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Grasslands are the largest contributor of nitrous oxide (N2O) emissions in the agriculture sector due to livestock excreta and nitrogen fertilizers applied to the soil. Nitrification inhibitors (NIs) added to N input have reduced N2O emissions, but can show a range of efficiencies depending on climate, soil, and management conditions. A meta-analysis study was conducted to investigate the factors that influence the efficiency of NIs added to fertilizer and excreta in reducing N2O emissions, focused on grazing systems. Data from peer-reviewed studies comprising 2164 N2O emission factors (EFs) of N inputs with and without NIs addition were compared. The N2O EFs varied according to N source (0.0001–8.25%). Overall, NIs reduced the N2O EF from N addition by 56.6% (51.1–61.5%), with no difference between NI types (Dicyandiamide—DCD; 3,4-Dimethylpyrazole phosphate—DMPP; and Nitrapyrin) or N source (urine, dung, slurry, and fertilizer). The NIs were more efficient in situations of high N2O emissions compared with low; the reduction was 66.0% when EF > 1.5% of N applied compared with 51.9% when EF ≤ 0.5%. DCD was more efficient when applied at rates > 10 kg ha−1. NIs were less efficient in urine with lower N content (≤ 7 g kg−1). NI efficiency was negatively correlated with soil bulk density, and positively correlated with soil moisture and temperature. Better understanding and management of NIs can optimize N2O mitigation in grazing systems, e.g., by mapping N2O risk and applying NI at variable rate, contributing to improved livestock sustainability.

Grasslands play an important role in global food security. However, there are increasing pressures to improve the sustainability of ruminant farming. Precision nutrient management tools (e.g., proximal soil sensors for soil mapping) offer opportunities to improve nutrient use efficiency through spatially-variable nutrient application rate maps. Despite little research validating these technologies on grasslands, commercial companies promote these technologies to grassland farmers. In this study, the accuracy of commercial companies offering these services was evaluated by comparing soil pH, P, K, Mg and SOM measurements derived from conventional soil sampling and laboratory analyses to measurements derived from the commercial operators, across a range of soils that are typical found in UK grasslands. Results showed that soil mapping services utilising gamma-ray spectroscopy (GRS) were not sufficiently accurate to predict soil pH, P, K and Mg on grasslands, and subsequently inappropriate for nutrient management planning for variable rate lime and nutrient application. Conversely, both GRS and visible-near infrared spectroscopy (Vis–NIR) accurately predicted between-field SOM variations in grassland soils but not within-field variation. This study emphasises the need for further research to explore the limitations of, and opportunities for, the universal application of these technologies across different soil types and/or land uses before their commercial application. It is therefore highly recommended that commercially-available soil mapping services are subject to certification, similar to centralised soil testing laboratories, to ensure data are accurate for soil management interpretation. The lack of reliability of such systems risks farmers’ confidence in the value of soil mapping, which could severely hinder future adoption of potentially valuable technologies.

Controversy persists regarding the ideal surgical approach for repair of esophageal atresia with tracheoesophageal fistula (EA/TEF). We examined complications and outcomes of infants undergoing thoracoscopy and thoracotomy for repair of Type C EA/TEF using propensity score-based overlap weights to minimize the effects of selection bias.Secondary analysis of two databases from multicenter retrospective and prospective studies examining outcomes of infants with proximal EA and distal TEF who underwent repair at 11 institutions was performed based on surgical approach. Regression analysis using propensity score-based overlap weights was utilized to evaluate outcomes of patients undergoing thoracotomy or thoracoscopy for Type C EA/TEF repair.Of 504 patients included, 448 (89%) underwent thoracotomy and 56 (11%) thoracoscopy. Patients undergoing thoracoscopy were more likely to be full term (37.9 vs. 36.3 weeks estimated gestational age, p 0.001), have a higher weight at operative repair (2.9 vs. 2.6 kg, p 0.001), and less likely to have congenital heart disease (16% vs. 39%, p 0.001). Postoperative stricture rate did not differ by approach, 29 (52%) thoracoscopy and 198 (44%) thoracotomy (p = 0.42). Similarly, there was no significant difference in time from surgery to stricture formation (p 0.26). Regression analysis using propensity score-based overlap weighting found no significant difference in the odds of vocal cord paresis or paralysis (OR 1.087 p = 0.885), odds of anastomotic leak (OR 1.683 p = 0.123), the hazard of time to anastomotic stricture (HR 1.204 p = 0.378), or the number of dilations (IRR 1.182 p = 0.519) between thoracoscopy and thoracotomy.Infants undergoing thoracoscopic repair of Type C EA/TEF are more commonly full term, with higher weight at repair, and without congenital heart disease as compared to infants repaired via thoracotomy. Utilizing propensity score-based overlap weighting to minimize the effects of selection bias, we found no significant difference in complications based on surgical approach. However, our study may be underpowered to detect such outcome differences owing to the small number of infants undergoing thoracoscopic repair.Level III.

