Deep Learning-Based Digitally Reconstructed Tomography of the Chest in the Evaluation of Solitary Pulmonary Nodules: A Feasibility Study.

RATIONALE AND OBJECTIVES: Computed tomography (CT) is preferred for evaluating solitary pulmonary nodules (SPNs) but access or availability may be lacking, in addition, overlapping anatomy can hinder detection of SPNs on chest radiographs. We developed and evaluated the clinical feasibility of a deep learning algorithm to generate digitally reconstructed tomography (DRT) images of the chest from digitally reconstructed frontal and lateral radiographs (DRRs) and use them to detect SPNs. METHODS: This single-institution retrospective study included 637 patients with noncontrast helical CT of the chest (mean age 68 years, median age 69 years, standard deviation 11.7 years; 355 women) between 11/2012 and 12/2020, with SPNs measuring 10-30 mm. A deep learning model was trained on 562 patients, validated on 60 patients, and tested on the remaining 15 patients. Diagnostic performance (SPN detection) from planar radiography (DRRs and CT scanograms, PR) alone or with DRT was evaluated by two radiologists in an independent blinded fashion. The quality of the DRT SPN image in terms of nodule size and location, morphology, and opacity was also evaluated, and compared to the ground-truth CT images RESULTS: Diagnostic performance was higher from DRT plus PR than from PR alone (area under the receiver operating characteristic curve 0.95-0.98 versus 0.80-0.85; p < 0.05). DRT plus PR enabled diagnosis of SPNs in 11 more patients than PR alone. Interobserver agreement was 0.82 for DRT plus PR and 0.89 for PR alone; and interobserver agreement for size and location, morphology, and opacity of the DRT SPN was 0.94, 0.68, and 0.38, respectively. CONCLUSION: For SPN detection, DRT plus PR showed better diagnostic performance than PR alone. Deep learning can be used to generate DRT images and improve detection of SPNs.

Validation of a deep learning, value-based care model to predict mortality and comorbidities from chest radiographs in COVID-19.

We validate a deep learning model predicting comorbidities from frontal chest radiographs (CXRs) in patients with coronavirus disease 2019 (COVID-19) and compare the model's performance with hierarchical condition category (HCC) and mortality outcomes in COVID-19. The model was trained and tested on 14,121 ambulatory frontal CXRs from 2010 to 2019 at a single institution, modeling select comorbidities using the value-based Medicare Advantage HCC Risk Adjustment Model. Sex, age, HCC codes, and risk adjustment factor (RAF) score were used. The model was validated on frontal CXRs from 413 ambulatory patients with COVID-19 (internal cohort) and on initial frontal CXRs from 487 COVID-19 hospitalized patients (external cohort). The discriminatory ability of the model was assessed using receiver operating characteristic (ROC) curves compared to the HCC data from electronic health records, and predicted age and RAF score were compared using correlation coefficient and absolute mean error. The model predictions were used as covariables in logistic regression models to evaluate the prediction of mortality in the external cohort. Predicted comorbidities from frontal CXRs, including diabetes with chronic complications, obesity, congestive heart failure, arrhythmias, vascular disease, and chronic obstructive pulmonary disease, had a total area under ROC curve (AUC) of 0.85 (95% CI: 0.85-0.86). The ROC AUC of predicted mortality for the model was 0.84 (95% CI,0.79-0.88) for the combined cohorts. This model using only frontal CXRs predicted select comorbidities and RAF score in both internal ambulatory and external hospitalized COVID-19 cohorts and was discriminatory of mortality, supporting its potential use in clinical decision making.

Predicting Prolonged Hospitalization and Supplemental Oxygenation in Patients with COVID-19 Infection from Ambulatory Chest Radiographs using Deep Learning.

