disease extent, and the effect on patient management following diagnosis were retrospectively reviewed. Inclusion criteria included 18F-PET/CT imaging and diagnosis of the intrathyroid metastasis matching the remote primary tumor. RESULTS: Intrathyroid metastasis were detected in 24 patients. The intrathyroid metastases presented on 18F-PET/CT as focal nodular uptake (n = 21), multiple nodular uptake (n = 2), or diffuse uptake/infiltration of the thyroid gland (n = 1). The SUV ranged between 3.9 and 42 (median 12.5 ± 7.5); in 2 patients, the FDG-avidity was minimal. On 18F-PET/CT, distant metastases were present outside the neck (n = 18), or limited to the neck (n = 6). In 2 of these 6 patients, the thyroid was the only site of metastatic disease. Due to the metastatic disease, the therapy was changed in 23 of 24 patients; 1 patient was lost to follow-up. CONCLUSION: In any patient with a previous or current history of an extrathyroid malignancy, an 18FDG-avid thyroid mass or diffuse infiltration of the thyroid on 18F-PET/CT should be considered a potential intrathyoid metastasis until proven otherwise. Knowledge of an intrathyroid metastasis may impact patient management, especially if the thyroid or neck are the only sites of metastatic disease.

Sonographic Evaluation of Intrathyroid Metastases.

OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy. RESULTS: The study included 52 patients. The most frequent primary tumor sites were lung, head and neck, and breast. Intrathyroid metastases presented as a discrete nodule in 34 patients and as diffuse infiltration of the gland in 18 patients. The discrete nodules ranged in size from 1.1 to 5.6 cm (mean ± SD, 2.5 ± 1.2 cm). Thirty-three lesions (63%) had irregular margins, and 19 (37%) had well-defined margins. Most of the lesions were heterogeneously hypoechoic (n = 50, 96%). Vascularity was present in 32 of 50 measured lesions (64%) that were evaluated with Doppler sonography. Cervical adenopathy was present in 37 patients (71%). CONCLUSIONS: Intrathyroid metastases have sonographic characteristics similar to those described for both benign and malignant thyroid diseases. In patients with a previous or current extrathyroid malignancy, thyroid nodules or diffuse infiltration of the thyroid gland on sonography should be viewed as a potential intrathyroid metastasis and evaluated via ultrasound-guided fine-needle aspiration regardless of the site of the primary tumor.