Disparities in surgical management have been documented across a range of disease processes. The objective of this study was to investigate sociodemographic disparities in young females undergoing excision of a breast mass.A retrospective study of females aged 10-21 y who underwent surgery for a breast lesion across eleven pediatric hospitals from 2011 to 2016 was performed. Differences in patient characteristics, workup, management, and pathology by race/ethnicity, insurance status, median neighborhood income, and urbanicity were evaluated with bivariate and multivariable regression analyses.A total of 454 females were included, with a median age of 16 y interquartile range (IQR: 3). 44% of patients were nonHispanic (NH) Black, 40% were NH White, and 7% were Hispanic. 50% of patients had private insurance, 39% had public insurance, and 9% had other/unknown insurance status. Median neighborhood income was $49,974, and 88% of patients resided in a metropolitan area. NH Whites have 4.5 times the odds of undergoing preoperative fine needle aspiration or core needle biopsy compared to NH Blacks (CI: 2.0, 10.0). No differences in time to surgery from the initial imaging study, size of the lesion, or pathology were observed on multivariable analysis.We found no significant differences by race/ethnicity, insurance status, household income, or urbanicity in the time to surgery after the initial imaging study. The only significant disparity noted on multivariable analysis was NH White patients were more likely to undergo preoperative biopsy than were NH Black patients; however, the utility of biopsy in pediatric breast masses is not well established.

To assess the preoperative imaging impression and surgeon diagnostic accuracy for pediatric ovarian mature cystic teratomas (MCTs) DESIGN: Retrospective review SETTING: Eleven pediatric hospitals PARTICIPANTS: Patients ages 2 to 21 who underwent surgical management of an ovarian neoplasm or adnexal torsion with an associated ovarian lesion INTERVENTION: None MAIN OUTCOME MEASURES: Preoperative imaging impression, surgeon diagnosis, tumor markers, and pathology RESULTS: Our cohort included 946 females. Final pathology identified 422 (45%) MCTs, 405 (43%) other benign pathologies, and 119 (12%) malignancies. Preoperative imaging impression for MCTs had a 70% sensitivity, 92% specificity, 88% positive predictive value (PPV), and 79% negative predictive value (NPV). For the preoperative surgeon diagnosis, sensitivity was 59%, specificity 96%, PPV 92%, and NPV 74%. Some measures of diagnostic accuracy were affected by the presence of torsion, size of the lesion on imaging, imaging modality, and surgeon specialty. Of the 352 masses preoperatively thought to be MCTs, 14 were malignancies (4%). Eleven patients with inaccurately diagnosed malignancies had tumor markers evaluated and 82% had at least 1 elevated tumor marker, compared with 49% of those with MCTs.Diagnostic accuracy for the preoperative imaging impression and surgeon diagnosis is lower than expected for pediatric ovarian MCTs. For all ovarian neoplasms, preoperative risk assessment including a panel of tumor markers and a multidisciplinary review is recommended. This process could minimize the risk of misdiagnosis and improve operative planning to maximize the use of ovarian-sparing surgery for benign lesions and allow for appropriate resection and staging for lesions suspected to be malignant.