RATIONALE AND OBJECTIVES: The clinical prognosis of outpatients with coronavirus disease 2019 (COVID-19) remains difficult to predict, with outcomes including asymptomatic, hospitalization, intubation, and death. Here we determined the prognostic value of an outpatient chest radiograph, together with an ensemble of deep learning algorithms predicting comorbidities and airspace disease to identify patients at a higher risk of hospitalization from COVID-19 infection. MATERIALS AND METHODS: This retrospective study included outpatients with COVID-19 confirmed by reverse transcription-polymerase chain reaction testing who received an ambulatory chest radiography between March 17, 2020 and October 24, 2020. In this study, full admission was defined as hospitalization within 14 days of the COVID-19 test for > 2 days with supplemental oxygen. Univariate analysis and machine learning algorithms were used to evaluate the relationship between the deep learning model predictions and hospitalization for > 2 days. RESULTS: The study included 413 patients, 222 men (54%), with a median age of 51 years (interquartile range, 39-62 years). Fifty-one patients (12.3%) required full admission. A boosted decision tree model produced the best prediction. Variables included patient age, frontal chest radiograph predictions of morbid obesity, congestive heart failure and cardiac arrhythmias, and radiographic opacity, with an internally validated area under the curve (AUC) of 0.837 (95% CI: 0.791-0.883) on a test cohort. CONCLUSION: Deep learning analysis of single frontal chest radiographs was used to generate combined comorbidity and pneumonia scores that predict the need for supplemental oxygen and hospitalization for > 2 days in patients with COVID-19 infection with an AUC of 0.837 (95% confidence interval: 0.791-0.883). Comorbidity scoring may prove useful in other clinical scenarios.

Bacterial efflux inhibitors are widely distributed in land plants.

ETHNOPHARMACOLOGICAL RELEVANCE: Secondary metabolites play a critical role in plant defense against disease and are of great importance to ethnomedicine. Bacterial efflux pumps are active transport proteins that bacterial cells use to protect themselves against multiple toxic compounds, including many antimicrobials. Efflux pump inhibitors from plants can block these efflux pumps, increasing the potency of antimicrobial compounds. This study demonstrates that efflux pump inhibition against the Gram-positive bacterial pathogen Staphylococcus aureus is widespread in extracts prepared from individual species throughout the land plant lineage. It therefore suggests a general mechanism by which plants used by indigenous species may be effective as a topical treatment for some bacterial infections. AIM OF THE STUDY: The goal of this research was to evaluate the distribution of efflux pump inhibitors in nine plant extracts with an ethnobotanical use suggestive of an antimicrobial function for the presence of efflux pump inhibitory activity against Staphylococcus aureus. MATERIALS AND METHODS: Plants were collected, dried, extracted, and vouchers submitted to the Herbarium of the University of North Carolina Chapel Hill (NCU). The extracts were analyzed by quantitative mass spectrometry (UPLC-MS) to determine the presence and concentration of flavonoids with known efflux pump inhibitory activity. A mass spectrometry-based assay was employed to measure efflux pump inhibition for all extracts against Staphylococcus aureus. The assay relies on UPLC-MS measurement of changes in ethidium concentration in the spent culture broth when extracts are incubated with bacteria. RESULTS: Eight of these nine plant extracts inhibited toxic compound efflux at concentrations below the MIC (minimum inhibitory concentration) value for the same extract. The most active extracts were those prepared from Osmunda claytoniana L. and Pinus strobes L., which both demonstrated IC50 values for efflux inhibition of 19 ppm. CONCLUSIONS: Our findings indicate that efflux pump inhibitors active against Staphylococcus aureus are common in land plants. By extension, this activity is likely to be important in many plant-derived antimicrobial extracts, including those used in traditional medicine, and evaluation of efflux pump inhibition may often be valuable when studying natural product efficacy.

Response to underwater laser pointer in the Orange-finned Anemonefish Amphiprion chrysopterus and three-spot damselfish Dascyllus trimaculatus.

Response of orange-finned anemonefish Amphiprion chrysopterus and three-spot damselfish Dascyllus trimaculatus to red laser-pointer light was studied in Mo'orea, French Polynesia. Four magnificent anemones Heteractis magnifica and their resident fish were observed for typical behaviours (biting, chasing, hiding, posing, lunging and retreating) with and without exposure to laser-pointer light. Lunging behaviour increased significantly for both fish species upon exposure to laser-pointer light; none of the other behaviours changed significantly. We advance the hypothesis that orange-finned anemonefish and three-spot damselfish interpret laser pointer stimulation as a territorial threat.

