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With their extensive coverage, marine low clouds greatly impact global climate. Presently, marine low clouds are poorly represented in global climate models, and the response of marine low clouds to changes in atmospheric greenhouse gases and aerosols remains the major source of uncertainty in climate simulations. The eastern North Atlantic (ENA) is a region of persistent but diverse subtropical marine boundary layer clouds, whose albedo and precipitation are highly susceptible to perturbations in aerosol properties. In addition, the ENA is periodically impacted by continental aerosols, making it an excellent location to study the cloud condensation nuclei (CCN) budget in a remote marine region periodically perturbed by anthropogenic emissions, and to investigate the impacts of long-range transport of aerosols on remote marine clouds. The Aerosol and Cloud Experiments in Eastern North Atlantic (ACE-ENA) campaign was motivated by the need of comprehensive in situ measurements for improving the understanding of marine boundary layer CCN budget, cloud and drizzle microphysics, and the impact of aerosol on marine low cloud and precipitation. The airborne deployments took place from 21 June to 20 July 2017 and from 15 January to 18 February 2018 in the Azores. The flights were designed to maximize the synergy between in situ airborne measurements and ongoing long-term observations at a ground site. Here we present measurements, observation strategy, meteorological conditions during the campaign, and preliminary findings. Finally, we discuss future analyses and modeling studies that improve the understanding and representation of marine boundary layer aerosols, clouds, precipitation, and the interactions among them.

Background Rotator cuff repair (RCR) is one of the most common elective orthopedic procedures with predictable indications, technique, and outcomes. As a result, this surgery is an ideal choice for studying value. The purpose of this study was to utilize Patient-level value-analysis (PLVA) within the setting of RCR over the one-year episode-of-care. Methods Included patients (n=396) underwent RCR between 2009 and 2016 at a single outpatient orthopedic surgery center. The episode-of-care was defined as one-year following surgery. The Western Ontario Rotator Cuff (WORC) index was collected at both the initial preoperative baseline and the one-year postoperative mark. The total cost-of-care was determined using time-driven activity-based costing (TDABC). Both patient (PLVA) and provider-level value-analysis (pLVA) were performed. Results The average TDABC cost-of-care was derived at $5413.78 ± $727.41 [$5341.92, $5485.64]. At the patient-level, arthroscopic isolated supraspinatus tears yielded the highest value coefficient, 0.82 (ANOVA F-Test, p=0.01). There was a poor correlation between the change in one-year WORC score and the TDABC cost-of-care (r2=0.03). Provider-level value demonstrated significant variation between the 8 evaluated providers (p Conclusion RCR is one of the most common orthopedic procedures, yet the correlations between cost-of-care and patient outcomes is unknown. PLVA quantifies the ratio of functional improvement to the TDABC estimated cost-of-care at the patient-level. This is the first study to apply patient-level value analysis over the first-year episode-of-care. With healthcare transitioning towards value-based delivery, PLVA offers a quantitative tool to measure the value of individual patient care delivery over the entire episode-of-care.

We demonstrate an RF photonic fractional Hilbert transformer based on an integrated Kerr micro-comb source featuring a record low free spectral range of 48.9 GHz, yielding 75 microcomb lines across the C-band. By programming and shaping the comb lines according to calculated tap weights, we demonstrate that the Hilbert transformer can achieve tunable bandwidths ranging from 1.2 to 15.3 GHz, switchable centre frequencies from baseband to 9.5 GHz, and arbitrary fractional orders. We experimentally characterize the RF amplitude and phase response of the tunable bandpass and lowpass Hilbert transformers with 90 and 45-degree phase shift. The experimental results show good agreement with theory, confirming the effectiveness of our approach as a powerful way to implement the standard as well as fractional Hilbert transformers with broad and switchable processing bandwidths and centre frequencies, together with high reconfigurability and greatly reduced size and complexity.

Many kidney donor candidates with impaired fasting glucose (IFG) and all candidates with diabetes are currently excluded from kidney donation, fearing the development of an accelerated course of diabetic kidney disease in the remaining kidney.We studied mortality, proteinuria, and end-stage kidney disease (ESKD) in 8280 donors who donated between 1963 and 2007 according to donation fasting plasma glucose (FPG):100 mg/dL (n = 6204), 100-125 mg/dL (n = 1826), and ≥126 mg/dL (n = 250).Donors with IFG and those with FPG ≥126 mg/dL were older, less likely to be non-Hispanic White, had a higher body mass index, and were more likely to be related to their recipient. After 15.7 ± 10.5 y from donation to study close, 4.4% died, 29.4% developed hypertension, 13.8% developed proteinuria, and 41 (0.5%) developed ESKD. In both the logistic and Cox models, IFG was associated with a higher diabetes risk (adjusted hazard ratio [aHR], 1.65; 95% confidence interval [CI], 1.18-2.30) and hypertension (aHR, 1.35; 95% CI, 1.10-1.65; P = 0.003 for both), but not higher risk of proteinuria or ESKD. The multivariable risk of mortality in donors with ≥126 mg/dL was higher than the 2 other groups, but risks of proteinuria, cardiovascular disease, and reduced estimated glomerular filtration rate were similar to those with FPG126 mg/dL. Three cases of ESKD developed in the 250 donors with FPG ≥126 mg/dL at 18.6 ± 10.3 y after donation (aHR, 5.36; 95% CI, 1.0-27.01; P = 0.04).Donors with IFG and the majority of donors with ≥126 mg/dL do well and perhaps should not be routinely excluded from donation.

Purpose The aim of this study was to examine current practice patterns in pediatric total body irradiation (TBI) techniques among COG member institutions. Methods and Materials Between November 2019 and February 2020, a questionnaire containing 52 questions related to the technical aspects of TBI was sent to medical physicists at 152 COG institutions. The questions were designed to obtain technical information on commonly used TBI treatment techniques. Another set of 9 questions related to the clinical management of patients undergoing TBI was sent to 152 COG member radiation oncologists at the same institutions. Results Twelve institutions were excluded because TBI was not performed in their institutions. A total of 88 physicists from 88 institutions (63% response rate) and 96 radiation oncologists from 96 institutions (69% response rate) responded. The anterior-posterior/posterior-anterior (AP/PA) technique was the most common technique reported (49 institutions [56%]); 44 institutions (50%) used the lateral technique, and 14 (16%) used volumetric modulated arc therapy or tomotherapy. Midplane dose rates of 6 to 15 cGy/min were most commonly used. The most common specification for lung dose was the midlung dose for both AP/PA techniques (71%) and lateral techniques (63%). Almost all physician responders agreed with the need to refine current TBI techniques, and 79% supported the investigation of new TBI techniques to further lower the lung dose. Conclusions There was no consistency in the practice patterns, methods for dose measurement, and reporting of TBI doses among COG institutions. The lack of standardization precludes meaningful correlation between TBI doses and clinical outcomes including disease control and normal tissue toxicity. The COG radiation oncology discipline is currently undertaking several steps to standardize the practice and dose reporting of pediatric TBI using detailed questionnaires and phantom-based credentialing for all COG centers.