We aimed to develop and test a relatively objective method for rapidly and accurately assessing the priority for research of interventions tendered as potential solutions to a prevailing problem in agriculture. In this test, our method aimed to direct research of evidenced-based strategies to ameliorate consistently high rates of foetal and calf loss experienced in northern Australia’s beef herd. Detailed reviews of factors affecting foetal and calf loss and potential solutions were conducted. A simple economic analysis, based on rating management interventions for their impact on earnings before interest and tax, was then developed to enable rapid simultaneous business-impact comparison of multiple options. If the outcome value for an option is negative, it suggests that the option is less profitable than is prevailing practice, if approximately zero, it suggests that the option is very marginal, and more positive values suggest a higher potential benefit. The values obtained were further analysed by rating for incidence and researchability to derive research priority. This sequence of activities was conducted by peers representing a broad spectrum of beef business (managing an estimated 0.4 million cattle), science and agribusiness representatives from across northern Australia. A sensitivity analysis demonstrated that the method was robust in ranking both business impact and research priority. Ten foetal and calf-loss minimisation interventions were rated by producer and agribusiness representatives and the project team as a high priority for business. Four of these were excluded because of low incidence or low researchability, leaving six rated as having highest priority for research. Informal feedback from many participants indicated high satisfaction with the proposed method. The conclusion was that this method, with suggested variations, successfully discriminated priority for a large range of potential interventions for calf loss research, development and extension (RD&E). The method described could readily supplant commonly used more subjective methods and be used to assess priority for RD&E of other issues for multiple agricultural commodities, as well as simply for rapid assessment of management options within a production enterprise.

Anastomotic stricture is the most common complication after esophageal atresia (EA) repair. We sought to determine if postoperative acid suppression is associated with reduced stricture formation.A prospective, multi-institutional cohort study of infants undergoing primary EA repair from 2016 to 2020 was performed. Landmark analysis and multivariate Cox regression were used to explore if initial duration of acid suppression was associated with stricture formation at hospital discharge (DC), 3-, 6-, and 9-months postoperatively.Of 156 patients, 79 (51%) developed strictures and 60 (76%) strictures occurred within three months following repair. Acid suppression was used in 141 patients (90%). Landmark analysis showed acid suppression was not associated with reduction in initial stricture formation at DC, 3-, 6- and 9-months, respectively (p = 0.19-0.95). Multivariate regression demonstrated use of a transanastomotic tube was significantly associated with stricture formation at DC (Hazard Ratio (HR) = 2.21 (95% CI 1.24-3.95, p0.01) and 3-months (HR 5.31, 95% CI 1.65-17.16, p0.01). There was no association between acid suppression duration and stricture formation.No association between the duration of postoperative acid suppression and anastomotic stricture was observed. Transanastomotic tube use increased the risk of anastomotic strictures at hospital discharge and 3 months after repair.

Trace gases of nitrogen (N), such as NOx (nitric oxide, NO + nitrogen dioxide, NO2) have a negative impact on human health and the environment. Although NOx are naturally produced in volcanic eruptions, forest fires and biotic nitrification and denitrification in soils, human activity is a major source of these contaminants via e.g. the combustion of fossil fuels. Additionally, N fertilization in agricultural soils is also an important source of NOx emissions. These emissions involve a loss of soil N to the atmosphere and have a negative impact in air quality. The abiotic part of the N cycle in terrestrial ecosystems has not received as much attention as the biotic part and certain abiotic reactions could play a key role in regulating NOx emissions. Photocatalysis is an example as this is used to abate NOx gases in urban and industrial areas. This reaction requires the presence of a catalyst (e.g. titanium oxide), oxygen, water, and energy from the sun (UV-visible light) to transform NO from the atmosphere into innocuous inorganic N forms (mainly nitrate, NO3-). There is a continuous investment in the production of catalysts by the industry. However, a variety of soil minerals such as anatase or rutile (titanium oxides), hematite and goethite (iron oxides), are found in soils and they could act as catalysts; however, the occurrence of photocatalysis in soils has not been evaluated so far. In this study, we assess (i) the potential of a selection of soils with different mineralogy and a wide variety of soil properties to fix or emit NOx through photocatalysis, and (ii) the possible alterations in the fixation or emission of other N gases from the soil, i.e., nitrous oxide (N2O) and ammonia (NH3), when photocatalysis is induced. Around thirty agricultural soils were selected to meet the first objective and irradiated for 1 hour with UV-visible light under a constant flux of air and NO (100 ppm). Similar experiments were carried out with a selection of soils, whose potential to fix NO was different and tested in the previous experiment, to satisfy the second objective. However, only air (without NO) was pumped within the soil chamber in this case and the soils were previously fertilized with different N fertilisers (urea or KNO3-) and rates (0 to 250 mg N kg-1 soil). Our experiments show that weathered soils (with a high content in titanium and iron oxides) were able to fix more atmospheric NO through photocatalysis (objective i), and that NO and NH3 fixation and emissions after N fertilization depended not only on the N fertilizer and rate but also on soil properties, mainly soil pH and N content (objective ii). Soil mineralogy and properties play a key role in soil photocatalysis, and this abiotic reaction should be considered in order to design more sustainable strategies for agriculture.