Spastic Paralysis of the Elbow and Forearm.

As the physiologic recovery period concludes, the patient is evaluated for surgical procedures that may rebalance muscle function and correct deformity. Upper extremity function is the product of complex and highly sophisticated mechanisms working in unison, and a careful, systematic preoperative evaluation is critical. A good function of the hand cannot be achieved without adequate position of the shoulder, elbow, forearm, and wrist. The goals of surgery must be practical and clearly understood by the patient and the family.

A mass spectrometry-based assay for improved quantitative measurements of efflux pump inhibition.

Bacterial efflux pumps are active transport proteins responsible for resistance to selected biocides and antibiotics. It has been shown that production of efflux pumps is up-regulated in a number of highly pathogenic bacteria, including methicillin resistant Staphylococcus aureus. Thus, the identification of new bacterial efflux pump inhibitors is a topic of great interest. Existing assays to evaluate efflux pump inhibitory activity rely on fluorescence by an efflux pump substrate. When employing these assays to evaluate efflux pump inhibitory activity of plant extracts and some purified compounds, we observed severe optical interference that gave rise to false negative results. To circumvent this problem, a new mass spectrometry-based method was developed for the quantitative measurement of bacterial efflux pump inhibition. The assay was employed to evaluate efflux pump inhibitory activity of a crude extract of the botanical Hydrastis Canadensis, and to compare the efflux pump inhibitory activity of several pure flavonoids. The flavonoid quercetin, which appeared to be completely inactive with a fluorescence-based method, showed an IC50 value of 75 µg/mL with the new method. The other flavonoids evaluated (apigenin, kaempferol, rhamnetin, luteolin, myricetin), were also active, with IC50 values ranging from 19 µg/mL to 75 µg/mL. The assay described herein could be useful in future screening efforts to identify efflux pump inhibitors, particularly in situations where optical interference precludes the application of methods that rely on fluorescence.

Contemporary techniques for the correction of temporal hollowing: augmentation temporoplasty with the classic dermal fat graft.

INTRODUCTION: Temporal hollowing is a depression within the soft tissues overlying the temporal fossa, sometimes seen after surgical dissection for access to the facial skeleton. Surgeons have successfully used bone grafts, hydroxyapatite, methyl methacrylate, and autogenous tissue to correct the deformity. A systematic review of the literature demonstrated that the most popular technique for the correction of temporal hollowing seems to be the use of nonbiologic materials. These materials have been used successfully but are associated with some complications. There has been a growing experience with augmentation of the soft tissues of the temporal fossa using dermal fat grafts at our institutions, and this article describes this experience. METHODS: Two senior surgeons' recent experience with the correction of temporal hollowing was reviewed and analyzed. RESULTS: The retrospective review revealed 5 cases of temporal hollowing treated with dermal fat graft placement. Follow-up at 1 year revealed aesthetically pleasing results. CONCLUSIONS: A thorough understanding of temporal anatomy and conscious effort to respect structural integrity during dissection are essential in avoiding temporal hollowing. Sometimes, however, this deformity is impossible to avoid. In these patients, there are a number of options for correction. Open placement of the classic dermal fat graft is a technique that seems to offer good long-term aesthetic results.

A paradigm shift in correcting medial orbital fracture-related enophthalmos: volumetric augmentation through a lateral approach.