Radiation pneumonitis is a rare but possibly fatal side effect of Yttrium-90 (90Y) radioembolization. It may occur 1 to 6 months after therapy, in case a significant part of the 90Y microspheres shunt to the lungs. In current clinical practice, a predicted value of lung dose greater than 30Gy is considered a criterion to exclude patients from treatment. However, contrasting findings regarding the occurrence of radiation pneumonitis and lung dose were previously reported in literature. In this study, the relationship between the lung dose value and the eventual occurrence of radiation pneumonitis after 90Y radioembolization was investigated. Methods: A total of 317 90Y liver radioembolization procedures performed during an 8-years period (Feb.2012-Sep.2020) were retrospectively analyzed. Predicted lung mean dose using 99mTc-MAA planar scintigraphy (LMDMAA) acquired during the planning phase and left lung mean dose (LMDY-90) using the 90Y PET/CT acquired after the treatment were calculated. For the lung dose computation, it was chosen to use the left lung as representative lung volume, to compensate for the scatter from the liver moving in the cranial-caudal direction due to breathing and mainly affecting the right lung. Results: Two hundred and seventy-two patients underwent 90Y procedures, of which 63% performed with glass microspheres and 37% with resin microspheres. Median injected activity was 1974MBq (range: 242-9538MBq). Median LMDMAA was 3.5Gy (range: 0.2-89.0Gy). For 14 procedures LMDMAA was >30Gy. Median LMDY-90 was 1Gy (range: 0.0-22.1Gy). No patients had a LMDY-90 >30Gy. Of the three patients with a LMDY-90 >12Gy, two patients (LMDY-90 = 22.1Gy, LMDMAA = 89Gy and LMDY-90 = 17.7Gy, LMDMAA = 34.1Gy, respectively) developed radiation pneumonitis and consequently died. A third patient with a LMDY-90 equal to 18.4Gy (LMDMAA = 29.1Gy) died 2 months after treatment, before imaging evaluation, due to progressive disease. Conclusion: The occurrence of radiation pneumonitis as a consequence of lung shunt following 90Y radioembolization is rare (

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs

Accumulating evidence now shows that supplemental antioxidants including vitamin C, vitamin E and N-Acetylcysteine consumption can suppress adaptations to endurance-type exercise by attenuating reactive oxygen and nitrogen species (RONS) formation within skeletal muscle. This emerging evidence points to the importance of pro-oxidation as an important stimulus for endurance-training adaptations, including mitochondrial biogenesis, endogenous antioxidant production, insulin signalling, angiogenesis and growth factor signaling. Although sustained oxidative distress is associated with many chronic diseases, athletes have, on average, elevated levels of certain endogenous antioxidants to maintain redox homeostasis. As a result, trained athletes may have a better capacity to buffer oxidants during and after exercise, resulting in a reduced oxidative eustress stimulus for adaptations. Thus, higher levels of RONS input and exercise-induced oxidative stress may benefit athletes in the pursuit of continuous endurance training redox adaptations. This review addresses why athletes should be looking to enhance exercise-induced oxidative stress and how it can be accomplished. Methods covered include high-intensity interval training, hyperthermia and heat stress, dietary antioxidant restriction and modified antioxidant timing, dietary antioxidants and polyphenols as adjuncts to exercise, and vitamin C as a pro-oxidant.

BACKGROUND: Obesity is associated with the two archetypal kidney disease risk factors: hypertension and diabetes. Concerns that the effects of diabetes and hypertension in obese kidney donors might be magnified in their remaining kidney have led to the exclusion of many obese candidates from kidney donation. METHODS: We compared mortality, diabetes, hypertension, proteinuria, reduced eGFR and its trajectory, and the development of kidney failure in 8583 kidney donors, according to body mass index (BMI). The study included 6822 individuals with a BMI of

Objective To evaluate intravenous scleral and intracameral aqueous angiography in normotensive (n = 4) and hypertensive glaucomatous (n = 6) ADAMTS10-mutant canine eyes. Animals studied Ten ADAMTS10-mutant dogs were used in this study. Procedures Dogs were sedated and one eye from each dog underwent scleral angiography following intravenous injection of 0.25% indocyanine green (ICG). After a 24-h recovery period, the same eye underwent aqueous angiography via intracameral administration of ICG. Imaging of identical scleral sectors from the same eye was performed using a Heidelberg Spectralis® Confocal Scanning Laser Ophthalmoscope. Intrascleral vessel depth and lumen diameters were measured using Heidelberg Spectralis® optical coherence tomography and computer software. Results Scleral angiography permitted visualization of vascular components associated with conventional aqueous humor outflow pathways with an average time from injection to fluorescence of 35.8 ± 10.6 s (mean ± SD). Two normotensive eyes (2/10;20%) demonstrated turbulent dye movement, while 4 hypertensive eyes (4/10;40%) exhibited laminar flow. Aqueous angiography demonstrated dye fluorescence within the post-trabecular conventional aqueous humor outflow pathways in all 10 eyes at 34.3 ± 11.0 s post-injection. Sectoral and dynamic outflow patterns were observed primarily within the superotemporal sector in nine eyes (9/10; 90%). Seven eyes (7/10; 70%) demonstrated pulsatile dye movement and five eyes (5/10; 50%) exhibited laminar flow. The degree of laminar movement of dye was greatest in hypertensive eyes. Vessel lumen diameters measured 133.85 ± 28.36 µm and 161.18 ± 6.02 µm in hypertensive and normotensive eyes, respectively. Conclusions Aqueous angiography allowed for visualization of fluorescent dye in the superotemporal sclera. Laminar flow and smaller lumen vessels were observed mainly in hypertensive eyes.

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries and is threatening worldwide tomato production. Various strategies have been developed and implemented to manage this pest. Here, we present a timely review on the up-to-date development and practical implementation of integrated pest management (IPM) programs for tomato crops across different world regions infested by T. absoluta. While insecticide resistance is a growing concern, biological control via releasing or conserving arthropod natural enemies and sex pheromone-based biotechnical control are the most successful management practices. Agronomic control-related research is an emerging area where the soil fertilization and/or irrigation, as well as breeding of resistant cultivars, has the potential to enhance IPM effectiveness. Grower survey responses in the native areas (i.e., South America), early-invaded areas (i.e., first report between 2006 and 2012) and newly invaded areas (i.e., first report after 2012) showed that the control programs evolved along with the areas and time since invasion. Growers in the early-invaded areas shifted more rapidly from chemical control to biological control compared to those from the native area. In all concerned regions, the pest control failure risk following chemical insecticide applications and the high cost associated with either biological or biotechnical control methods have been the greatest concerns for growers. The information gathered from the native and/or early-invaded areas may help achieve a more effective management in newly invaded areas. Lastly, researchers are expected to break the bottlenecks of some key issues that would enable lowering application cost of novel biorational alternative management options.

BACKGROUND Glomerular size in renal allografts is impacted by donor-recipient factors and response to injury. In serial biopsies of patients with well-functioning grafts, increased glomerular size correlates with better survival. However, no previous study has addressed the association of glomerular size at the time of a for-cause biopsy and clinical/histopathologic markers of injury, or effect on long-term graft outcome. METHODS Two cohorts of kidney transplant recipients enrolled in the Deterioration of Kidney Allograft Function study were evaluated. The prospective cohort (PC, n = 581): patients undergoing first for-cause kidney biopsy 1.7 ± 1.4 (mean ± SD) y posttransplant; and the cross-sectional cohort (CSC, n = 446): patients developing new-onset renal function deterioration 7.7 ± 5.6 y posttransplant. Glomerular planar surface area and diameter were measured on all glomeruli containing a vascular pole. Kidney biopsy was read centrally in a blinded fashion according to the Banff criteria. RESULTS Glomerular area was significantly higher in the CSC than the PC; time from transplant to indication biopsy was associated with glomerular area in both cohorts (P values ≤ 0.001). Glomerular area was associated with indices of microvascular inflammation (glomerulitis, peritubular capillary infiltrates; P values ≤ 0.001) and segmental glomerulosclerosis (P value < 0.0001). In the CSC, higher glomerular area was associated with higher estimated glomerular filtration rate (P value ≤ 0.001) and increased graft survival after accounting for microvascular inflammation (adjusted hazard ratio = 0.967; 95% confidence interval: 0.948-0.986; hazard ratio in biopsies without evidence of diabetes or antibody mediated rejection = 0.919, 95% confidence interval: 0.856-0.987). CONCLUSIONS Glomerular size is associated with histopathologic features present at the time of indication biopsy and with increased graft survival in the CSC.