Supplementary Table 1 from New Derivatives of Vitamin B12 Show Preferential Targeting of Tumors

Supplementary Table 2 from New Derivatives of Vitamin B12 Show Preferential Targeting of Tumors

In-barn heat processing of mass swine mortalities to inactivate pathogens could facilitate more carcass disposal options and reduce the risk of pathogen spread in the event of a foreign animal disease (FAD) outbreak. A 12.2 × 12.2 × 2.4 m (W × L × H) heat processing room was created using a temporary wall inside a de-commissioned commercial gestation barn in northwest Iowa. Eighteen swine carcasses (six per group) divided into three weight groups (mean ± SD initial carcass weights: 31.8 ± 3.3, 102.7 ± 8.1, and 226.3 ± 27.6 kg) were randomly assigned a location inside the room. Three carcasses per weight group were placed directly on concrete slats and on a raised platform. One carcass per weight group and placement (n=6) was instrumented with five temperature sensors, inserted into the brain, pleura, peritoneal, ham, and bone marrow of the femur, and a sensor was attached directly to the skin surface. Environmental conditions (ambient and room) and carcass temperatures were collected at 15-min intervals. Carcasses were subjected to an average room temperature of 57.3 ± 1.2°C for 14 days. The average (±SD) reduction from initial weight for the carcasses on slats was 45.0 ± 4.70% (feeder), 33.0 ± 8.30% (market), and 34.0 ± 15.80% (sow), and for the carcasses on a raised platform, it was 39.0 ± 6.80% (feeder), 49.0 ± 11.30% (market), and 45.0 ± 6.70% (sow). There was a significant interaction between carcass placement (slats and raised) and carcass weight loss for the market weight group. When average carcass surface temperature was at 40.6, 43.3, and 46.1°C (data grouped for analysis), the average internal carcass temperature for most measurement locations was significantly different across carcass weight groups and between the carcasses on a raised platform and those on slats. This preliminary analysis of carcass weight loss, leachate production, and temperature variation in carcasses of different sizes can be used for planning and evaluating mass swine mortality management strategies.

Mid-infrared observations are powerful in identifying heavily obscured Active Galactic Nuclei (AGN) which have weak emission in other wavelengths. Data from the Mid-Infrared Instrument (MIRI) onboard JWST provides an excellent opportunity to perform such studies. We take advantage of the MIRI imaging data from the Cosmic Evolution Early Release Science Survey (CEERS) to investigate the AGN population in the distant universe. We estimate the source properties of MIRI-selected objects by utilizing spectral energy distribution (SED) modelling, and classify them into star-forming galaxies (SF), SF-AGN mixed objects, and AGN. The source numbers of these types are 418, 111, and 31, respectively, from 4 MIRI pointings covering $\sim 9$ arcmin$^2$. The sample spans a redshift range of $\approx 0$--5. We derive the median SEDs for all three source types, respectively, and publicly release them. The median MIRI SED of AGN is similar to the typical SEDs of hot dust-obscured galaxies and Seyfert 2s, for which the mid-IR SEDs are dominantly from AGN-heated hot dust. Based on our SED-fit results, we estimate the black-hole accretion density (BHAD; i.e., total BH growth rate per comoving volume) as a function of redshift. At $z3$, we identify a total of 27 AGN and SF-AGN mixed objects, leading to that our high-$z$ BHAD is substantially higher than the X-ray results ($\sim 0.5$ dex at $z \approx 3$--5). This difference indicates MIRI can identify a large population of heavily obscured AGN missed by X-ray surveys at high redshifts., ApJL in press, as part of the CEERS Focus Issue. 13 pages and 7 figures (median SEDs in Fig. 5 are available upon request)