BACKGROUND: Posttraumatic enophthalmos resulting from medial orbital wall fractures presents a complex challenge. Access to this area through traditional incisions is limited, making visualization of the fracture site difficult. This can be ameliorated by the transcaruncular approach, but with the potential for complications both with access and with reconstructive materials. The authors sought a new technique where enophthalmos correction would be based on augmenting soft tissue volume, rather than reducing the volume of the bony orbital cone. This was successfully accomplished using porous high-density polyethylene wedges. In an effort to increase overall knowledge of this technique, a retrospective review was undertaken. METHODS: A retrospective chart review was undertaken to examine the senior authors' (J.F.T. and L.H.H.) experience using a lateral approach to address medial orbital fracture-related enophthalmos, aided by porous high-density polyethylene wedges to increase orbital volume. The relevant literature was reviewed and reported here. RESULTS: Three patients with post-medial orbital wall fracture enophthalmos were treated using a lateral approach to place porous high-density polyethylene wedges; this technique adequately corrected enophthalmos in these patients. CONCLUSIONS: Porous high-density polyethylene wedges can be placed into the orbit through a small lateral incision to reverse enophthalmos secondary to loss of volume after medial orbital wall fractures. Current techniques for orbital reconstruction typically focus on reduction of bony volume; this technique focuses on augmentation of soft tissue volume.

Optimizing pediatric interdental fixation by use of a paramedian palatal fixation site.

Condylar fractures are the most common injury seen in pediatric mandibular trauma. These injuries often cannot be adequately stabilized by conservative techniques such as splinting. The pediatric condyle fracture often requires a period of intermaxillary fixation. Because of the characteristics of the developing dentition, circumdental wiring is often not possible. Surgeons commonly achieve interdental stabilization by the connection of a circum-mandibular wire and a second wire placed through a drill hole in the piriform aperture. This method can be problematic in the young patient whose palatal suture is still patent. In this brief technical note, the use of a paramedian drill hole through the palate posterior to the maxillary incisors is described. It is believed that this method is superior to other techniques because it avoids injury to the deciduous tooth buds and allows for the maxillary wire to be seated in more structurally sound tissues.

A comparative, long-term assessment of four soft tissue substitutes.

BACKGROUND: The ideal product for soft tissue replacement is durable, nonimmunogenic, and noninfectious. AlloDerm (LifeCell Corp., Branchburg, New Jersey), Enduragen (Stryker Corp., Kalamazoo, Michigan), and DermaMatrix (Synthes, Inc., West Chester, Pennsylvania) are frequently used for soft tissue replacement, but comparative analysis of these materials over an extended time period has not been reported. DuraMatrix (bovine tendon matrix; Stryker Corp.) is also promising, demonstrating desirable properties not only as a dural substitute but also for soft tissue replacement. OBJECTIVES: The authors analyze in vivo gross and microscopic changes over time with four commercially available dermal matrices, utilizing the murine model for a controlled environment. METHODS: AlloDerm, Enduragen, DermaMatrix, and DuraMatrix implants measuring 1 × 1 cm were each implanted in 40 adult mice, in individual dorsal submuscular pockets. The mice were then sacrificed in groups of 10 at three, six, nine, and 12 months. The implants and surrounding tissues were excised and evaluated for gross and microscopic appearance. RESULTS: Histological analysis of the specimens demonstrated similar encapsulation, implant infiltration, and surrounding inflammation over time. Enduragen implants demonstrated the least amount of host cell infiltration, whereas AlloDerm demonstrated the most. Grossly, Enduragen maintained its original shape and became firmer over time, whereas AlloDerm became spherical and softer. DermaMatrix and DuraMatrix both maintained their original shape and consistency. Implant migration, explantation, infection, or allergic reactions were not noted. CONCLUSIONS: All of the materials studied demonstrated high levels of host tolerance and tissue integration. AlloDerm demonstrated signs of resorption, whereas Enduragen maintained its size and became firmer in consistency. Together with the histological results, this suggests a proportional relationship between the amount of host cell integration and implant resorption.

Is primary thinning of the anterolateral thigh flap recommended?

BACKGROUND: Although primary thinning of the anterolateral thigh (ALT) flap has been successful in Asia, clinical and anatomic studies have demonstrated that this may be inadvisable in Western patients. Recent reports have demonstrated successful thinning of the ALT using smaller flaps. A systematic review was attempted, to assess whether ALT size affects the incidence of vascular compromise after primary thinning. METHODS: A systematic review was undertaken to examine the relevant literature. Student t-test was used to compare flaps that did and did not have complications. Fisher exact test was used to compare outcomes of flaps measuring less than and greater than 150 cm2. RESULTS: Eleven articles met the inclusion criteria. Eighty-eight ALT flaps were reported, and vascular compromise was seen in 11 (12.5%). The average size of flaps that demonstrated necrosis was 180.73 cm2; those without necrosis averaged 123.19 cm2 (P = 0.06). Flaps >150 cm2 had a significantly increased rate of compromise (25.93% vs. 6.56%; P < 0.05). CONCLUSIONS: A systematic literature review confirms that it is inadvisable to primarily thin large ALT flaps in the Western population. When large ALT flaps are required, primary thinning must be avoided to keep linking vessels intact.