INTRODUCTION The digital age and global pandemic have transformed the way patients select their plastic surgeon. However, as more patients turn to online resources, there is little information on the digital presence of academic plastic surgeons. METHODS We identified all academic faculty from integrated and independent plastic surgery residency programs. Using a Google-based custom search, the top 10 search results for each surgeon were extracted and categorized as surgeon noncontrolled (eg, physician rating websites) or controlled (eg, social media, institutional, and research profiles). RESULTS Eight hundred four academic plastic surgeons were included. Most search results were surgeon-noncontrolled sites (57%, n = 4547). Being male (odds ratio [OR], 0.60, P = 0.0020) and holding a higher academic rank (OR = 0.61, P < 0.0001) significantly decreased the prevalence of physician rating websites, whereas career length was significantly associated with a greater number of rating websites (OR = 1.04, P < 0.0001). Surgeon-controlled websites were significantly influenced by academic rank and years in practice; higher academic rank was associated with more social media platforms (OR = 1.42, P = 0.0008), institutional webpages (OR = 1.57, P < 0.0001), and research profiles (OR = 1.62, P = 0.0008). Conversely, longer career duration was a predictor for fewer social media platforms (OR = 0.95, P < 0.0001) and institutional webpages (OR = 0.95, P < 0.0001). CONCLUSIONS Academic plastic surgeons do not hold control of the majority of their search results. However, digitally savvy plastic surgeons can focus attention by building on certain areas to optimize their digital footprint. This study can serve as a guide for academic plastic surgeons wishing to control their online presence.

Background There are limited data regarding the factors associated with hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients without cirrhosis. We sought to determine the prevalence and factors associated with HCC in NAFLD patients with or without cirrhosis. Methods Adults with NAFLD (June 2015 to May 2020) were identified using the electronic health record database (Explorys Inc, Cleveland, OH) from 26 major integrated US healthcare systems. The prevalence of HCC was calculated. Multivariable analyses adjusting for covariates were performed to evaluate the associated risk factors and the presence of HCC. Results A total of 392,800 NAFLD patients were identified. Among 1110 patients with HCC, 170 (15.3%) had no cirrhosis. The prevalence of HCC in non-cirrhotic and cirrhotic NAFLD patients was 4.6/10,000 persons (95% CI 3.9–5.3), and 374.4/10,000 persons (95% CI 350.9–398.8), respectively. Age > 65 years (adjusted OR; 3.37, 95% CI 2.47–4.59), ever had elevated alanine aminotransferase (2.69; 2.14–3.37), male gender (2.57; 1.88–3.49), smoker (1.75; 1.23–2.49), and diabetes (1.56; 1.15–2.11) were associated with HCC in non-cirrhotic NAFLD (all P 65 years, male gender, Hispanic race, elevated alanine aminotransferase, diabetes and smoker (all P Conclusions These data identified the major risk factors for the development of HCC in NAFLD patients. In the non-cirrhotics, older male patients with smoking history, diabetes and an elevated alanine aminotransferase had highest risk and may need increased judicious monitoring.

The intervertebral disc (IVD) annulus fibrosus (AF) is composed of concentric lamellae with alternating right- and left-handed helically oriented collagen fiber bundles. This arrangement results in anisotropic material properties, which depend on local fiber orientations. Prior measurements of fiber inclination angles in human lumbar and bovine caudal IVDs found a significantly higher inclination angle in the inner AF than outer, though it is currently unknown if this pattern is conserved in smaller mammalian species. Additionally, the physical mechanism behind this pattern remains un-determined. In this study, AF fiber angles were measured histologically in murine caudal IVDs and compared to previously published values from bovine caudal IVDs. Fiber angles were also predicted using three theoretical models, including two based on adaptation to internal swelling pressure and one based on vertebral body growth. Fiber angle was found to significantly decrease from 49.5 ± 3.8° in the inner AF to 34.5 ± 6.6° in the outer AF. While steeper than in bovine discs at all locations, the trend with radial position was comparable between species. This trend was best fit by growth-based model and opposite of that predicted by the pressure vessel models. Trends in AF fiber orientation are conserved between mammalian species. Modeling results suggest that the AF tissue microstructure is more likely to be driven by adjacent vertebral body growth than adapted for optimal mechanical performance.

Severe maternal morbidity and mortality continue to increase in the United States, largely owing to chronic and newly diagnosed medical comorbidities. Interconception care, or care and management of medical conditions between pregnancies, can improve chronic disease control before, during, and after pregnancy. It is a crucial and time-sensitive intervention that can decrease maternal morbidity and mortality and improve overall health. Despite these potential benefits, interconception care has not been well implemented by the primary care community. Furthermore, there is a lack of guidelines for optimizing preconception chronic disease, risk stratifying postpartum chronic diseases, and recommending general collaborative management principles for reproductive-age patients in the period between pregnancies. As a result, many primary care providers, especially those without obstetric training, are unclear about their specific role in interconception care and may be unsure of effective methods for collaborating with obstetric care providers. In particular, internal medicine physicians, the largest group of primary care physicians, may lack sufficient clinical exposure to medical conditions in the obstetric population during their residency training and may feel uncomfortable in caring for these patients in their subsequent practice. The objective of this article is to review concepts around interconception care, focusing specifically on preconception care for patients with chronic medical conditions (eg, chronic hypertension, chronic diabetes mellitus, chronic kidney disease, venous thromboembolism, and obesity) and postpartum care for those with medically complicated pregnancies (eg, hypertensive disorders of pregnancy, gestational diabetes mellitus, excessive gestational weight gain, peripartum cardiomyopathy, and peripartum mood disorders). We also provide a pragmatic checklist for preconception and postpartum management.

Physical models have a long and important role in exploring and communicating scientific and medical concepts and structures. One of the earliest physical scientific visualizations was the orrery, a mechanical model of the solar system, which first appeared in Greece around 150 BC. Early anatomical models, such as those made from Papier-Mache were developed in the early 19th Century. The earliest molecular models were those produced in the mid 19th century by chemists (such as Hoffman and Kekule) to visualize the nature of chemical composition. These models brought abstract or unseen structures into the context of human experience.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Purpose To review the current published literature on the use of OCT angiography (OCTA) to help detect changes associated with the diagnosis of primary open-angle glaucoma. Methods Searches of the peer-reviewed literature were conducted in March 2018, June 2018, April 2019, December 2019, and June 2020 in the PubMed and Cochrane Library databases. Abstracts of 459 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 75 articles were selected and the panel methodologist rated them for strength of evidence. Three articles were rated level I and 57 articles were rated level II. The 15 level III articles were excluded. Results OCT angiography can detect decreased capillary vessel density within the peripapillary nerve fiber layer (level II) and macula (level I and II) in patients with suspected glaucoma, preperimetric glaucoma, and perimetric glaucoma. The degree of vessel density loss correlates significantly with glaucoma severity both overall and topographically (level II) as well as longitudinally (level I). For differentiating glaucomatous from healthy eyes, some studies found that peripapillary and macular vessel density measurements by OCTA show a diagnostic ability (area under the receiver operating characteristic curve) that is comparable with structural OCT retinal nerve fiber and ganglion cell thickness measurements, whereas other studies found that structural OCT measurements perform better. Choroidal or deep-layer microvasculature dropout as measured by OCTA is also associated with glaucoma damage (level I and II). Lower peripapillary and macular vessel density and choroidal microvasculature dropout are associated with faster rates of disease progression (level I and II). Conclusions Vessel density loss associated with glaucoma can be detected by OCTA. Peripapillary, macular, and choroidal vessel density parameters may complement visual field and structural OCT measurements in the diagnosis of glaucoma.

The purpose of our study was to evaluate the factors that influence the timing of definitive fixation in the management of bilateral femoral shaft fractures and the outcomes for patients with these injuries.Patients with bilateral femur fractures treated between 1998 to 2019 at ten level-1 trauma centers were retrospectively reviewed. Patients were grouped into early or delayed fixation, which was defined as definitive fixation of both femurs within or greater than 24 hours from injury, respectively. Statistical analysis included reversed logistic odds regression to predict which variable(s) was most likely to determine timing to definitive fixation. The outcomes included age, sex, high-volume institution, ISS, GCS, admission lactate, and admission base deficit.Three hundred twenty-eight patients were included; 164 patients were included in the early fixation group and 164 patients in the delayed fixation group. Patients managed with delayed fixation had a higher Injury Severity Score (26.8 vs 22.4; p0.01), higher admission lactate (4.4 and 3.0; p0.01), and a lower Glasgow Coma Scale (10.7 vs 13; p0.01). High-volume institution was the most reliable influencer for time to definitive fixation, successfully determining 78.6% of patients, followed by admission lactate, 64.4%. When all variables were evaluated in conjunction, high-volume institution remained the strongest contributor (XIn this study, high-volume institution was the strongest predictor of timing to definitive fixation in patients with bilateral femur fractures. This study demonstrates an opportunity to create a standardized care pathway for patients with these injuries.Level III.

