Refractory hypoxia and saturation gap in a COVID-19 patient.

Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen irreversibly leading to functional anemia, cyanosis, and tissue hypoxia. We report a case of a 60-year-old man with multiple comorbidities who was diagnosed with coronavirus disease 2019 (COVID-19) and developed methemoglobinemia after consumption of prescribed supplements. He presented with dyspnea and cyanosis. An oxygen saturation gap with characteristic chocolate-brown arterial blood indicated methemoglobinemia. Outsourced methemoglobin (MetHb) was increased at 9.0%. Despite aggressive intervention, he succumbed to his illness. In this case, we discuss the pathophysiology of why some individuals, especially the elderly with COVID-19 are more susceptible to develop methemoglobinemia after possibly being exposed to oxidizing agents. Laboratory methods for assessing oxygen saturation, including pulse oximetry, arterial blood gas and co-oximetry are examined in relation to this case. The importance of considering a diagnosis of methemoglobinemia based on clinical and biochemical findings although MetHb assay or co-oximetry are not readily available is also emphasized.

Effects of a culturally tailored low-glycaemic index dietary educational intervention on reducing cardiometabolic risk among Chinese adults with obesity: a randomised controlled trial.

AIMS: An assessor-blinded randomised controlled trial was conducted to assess the effect of a culturally tailored low-glycaemic index (GI) dietary educational intervention on body mass index and cardiometabolic risks for Chinese people with obesity in Hong Kong. METHODS AND RESULTS: A total of 166 Chinese adults in Hong Kong with obesity were randomised to the intervention group (n=83) or the control group (n=83). The intervention group received the culturally sensitive low-GI dietary educational intervention based on the Health Belief Model, consisting of an educational booklet, one individual interactive educational session, and three follow-up telephone calls. The control group received general advice on a healthy diet, including a pamphlet, one individual education session, and three follow-up telephone calls. Outcome measures included body mass index, cardiometabolic risk-factors, dietary intake variables and sense of satiety. Data collection was conducted at baseline and post-intervention at 12-week. Generalized estimating equation model was used to compare the difference in changes in outcome variables between groups. Compared with the control group, the intervention group exhibited a significant reduction in dietary glycaemic load (ß=-6.963, p=0.026) at post intervention. No significant effects were found on other outcomes. CONCLUSION: A 12-week culturally tailored and Health Belief Model-based low-GI dietary educational intervention significantly reduced the dietary glycaemic load and showed the feasibility of the low-GI dietary intervention in Chinese adults in Hong Kong with obesity. A longer intervention period and follow-up might be required to achieve improvements in reducing cardiometabolic risk factors in people with obesity. REGISTRATION: ClinicalTrials.gov Identifier: NCT04152213.

Menthol alleviates post-race elevations in muscle soreness and metabolic and respiratory stress during running.

PURPOSE: We evaluated (1) whether participating in middle- and long-distance running races augments muscle soreness, oxygen cost, respiration, and exercise exertion during subsequent running, and (2) if post-race menthol application alleviates these responses in long-distance runners. METHODS: Eleven long-distance runners completed a 1500-m race on day 1 and a 3000-m race on day 2. On day 3 (post-race day), either a 4% menthol solution (Post-race menthol) or a placebo solution (Post-race placebo) serving as a vehicle control, was applied to their lower leg skin, and their perceptual and physiological responses were evaluated. The identical assessment with the placebo solution was also conducted without race participation (No-race placebo). RESULTS: The integrated muscle soreness index increased in the Post-race placebo compared to the No-race placebo (P < 0.001), but this response was absent in the Post-race menthol (P = 0.058). Oxygen uptake during treadmill running tended to be higher (4.3%) in the Post-race placebo vs. No-race placebo (P = 0.074). Oxygen uptake was 5.4% lower in the Post-race menthol compared to the Post-race placebo (P = 0.018). Minute ventilation during treadmill running was 6.7-7.6% higher in the Post-race placebo compared to No-race placebo, whereas it was 6.6-9.0% lower in the Post-race menthol vs. Post-race placebo (all P ≤ 0.001). The rate of perceived exertion was 7.0% lower in the Post-race menthol vs. Post-race placebo (P = 0.007). CONCLUSIONS: Middle- and long-distance races can subsequently elevate muscle soreness and induce respiratory and metabolic stress, but post-race menthol application to the lower legs can mitigate these responses and reduce exercise exertion in long-distance runners.

