Training Robust T1-Weighted Magnetic Resonance Imaging Liver Segmentation Models Using Ensembles of Datasets with Different Contrast Protocols and Liver Disease Etiologies.

Image segmentation of the liver is an important step in several treatments for liver cancer. However, manual segmentation at a large scale is not practical, leading to increasing reliance on deep learning models to automatically segment the liver. This manuscript develops a deep learning model to segment the liver on T1w MR images. We sought to determine the best architecture by training, validating, and testing three different deep learning architectures using a total of 819 T1w MR images gathered from six different datasets, both publicly and internally available. Our experiments compared each architecture's testing performance when trained on data from the same dataset via 5-fold cross validation to its testing performance when trained on all other datasets. Models trained using nnUNet achieved mean Dice-Sorensen similarity coefficients > 90% when tested on each of the six datasets individually. The performance of these models suggests that an nnUNet liver segmentation model trained on a large and diverse collection of T1w MR images would be robust to potential changes in contrast protocol and disease etiology.

Shear wave elastography of the ulnar collateral ligament in division IA pitchers across a competitive collegiate season.

Background: The ulnar collateral ligament (UCL) is a commonly injured elbow stabilizer during throwing. Shear wave elastography (SWE) is a technique that may reveal structural changes in the UCL that are indicative of ligament health and injury risk. The purpose of this study was to assess preseason and inseason shear wave velocity (SWV) in the UCL of collegiate pitchers and to asses repeatability of this measurement technique in healthy volunteers. Methods: Seventeen collegiate baseball pitchers and 11 sex-matched volunteers were recruited. Two-dimensional SWE of the UCL was performed by a single radiologist. In pitchers, SWV was measured at the proximal, midsubstance, and distal UCL for dominant and nondominant elbows preseason, midseason, and postseason, and Kerlan-Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow questionnaire scores were recorded. In volunteers, SWV was measured at UCL midsubstance in dominant elbows at 3 separate occasions over 1 week. An independent samples t-test was used to compare preseason midsubstance measures between pitchers and the healthy volunteers. A mixed-model analysis of covariance (covaried on preseason measures) was used to compare SWV measures at the preseason, midseason, and postseason time points. A similar generalized linear model for nonparametric data was used to compare KJOC scores. Type-I error was set at P < .05. Results: Mean preseason midsubstance dominant arm UCL SWV did not significantly differ between the pitchers (5.40 ± 1.65 m/s) compared to the healthy volunteers (4.35 ± 1.45 m/s). For inseason measures among the pitchers, a decrease in midsubstance (-1.17 ± 0.99 m/s, P = .021) and proximal (-1.55 ± 0.91 m/s, P = .001) SWV was observed at midseason compared to preseason. The proximal measure was also observed to be significantly lower than the nondominant arm (-1.97 ± 0.95 m/s, P < .001). Proximal SWV remained reduced relative to the preseason and the postseason mark (-1.13 ± 0.91 m/s, P = .015). KJOC scores decreased at midseason compared to preseason (P = .003) but then increased to a similar preseason value at the postseason measurement (preseason = 92 ± 3, midseason = 87 ± 3, postseason = 91 ± 3). The repeatability coefficient of SWE in the volunteer cohort was 1.98 m/s. Conclusion: Decreased SWV in the proximal and midsubstance of the dominant arm UCL at midseason suggests structural changes indicative of increasing laxity or 'softening' of the UCL. Associated decline in KJOC scores suggests that these changes are associated with functional decline. Future studies with more frequent sampling would be invaluable to further explore this observation and its significance for predicting and managing UCL injury risk.

Quantitative high-resolution 7T MRI to assess longitudinal changes in articular cartilage after anterior cruciate ligament injury in a rabbit model of post-traumatic osteoarthritis.