Soft tissue wounds in the scalp are a common occurrence after trauma or resection of a malignancy. The reconstructive surgeon should strive to use the simplest reconstructive technique while optimizing aesthetic outcomes. In general, large defects with infection, previous irradiation (or require postoperative radiation), or with calvarial defects usually require reconstruction with vascularized tissue (ie, microvascular free tissue transfer). Smaller defects greater than 3 cm that are not amenable to primary closure can be treated with local flap reconstruction. In all cases, the reconstruction method will need be tailored to the patient's health status, desires, and aesthetic considerations.

PurposeTo assess the feasibility of needle arthroscopy for management of suspected bacterial arthritis in native joints.MethodsDuring a pilot period, patients presenting with symptoms suggestive of native joint bacterial arthritis were eligible for initial management with needle arthroscopy. Procedures were performed in the operating theatre or at the patient bedside in the emergency department or inpatient ward. As our primary outcome measure, it was assessed whether needle arthroscopic lavage resulted in a clear joint. In addition, the need for conversion to standard arthroscopy or arthrotomy, the need for conversion from local to general anaesthesia, complications and the need for additional surgical intervention at follow-up during admission were recorded.ResultsEleven joints in 10 patients (four males, age range 35 – 77) were managed with needle arthroscopy. Needle arthroscopic lavage resulted in a clear joint in all cases. Conversion to standard arthroscopy or arthrotomy was not needed. Seven procedures were performed at the patient bedside using local anaesthesia. These procedures were well tolerated and conversion to general or spinal anaesthesia was not required. There were no procedure complications. One patient received multiple needle arthroscopic lavages. No further surgical interventions beside the initial needle arthroscopic lavage were required for successful management in other cases.ConclusionsNeedle arthroscopy can be a feasible tool in the initial management of complaints suggestive for native joint bacterial arthritis, providing an effective, quick and well-tolerable intervention in the operating theatre or at the patient bedside, with the potential to relief health systems from need for scarce operating theatre time.

Women with pregnancy-induced hypertension, defined as gestational hypertension and preeclampsia/eclampsia, are at increased risk of long-term cardiovascular disease, but less is known about the spectrum of acute cardiovascular outcomes, especially across racial/ethnic groups. We evaluated the risk of cardiovascular events at delivery associated with gestational hypertension and preeclampsia/eclampsia, compared with no pregnancy-induced hypertension, overall and by race/ethnicity. We used the 2016 to 2018 National Inpatient Sample data.International Classification of Diseases,Tenth Revision, Clinical Modification codes identified delivery hospitalizations and clinical diagnoses. Using survey weights, cardiovascular events were examined using logistic regression by pregnancy-induced hypertension status, with subsequent stratification by race/ethnicity. Among 11 304 996 deliveries in 2016 to 2018, gestational hypertension occurred in 614 995 (5.4%) and preeclampsia in 593 516 (5.2%). Black women had higher odds for preeclampsia independent of underlying comorbidities (adjusted odds ratio, 1.45 [95% CI, 1.42–1.49]) and had the highest rates for several complications (peripartum cardiomyopathy, 506; heart failure, 660; acute renal failure, 953; and arrhythmias, 418 per 100 000 deliveries). After adjustment for socioeconomic factors and comorbidities, preeclampsia/eclampsia was associated with increased risk of cardiovascular events in women of all races/ethnicities. However, risk was highest among Asian/Pacific Islander women and lowest among Black women. In sum, while Black women were the most likely to experience preeclampsia, Asian/Pacific women were the most at risk for acute cardiovascular complications during delivery hospitalization.

Background Epithelial ovarian cancer (EOC) is often diagnosed late, with a 5-year relative survival of 30.2% for patients with metastatic disease. Residual disease following cytoreductive surgery is an important predictor for poor survival. EOC is characterized by diffuse peritoneal metastases and depositions of small size, challenging a complete resection. Targeted fluorescence imaging is a technique to enhance tumor visualization and can be performed intraoperatively. Folate receptor alpha (FRα) and human epidermal growth factor receptor 2 (HER2) are overexpressed in EOC in 80% and 20% of the cases, respectively, and have been previously studied as a target for intraoperative imaging. Objective To systematically review the literature on the feasibility of FRα and HER2 targeted fluorescence-guided cytoreductive surgery (FGCS) in women with EOC. Methods PubMed and Embase were searched for human and animal studies on FGCS targeting either HER2 or FRα in either women with EOC or animal models of EOC. Risk of bias and methodological quality were assessed with the SYRCLE and MINORS tool, respectively. Results All animal studies targeting either FRα or HER2 were able to detect tumor deposits using intraoperative fluorescence imaging. One animal study targeting HER2 compared conventional cytoreductive surgery (CCS) to FGCS and concluded that FGCS, either without or following CCS, resulted in statistically significant less residual disease compared to CCS alone. Human studies on FGCS showed an increased detection rate of tumor deposits. True positives ranged between 75%–77% and false positives between 10%–25%. Lymph nodes were the main source of false positive results. Sensitivity was 85.9%, though only reported by one human study. Conclusion FGCS targeting either HER2 or FRα appears to be feasible in both EOC animal models and patients with EOC. FGCS is a promising technique, but further research is warranted to validate these results and particularly study the survival benefit.

Context Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research. Objective A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems. Participants and setting Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research. Design A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement. Results A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications. Conclusion CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts.

There are several choices for induction immunosuppression in kidney-after-liver transplantation. We examined the impact of induction type on kidney graft and patient survival in kidney-after-liver recipients. We utilized the Scientific Registry of Transplant Recipients (SRTR) database and included patients transplanted between 1/1/2000 and 7/31/2017 to study kidney graft and patient outcomes of all kidney-after-liver transplant recipients in the United States. We only included those who were discharged on tacrolimus and mycophenolate with or without steroids and who had a negative crossmatch prior to kidney engraftment. We grouped recipients by kidney induction type into three groups: depletional (N=550), non-depletional (n=434), and no antibody induction (n=144). We studied patient and kidney allograft survival using Cox PH regression, with transplant center included as a random effect. Models were adjusted for liver induction regimen, recipient and donor age, gender, Human Leukocyte Antigen (HLA) mismatches, payor type, live-donor kidney transplant, dialysis status, time from liver engraftment, hepatitis C status, and the presence of diabetes mellitus at time of kidney transplant and transplant year. Six-month and one-year rejection rates did not differ between groups. In the multivariable models, as compared to no induction, neither depletional nor non-depletional induction was associated with improved recipient or graft survival. Depletional induction at the time of liver transplantation was associated with worse patient survival after kidney transplant [HR 1.71, 95%C.I. (1.09, 2.67), P 0.02]. Live-donor kidney transplantation was associated with a 48.1% improved graft survival [HR 0.52, 95%C.I. (0.33, 0.82), P 0.00]. In conclusion, in the settings of a negative crossmatch and maintenance with tacrolimus and mycophenolate, induction use was not associated with a patient or graft survival benefit in kidney after liver transplants.