Synthesis of Tetrasubstituted Alkenes by Rhodium-Catalyzed Regioselective Cyano Transfer.

We describe herein a novel, general, and robust approach to structurally diversified alkenyl nitriles through a Rh-catalyzed cyano transfer reaction between alkynyl-malononitrile derivatives and aryl/alkenyl boronic acids. This reaction exhibits high chemo- and regioselectivity and a broad substrate scope. The tetrasubstituted alkenyl dinitriles (34 examples, average 58% yield) are obtained through substrate tuning and ligand control.

Optimal treatment strategy and prognostic analysis of salvage liver transplantation for patients with early hepatocellular carcinoma recurrence after hepatectomy.

AIM: We aimed to investigate the prognostic factors for salvage liver transplant in patients with early hepatocellular carcinoma recurrence after hepatectomy. METHODS: This retrospective analysis included 53 patients who underwent salvage living-donor liver transplantation between January 2007 and January 2018. There were 24 and 29 patients in the early (recurrence ≤24 months after primary liver resection) and the late recurrence groups, respectively. RESULTS: In the multivariate Cox regression model, pre-liver transplant downstaging therapy, early recurrence (ER) after primary liver resection , and recurrence-to-liver-transplant ≥12 months were independent risks to predict recurrent hepatocellular carcinoma recurrence after salvage living-donor liver transplantation. Compared with the late recurrence group, the ER group showed lower disease-free survival rates (p < 0.001); however, the overall survival rates did not differ between the two groups (p = 0.355). The 1-, 3-, and 5-year disease-free survival rates were 83.3%, 70.6%, and 66.2%, and 96.0%, 91.6%, and 91.6% in the early and late recurrence groups, respectively. When stratified by recurrence-to-liver transplant time and pre-liver transplant downstaging therapy in the ER group, disease-free survival and overall survival rates were significantly different. CONCLUSION: ER after primary liver resection with advanced tumor status and a longer period of recurrence-to-liver-transplant (≥12 months) have a negative impact on salvage liver transplant. Our findings provide novel recommendations for treatment strategies and eligibility for salvage liver transplant candidates.

Reconstruction of multi-phase parametric maps in 4D-magnetic resonance fingerprinting (4D-MRF) by optimization of local T1 and T2 sensitivities.

BACKGROUND: Time-resolved magnetic resonance fingerprinting (MRF), or 4D-MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D-MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. PURPOSE: To develop a technique for the reconstruction of multi-phase parametric maps in four-dimensional magnetic resonance fingerprinting (4D-MRF) through the optimization of local T1 and T2 sensitivities. METHODS: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter-phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi-phase signal evolution curves were modified by sliding window reconstruction and inter-phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi-parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac-torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. RESULTS: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight-phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in-vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. CONCLUSIONS: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi-phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data.

Model Generalizability Investigation for GFCE-MRI Synthesis in NPC Radiotherapy Using Multi-Institutional Patient-Based Data Normalization.