Objective: To demonstrate an ultra-high field (UHF) 7 â€‹T delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) protocol for quantitative post-traumatic osteoarthritis (PTOA) detection and monitoring in a rabbit anterior cruciate ligament transection (ACLT) model. Design: ACL transections were performed unilaterally in 5 rabbits (33-weeks-old, 3.5 â€‹± â€‹0.5 â€‹kg) to induce PTOA. MRI exams were performed at 7 â€‹T prior to and 2, 4, 7 and 10-weeks after ACLT using a modified dGEMRIC protocol. Voxel-based T1 and T2 maps were created over manually drawn femoral cartilage ROIs from the center of the tibial plateau to the posterior meniscus. Femoral, tibial, and patellar epiphyses were harvested 10-weeks post-surgery and processed for µCT imaging and histology. Results: Quantitative analysis revealed a 35% and 39% decrease in dGEMRIC index in the medial ACLT knee compartment 7- and 10-weeks post-surgery, respectively (p â€‹= â€‹0.009 and p â€‹= â€‹0.006) when compared to baseline. There was no significant change in the lateral ACLT compartment or in either compartment of the control knees. Visual inspection of histology confirmed PTOA in the ACLT knees. Osteophytes were found only in ACLT knees (osteophyte volume in femur: 94.53 â€‹± â€‹44.08 â€‹mm3, tibia: 29.35 â€‹± â€‹13.79 â€‹mm3, and patella: 3.84 â€‹± â€‹0.92 â€‹mm3) and were significantly larger in the medial compartments of the femur than lateral (p â€‹= â€‹0.0312). Conclusion: The dGEMRIC technique quantitatively applied at 7 â€‹T UHF-MRI demonstrates site-specific cartilage degeneration in a large animal PTOA model. This should encourage further investigation, with potential applications in drug and therapeutic animal trials as well as human studies.

Impact of Foliar Application of ZnO and Fe3O4 Nanoparticles on Seed Yield and Physio-Biochemical Parameters of Cucumber (Cucumis sativus L.) Seed under Open Field and Protected Environment vis a vis during Seed Germination.

Nutritionally rich cucumber seeds remain in demand in the agricultural, health and cosmetic sectors as they are essential for a successful crop stand establishment and seed-based products. However, the production of cucumber seeds is impeded by source limitation and nutrient deficiency. The foliar application of micronutrients can supplement this deficiency and overcome the physiological setback. An experiment was undertaken to compare the impacts of the foliar application of Fe and Zn, as nanoparticles and fertilizers, on the yield and seed quality of cucumber under open and protected environments. A foliar spray of nano-ZnO (ZnNPs) and nano-Fe3O4 (FeNPs) at 100, 200 and 300 mg L-1, as well as ZnSO4 and FeSO4 as fertilizer (0.5%), was conducted at the vegetative stage and pre- and post-flowering stages. The NPs had a greater efficacy in an open field than in the protected (naturally ventilated poly house) environment. The application of both NPs increased seed yield (51.7-52.2%), total chlorophyll content (15.9-17.3%) and concentration of Zn and Fe in the fruit and the seed, by 2.0-58.5% and 5.0-30.5%, respectively. A significant increase in starch, soluble proteins, soluble sugars and oil content was observed in the seeds from the NP treated plants. NP treatment also enhanced the germination-related parameters, such as percent germination (16.8-17.0%), rate of germination (18.0-22.2%) and seedling vigor (59.8-72.6%). The biochemical characterization showed a significant improvement in the seed water uptake and the activity of hydrolytic enzymes (amylase and protease) in the germinating seed. The involvement of reactive oxygen species (superoxide anion and hydrogen peroxide) and antioxidant enzymes (Superoxide dismutase, Catalase and Peroxidase) in the germination process was indicated by an increase in their activities in the seeds from NP treated plants. Hence, the study proposes the potential benefit of the foliar application of 300 mg L-1 ZnNPs and 200 mg L-1 FeNPs at crucial stages of plant growth to improve the yield and seed quality in cucumbers.

Seed Priming with ZnO and Fe3O4 Nanoparticles Alleviate the Lead Toxicity in Basella alba L. through Reduced Lead Uptake and Regulation of ROS.