Background : : Five to ten percent of all patients undergoing radiofrequency ablation (RFA), which is the most established technique for Barrett's esophagus (BE) ablation-develop strictures. Hybrid-argon plasma coagulation (APC) combines APC with submucosal saline injection that was recently developed to tackle this problem. The aims of this pilot study were to evaluate the feasibility, tolerance, safety and long-term efficacy of hybrid-APC for the treatment of BE. Methods : : Patients with histological proven BE were selected for hybrid-APC. Prior to APC thermal ablation the mucosa was lifted using a submucosal high-pressure water jet injection system (Erbejet 2; Erbe, Tuebingen, Germany). Short-term (< 48 hours) and long-term (> 48 hours) safety were evaluated. Efficacy of ablation was measured at 3, 6, 12 and 24 months at follow-up endoscopy by evidence of macroscopically complete resolution of BE mucosa and/or histologically complete resolution of intestinal metaplasia (CRIM). Results : : Eleven patients were included in the study (average age, 68.2 years; male 72.7%). Eight patients (72.7%) were treatment naive, 9.1% (n = 1) had prior RFA and 18.2% (n = 2) had prior endoscopic mucosal resection. Two patients were excluded from the study. Nine patients (100%) had macroscopic remission and 88.9% (n = 8) had macroscopic remission and microscopic CRIM at 24 months after hybrid-APC ablation. No treatment-related stricture or other major complications were observed, 1 patient (11.1%) reported minor adverse effects. Conclusion : : In this prospective pilot study, hybrid-APC appears safe, feasible and effective after 24 months, which has not been evaluated so far. Further large, multi-centre trials are warranted to confirm the present results.

OBJECTIVES To evaluate neurodevelopmental and mental disorders after PICU hospitalization in children requiring invasive mechanical ventilation for severe respiratory illness. DESIGN Retrospective longitudinal observational cohort. SETTING Texas Medicaid Analytic eXtract data from 1999 to 2012. PATIENTS Texas Medicaid-enrolled children greater than or equal to 28 days old to less than 18 years old hospitalized for a primary respiratory illness, without major chronic conditions predictive of abnormal neurodevelopment. INTERVENTIONS We examined rates of International Classification of Diseases, 9th revision-coded mental disorder diagnoses and psychotropic medication use following discharge among children requiring invasive mechanical ventilation for severe respiratory illness, compared with general hospital patients propensity score matched on sociodemographic and clinical characteristics prior to admission. Children admitted to the PICU for respiratory illness not necessitating invasive mechanical ventilation were also compared with matched general hospital patients as a negative control exposure. MEASUREMENTS AND MAIN RESULTS Of 115,335 eligible children, 1,351 required invasive mechanical ventilation and were matched to 6,755 general hospital patients. Compared with general hospital patients, children requiring invasive mechanical ventilation had increased mental disorder diagnoses (hazard ratio, 1.43 [95% CI, 1.26-1.64]; p < 0.0001) and psychotropic medication use (hazard ratio, 1.67 [1.34-2.08]; p < 0.0001) following discharge. Seven-thousand seven-hundred eighty children admitted to the PICU without invasive mechanical ventilation were matched to 38,900 general hospital patients and had increased mental disorder diagnoses (hazard ratio, 1.08 [1.02-1.15]; p = 0.01) and psychotropic medication use (hazard ratio, 1.11 [1.00-1.22]; p = 0.049). CONCLUSIONS Children without major comorbidity requiring invasive mechanical ventilation for severe respiratory illness had a 43% higher incidence of subsequent mental disorder diagnoses and a 67% higher incidence of psychotropic medication use. Both increases were substantially higher than in PICU patients with respiratory illness not necessitating invasive mechanical ventilation. Invasive mechanical ventilation is a life-saving therapy, and its application is interwoven with underlying health, illness severity, and PICU management decisions. Further research is required to determine which factors related to invasive mechanical ventilation and severe respiratory illness are associated with abnormal neurodevelopment. Given the increased risk in these children, identification of strategies for prevention, neurodevelopmental surveillance, and intervention after discharge may be warranted.

BACKGROUND & AIMS: Benign biliary strictures (BBS) are complications of chronic pancreatitis (CP). Endotherapy using multiple plastic stents (MPS) or a fully covered self-expanding metal stent (FCSEMS) are acceptable treatment options for biliary obstructive symptoms in these patients. METHODS: Patients with symptomatic CP-associated BBS enrolled in a multicenter randomized noninferiority trial comparing 12-month treatment with MPS vs FCSEMS. Primary outcome was stricture resolution status at 24 months, defined as absence of restenting and 24-month serum alkaline phosphatase not exceeding twice the level at stenting completion. Secondary outcomes included crossover rate, numbers of endoscopic retrograde cholangiopancreatography (ERCPs) and stents, and stent- or procedure-related serious adverse events. RESULTS: Eighty-four patients were randomized to MPS and 80 to FCSEMS. Baseline technical success was 97.6% for MPS and 98.6% for FCSEMS. Eleven patients crossed over from MPS to FCSEMS, and 10 from FCSEMS to MPS. For MPS vs FCSEMS, respectively, stricture resolution status at 24 months was 77.1% (54/70) vs 75.8% (47/62) (P = .008 for noninferiority intention-to-treat analysis), mean number of ERCPs was 3.9 ± 1.3 vs 2.6 ± 1.3 (P < .001, intention-to-treat), and mean number of stents placed was 7.0 ± 4.4 vs 1.3 ± .6 (P < .001, as-treated). Serious adverse events occurred in 16 (19.0%) MPS and 19 (23.8%) FCSEMS patients (P = .568), including cholangitis/fever/jaundice (9 vs 7 patients respectively), abdominal pain (5 vs 5), cholecystitis (1 vs 3) and post-ERCP pancreatitis (0 vs 2). No stent- or procedure-related deaths occurred. CONCLUSIONS: Endotherapy of CP-associated BBS has similar efficacy and safety for 12-month treatment using MPS compared with a single FCSEMS, with FCSEMS requiring fewer ERCPs over 2 years. (ClinicalTrials.gov, Number: NCT01543256.). ispartof: GASTROENTEROLOGY vol:161 issue:1 pages:185-195 ispartof: location:United States status: published

Athletic preinjury function is typically determined via subjective recall; however, obtaining preinjury function before injury occurs should be attempted in order to establish an individual baseline for postinjury comparison. The purpose of this study was to obtain preinjury baseline values for the Foot and Ankle Disability Index (FADI) and Foot and Ankle Disability Index sport version (FADISP), single-leg hop for distance, and Star Excursion Balance Test anterior reach and determine if athletes returned to those values following ankle injury. Out of 41 qualifying injuries, FADI/FADISP scores were significantly reduced at initial injury compared with baseline and all other time points (p p ≥ .98). Subjective and objective preinjury function can be reestablished by discharge from supervised treatment following low-grade ankle injury and maintained for at least 6 months following the cessation of treatment. However, testing metrics should be reviewed on an individual athlete basis, because group data may mask individual patient needs.

Introduction:In the early phase of the coronavirus disease 2019 (COVID-19) pandemic, United States Emergency Medical Services (EMS) experienced a decrease in calls, and at the same time, an increase in out-of-hospital deaths. This finding led to a concern for the implications of potential delays in care for the obstetric population.Hypothesis/Problem:This study examines the impact of the pandemic on prehospital care amongst pregnant women.Methods:A retrospective observational study was conducted comparing obstetric-related EMS activations in Maryland (USA) during the pandemic (March 10-July 20, 2020) to a pre-pandemic period (March 10-July 20, 2019). Comparative analysis was used to analyze the difference in frequency and acuity of calls between the two periods.Results:There were fewer obstetric-related EMS encounters during the pandemic compared to the year prior (daily average during the pandemic 12.5 [SD = 3.8] versus 14.6 [SD = 4.1] pre-pandemic; P Conclusions:In this state-wide analysis of EMS calls in Maryland early in the pandemic, no significant differences existed in the utilization of EMS by pregnant women. Prehospital EMS activations amongst pregnant women in Maryland only decreased slightly without an increase in acuity. Of note, over-representation by African-American women compared to population statistics raises concern for broader systemic differences in access to obstetric care.