Recently, deep learning has been demonstrated to be feasible in eliminating the use of gadoliniumbased contrast agents (GBCAs) through synthesizing gadolinium-free contrast-enhanced MRI (GFCE-MRI) from contrast-free MRI sequences, providing the community with an alternative to get rid of GBCAs-associated safety issues in patients. Nevertheless, generalizability assessment of the GFCE-MRI model has been largely challenged by the high inter-institutional heterogeneity of MRI data, on top of the scarcity of multi-institutional data itself. Although various data normalization methods have been adopted to address the heterogeneity issue, it has been limited to single-institutional investigation and there is no standard normalization approach presently. In this study, we aimed at investigating generalizability of GFCE-MRI model using data from seven institutions by manipulating heterogeneity of MRI data under five popular normalization approaches. Three state-of-the-art neural networks were applied to map from T1-weighted and T2-weighted MRI to contrast-enhanced MRI (CE-MRI) for GFCE-MRI synthesis in patients with nasopharyngeal carcinoma. MRI data from three institutions were used separately to generate three uni-institution models and jointly for a tri-institution model. The five normalization methods were applied to normalize the data of each model. MRI data from the remaining four institutions served as external cohorts for model generalizability assessment. Quality of GFCE-MRI was quantitatively evaluated against ground-truth CE-MRI using mean absolute error (MAE) and peak signal-to-noise ratio(PSNR). Results showed that performance of all uni-institution models remarkably dropped on the external cohorts. By contrast, model trained using multi-institutional data with Z-Score normalization yielded the best model generalizability improvement.

An international prospective study of INICC analyzing the incidence and risk factors for catheter-associated urinary tract infections in 235 ICUs across 8 Asian Countries.

BACKGROUND: Identify urinary catheter (UC)-associated urinary tract infections (CAUTI) incidence and risk factors (RF) in 235 ICUs in 8 Asian countries: India, Malaysia, Mongolia, Nepal, Pakistan, the Philippines, Thailand, and Vietnam. METHODS: From January 1, 2014, to February 12, 2022, we conducted a prospective cohort study. To estimate CAUTI incidence, the number of UC days was the denominator, and CAUTI was the numerator. To estimate CAUTI RFs, we analyzed 11 variables using multiple logistic regression. RESULTS: 84,920 patients hospitalized for 499,272 patient days acquired 869 CAUTIs. The pooled CAUTI rate per 1,000 UC-days was 3.08; for those using suprapubic-catheters (4.11); indwelling-catheters (2.65); trauma-ICU (10.55), neurologic-ICU (7.17), neurosurgical-ICU (5.28); in lower-middle-income countries (3.05); in upper-middle-income countries (1.71); at public-hospitals (5.98), at private-hospitals (3.09), at teaching-hospitals (2.04). The following variables were identified as CAUTI RFs: Age (adjusted odds ratio [aOR] = 1.01; 95% CI = 1.01-1.02; P < .0001); female sex (aOR = 1.39; 95% CI = 1.21-1.59; P < .0001); using suprapubic-catheter (aOR = 4.72; 95% CI = 1.69-13.21; P < .0001); length of stay before CAUTI acquisition (aOR = 1.04; 95% CI = 1.04-1.05; P < .0001); UC and device utilization-ratio (aOR = 1.07; 95% CI = 1.01-1.13; P = .02); hospitalized at trauma-ICU (aOR = 14.12; 95% CI = 4.68-42.67; P < .0001), neurologic-ICU (aOR = 14.13; 95% CI = 6.63-30.11; P < .0001), neurosurgical-ICU (aOR = 13.79; 95% CI = 6.88-27.64; P < .0001); public-facilities (aOR = 3.23; 95% CI = 2.34-4.46; P < .0001). DISCUSSION: CAUTI rate and risk are higher for older patients, women, hospitalized at trauma-ICU, neurologic-ICU, neurosurgical-ICU, and public facilities. All of them are unlikely to change. CONCLUSIONS: It is suggested to focus on reducing the length of stay and the Urinary catheter device utilization ratio, avoiding suprapubic catheters, and implementing evidence-based CAUTI prevention recommendations.

Multigene Profiling of Circulating Tumor Cells in Esophageal Squamous Cell Carcinoma Identifies Prognostic Cancer Driver Genes Associated with Epithelial-Mesenchymal-Transition Progression and Chemoresistance.