The increased lead (Pb) content in the environment has an impact on all living beings, including plant growth and quality. The present study aims to investigate the protective roles of zinc (Zn)- and iron (Fe)- nanoparticles (NPs) in alleviating stress symptoms caused by lead (Pb) exposure in Basella alba seedlings. For this purpose, 15 different treatment combinations of seed priming with two NPs at 0 and 200 mg L−1, and five Pb levels (0, 4, 8, 15, 20 mM) were chosen. Pb stress (20 mM) was found to reduce seed germination by 72.8% and seedling growth, particularly root length, by 92% when compared to the control. Under different Pb concentrations, seed priming with ZnNPs (200 mg L−1) and FeNPs (200 mg L−1) increased seed germination by 34.7% and 54.9%, respectively, and root length by 152.9% and 252.9%, respectively. In 20 mM Pb stress, NPs primed seedling showed decrease in Pb content by 33.7% with ZnNPs and 32.6% with FeNPs. Increased Pb stress resulted in increased reactive oxygen species (ROS) generation (H2O2) and lipid peroxidation (MDA) compared to non-Pb stressed seedlings. However, increased antioxidants in the NPs treatments such as SOD, CAT, POD and proline content, scavenged these ROS. Considering all the parameters under study, priming alleviated Pb stress in the following order: FeNPs > ZnNPs > hydropriming > control. To summarise, seed priming with Zn- and Fe-NPs has the potential to alleviate Pb toxicity via reduced Pb uptake, ROS generation and lipid peroxidation as well as increased proline content and activation of antioxidant enzymatic system.

Performance Evaluation of Bio Concrete by Cluster and Regression Analysis for Environment Protection.

The focus of this research is to isolating and identifying bacteria that produce calcite precipitate, as well as determining whether or not these bacteria are suitable for incorporation into concrete in order to enhance the material's strength and make the environment protection better. In order to survive the high "potential of hydrogen" of concrete, microbes that are going to be added to concrete need to be able to withstand alkali, and they also need to be able to develop endospores so that they can survive the mechanical forces that are going to be put on the concrete while it is being mixed. In order to precipitate CaCO3 in the form of calcite, they need to have a strong urease activity. Both Bacillus sphaericus and the Streptococcus aureus bacterial strains were evaluated for their ability to precipitate calcium carbonate (CaCO3). These strains were obtained from the Department of Biotechnology at GLA University in Mathura. This research aims to solve the issue of augmenting the tension and compression strengths of concrete by investigating possible solutions for environmentally friendly concrete. The sterile cultures of the microorganisms were mixed with water, which was one of the components of the concrete mixture, along with the nutrients in the appropriate proportions. After that, the blocks were molded, and then pond-cured for 7, 28, 56, 90, 120, 180, 270, and 365 days, respectively, before being evaluated for compressibility and tensile strength. An investigation into the effect that bacteria have on compression strength was carried out, and the outcomes of the tests showed that bacterial concrete specimens exhibited an increase in mechanical strength. When compared to regular concrete, the results showed a maximum increase of 16 percent in compressive strength and a maximum increase of 12 percent in split tensile strength. This study also found that both bacterial concrete containing 106, 107, and 108 cfu/ml concentrations made from Bacillus sphaericus and Streptococcus aureus bacteria gave better results than normal concrete. Both cluster analysis (CA) and regression analysis (RA) were utilized in this research project in order to measure and analyze mechanical strength.

A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.

PURPOSE: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. PATIENTS AND METHODS: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. RESULTS: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. CONCLUSIONS: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Heat stress tolerance in peas (Pisum sativum L.): Current status and way forward.