Accelerating drug development and approval.

Regulatory agencies are the gateway between the pharma/biotech industry and patients and can serve as stimulators of new drug development. This article highlights several means of doing so implemented thus far, many with already impressive histories, such as orphan drug legislation, and others of a more experimental nature, such as the FDA's priority review voucher program. These initiatives represent different approaches to finding treatments for rare and widespread but neglected diseases, as well as speeding the development process for pharmaceutical and biological agents more generally. Commercial incentives, streamlined regulatory processing, exploratory trial designs, research assistance and cash infusions are all means of promoting drug development being explored in the United States, Europe and beyond. In some cases, such as fast track designation and priority review vouchers, regulatory agencies have turned their own processes into incentives, offering advantageous alternative routes to product approval, like a faster lane on the highway for vehicles carrying multiple passengers. In 2009, regulatory agencies and the governments they represent also had to confront two tremendous challenges: the global recession and the H1N1 influenza virus pandemic. These tests have been met with increased funding in the former case and coordinated efforts to develop, approve and stockpile H1N1 vaccines in the latter.

Facial clefting and oroauditory pathway manifestations in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome.

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) Syndrome is a rare disorder characterized by ectodermal dysplasia, along with other malformations such as cleft lip and palate, and various secondary issues such as chronic sinusitis, otitis media, and conductive hearing loss (CHL). The International Research Symposium for AEC Syndrome convened at Baylor College of Medicine in Houston, Texas. Patients with a suspected diagnosis of AEC syndrome attended, and members of the dental, dermatology, plastic surgery, otolaryngology, and audiology services examined each patient. Eighteen patients with a diagnosis of AEC were evaluated. Mean age was 7.5 years (range: 4 months-30 years). Fourteen of the 15 subjects tested (93.33%) demonstrated CHL, with seven showing moderate to severe hearing deficits (41-90 dB). Nine of 13 respondents reported hoarseness or voice problems; 8 were noted to display this on examination. Fourteen of 16 subjects reported speech was below average for age; 8 were in speech therapy. All 18 subjects reported a history of otitis externa or otitis media. Eleven of the subjects (61.11%) required myringotomy and pressure equalizing (PE) tubes. All patients demonstrated cleft palate defects. Of these, 16 (94.11%) presented with clefting of the soft palate, and 10 (58.82%) showed hard palate defects. Three subjects (16.67%) were noted to have submucous clefts. Our experience leads us to propose that while the oroauditory problems in those with AEC syndrome is likely multifactorial, many issues may stem from palatal clefting. Despite this, some abnormalities persist following surgical cleft closure, which indicates other complicating factors are also involved.

Treatment of prominent and constricted ear anomalies.

Although the physiologic effects of ear deformity are negligible, the aesthetic and psychological impact on the patient can be profound. Significant ear malformations are prevalent in today's society and affect more than 5 percent of the population. Although the prominent ear results from either underdevelopment of the antihelix or an enlarged conchal bowl, the constricted ear is a product of helical down-folding and height deficiency. After a thorough evaluation, surgical management of the prominent ear must be approached in a careful, rational fashion. Although the surgeon may enjoy the wide latitude that hundreds of corrective techniques offer, he or she must always proceed with an algorithmic application of technique best suited to the specific auricular deformity. By using this approach, correction of the prominent ear can go beyond patient satisfaction to predictably maximize outcome in both form and symmetry. From the clinical evaluation and anatomical basis to surgical management of the deformed ear, the true art of otoplasty is in the surgeon's ability to thoroughly understand auricular structure and appropriately apply technique for maximal aesthetic outcome.