We investigated the clinical significance of CTCs in cancer progression by detecting multiple cancer driver genes associated with epithelial-to-mesenchymal transition (EMT) at the transcript level. The 10-gene panel, comprising CCND1, ECT2, EpCAM, FSCN1, KRT5, KRT18, MET, TFRC, TWIST1, and VEGFC, was established for characterizing CTCs from mouse ESCC xenograft models and clinical ESCC peripheral blood (PB) samples. Correlations between gene expression in CTCs from PB samples (n = 77) and clinicopathological features in ESCC patients (n = 55) were examined. The presence of CTCs at baseline was significantly correlated with tumor size (p = 0.031). The CTC-high patients were significantly correlated with advanced cancer stages (p = 0.013) and distant metastasis (p = 0.029). High mRNA levels of TWIST1 (Hazard Ratio (HR) = 5.44, p = 0.007), VEGFC (HR = 6.67, p < 0.001), TFRC (HR = 2.63, p = 0.034), and EpCAM (HR = 2.53, p = 0.041) at baseline were significantly associated with a shorter overall survival (OS) in ESCC patients. This study also revealed that TWIST1 facilitates EMT and enhances malignant potential by promoting tumor migration, invasion, and cisplatin chemoresistance through the TWIST1-TGFBI-ZEB1 axis in ESCC, highlighting the prognostic and therapeutic potential of TWIST1 in clinical ESCC treatment.

External validation of the first prognostic nomogram for older adults with cancer.

Background: The geriatric oncology population tends to be complex because of multimorbidity, functional and cognitive decline, malnutrition and social frailty. Prognostic indices for predicting survival of elderly cancer patients to guide treatment remain scarce. A nomogram based on all domains of the geriatric assessment was previously developed at the National Cancer Centre Singapore (NCCS) to predict overall survival (OS) in elderly cancer patients. This nomogram comprised of six variables (age, eastern cooperative oncology group performance status, disease stage, geriatric depression scale (GDS), DETERMINE nutritional index and serum albumin). Objectives: To externally validate the NCCS prognostic nomogram. Design: This is a prospective cohort study. Methods: The nomogram was developed based on a training cohort of 249 patients aged ⩾70 years who attended the NCCS outpatient geriatric oncology clinic between May 2007 and November 2010. External validation of the nomogram using the Royston and Altman approach was carried out on an independent testing cohort of 252 patients from the same clinic between July 2015 and June 2017. Model misspecification, discrimination and calibration were assessed. Results: Median OS of the testing cohort was 3.1 years, which was significantly higher than the corresponding 1.0 year for the training cohort (log-rank p < 0.001). The nomogram achieved a high level of discrimination in the testing cohort (0.7112), comparable to the training cohort (0.7108). Predicted death probabilities were generally well calibrated with the observed death probabilities, as the joint test of calibration-in-the-large estimates at year 1, 2 and 3 from zeros and calibration slope from one was insignificant with p = 0.432. There were model misspecifications in GDS and serum albumin. Conclusion: This study externally validated the prognostic nomogram in an independent cohort of geriatric oncology patients. This supports the use of this nomogram in clinical practice.

Ultra-fast multi-parametric 4D-MRI image reconstruction for real-time applications using a downsampling-invariant deformable registration (D2R) model.