In the era of climate change, the overall productivity of pea (Pisum sativum L.) is being threatened by several abiotic stresses including heat stress (HS). HS causes severe yield losses by adversely affecting several traits in peas. A reduction in pod yield has been reported from 11.1% to 17.5% when mean daily temperature increase from 1.4 to 2.2°C. High-temperature stress (30.5-33°C) especially during reproductive phase is known to drastically reduce both seed yield and germination. HS during germination and early vegetative stage resulted in poor emergence and stunted plant growth along with detrimental effects on physiological functions of the pea plant. To combat HS and continue its life cycle, plants use various defense strategies including heat escape, avoidance or tolerance mechanisms. Ironically, the threshold temperatures for pea plant and its responses are inconsistent and not yet clearly identified. Trait discovery through traditional breeding such as semi leaflessness (afila), upright growing habit, lodging tolerance, lower canopy temperature and small seeded nature has highlighted their utility for greater adaptation under HS in pea. Screening of crop gene pool and landraces for HS tolerance in a targeted environment is a simple approach to identify HS tolerant genotypes. Thus, precise phenotyping using modern phenomics tools could lead to increased breeding efficiency. The NGS (next generation sequencing) data can be associated to find the candidate genes responsible for the HS tolerance in pea. In addition, genomic selection, genome wide association studies (GWAS) and marker assisted selection (MAS) can be used for the development of HS tolerant pea genotypes. Additionally, development of transgenics could be an alternative strategy for the development of HS tolerant pea genotypes. This review comprehensively covers the various aspects of HS tolerance mechanisms in the pea plant, screening protocols, omic advances, and future challenges for the development of HS tolerant genotypes.

A phase 1/2 clinical trial of the nitric oxide synthase inhibitor L-NMMA and taxane for treating chemoresistant triple-negative breast cancer.

The inducible nitric oxide signaling (iNOS) pathway is associated with poor prognosis in triple-negative breast cancer (TNBC). Prior studies using in vivo models showed that inhibition of the iNOS signaling pathway using the pan-NOS inhibitor NG-monomethyl-l-arginine (L-NMMA) reduced tumor growth and enhanced survival in patients with TNBC. Here, we report a first-in-class phase 1/2 trial of L-NMMA combined with taxane for treating patients with chemorefractory, locally advanced breast cancer (LABC) or metastatic TNBC. We also examined immune cell correlates of chemotherapy response. 35 patients with metastatic TNBC were recruited: 15 in the phase 1 trial and 24 in the phase 2 trial (including 4 recommended phase 2 dose patients from the phase 1 trial). The overall response rate was 45.8% (11 of 24): 81.8% (9 of 11) for patients with LABC and 15.4% (2 of 13) for patients with metastatic TNBC. Among the patients with LABC, three patients had a pathological complete response at surgery (27.3%). Grade ≥3 toxicity was noted in 21% of patients; however, no adverse events were attributed to L-NMMA. Immune cells analyzed by CyTOF indicated that chemotherapy nonresponders showed greater expression of markers associated with M2 macrophage polarization and increased concentrations of circulating IL-6 and IL-10 cytokines. In contrast, chemotherapy responders showed an increase in CD15+ neutrophils in blood, as well as a decrease in arginase (a marker of protumor N2 neutrophils) in tumor biopsies obtained at the end of treatment. L-NMMA combined with taxane warrants further investigation in larger clinical studies of patients with breast cancer.

Machine learning automatically detects COVID-19 using chest CTs in a large multicenter cohort.