The 2019–2020 COVID-19 pandemic has caused an economic turndown and high volatility in the global financial markets. Determining the factors that influence services to high-net-worth customers who typically have large investments in the financial markets is important for wealth management banks. This study constructs a hybrid approach by integrating the fuzzy logic and Decision-making Trial and Evaluation Laboratory (DEMATEL) methods to identify the most influential criteria affecting the performance of wealth management banks in Taiwan during the 2019–2020 COVID-19 pandemic. Surveys and interviews are designed using four dimensions (bank performance, service quality, customer relationship, and COVID-19) and 16 criteria for 10 banking executives using fuzzy linguistic scales, to obtain their expert opinions. The results show the order of influence as being service quality, customer relationships, bank performance, and COVID-19. The most important criteria are customized investment information (in-service quality), switching behavior (in-customer relationship), fee income (in-bank performance), and the number of confirmed cases in the top five countries affected by COVID-19. The managerial implication is that wealth management banks should focus on improving their service quality. Banks may strive to provide a wide range of customized investment information and increase customers’ usage of personalized financial products and services. The results of this study will benefit bank managers in serving high-net-worth individuals during the crisis period.

T-cell–redirecting therapies are promising new therapeutic options in the field of cancer immunotherapy, but the development of these modalities is challenging. A commonly observed adverse event in patients treated with T-cell–redirecting therapies is cytokine release syndrome (CRS). Its clinical manifestation is a burden on patients, and continues to be a big hurdle in the clinical development of this class of therapeutics. We review different T-cell–redirecting therapies, discuss key factors related to cytokine release and potentially leading to CRS, and present clinical mitigation strategies applied for those modalities. We propose to dissect those risk factors into drug-target-disease–related factors and individual patient risk factors. Aiming to optimize the therapeutic intervention of these modalities, we illustrate how the knowledge on drug-target-disease–related factors, such as target expression, binding affinity, and target accessibility, can be leveraged in a model-based framework and highlight with case examples how modeling and simulation is applied to guide drug discovery and development. We draw attention to the current gaps in predicting the individual patient's risk towards a high-grade CRS, which requires further considerations of risk factors related, but not limited to, the patient's demographics, genetics, underlying pathologies, treatment history, and environmental exposures. The drug-target-disease–related factors together with the individual patient's risk factors can be regarded as the patient's propensity for developing CRS in response to therapy. As an outlook, we suggest implementing a risk scoring system combined with mechanistic modeling to enable the prediction of an individual patient's risk of CRS for a given therapeutic intervention.

Wealth management services for high-net-worth individuals in Taiwan have grown rapidly over the last decade. This study used a decision-making trial and evaluation laboratory approach to identify the criteria affecting the performance of Taiwan wealth management banks during the coronavirus disease (COVID-19) period. This research surveyed 17 executives from Taiwanese banks using 13 criteria covering three dimensions: bank performance, professionalism, and customer relationship. The results indicated that customer relationship and professionalism have an influence on key performance. Customer involvement (in customer relationship), innovative products and services (in professionalism), and customer satisfaction (in key performance) are the most influential criteria. The results suggest that banks can attract and retain customers by increasing their uses of products and services, developing innovative products, and improving customer satisfaction despite the negative effect of COVID-19. The findings of this study benefit wealth management bank managers in sustaining fee and commission income from high-net-worth customers in the midst of adverse social and economic events.

Endothelial cells (ECs) secrete different paracrine signals that modulate the function of adjacent cells; two examples of these paracrine signals are nitric oxide (NO) and neuregulin-1 (NRG1), a cardioprotective growth factor. Currently, it is undetermined whether one paracrine factor can compensate for the loss of another. Herein, we hypothesized that NRG1 can compensate for endothelial NO synthase (eNOS) deficiency. We characterized eNOS null and wild-type (WT) mice by cardiac ultrasound and histology and we determined circulating NRG1 levels. In a separate experiment, eight groups of mice were divided into four groups of eNOS null mice and WT mice; half of the mice received angiotensin II (ANG II) to induce a more severe phenotype. Mice were randomized to daily injections with NRG1 or vehicle for 28 days. eNOS deficiency increased NRG1 plasma levels, indicating that ECs increase their NRG1 expression when NO production is deleted. eNOS deficiency also increased blood pressure, lowered heart rate, induced cardiac fibrosis, and affected diastolic function. In eNOS null mice, ANG II administration not only increased cardiac fibrosis but also induced cardiac hypertrophy and renal fibrosis. NRG1 administration prevented cardiac and renal hypertrophy and fibrosis caused by ANG II infusion and eNOS deficiency. Moreover, Nrg1 expression in the myocardium is shown to be regulated by miR-134. This study indicates that administration of endothelium-derived NRG1 can compensate for eNOS deficiency in the heart and kidneys. NEW & NOTEWORTHY ECs compensate for eNOS deficiency by increasing the secretion of NRG1. NRG1 administration prevents cardiac and renal hypertrophy and fibrosis caused by ANG II infusion and eNOS deficiency. NRG1 expression is regulated by miR-134.

Blood cultures are among the most important specimen types received and processed by the microbiology laboratory. Several publications list which variables should be measured to ensure quality. We undertook a qualitative structured questionnaire of Australian and New Zealand clinical microbiology laboratories to document current blood culture practices and to determine whether expected quality standards are being met. Questions included a wide range of pre-analytical, analytical, and post-analytical aspects of blood cultures from adults. The responses from 71 laboratories were analysed. Compliance was high for use of a biological safety cabinet (90%), incubating for 5 days (86%), and commenting on likely contaminants (85%). While Gram stains were reported within 2 hours during normal hours (93%), reporting was slower after hours (59%), p0.001. The volume of blood collected for a clinical episode was poorly monitored with only 11% (n=8) of laboratories regularly auditing the number of blood culture sets and 3% (n=2) monitoring adequacy of fill. Most laboratories received blood cultures from off-site with just 34% (n=21) meeting guidance for loading bottles onto the analyser within 4 hours. More laboratories met standards for loading bottles onto the analyser during working hours than after hours: 87% vs 56%, p0.001. Most laboratories did not monitor the contamination rate, 56% (n=40), and only 27% (n=19) knew their rate was below the guidance threshold of less than -3%. Considerable opportunities exist to improve quality assurance of blood culture practice in Australia and New Zealand, especially for the most critical aspect affecting culture sensitivity, the volume of blood collected.

PURPOSE Intraocular pressure (IOP) reduction is key to controlling primary open angle glaucoma (POAG). Pharmacotherapies for POAG or ocular hypertension (OHT) commonly lower IOP by increasing uveoscleral outflow or decreasing aqueous humor production. Netarsudil (Rhopressa), a Rho kinase inhibitor, reduces IOP by improving trabecular outflow facility, which is reduced in POAG. We investigated the effects of netarsudil on aqueous humor dynamics in patients with POAG or OHT. DESIGN Double-masked, randomized, vehicle-controlled, Phase 2 trial. METHODS Netarsudil 0.02% was instilled in 1 eye and vehicle into the contralateral eye of 20 patients once daily in the morning for 7 days. The primary endpoint was change in mean diurnal outflow facility on day 8 versus that on day 1 (baseline). Outflow facility was measured by using Schiotz tonography, IOP by pneumotonometry, and episcleral venous pressure (EVP) by automated venomanometry. RESULTS Eighteen patients (90%) completed the study. Mean diurnal outflow facility increased 0.039 versus 0.007 µL/min/mm Hg from baseline in the netarsudil- and the vehicle-treated groups, respectively (P < .001 vs. baseline for netarsudil), a treatment difference of 0.03 µL/min/mm Hg (P ≤ .001). Mean diurnal IOP change from baseline at day 8 was -4.52 mm Hg for netarsudil versus -0.98 mm Hg for vehicle, a treatment difference of -3.54 mm Hg (P < .0001). Mean diurnal EVP change from baseline was -0.79 mm Hg in the netarsudil-treated group versus 0.10 mm Hg for vehicle, a treatment difference of -0.89 mm Hg (P < .001). All patients reporting an adverse event reported conjunctival hyperemia of mild or moderate severity. CONCLUSIONS Netarsudil acts on the conventional outflow pathway, both proximal and distal, to significantly reduce IOP in POAG and OHT by improving trabecular outflow facility and decreasing EVP.

