Prediction of Wound Failure in Patients with Head and Neck Cancer Treated with Free Flap Reconstruction: Utility of CT Perfusion and MR Perfusion in the Early Postoperative Period.

BACKGROUND AND PURPOSE: Free flap reconstruction in patients with head and neck cancer carries a risk of postoperative complications, and radiologic predictive factors have been limited. The aim of this study was to assess the factors that predict free flap reconstruction failure using CT and MR perfusion. MATERIALS AND METHODS: This single-center prospective study included 24 patients (mean age, 62.7 [SD, 9.0] years; 16 men) who had free flap reconstruction from January 2016 to May 2018. CT perfusion and dynamic contrast-enhanced MR imaging with conventional CT and MR imaging were performed between 2 and 4 days after the free flap surgery, and the wound assessments within 14 days after the surgery were conducted by the surgical team. The parameters of CT perfusion and dynamic contrast-enhanced MR imaging with conventional imaging findings and patient demographics were compared between the patients with successful free flap reconstruction and those with wound failure as appropriate. P < .05 was considered significant. RESULTS: There were 19 patients with successful free flap reconstruction and no wound complications (mean age, 63.9 [SD, 9.5] years; 14 men), while 5 patients had wound failure (mean age, 58.0 [SD, 5.7] years; 2 men). Blood flow, blood volume, MTT, and time maximum intensity projection (P = .007, .007, .015, and .004, respectively) in CT perfusion, and fractional plasma volume, volume transfer constant, peak enhancement, and time to maximum enhancement (P = .006, .039, .004, and .04, respectively) in dynamic contrast-enhanced MR imaging were significantly different between the 2 groups. CONCLUSIONS: CT perfusion and dynamic contrast-enhanced MR imaging are both promising imaging techniques to predict wound complications after head and neck free flap reconstruction.

Dental Services and Health Outcomes in the New York State Medicaid Program.

Previous reports suggest that periodontal treatment is associated with improved health care outcomes and reduced costs. Using data from the New York State Medicaid program, rates of emergency department (ED) use and inpatient admissions (IPs), as well as costs for ED, IPs, pharmacy, and total health care, were studied to determine the association of preventive dental care to health care outcomes. Utilization of dental services in the first 2 y (July 2012-June 2014) was compared to health care outcomes in the final year (July 2014-June 2015). Costs and utilization for members who did not receive dental services (No Dental) were compared to those who received any dental care (Any Dental), any preventive dental care (PDC), PDC without an extraction and/or endodontic treatment (PDC without Ext/Endo), PDC with an Ext/Endo (PDC with Ext/Endo), or Ext/Endo without PDC (Ext/Endo without PDC). Propensity scores were used to adjust for potential confounders. After adjustment, ED rate ratios were significantly lower for PDC and PDC without Ext/Endo but higher for the Any Dental and Ext/Endo without PDC. IP ratios were lower for all treatment groups except Ext/Endo without PDC. ED costs differed little compared to the No Dental group except for Ext/Endo without PDC. For IPs, costs per member were significantly lower for all groups (-$262.91 [95% confidence interval (CI), -325.40 to -200.42] to -$379.82 [95% CI, -451.27 to -308.37]) except for Ext/Endo without PDC. For total health care costs, Ext/Endo without PDC had a significantly greater total health care cost ($530.50 [95% CI, 156.99-904.01]). Each additional PDC visit was associated with a 3% reduction in the relative risk for ED and 9% reduction for IPs. Costs also decreased for total health care (-$235.64 [95% CI, -299.95 to -171.33]) and IP (-$181.39 [95% CI, -208.73 to -154.05]). In conclusion, an association between PDC and improved health care outcomes was observed, with the opposite association for Ext/Endo without PDC.

Predictors and Prevalence of Nodal Disease in Salvage Oropharyngectomy.

BACKGROUND: Patients with recurrent oropharyngeal cancer often require extensive salvage surgery. For patients with clinically N0 necks, the indication for concurrent neck dissection remains unclear. This study aimed to determine predictors, prevalence, and distribution of nodal disease in patients treated with salvage oropharyngectomy. METHODS: In a case series with data collection at a single tertiary academic National Cancer Institute (NCI)-designated comprehensive cancer center, this study analyzed patients treated with prior radiation or chemoradiation who had persistent, recurrent, or second primary squamous cell carcinoma of the oropharynx requiring oropharyngeal resection between 1998 and 2017 (n = 95). Clinical and oncologic characteristics and treatment outcomes were collected, and statistical analyses were performed. RESULTS: The overall rate of nodal positivity was 21% (24/95), and the rate of occult nodal disease was 6% (4/65). Ipsilateral and contralateral level 2 were the most common areas harboring positive nodes. Bivariate analysis showed female sex (p = 0.01), initial overall stage (p = 0.02), and N status (p = 0.03), as well as recurrent overall and T stage (p = 0.05) to be predictors of nodal disease. In the multivariate analysis, recurrent T stage continued to be significantly predictive of pathologic nodal disease. Both computed tomography (CT) and positron emission tomography-CT were moderately accurate in predicting nodal disease in the salvage setting (area under the curve, 0.79 and 0.80, respectively). CONCLUSION: Occult nodal disease is observed in few patients undergoing salvage oropharyngeal resection. This study identified factors predictive of nodal disease in patients undergoing salvage oropharyngectomy and appropriate diagnostic tests in this setting.

Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research.

In children with acute lymphoblastic leukemia (ALL) with isolated central nervous system (CNS) relapse and a human leucocyte antigen (HLA)-matched sibling, the optimal treatment after attaining second remission is unknown. We compared outcomes in 149 patients enrolled on chemotherapy trials and 60 HLA-matched sibling transplants, treated in 1990-2000. All patients achieved a second complete remission. Groups were similar, except the chemotherapy recipients were younger at diagnosis, less likely to have T-cell ALL and had longer duration (> or = 18 months) first remission. To adjust for time-to-transplant bias, left-truncated Cox's regression models were constructed. Relapse rates were similar after chemotherapy and transplantation. In both treatment groups, relapse rates were higher in older children (11-17 years; RR 2.81, P=0.002) and shorter first remission (< 18 months; RR 3.89, P<0.001). Treatment-related mortality rates were higher after transplantation (RR 4.28, P=0.001). The 8-year probabilities of leukemia-free survival adjusted for age and duration of first remission were similar after chemotherapy with irradiation and transplantation (66 and 58%, respectively). In the absence of an advantage for one treatment option over another, the data support use of either intensive chemotherapy with irradiation or HLA-matched sibling transplantation with total body irradiation containing conditioning regimen for children with ALL in second remission after an isolated CNS relapse.

Optical negative-index bulk metamaterials consisting of 2D perforated metal-dielectric stacks.

Numerical simulations of a near-infrared negative-index metamaterial (NIM) slab consisting of multiple layers of perforated metal-dielectric stacks exhibiting a small imaginary part of the index over the wavelength range for negative refraction are presented. A consistent effective index is obtained using both scattering matrix and modal analysis approaches. Backward phase propagation is verified by calculation of fields inside the metamaterial. The NIM figure of merit, [ -Re(n)/Im(n) ], for these structures is improved by ~ 10x compared with previous reports, establishing a new approach to thick, low-loss metamaterials at infrared and optical frequencies.

Second harmonic generation from patterned GaAs inside a subwavelength metallic hole array.

By extending GaAs dielectric posts with a large second-order nonlinear susceptibility through the holes of a subwavelength metallic hole array coupled to the metal surface-plasma wave, strong second harmonic (SH) signal is observed. The SH signal is strengthened as a result of the enhanced electromagnetic fields inside the hole apertures.

Experimental demonstration of near-infrared negative-index metamaterials.

Metal-based negative refractive-index materials have been extensively studied in the microwave region. However, negative-index metamaterials have not been realized at near-IR or visible frequencies due to difficulties of fabrication and to the generally poor optical properties of metals at these wavelengths. In this Letter, we report the first fabrication and experimental verification of a transversely structured metal-dielectric-metal multilayer exhibiting a negative refractive index around 2 microm. Both the amplitude and the phase of the transmission and reflection were measured experimentally, and are in good agreement with a rigorous coupled wave analysis.

Midinfrared resonant magnetic nanostructures exhibiting a negative permeability.

We experimentally demonstrate the first midinfrared (mid-IR) resonant magnetic nanostructures exhibiting a strong magnetic response corresponding to a negative permeability. This result is an important step toward the achievement of a negative refractive index in the IR. The possibility of extending negative permeability to higher frequencies is discussed; a structure with a negative effective permeability at a near-IR resonance frequency of 230 THz (1.3 microm) is proposed.

Enhanced mid-infrared transmission through nanoscale metallic coaxial-aperture arrays.

Using a single interferometric lithography patterning step along with self-aligned pattern-definition techniques, uniform, large-area metallic coaxial arrays with ~ 100-nm toroidal gaps are fabricated. Enhanced (5x) mid-infrared (4 mum) transmission through these sub-wavelength coaxial arrays is observed as compared with that through the same fractional opening area hole arrays as a result of the complex coaxial unit cell. Varying the coaxial dimensions shifts the resonance wavelength and impacts the maximum transmission; design rules are derived. The ability to control the transmission wavelength combined with dramatically enhanced transmission represent a promising path toward nanophotonic applications.