OBJECTIVES: To investigate machine learning classifiers and interpretable models using chest CT for detection of COVID-19 and differentiation from other pneumonias, interstitial lung disease (ILD) and normal CTs. METHODS: Our retrospective multi-institutional study obtained 2446 chest CTs from 16 institutions (including 1161 COVID-19 patients). Training/validation/testing cohorts included 1011/50/100 COVID-19, 388/16/33 ILD, 189/16/33 other pneumonias, and 559/17/34 normal (no pathologies) CTs. A metric-based approach for the classification of COVID-19 used interpretable features, relying on logistic regression and random forests. A deep learning-based classifier differentiated COVID-19 via 3D features extracted directly from CT attenuation and probability distribution of airspace opacities. RESULTS: Most discriminative features of COVID-19 are the percentage of airspace opacity and peripheral and basal predominant opacities, concordant with the typical characterization of COVID-19 in the literature. Unsupervised hierarchical clustering compares feature distribution across COVID-19 and control cohorts. The metrics-based classifier achieved AUC = 0.83, sensitivity = 0.74, and specificity = 0.79 versus respectively 0.93, 0.90, and 0.83 for the DL-based classifier. Most of ambiguity comes from non-COVID-19 pneumonia with manifestations that overlap with COVID-19, as well as mild COVID-19 cases. Non-COVID-19 classification performance is 91% for ILD, 64% for other pneumonias, and 94% for no pathologies, which demonstrates the robustness of our method against different compositions of control groups. CONCLUSIONS: Our new method accurately discriminates COVID-19 from other types of pneumonia, ILD, and CTs with no pathologies, using quantitative imaging features derived from chest CT, while balancing interpretability of results and classification performance and, therefore, may be useful to facilitate diagnosis of COVID-19. KEY POINTS: • Unsupervised clustering reveals the key tomographic features including percent airspace opacity and peripheral and basal opacities most typical of COVID-19 relative to control groups. • COVID-19-positive CTs were compared with COVID-19-negative chest CTs (including a balanced distribution of non-COVID-19 pneumonia, ILD, and no pathologies). Classification accuracies for COVID-19, pneumonia, ILD, and CT scans with no pathologies are respectively 90%, 64%, 91%, and 94%. • Our deep learning (DL)-based classification method demonstrates an AUC of 0.93 (sensitivity 90%, specificity 83%). Machine learning methods applied to quantitative chest CT metrics can therefore improve diagnostic accuracy in suspected COVID-19, particularly in resource-constrained environments.

Head and Neck Injuries Associated With Cell Phone Use.

Importance: As cell phones gain more influence in daily life, they also become potentially more hazardous. Injuries resulting from cell phone use have long been reported largely in the context of driving-related incidents, but other mechanisms of injury have been underreported. Objective: To assess the incidence, types, and mechanisms of head and neck injuries associated with cell phone use. Design, Setting, and Participants: Retrospective cross-sectional study using data from a national database of individuals with head and neck injuries related to cell phone use who presented to emergency departments in the United States between January 1998 and December 2017. Main Outcomes and Measures: Incidence, types, and mechanisms of injury related to cell phone use in the US population. Results: A reported total of 2501 patients (1129 [55.0%] female, 795 [38.8%] white, and 772 [37.6%] aged 13-29 years) presented with injuries of the head and neck related to cell phone use; the estimated weighted national total was 76 043 patients (42 846 females [56.3%], 34 894 [45.9%] white, and 29 956 [39.4%] aged 13-29 years). The most commonly reported subsites of injuries in the head and neck region included the head (33.1% of estimated total); face, including eyelid, eye area, and nose (32.7%); and neck (12.5%). The most common injury diagnoses included laceration (26.3% of estimated total), contusion/abrasion (24.5%), and internal organ injury (18.4%). Age group distributions showed that most injuries associated with cell phone user distraction occurred among individuals aged 13 to 29 years (60.3%; Cramer V = 0.29). In addition, those younger than 13 years were significantly more likely to sustain direct mechanical injury from a cell phone (82.1%) than to have a cell phone use-associated injury (17.9%) (Cramer V = 0.305), whereas a cell phone use-associated injury was more likely than a direct mechanical injury to occur among those aged 50 to 64 years (68.2% vs 31.8%; Cramer V = 0.11) and those older than 65 years (90.3% vs 9.7%; Cramer V = 0.29). Conclusions and Relevance: Cell phone-related injuries to the head and neck have increased steeply over the recent 20-year period, with many cases resulting from distraction. Although the disposition of most cases is simple, some injuries bear a risk of long-term complications. Many of these injuries occurred among those aged 13 to 29 years and were associated with common activities, such as texting while walking. These findings suggest a need for patient education about injury prevention and the dangers of activity while using these devices.