The impact of thoracoscopic surgery on outcomes in children with congenital lung malformations (CLM) remains controversial. The purpose of this study was to determine the effect of operative approach on perioperative outcomes in infants undergoing lobectomy for an asymptomatic CLM.After IRB approval, a retrospective cohort study was conducted on 506 children with a CLM resected at one of eleven children's hospitals over a seven-year period. Infants undergoing elective lobectomy were identified, and covariates were balanced based on operative approach using propensity scores with full matching. Outcomes were analyzed based on intention to treat with weighted conditional regression.One hundred seventy-five infants met inclusion criteria. There were 67 (38.3%) open, 89 (50.9%) thoracoscopic, and 19 (10.9%) thoracoscopic-converted-to-open lobectomies. Thoracoscopic lobectomy was associated with significantly longer operative times (26 min, 95% CI 6-47 min, p = 0.012) but used less epidural anesthesia (OR 0.02, 95% CI 0.004-0.11, p0.001) when compared to open lobectomy. There were no significant differences in intraoperative blood loss, postoperative complications, chest tube duration, or length of stay.Thoracoscopy has become the most common operative approach for elective lobectomy in infants with asymptomatic CLMs. The non-inferiority of thoracoscopic lobectomy in postoperative outcomes supports its continued use as an alternative to open lobectomy.Treatment study, Level III.

Background The objective of our study was to describe the workup, management, and outcomes of pediatric patients with breast masses undergoing operative intervention. Materials and methods A retrospective cohort study was conducted of girls 10-21 y of age who underwent surgery for a breast mass across 11 children's hospitals from 2011 to 2016. Demographic and clinical characteristics were summarized. Results Four hundred and fifty-three female patients with a median age of 16 y (IQR: 3) underwent surgery for a breast mass during the study period. The most common preoperative imaging was breast ultrasound (95%); 28% reported the Breast Imaging Reporting and Data System (BI-RADS) classification. Preoperative core biopsy was performed in 12%. All patients underwent lumpectomy, most commonly due to mass size (45%) or growth (29%). The median maximum dimension of a mass on preoperative ultrasound was 2.8 cm (IQR: 1.9). Most operations were performed by pediatric surgeons (65%) and breast surgeons (25%). The most frequent pathology was fibroadenoma (75%); 3% were phyllodes. BI-RADS scoring ≥4 on breast ultrasound had a sensitivity of 0% and a negative predictive value of 93% for identifying phyllodes tumors. Conclusions Most pediatric breast masses are self-identified and benign. BI-RADS classification based on ultrasound was not consistently assigned and had little clinical utility for identifying phyllodes.

Background Management of ovarian torsion has evolved toward ovarian preservation regardless of ovarian appearance during surgery. However, patients with torsion and an ovarian neoplasm undergo a disproportionately high rate of oophorectomy. Our objectives were to identify factors associated with ovarian torsion among females with an ovarian mass and to determine if torsion is associated with malignancy. Methods A retrospective review of females aged 2-21 y who underwent an operation for an ovarian cyst or neoplasm between 2010 and 2016 at 10 children's hospitals was performed. Multivariate logistic regression was used to assess factors associated with torsion. Imaging data were assessed for sensitivity, specificity, and predictive value in identifying ovarian torsion. Results Of 814 girls with an ovarian neoplasm, 180 (22%) had torsion. In risk-adjusted analyses, patients with a younger age, mass size >5 cm, abdominal pain, and vomiting had an increased likelihood of torsion (P 5 cm had two times the odds of torsion (odds ratio: 2.1; confidence interval: 1.2, 3.6). Imaging was not reliable at identifying torsion (sensitivity 34%, positive predictive value 49%) or excluding torsion (specificity 72%, negative predictive value 87%). The rates of malignancy were lower in those with an ovarian mass and torsion than those without torsion (10% versus 17%, P = 0.01). Among the 180 girls with torsion and a mass, 48% underwent oophorectomy of which 14% (n = 12) had a malignancy. Conclusions In females with an ovarian neoplasm, torsion is not associated with an increased risk of malignancy and ovarian preservation should be considered.