Near-infrared double negative metamaterials.

We numerically demonstrate a metamaterial with both negative epsilon and negative mu over an overlapping near-infrared wavelength range resulting in a low loss negative-index material. Parametric studies optimizing this negative index are presented. This structure can be easily fabricated with standard semiconductor processing techniques.

Metallic inductive and capacitive grids: theory and experiment.

We present theoretical modeling and experimental validation of both capacitive (dot) and inductive (hole) metallic crossed gratings in the mid-infrared (2-5 microm). The gratings are fabricated by use of interferometric lithography and modeled by use of rigorous coupled-wave analysis. Our experimental and numerical investigations of the transmittance spectra of these gratings suggest that, as in inductive grids, the behavior of capacitive grids is described by the coupling of the incident light into surface plasma waves.

Movement and sound generation by the toadfish swimbladder.

Although sound-producing (sonic) muscles attached to fish swimbladders are the fastest known vertebrate muscles, the functional requirement for such extreme speed has never been addressed. We measured movement of the swimbladder caused by sonic muscle stimulation in the oyster toadfish Opsanus tau and related it to major features of the sound waveform. The movement pattern is complex and produces sound inefficiently because the sides and bottom of the bladder move in opposite in and out directions, and both movement and sound decay rapidly. Sound amplitude is related to speed of swimbladder movement, and slow movements do not produce perceptible sound. Peak sound amplitude overlaps fundamental frequencies of the male's mating call because of muscle mechanics and not the natural frequency of the bladder. These findings suggest that rapid muscle speed evolved to generate sound from an inefficient highly damped system.

Cardiovascular disease and arrhythmias: unique risks in women.

Women have higher risks for symptomatic arrhythmias and sudden death than men. A significantly higher resting heart rate and longer QT interval on electrocardiogram may be factors that predispose women to a serious form of ventricular arrhythmia known as torsades de pointes. Recent studies have demonstrated hormonal effects on the expression of cardiac potassium and calcium ion channels, indicating their possible regulatory role in the modulation of cardiac repolarization and QT interval. These results demonstrate a need for greater awareness and further research into the mechanistic differences between men and women with respect to arrhythmia and cardiovascular disease.

The presentation of self and allogeneic MHC peptides to T lymphocytes.

The presentation of donor-derived MHC peptides by recipient APCs to T cells is an essential component of the rejection of allografts (indirect allorecognition). Initial alloreactive T cell response is confined to a few well processed and presented dominant determinants on donor MHC. However, during long-term graft rejection, T cell response spreads to formerly poorly presented cryptic allogeneic MHC peptides. This phenomenon is likely to play an important role in the amplification and the perpetuation of the rejection process. Additionally, we present evidence that T cell repertoire selection to allogeneic MHC peptides is acquired via recognition of self-MHC peptides presented in the thymus during ontogeny. Supporting this view, we have shown that indirect alloresponses can lead to self-T cell tolerance breakdown to cross-reactive determinants on self-MHC molecules or alternatively that sensitization of recipients to self-MHC peptides can lead to accelerated graft rejection. It is therefore essential to determine the factors which govern the processing and presentation of self and allogeneic MHC molecules and to elucidate the mechanisms regulating subsequent T cell responses in order to design antigen-specific based immune therapies in transplantation.

The enigma of giant cell arteritis: multidisciplinary management of two cases.

BACKGROUND: Giant cell arteritis is an enigmatic disease that is characterized by chronic granulomatous inflammation of the walls of large and medium-sized arteries. The process has a predilection for the extradural cranial arteries, which include the ophthalmic and the posterior ciliary arteries. A multisymptom disease of older individuals, giant cell arteritis often manifests challenging issues and diagnostic dilemmas. CASE REPORTS: We illustrate two cases with initial symptoms of intermittent headache, malaise, and decreased visual acuity that were incorrectly diagnosed or ultimately misdiagnosed. The first case represents a patient who was diagnosed as having migraine headache and an erythrocyte sedimentation rate (ESR) that was interpreted by the attending physician as too low to warrant temporal artery biopsy. The second case is that of a patient who had a history of headaches, jaw claudication, and numerous medical evaluations. CONCLUSION: Giant cell arteries is an enigmatic disease with multiple manifestations. The differential diagnoses can range from temporal mandibular joint dysfunction to tension headache. Imminent vision loss as a sequelae of this condition warrants careful review of ocular and constitutional history and prompt treatment.

Solar UVB-induced DNA damage and photoenzymatic DNA repair in antarctic zooplankton.