Iodine quantification and detectability thresholds among major dual-energy CT platforms.

OBJECTIVES: To estimate the minimum detectable iodine concentration on multiple dual-energy CT (DECT) platforms. METHODS AND MATERIALS: A phantom containing iodine concentrations ranging from 0 to 10 mg ml-1 was scanned with five dual-energy platforms (two rapid kilo volt switching (r-kVs), one dual source (DS), one sequential acquisition and one split-filter). Serial dilutions of 300 mg ml-1 iodinated contrast material were used to generate concentrations below 2 mg ml-1. Iodine density and virtual monoenergetic images were reviewed by three radiologists to determine the minimum visually detectable iodine concentration. Contrast-to-noise ratios (CNRs) were calculated. RESULTS: 1 mg mL-1 (~0.8 mg mL-1 corrected) was the minimum visually detectable concentration among the platforms and could be seen by all readers on the third-generation r-kVs and DS platforms. CONCLUSIONS: At low concentrations, CNR for monoenergetic images was highest on the DS platform and lowest in the sequential acquisition and split-filter platforms. ADVANCES IN KNOWLEDGE: The results of this study corroborate previous in vivo estimates of iodine detection limits at DECT and provide a comparison for the performance of different DECT platforms at low iodine concentrations in vitro.

Shear-wave elastography of the ulnar collateral ligament of the elbow in healthy volunteers: a pilot study.

OBJECTIVE: To estimate the intra-observer repeatability of shear wave elastography in the UCL of the elbow, and to compare shear wave velocities between dominant and non-dominant arms. MATERIALS AND METHODS: Twenty elbows in ten healthy volunteers were evaluated [five males, five females; mean age, 31.8 ± 10.3 years]. Shear wave velocity was measured on three separate days during the span of 1 week utilizing a linear 18-MHz transducer. Elastograms were obtained until ten ROIs were drawn, not drawing more than two ROIs on any elastogram. Elastograms were considered diagnostic if any portion of the UCL was colored in and free of boundary artifacts. Median velocity and interquartile range were recorded. A result was considered reliable if the IQR/median ratio of the ten measurements was < 0.3. RESULTS: IQR/median was < 0.3 in 88% of sessions, although in 28% of sessions fewer than 60% of elastograms were diagnostic. The ICC was 0.05 (95% CI; - 0.18-0.36; poor). Repeatability coefficient (95% limits of agreement) was 1.95 m/s (95% CI; 1.61-2.37 m/s). Mean velocity in dominant arms was 5.14 ± 0.53 m/s and 5.24 ± 0.39 m/s in non-dominant (p = 0.558). CONCLUSIONS: Mean shear wave velocity was similar between dominant and non-dominant arms. Although repeatability was poor as assessed by ICC, the repeatability coefficient may be a more useful indicator of clinical utility once shear wave velocities in diseased ligaments are explored. Future studies should therefore evaluate velocities in diseased ligaments and develop techniques to improve elastogram quality.

Computed tomography criteria for the use of advanced localization techniques in minimally invasive thoracoscopic lung resection.