To compare logistic regression to elastic net for identifying and ranking clinical risk factors for blunt cerebrovascular injury (BCVI). Consecutive trauma patients undergoing screening CTA at a level 1 trauma center over a 2-year period. Each internal carotid artery (ICA) and vertebral artery (VA) was independently graded by 2 neuroradiologists using the Denver grading scale. Unadjusted odds ratios were calculated by univariate and adjusted odds ratios by multiple logistic regression with FDR correction. We applied logistic regression with the elastic net penalty and tenfold cross-validation. Total of 467 patients; 73 patients with BCVI. Maxillofacial fracture, basilar skull fracture, and GCS had significant unadjusted odds ratios (OR) for ICA injury and C-spine fracture, spinal ligamentous injury, and age for VA injury. Only transverse foramen fracture had significant adjusted OR for VA injury, with none for ICA injury, after FDR correction. Using elastic net, ICA injury variables included maxillofacial fracture, basilar skull fracture, GCS, and carotid canal fracture. For VA injury, these included cervical spine transverse foramen fracture, ligamentous injury, C1–C3 fractures, posterior element fracture, and vertebral body fracture. Elastic net statistical learning methods identified additional risk factors and outperformed multiple logistic regression for BCVI. Elastic net allows the study of a large number of variables, and is useful when covariates are correlated.

Precis Diplopia was present in ~20% of patients with Ahmed FP7 (FP7) or Baerveldt 350 (B350), compared with 5% to 6% in those with Baerveldt 250 (B250) or controls, suggesting risk of diplopia should be included in preoperative counseling. Purpose The purpose of this study was to examine the prevalence of diplopia and strabismus in patients with B250, B350, or FP7 glaucoma drainage devices (GDD). Materials and methods In this cohort study, glaucoma patients 18 years and above who had received, or would be receiving, a B250, B350, or FP7 GDD, and medically treated controls were consecutively enrolled from August 8, 2017, through July 31, 2019. The Diplopia Questionnaire was administered ≥30 days postoperatively, and upon enrollment to the controls. All diplopic patients underwent orthoptic measurements, which were reviewed by a strabismus specialist. Patients with GDDs in quadrants other than superotemporal, multiple GDDs, or scleral buckles were excluded. Bonferroni correction was applied for pairwise comparisons. Results Diplopia was reported in 23/129 (17.8%) GDD patients and 5/99 (5.1%) control patients (P=0.003): 8/35 (22.9%) FP7, 2/32 (6.3%) B250, and 13/62 (21.0%) B350, with significant differences between FP7 versus controls (P=0.014) and B350 versus controls (P=0.011). Diplopia was attributable to GDD in 2 FP7 (5.9%, 95% confidence interval: 0.7-19.2), 0 B250, and 4 B350 (6.5%, 95% confidence interval: 1.7-15.2) patients, without significant differences between the GDDs. Conclusions Patients with the larger (B350) or the higher profile plate (FP7) GDDs were more likely to experience diplopia than controls, and diplopia was attributable to the GDD in ~6% of patients with either a FP7 or a B350 GDD. Since diplopia can affect patients' quality of life, preoperative counseling for GDD surgery, particularly B350 and FP7, should include a discussion of the risk of diplopia.

Kramers-Kronig (KK) receivers have been shown to be able to cancel the signal-signal beat interference that occurs upon direct-photodetection in optical single-sideband systems, where the transmitted optical field is proportional to the modulation signal (Field-Modulated Direct-Detection systems). They can support complex modulation formats, and being single-sideband, electronic dispersion compensation, without the need for a coherent receiver. All current research has used digital-signal processing (DSP) to implement the KK algorithm. Radio-frequency KK receivers using analog processing were first introduced in the 1960's, and offer an alternative to DSP, particularly in their approximate form. Analog processing is inherently real-time and offers the lowest latency (processing delay). In this paper, we show that with minor changes, analog processing can also be used with signals from a photodetector. We have built an experimental receiver, using standard parts that have functionality that approximates to the desired algorithm. In particular, we show that a differential pair of bipolar transistors can approximate a square-root function, that the Hilbert transform can be approximated by an 8-tap transmission-line delay, and that a commercial analog multiplier chip can be used for a squaring and subtraction function. The system is demonstrated with 16-QAM at 500 Mbit/s with the photocurrent emulated in software and the KK algorithm performed in hardware. Finally, software band-limits the signal, down-converts it to form a constellation, and calculates symbol error rates. We show that the analog KK reduces the symbol error rate by at least a factor of ten, enabling low carrier-to-signal power ratios to be used with standard forward error correction. Much higher data rates could be supported using custom-designed microwave ASICs, which could be incorporated in packaged receivers. This would enable miniaturized receivers using standard DSP to work with dispersion-limited links. Interestingly, half the benefit could be gained by simply re-biasing the differential stage of a standard photoreceiver.

Introduction As many as 50% of U.S. transplant centers do not accept kidney donor candidates with hypertension, citing the link between hypertension, kidney disease, and cardiovascular disease (CVD). Methods We ascertained mortality, CVD, proteinuria, estimated glomerular filtration rate (eGFR) trajectory, reduced eGFR, and end-stage kidney disease (ESKD) in 904 hypertensive donors (blood pressure [BP] ≥140/90 mm Hg or receiving treatment) versus 7817 donors with BP Results Hypertensive donors were older, 58.1% were Conclusions Kidney donors with hypertension defined by past criteria do not appear to incur higher mortality, CVD, or ESKD. Donors with current definition of hypertension enjoyed similar renal outcomes but were more likely to develop CVD.

As advances in prehospital and early hospital care improve survival of the head-injured patient, radiologists are increasingly charged with understanding the myriad skull base fracture management implications conferred by CT. Successfully parlaying knowledge of skull base anatomy and fracture patterns into precise actionable clinical recommendations is a challenging task. The authors aim to provide a pragmatic overview of CT for skull base fractures within the broader context of diagnostic and treatment planning algorithms. Laterobasal, frontobasal, and posterior basal fracture patterns are emphasized. CT often plays a complementary, supportive, or confirmatory role in management of skull base fractures in conjunction with results of physical examination, laboratory testing, and neurosensory evaluation. CT provides prognostic information about short- and long-term risk of cerebrospinal fluid (CSF) leak, encephalocele, meningitis, facial nerve paralysis, hearing and vision loss, cholesteatoma, vascular injuries, and various cranial nerve palsies and syndromes. The radiologist should leverage understanding of specific strengths and limitations of CT to anticipate next steps in the skull base fracture management plan. Additional imaging is warranted to clarify ambiguity (particularly for potential sources of CSF leak); in other cases, clinical and CT criteria alone are sufficient to determine the need for intervention and the choice of surgical approach. The radiologist should be able to envision stepping into a multidisciplinary planning discussion and engaging neurotologists, neuro-ophthalmologists, neurosurgeons, neurointerventionalists, and facial reconstructive surgeons to help synthesize an optimal management plan after reviewing the skull base CT findings at hand.

Radioembolization is usually performed with microspheres containing yttrium-90 (90Y). Holmium-166 (166Ho)-microspheres were developed as an alternative new product for radioembolization. The unique characteristics of 166Ho-microspheres allow for improved imaging possibilities. They can be visualized and quantified, already at low numbers and activities, to predict treatment distribution using 166Ho-microspheres at scout quantity during pre-treatment simulation. The option to reliably predict the distribution of microspheres provides physicians control over the treatment, allowing them to select and treat patients with a personalized treatment plan. Safety and efficacy were established in several clinical studies. 166Ho-microspheres radioembolization aims to optimize individualized treatment planning in order to improve treatment outcomes.