The prevalence and natural history of patent processus vaginalis (PPV) are unknown. An interim analysis was performed of a multi-institutional, prospective, observational study in neonates undergoing laparoscopic pyloromyotomy during which bilateral inguinal canals were evaluated.Infants under 4 months undergoing laparoscopic pyloromyotomy were enrolled at 8 children's hospitals. The presence of a PPV was evaluated and measurements recorded. Patients with a PPV are undergoing annual phone follow-up to 18 years of age. Interim analysis was performed.In a cohort of 610 patient, 80 did not have a PPV examined, 4 had consent issues and were excluded, leaving 526 patients. Of these, 433 (82%) were male, median age 1.2 months (IQR 0.9, 1.6), median weight 3.89 kg (IQR 3.4, 4.46), and EGA 39 weeks (IQR 37, 40). There were 283 PPVs, 132 bilateral (47%), 116 right (41%), and 35 left (12%). Patients with a PPV were significantly younger (1.1 months (IQR 0.9, 1.5) vs 1.3 months (IQR 0.9, 1.7), p=0.02), weighed less (3.76kg (IQR 3.35, 4.26) vs 3.9kg (IQR 3.4, 4.5) p=0.03) and had a significantly lower EGA at birth (38 weeks (IQR 37, 40) vs 39 weeks (IQR 38, 40) p=0.003). Of 246 eligible infants, 208 (85%) responded to at least one annual follow-up. Two patients had an inguinal hernia repair for a symptomatic hernia, 49- and 51-days post pyloromyotomy. One had an orchiopexy and incidental inguinal hernia repair 120 days post pyloromyotomy; for a total of 3 (1.2%) hernia repairs. No additional hernias were identified in 116 patients with the PPV patients who have been followed for1 year.The presence of a PPV at the time of pyloromyotomy is common but the need for hernia repair is rare within the first year of life. Continued long-term longitudinal follow-up of this cohort is needed.II.

Describe the current practice patterns and diagnostic accuracy of frozen section (FS) pathology for children and adolescents with ovarian masses DESIGN: Prospective cohort study from 2018 to 2021 SETTING: Eleven children's hospitals PARTICIPANTS: Females age 6-21 years undergoing surgical management of an ovarian mass INTERVENTIONS: Obtaining intraoperative FS pathology MAIN OUTCOME MEASURE: Diagnostic accuracy of FS pathology RESULTS: Of 691 patients who underwent surgical management of an ovarian mass, FS was performed in 27 (3.9%), of which 9 (33.3%) had a final malignant pathology. Among FS patients, 12 of 27 (44.4%) underwent ovary-sparing surgery, and 15 of 27 (55.5%) underwent oophorectomy with or without other procedures. FS results were disparate from final pathology in 7 of 27 (25.9%) cases. FS had a sensitivity of 44.4% and specificity of 94.4% for identifying malignancy, with a c-statistic of 0.69. Malignant diagnoses missed on FS included serous borderline tumor (n = 1), mucinous borderline tumor (n = 2), mucinous carcinoma (n = 1), and immature teratoma (n = 1). FS did not guide intervention in 10 of 27 (37.0%) patients: 9 with benign FS underwent oophorectomy, and 1 with malignant FS did not undergo oophorectomy. Of the 9 patients who underwent oophorectomy with benign FS, 5 (55.6%) had benign and 4 (44.4%) had malignant final pathology.FSs are infrequently utilized for pediatric and adolescent ovarian masses and could be inaccurate for predicting malignancy and guiding operative decision-making. We recommend continued assessment and refinement of guidance before any standardization of use of FS to assist with intraoperative decision-making for surgical resection and staging in children and adolescents with ovarian masses.

The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020.Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors.Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%.This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.

In primary Total Knee Arthroplasty (TKA), it is still not clear if cemented or uncemented fixation has the best long-term survival. The Low Contact Stress (LCS) mobile-bearing (MB) knee system was introduced in 1977. The aim of this study is to investigate the long-term survival of this design with a minimum of 15-year follow-up. A retrospective analysis was performed, with the primary endpoint for survival defined as revision. Cox regression analysis was performed to assess the association between type of fixation and the risk of revision, while correcting for potential confounders (diagnosis, design, age and sex). 1271 cases were included with inflammatory joint disease (IJD) (657 cases) and non-IJD (614 cases). TKAs were performed cemented in 522 cases and uncemented in 749 cases. A bicruciate retaining design was used in 180 cases, a rotating platform design in 174 cases and an anterior posterior glide posterior cruciate-retaining (PCR) design in 916 cases. Cumulative incidence of component revision at 15 years was 2.7% (95% CI 1.6; 4.5) for cemented and 10% (95% CI 8.1; 12.4) for uncemented TKA, respectively. The 20-year cumulative incidence was 2.9% (95% CI 1.7; 4.7) for cemented and 10.9% (95% CI 8.8; 13.4) for uncemented TKA, respectively. Age, non-IJD and PCR design were associated with a significantly higher risk of revision, regardless of the type of fixation. Long-term survival for patients undergoing cemented or uncemented TKA using the LCS MB system revealed lower revision rates for cemented fixation. Revision risk was higher in younger, non-IJD patients who had the PCR design, regardless of the type of fixation. For the LCS MB TKA design, it is recommended to use cemented fixation.