BACKGROUND: The significant improvement of patient outcomes from minimally invasive lung surgery has led to the development of advanced lung nodule localization techniques to help manage patients with small suspicious lung nodules or to help resect patients with small pulmonary metastases. However, there are no clear computed tomography (CT) criteria to guide the use of advanced localization techniques for this group of patients. METHODS: We conducted a retrospective chart review of patients who had undergone initial wedge resection of single or multiple lung nodules. We collected demographics, surgical information and surgical outcomes as well as CT scan features. Multiple logistic regression was performed to determine which factors were most predictive of the need for advanced localization techniques. RESULTS: A total of 45 patients (73%) were resected by direct identification alone while 17 patients (27%) required advanced localization techniques. Of those requiring advanced localization, 11 patients had cone beam CT, 3 patients had transbronchial localization using electromagnetic navigation and 3 patients had preoperative CT guided wire localization. Patients requiring advanced localization had significantly smaller lung nodules at 0.8 cm compared to 1.4 cm (P=0.01), nodules that were further away from the pleura at 1.3 cm compared 0.1 cm (P<0.001) and were more likely to have ground glass nodules (P=0.01) compared to patients who were resected by direct identification alone. Multiple logistic regression confirmed that nodule size, distance to pleura and ground glass attenuation were predictive factors for requiring advanced localizing techniques. Every patient was treated with minimally invasive lung resection. A 1.3-cm or greater solitary pulmonary nodule less than 5 mm from the pleura can be removed without advanced techniques with a 96% success rate. CONCLUSIONS: Overall, in patients undergoing resection of a suspicious primary or metastatic lung nodule, advanced localization techniques should be considered in those with small non-solid nodules, which are not near the pleural surface on CT scan.

Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series.

BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS: In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS: Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION: Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING: None.

Management of the Solitary Pulmonary Nodule.

CONTEXT: - Optimal management of the patient with a solitary pulmonary nodule entails early diagnosis and appropriate treatment for patients with malignant tumors, and minimization of unnecessary interventions and procedures for those with ultimately benign nodules. With the growing number of high-resolution imaging modalities and studies available, incidentally found solitary pulmonary nodules are an increasingly common occurrence. OBJECTIVE: - To provide guidance to clinicians involved in the management of patients with a solitary pulmonary nodule, including aspects of risk stratification, workup, diagnosis, and management. DATA SOURCES: - Data for this review were gathered from an extensive literature review on the topic. CONCLUSIONS: - Logical evaluation and management pathways for a patient with a solitary pulmonary nodule will allow providers to diagnose and treat individuals with early stage lung cancer and minimize morbidity from invasive procedures for patients with benign lesions.

Multiple Renal Artery Pseudoaneurysms in Patients Undergoing Renal Artery Embolization Following Partial Nephrectomy: Correlation with RENAL Nephrometry Scores.

PURPOSE: To describe the incidence of multiple renal artery pseudoaneurysms (PSA) in patients referred for renal artery embolization following partial nephrectomy and to study its relationship to RENAL nephrometry scores. MATERIALS AND METHODS: The medical records of 25 patients referred for renal artery embolization after partial nephrectomy were retrospectively reviewed for the following parameters: size and number of tumors, RENAL nephrometry scores, angiographic abnormalities, technical and clinical outcomes, and estimated glomerular filtration rates (eGFRs) after embolization. RESULTS: Twenty-four patients had primary renal tumors, while 1 patient had a pancreatic tumor invading the kidney. Multiple tumors were resected in 4 patients. Most patients (92 %) were symptomatic, presenting with gross hematuria, flank pain, or both. Angiography revealed PSA with (n = 5) or without (n = 20) AV fistulae. Sixteen patients (64 %) had multiple PSA involving multiple renal vessels. Higher RENAL nephrometry scores were associated with an increasing likelihood of multiple PSA. Multiple vessels were embolized in 14 patients (56 %). Clinical success was achieved after one (n = 22) or two (n = 3) embolization sessions in all patients. Post-embolization eGFR values at different time points after embolization were not significantly different from the post-operative eGFR. CONCLUSION: A majority of patients requiring renal artery embolization following partial nephrectomy have multiple pseudoaneurysms, often requiring selective embolization of multiple vessels. Higher RENAL nephrometry score is associated with an increasing likelihood of multiple pseudoaneurysms. We found transarterial embolization to be a safe and effective treatment option with no long-term adverse effect on renal function in all but one patient with a solitary kidney.

Safety and Efficacy of High-Flow Nasal Cannula Therapy in Preterm Infants: A Meta-analysis.