Objective To evaluate the association of sex and pregnancy status with rates of naloxone administration during opioid overdose-related emergency department (ED) visits by using the Nationwide Emergency Department Sample. Methods A retrospective cohort study was conducted using the Nationwide Emergency Department Sample 2016 and 2017 data sets. Eligible records included men and women, 15-49 years of age, with an opioid overdose-related ED visit; records for women were stratified by pregnancy status (International Classification of Diseases, Tenth Revision O codes). A multivariable logistic regression model was used to assess the primary outcome of naloxone administration (Current Procedural Terminology code: J2310). Secondary outcomes included subsequent admission and mortality. A subgroup analysis compared pregnant women who did receive naloxone compared with those who did not receive naloxone. Results Records from 443,714 men, 304,364 nonpregnant women, and 25,056 pregnant women were included. Nonpregnant women had lower odds for naloxone administration (1.70% vs 2.10%; adjusted odds ratio [aOR] 0.86 [95% CI 0.83-0.89]) and mortality (2.21% vs 2.99%; aOR 0.71 [95% CI 0.69-0.73]) but higher odds of subsequent admission (30.22% vs 27.18%; aOR 1.04 [95% CI 1.03-1.06]) compared with men. Pregnant women had lower odds for naloxone administration (0.27% vs 1.70%; aOR 0.16 [95% CI 0.13-0.21]) and mortality (0.41% vs 2.21%; aOR 0.28 [95% CI 0.23-0.35]) but higher odds of subsequent admission (40.50% vs 30.22%; aOR 2.04 [95% CI 2.00-2.10]) compared with nonpregnant women. Pregnant women who received naloxone had higher odds of mortality (14% vs 0.39%; aOR 6.30 [95% CI 2.11-18.78]) compared with pregnant women who did not receive naloxone. Pregnant women who did not receive naloxone were more likely to have Medicaid as their expected insurance payer, be in the lowest quartile of median household income for residence ZIP codes, and have a concurrent mental health diagnosis compared with pregnant women who did receive naloxone. Conclusion Reproductive-aged women who are nonpregnant and pregnant were less likely to receive naloxone during opioid overdose-related ED visits compared with reproductive-aged men. Naloxone administration for reproductive-aged women should be prioritized in the efforts to reduce opioid- and pregnancy-related morbidity and mortality in the United States.

Indeterminate biliary strictures present a balancing act between the potential morbidity from redundant operations and the risk of missed malignancy and disease progression. This review aims to compare and assess the efficacy of the different diagnostic techniques. Until today, endoscopic retrograde cholangiopancreatography with tissue sampling was considered the standard for distinguishing benign from malignant biliary strictures. However, it is hampered by a low diagnostic yield. Indeterminate biliary strictures remain a difficult clinical problem. Invariably, expert evaluation and review at an MDT setting should be the first step. If the diagnosis remains elusive despite the initial strategies including clinical evaluation, imaging with CT or MRI and initial sampling with either EUS or ERCP brushing, the patient should then be considered for expert IDBS evaluation. These patients should be selected for cholangioscopy with direct visualisation, direct sampling and, if available, advanced interpretive techniques such as confocal laser endomicroscopy and FISH etc. These techniques can assist in improving diagnosis and minimise delay to essential treatment and avoid unnecessary surgery. PSC remains a challenge; however, recent advances in cholangioscopy classification are proving useful in managing this cohort.

Radioembolization based on personalized treatment planning requires established dose-response and dose-toxicity relationships. The aim of this study was to investigate dose-response and dose-toxicity relationships in patients with colorectal liver metastases (CRLMs) treated with glass 90Y-microspheres. Methods: All CRLM patients treated with glass 90Y-microspheres in our institution were retrospectively analyzed. The tumor-absorbed dose was calculated for each measurable metastasis (i.e.,18F-FDG-positive and more than a 5-cm3 tumor volume) on posttreatment 90Y PET. Metabolic tumor response was determined on 18F-FDG PET/CT by measuring the total lesion glycolysis at baseline and at 3 mo after treatment. The relationship between tumor-absorbed dose and metabolic response was determined on a per-lesion and per-patient basis using a linear mixed-effects regression model. Clinical toxicity and laboratory toxicity were correlated with healthy liver-absorbed dose. Results: Thirty-one patients were included. The median tumor-absorbed dose of 85 measurable metastases was 133 Gy (range, 20-1001 Gy). Per response category, this was 196 Gy for complete response (CR), 177 Gy for partial response (PR), 72 Gy for stable disease, and 95 Gy for progressive disease (PD). A significant dose-response relationship was found on a tumor level, with a significantly higher tumor-absorbed dose in metastases with CR (+94%) and PR (+74%) than in metastases with PD (P < 0.001). A similar relationship was found on a patient level, with PR having a higher tumor-absorbed dose than did PD (+58%, P = 0.044). A tumor-absorbed dose of more than 139 Gy predicted a 3-mo metabolic response with the greatest accuracy (89% specificity and 77% sensitivity), whereas a tumor-absorbed dose of more than 189 Gy predicted response with 97% specificity and 45% sensitivity. The median healthy liver-absorbed dose was 63 Gy (range, 24-113 Gy). Toxicity was limited mostly to grades 1 and 2, with 1 case of radioembolization-induced liver disease in a patient who received the highest healthy liver-absorbed dose. A positive trend was seen for most laboratory parameters in our dose-toxicity analysis. Conclusion: A significant relationship was observed between dose and response in CRLM patients treated with glass 90Y radioembolization.

The purpose of this study was to determine the angular tolerance of the S1 and S2 segments to accommodate a transiliosacral screw across both sacroiliac joints. We hypothesized that the angular tolerance for transiliosacral screw placement would be more constrained than the angular tolerance for iliosacral fixation in pelves where a safe osseous corridor was measured. The cortical boundaries of the S1 and S2 sacral segments in 433 pelvic CTs were digitally mapped. A straight-line path was placed within each osseous corridor and extended across both SI joints past the outer iliac cortices. The diameter of the path was increased until it breached the cortex, geometrically determining maximum diameter (Dmax). Angular tolerance for screw placement was calculated with trigonometric analysis of the Dmax value of the corridor, and the average distance from the termination of the osseous corridor to the site of percutaneous insertion. Gender, age, and BMI were evaluated as independent predictors using binomial logistic regression. The transiliosacral angular tolerance for the S1 and S2 osseous corridors was 1.53 ± 0.57 degrees and 1.02 ± 0.33 degrees, respectively. 68.9% of S1 corridors and 81.1% of S2 corridors had a safe zone (corridor diameter ≥ 10 mm) for transiliosacral placement, 48.3% of the pelves had a safe zone for both corridors, while 5.1% had no safe zones. Females had a less frequent Dmax ≥ 10 mm at S1, 52% vs 67% (p = 0.001), and at S2, 64% vs 86% (p

Purpose Adult granulosa cell tumors (AGCTs) of the ovary represent a rare malignancy in which timing and choice of treatment is a clinical challenge. This study investigates the value of FDG-PET/CT and FES-PET/CT in monitoring recurrent AGCTs and assessing eligibility for anti-hormonal treatment. Materials and methods We evaluated 22 PET/CTs from recurrent AGCT patients to determine tumor FDG (n = 16) and FES (n = 6) uptake by qualitative and quantitative analysis. We included all consecutive patients from two tertiary hospitals between 2003-2020. Expression of ERα and ERβ and mitoses per 2 mm2 were determined by immunohistochemistry and compared to FES and FDG uptake, respectively. Results Qualitative assessment showed low-to-moderate FDG uptake in most patients (14/16), and intense uptake in 2/16. One patient with intense tumor FDG uptake had a high mitotic rate (18 per 2 mm2) Two out of six patients showed FES uptake on PET/CT at qualitative analysis. Lesion-based quantitative assessment showed a mean SUVmax of 2.4 (± 0.9) on FDG-PET/CT and mean SUVmax of 1.7 (± 0.5) on FES-PET/CT. Within patients, expression of ERα and ERβ varied and did not seem to correspond with FES uptake. In one FES positive patient, tumor locations with FES uptake remained stable or decreased in size during anti-hormonal treatment, while all FES negative locations progressed. Conclusions This study shows that in AGCTs, FDG uptake is limited and therefore FDG-PET/CT is not advised. FES-PET/CT may be useful to non-invasively capture the estrogen receptor expression of separate tumor lesions and thus assess the potential eligibility for hormone treatment in AGCT patients.