Aim Ecological communities that exist closer together in space are generally more compositionally similar than those far apart, as defined by the distance?decay of similarity relationship. However, recent research has revealed substantial variability in the distance?decay relationships of microbial communities between studies of different taxonomic groups, ecosystems and spatial scales and between those using different molecular methodologies (e.g., high-throughput sequencing versus molecular fingerprinting). Here, we test how these factors influence the strength of microbial distance?decay relationships, in order to draw generalizations about how microbial ?-diversity scales with space. Location Global. Time period Studies published between 2005 and 2019 (inclusive). Major taxa studied Bacteria, Archaea and microbial Eukarya. Methods We conducted a meta-analysis of microbial distance?decay relationships, using the Mantel correlation coefficient as a measure of the strength of distance?decay relationships. Our final dataset consisted of 452 data points, varying in environmental/ecological context or methodological approaches, and we used linear models to test the effects of each variable. Results Both ecological and methodological factors had significant impacts on the strength of microbial distance?decay relationships. Specifically, the strength of these relationships varied between environments and habitats, with soils showing significantly weaker distance?decay relationships than other habitats, whereas increasing spatial extents had no effect. Methodological factors, such as sequencing depth, were positively related to the strength of distance?decay relationships, and choice of dissimilarity metric was also important, with phylogenetic metrics generally giving weaker distance?decay relationships than binary or abundance-based indices. Main conclusions We conclude that widely studied microbial biogeographical patterns, such as the distance?decay relationship, vary by ecological context but are primarily distorted by methodological choices. Consequently, we suggest that by linking methodological approaches appropriately to the ecological context of a study, we can progress towards generalizable biogeographical relationships in microbial ecology.

Aims An anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) with an interarterial course can be assessed using computed tomography angiography (CTA) for the presence of high-risk characteristics associated with sudden cardiac death. These features include a slit-like ostium, acute angle take-off, proximal luminal narrowing, and an intramural segment. To date, no robust CTA criteria exist to determine the presence of an intramural segment. We aimed to deduct new CTA parameters to distinguish an intramural course of interarterial ACAOS. Methods and results Twenty-five patients with an interarterial ACAOS (64% female, mean age 46 years, 88% right ACAOS) from two academic hospitals were evaluated. Inclusion criteria were the availability of a preoperative CTA scan (0.51 mm slice thickness) and peroperative confirmation of the intramural segment. Using multiplanar reconstruction of the CTA, the distance between the lumen of the aorta and the lumen of the ACAOS [defined as ‘interluminal space’ (ILS)] was assessed at 2 mm intervals along the intramural segment. Analysis showed a mean ILS of 0.69 ± 0.15 mm at 2 mm from the ostium. At the end of the intramural segment where the ACAOS becomes non-intramural, the mean ILS was significantly larger (1.27 ± 0.29 mm, P Conclusion The ILS is introduced as a novel and robust CTA parameter to identify an intramural course of interarterial ACAOS. An ILS of

The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown.To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed.This study was a planned subgroup secondary analysis conducted in 10 children's hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022.Nonoperative management with antibiotics vs surgery.Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management.Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]).This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year.ClinicalTrials.gov Identifier: NCT02271932.

ObjectivesPaediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.DesignA multicentre, international, collaborative cohort study.Setting91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.ParticipantsPatients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measureAll-cause mortality at 30 days and 90 days.Results1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (pConclusionsThe COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.