BACKGROUND AND OBJECTIVE: High-flow therapy is the most recent, and popular, mode of respiratory support in neonates. However, the evidence supporting its efficacy and safety has not yet been established. We conducted a systematic review and meta-analysis of clinical trials comparing efficacy and safety of high-flow therapy compared with other modes of noninvasive ventilation (NIV) in preterm infants. METHODS: Articles were indexed by using Medline, Embase, Scopus, OpenSIGLE, Health Management Information Consortium, and Cochrane Central Register of Controlled Trials. Randomized or quasi-randomized clinical trials involving preterm infants, comparing high-flow therapy with other modes of NIV, and reporting extractable data on relevant outcomes, were selected. Data on efficacy, safety, and other common neonatal outcomes were extracted on predesigned forms. RESULTS: In this analysis, we included 1112 preterm infants, participating in 9 clinical trials. High-flow therapy was similar in efficacy to other modes of NIV in preterm infants when used as primary support (odds ratio of failure of therapy, 1.02 [95% confidence interval: 0.55 to 1.88]), as well as after extubation (1.09 [0.58 to 2.02]). There were no significant differences in odds of death (0.48 [0.18 to 1.24]) between the groups. Preterm infants supported on high-flow had significantly lower odds of nasal trauma (0.13 [0.02 to 0.69]). CONCLUSIONS: High-flow therapy appears to be similar in efficacy and safety to other conventional modes of NIV in preterm infants. It is associated with significantly lower odds of nasal trauma. Caution needs to be exercised in extreme preterm infants because of the paucity of published data.

CT findings in temporal bone osteoradionecrosis.

PURPOSE: The goal of this study was to describe computed tomographic findings in patients with clinically proven temporal bone (TB) osteoradionecrosis (ORN) (TB-ORN). MATERIALS AND METHODS: Computed tomographic scans of 20 patients were retrospectively evaluated for bony and soft tissue abnormalities. Clinical severity was graded based on level of therapy administered: mild (observation), moderate (antibiotics/hyperbaric oxygen), or severe (surgery). RESULTS: Radiation dose to the primary tumor ranged from 30 to 75.6 Gy. Time to onset of ORN from completion of radiation therapy was 2 to 22 years (median, 7 years). CLINICAL FINDINGS: exposed bone, 20 of the 20 patients; otorrhea, 17 of the 20 patients; hearing loss, 11 of the 20 patients; otalgia, 10 of the 20 patients; facial nerve paralysis, 2 of the 20 patients; gait imbalance, 2 of the 20 patients. Computed tomographic findings: external auditory canal erosions, 18 of the 20 patients; mastoid effusion, 18 of the 20 patients; mastoid bony coalescence, 5 of the 20 patients; enhancing soft tissue, 6 of the 20 patients; soft tissue gas, 6 of the 20 patients; temporomandibular joint/condylar erosion, 3 of the 20 patients.Three patients developed an abscess. CONCLUSION: Mastoid effusion and external auditory canal erosions are commonly seen with TB-ORN. Clinically moderate or severe cases of TB-ORN are more likely to demonstrate enhancing soft tissue (P = 0.002), soft tissue gas (P = 0.002), and temporomandibular joint involvement (P = 0.07).

Rhus coriaria ameliorates insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) rats.

We have investigated the effect of methanolic extract of Rhus coriaria (RC) on hyperinsulinemia, glucose intolerance and insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (STZ, 100 mg/kg) to 2 days old rat pups. RC (200 mg/kg and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e, 90 days after STZ injection). A group of citrate control rats were also maintained which has received citrate buffer on the 2nd day of their birth. There was a significant increase in blood glucose, glycosylated hemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with RC reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test (OGTT) was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with RC. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. RC treatment significantly improved insulin sensitivity index (K(ITT)) which was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas RC treatment significantly prevented the rise in HOMA-R in NIDDM treated rats. Our data suggest that methanolic extract of RC significantly delayed the onset of hyperinsulinemia and glucose intolerance and improved insulin sensitivity in NIDDM rats.