BACKGROUND AND PURPOSE: Motion estimation from severely downsampled 4D-MRI is essential for real-time imaging and tumor tracking. This simulation study developed a novel deep learning model for simultaneous MR image reconstruction and motion estimation, named the Downsampling-Invariant Deformable Registration (D2R) model. MATERIALS AND METHODS: Forty-three patients undergoing radiotherapy for liver tumors were recruited for model training and internal validation. Five prospective patients from another center were recruited for external validation. Patients received 4D-MRI scans and 3D MRI scans. The 4D-MRI was retrospectively down-sampled to simulate real-time acquisition. Motion estimation was performed using the proposed D2R model. The accuracy and robustness of the proposed D2R model and baseline methods, including Demons, Elastix, the parametric total variation (pTV) algorithm, and VoxelMorph, were compared. High-quality (HQ) 4D-MR images were also constructed using the D2R model for real-time imaging feasibility verification. The image quality and motion accuracy of the constructed HQ 4D-MRI were evaluated. RESULTS: The D2R model showed significantly superior and robust registration performance than all the baseline methods at downsampling factors up to 500. HQ T1-weighted and T2-weighted 4D-MR images were also successfully constructed with significantly improved image quality, sub-voxel level motion error, and real-time efficiency. External validation demonstrated the robustness and generalizability of the technique. CONCLUSION: In this study, we developed a novel D2R model for deformation estimation of downsampled 4D-MR images. HQ 4D-MR images were successfully constructed using the D2R model. This model may expand the clinical implementation of 4D-MRI for real-time motion management during liver cancer treatment.

Circulating Tumor DNA Dynamics as Prognostic Markers in Locally Advanced and Metastatic Esophageal Squamous Cell Carcinoma.

Importance: Esophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease. Objective: To examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival. Design, Setting, and Participants: This single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes. Intervention: Patients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT). Main Outcomes and Measures: Detection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS). Results: A total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4). Conclusions and Relevance: The findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

BiBr3 -Mediated Intramolecular Aza-Prins Cyclization of Aza-Achmatowicz Rearrangement Products: Asymmetric Total Synthesis of Suaveoline and Sarpagine Alkaloids.

An intramolecular aza-Prins cyclization of aza-Achmatowicz rearrangement products was developed in which bismuth tribromide (BiBr3 ) plays a dual role as an efficient Lewis acid and source of the bromide nucleophile. This approach enables the facile construction of highly functionalized 9-azabicyclo[3.3.1]nonanes (9-ABNs), which are valuable synthetic building blocks and a powerful platform for the synthesis of a variety of alkaloid natural products and drug molecules. Suitable substrates for the aza-Prins cyclization include 1,1-disubstituted alkenes, 1,2-disubstituted alkenes, alkynes, and allenes, with good to excellent yields observed. Finally, we showcase the application of this new approach to the enantioselective total synthesis of six indole alkaloids: (-)-suaveoline (1), (-)-norsuaveoline (2), (-)-macrophylline (3), (+)-normacusine B (4), (+)-Na -methyl-16-epipericyclivine (5) and (+)-affinisine (6) in a total of 9-14 steps. This study significantly expands the synthetic utility of the aza-Achmatowicz rearrangement, and the strategy (aza-Achmatowicz/aza-Prins) is expected to be applicable to the total synthesis of other members of the big family of macroline and sarpagine indole alkaloids.

A Prospective Study Evaluating the Feasibility and Accuracy of Post-operative Laryngeal Ultrasonography (LUSG) in Assessment of Vocal Cord Function After Esophagectomy.

BACKGROUND: Vocal cord paresis (VCP) is a serious complication after esophagectomy. Conventional diagnosis of VCP relies on flexible laryngoscopy (FL), which is invasive. Laryngeal ultrasonography (LUSG) is non-invasive and convenient. It has provided accurate VC evaluation after thyroidectomy but it is unclear if it is just as accurate following esophagectomy. This prospective study evaluated the feasibility and accuracy of LUSG in VC assessment on day-1 after esophagectomy. METHODS: Consecutive patients from a tertiary teaching hospital who underwent elective esophagectomy were prospectively recruited. All received pre-operative FL, and post-operative LUSG and FL on Day-1, each performed by a blinded, independent assessor. The primary outcomes were feasibility and accuracy of LUSG in the diagnosis of VCP on Day-1 post-esophagectomy. The accuracy of voice assessment (VA) was analyzed. RESULTS: Twenty-six patients were eligible for analysis. The median age was 70 years (66-73). Majority were male (84.6%). Twenty-five (96.2%) received three-phase esophagectomy. Twenty-four (96%) had same-stage anastomosis at the neck. Three (11.5%) developed temporary and one (3.8%) developed permanent unilateral VCP. Overall VC visualization rate by LUSG was 100%; sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy of LUSG were 75.0%, 100%, 100%, 98.0%, 98.1% respectively, and superior to VA. Combining LUSG with VA findings could pick up all VCPs i.e. improved sensitivity and NPV to 100%. CONCLUSION: LUSG is a highly feasible, accurate and non-invasive method to evaluate VC function early after esophagectomy. Post-operative FL may be avoided in patients with both normal LUSG and voice.