The detrimental effects of elevated intensities of mid-UV radiation (UVB), a result of stratospheric ozone depletion during the austral spring, on the primary producers of the Antarctic marine ecosystem have been well documented. Here we report that natural populations of Antarctic zooplankton also sustain significant DNA damage [measured as cyclobutane pyrimidine dimers (CPDs)] during periods of increased UVB flux. This is the first direct evidence that increased solar UVB may result in damage to marine organisms other than primary producers in Antarctica. The extent of DNA damage in pelagic icefish eggs correlated with daily incident UVB irradiance, reflecting the difference between acquisition and repair of CPDs. Patterns of DNA damage in fish larvae did not correlate with daily UVB flux, possibly due to different depth distributions and/or different capacities for DNA repair. Clearance of CPDs by Antarctic fish and krill was mediated primarily by the photoenzymatic repair system. Although repair rates were large for all species evaluated, they were apparently inadequate to prevent the transient accumulation of substantial CPD burdens. The capacity for DNA repair in Antarctic organisms was highest in those species whose early life history stages occupy the water column during periods of ozone depletion (austral spring) and lowest in fish species whose eggs and larvae are abundant during winter. Although the potential reduction in fitness of Antarctic zooplankton resulting from DNA damage is unknown, we suggest that increased solar UV may reduce recruitment and adversely affect trophic transfer of productivity by affecting heterotrophic species as well as primary producers.

The novel class III antiarrhythmics NE-10064 and NE-10133 inhibit IsK channels expressed in Xenopus oocytes and IKs in guinea pig cardiac myocytes.

Slowly activating, voltage-dependent IsK channels were expressed in Xenopus oocytes after injection of rat IsK protein cRNA and recorded with the two-microelectrode voltage-clamp technique. The IsK currents were inhibited by the new class III antiarrhythmic drugs NE-10064 and NE-10133. These compounds were equally potent in inhibiting a slowly activating potassium current (IKs) in guinea pig ventricular myocytes. No effects of these compounds could be observed on several other cloned delayed rectifier potassium channels, nor did they affect the inward rectifier current, IK1, in guinea pig cardiac myocytes at the concentrations tested. The blockade of IsK channels may contribute to the class III antiarrhythmic efficacy of these novel antiarrhythmics.

Sulfur-containing amino acids as precursors of thiols in anoxic coastal sediments.

Sulfur-containing amino acids were examined as precursors for thiols in anoxic coastal sediments. Substrates (10 to 100 muM) were anaerobically incubated with sediment slurries; thiols were assayed as isoindole derivatives by high-performance liquid chromatography; and microbial transformations of thiols, in contrast to their chemical binding by sediment particles, were identified by inhibition with a mixture of chloramphenicol and tetracycline. Methionine and homocysteine were transformed to methanethiol and 3-mercaptopropionate (3-MPA); methionine stimulated mainly methanethiol production, whereas homocysteine generated more 3-MPA than methanethiol. 2-Keto-4-methiolbutyrate yielded results similar to those with methionine, indicating that demethiolation yields methanethiol at the keto-acid level. Glutathione gave rise to cysteine, which was further transformed to 3-mercaptopyruvate and thence to mercaptoacetate and mercaptoethanol. Mercaptoethanol was oxidized to mercaptoacetate, which was biologically consumed. In conclusion, sulfurcontaining amino acids contribute to the range of thiols that occur in anoxic coastal sediments. New metabolic and environmental transformations were identified: the production of 3-MPA as a metabolite of methionine and the transformation of mercaptopyruvate to mercaptoethanol and mercaptoacetate.

Block of outward current in cardiac Purkinje fibers by injection of quaternary ammonium ions.

We have studied the effects of iontophoretic injection of the quaternary ammonium compounds tetraethylammonium (TEA) and tetrabutylammonium (TBA) in cardiac purkinje fibers. We find that TBA(+) is a more effective blocker than TEA(+), but injection of either compound reduces the time-dependent outward plateau currents, transient outward current (I(to)), and the delayed rectifier (I(x)). Our findings provide evidence that these outward cardiac currents are carried by channels that in some respects are pharmacologically similar to squid axon potassium channels. We demonstrate that this procedure is a new tool that can be useful in the analysis of membrane currents in the heart.

Effects of acute administration of delta9-tetrahydrocannabinol on pulmonary hemodynamics of anesthetized dogs.

I.v. administration of delta9-THC (2.5 mg/kg) To anesthetized dogs resulted in a decrease in heart rate, pulmonary blood flow (PBF), and a significant increase in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (PVR). The increase in PVR to delta9-THC was significantly reduced by cardiac pacing, and was virtually abolished either by bilateral vagotomy or by pretreatment with hexamethonium. The data indicated the delta9-THC induced elevation of PVR was mediated via reflexogenic mechanisms involving afferent vagi and efferent autonomic pathways.