Fatal Orbital Cellulitis With Intracranial Abscess: A Case Report.

Orbital cellulitis is a sight- and life-threatening condition. Prompt diagnosis and immediate intervention are required. We report a case of fatal odontogenic orbital cellulitis complicated with intracranial abscesses in a 55-year-old gentleman. The patient presented with painful swelling of the left eye associated with reduced eye movement, blurry vision, and a headache. There was generalized periodontitis. Initial imaging was suggestive of left eye orbital cellulitis with intracranial abscess, and intensive systemic antibiotic therapy was initiated. After six weeks of antibiotic therapy, there was an improvement in ocular signs and symptoms. However, the patient developed signs of meningism with a persistent fever. Serial brain imaging demonstrated worsening intracranial abscesses. The patient died eight weeks after the initial onset of presentation. This case emphasized that brain abscesses could be a fatal complication of odontogenic orbital cellulitis. A high index of suspicion is important in diagnosing orbital cellulitis and its complications. Early consideration of surgical intervention is necessary in cases not responding to antibiotic therapy.

An Integrated Analysis of Metabolome, Transcriptome, and Physiology Revealed the Molecular and Physiological Response of Citrus sinensis Roots to Prolonged Nitrogen Deficiency.

Citrus sinensis seedlings were supplied with a nutrient solution containing 15 (control) or 0 (nitrogen (N) deficiency) mM N for 10 weeks. Extensive metabolic and gene reprogramming occurred in 0 mM N-treated roots (RN0) to cope with N deficiency, including: (a) enhancing the ability to keep phosphate homeostasis by elevating the abundances of metabolites containing phosphorus and the compartmentation of phosphate in plastids, and/or downregulating low-phosphate-inducible genes; (b) improving the ability to keep N homeostasis by lowering the levels of metabolites containing N but not phosphorus, upregulating N compound degradation, the root/shoot ratio, and the expression of genes involved in N uptake, and resulting in transitions from N-rich alkaloids to carbon (C)-rich phenylpropanoids and phenolic compounds (excluding indole alkaloids) and from N-rich amino acids to C-rich carbohydrates and organic acids; (c) upregulating the ability to maintain energy homeostasis by increasing energy production (tricarboxylic acid cycle, glycolysis/gluconeogenesis, oxidative phosphorylation, and ATP biosynthetic process) and decreasing energy utilization for amino acid and protein biosynthesis and new root building; (d) elevating the transmembrane transport of metabolites, thus enhancing the remobilization and recycling of useful compounds; and (e) activating protein processing in the endoplasmic reticulum. RN0 had a higher ability to detoxify reactive oxygen species and aldehydes, thus protecting RN0 against oxidative injury and delaying root senescence.

Pre-clinical evaluation of APrevent® VOIS for unilateral vocal fold paralysis medialization.

Objective: To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini-pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex-vivo aerodynamic and acoustic analysis. Methods: Feasibility testing and prototype implantation were performed using in-vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS-Implant. Results: The prototype showed in the in-vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar "distance S" as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p = .0187), phonation threshold flow (p = .0001) and phonation threshold power (p = .0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p = .2976; p = .1771) but not significant. Conclusions: Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long-term implantation. Level of Evidence: N/A.