According to the available guidelines, good practices for calculating nitrous oxide (N

Continuous passive motion (CPM) has been used for decades, but we are not aware of any randomized controlled trials (RCTs) in which CPM has been compared with physical therapy (PT) for rehabilitation following release of elbow contracture.In this single-blinded, single-center RCT, we randomly assigned patients undergoing arthroscopic release of elbow contracture to a rehabilitation protocol involving either CPM or PT. The primary outcomes were the rate of recovery and the arc of elbow motion (range of motion) at 1 year. The rate of recovery was evaluated by measuring range of motion at 6 weeks and 3 months. The secondary outcomes included other range-of-motion-related outcomes, patient-reported outcome measures (PROMs), flexion strength and endurance, grip strength, and forearm circumference at multiple time points.A total of 24 patients were assigned to receive CPM, and 27 were assigned to receive PT. At 1 year, CPM was superior to PT with regard to the range of motion, with an estimated treatment difference of 9° (95% confidence interval [CI], 3° to 16°; p = 0.007). Similarly, the use of CPM led to a greater range of motion at 6 weeks and 3 months than PT. The percentage of lost motion recovered at 1 year was higher in the CPM group (51%) than in the PT group (36%) (p = 0.01). The probability of restoring a functional range of motion at 1 year was 62% higher in the CPM group than in the PT group (risk ratio for functional range of motion, 1.62; 95% CI, 1.01 to 2.61; p = 0.04). PROM scores were similar in the 2 groups at all time points, except for a difference in the American Shoulder and Elbow Surgeons (ASES) elbow function subscale, in favor of CPM, at 6 weeks. The use of CPM decreased swelling and reduced the loss of flexion strength, flexion endurance, and grip strength on day 3, with no between-group differences thereafter.Among patients undergoing arthroscopic release of elbow contracture, those who received CPM obtained a faster recovery and a greater range of motion at 1 year, with a higher chance of restoration of functional elbow motion than those who underwent routine PT.Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE To assess current clinical outcomes in children with prenatally diagnosed congenital lung malformations (CLMs) and to identify prenatal characteristics associated with adverse outcomes. SUMMARY BACKGROUND DATA Despite a wide spectrum of clinical disease, the identification of fetal CLM subgroups at increased risk for hydrops and respiratory compromise at delivery have not been well defined. METHODS A retrospective cohort study was conducted using an operative database of prenatally diagnosed CLMs managed at eleven children's hospitals from 2009-2016. Statistical analyses were performed using non-parametric bivariate or multivariable logistic regression. RESULTS Three hundred forty-four children were analyzed. Fifteen (5.5%) fetuses were managed with maternal steroids in the setting of hydrops, and prenatal surgical intervention was uncommon (1.7%). Seventy-five (21.8%) had respiratory symptoms at birth, and 34 (10.0%) required neonatal lung resection. Congenital pulmonary airway malformation volume ratio (CVR) measurements were recorded in 169 (49.1%) cases and were significantly associated with perinatal outcome, including hydrops, respiratory distress at birth, need for supplemental oxygen, neonatal ventilator use, and neonatal resection (p < 0.001). An initial CVR ≤ 1.4 was significantly correlated with a reduced risk for hydrops [area under the curve (AUC), 0.93; 95% confidence interval (CI), 0.87-1.00]. A maximum CVR < 0.9 (AUC, 0.72; 95% CI, 0.67-0.85) was associated with a low risk for respiratory symptoms at birth. CONCLUSION In this large, multi-institutional study, an initial CVR ≤ 1.4 identifies fetuses at very low risk for hydrops, and a maximum CVR < 0.9 is associated with asymptomatic disease at birth. These findings represent an opportunity for standardization and quality improvement for prenatal counseling and delivery planning.

Introduction The purpose of this study was to develop a multi-institutional registry to characterize the demographics, management, and outcomes of a contemporary cohort of children undergoing congenital lung malformation (CLM) resection. Methods After central reliance IRB approval, a web-based, secure database was created to capture retrospective cohort data on pathologically-confirmed CLMs performed between 2009 and 2015 within a multi-institutional research collaborative. Results Eleven children's hospitals contributed 506 patients. Among 344 prenatally diagnosed lesions, the congenital pulmonary airway malformation volume ratio was measured in 49.1%, and fetal MRI was performed in 34.3%. One hundred thirty-four (26.7%) children had respiratory symptoms at birth. Fifty-eight (11.6%) underwent neonatal resection, 322 (64.1%) had surgery at 1–12 months, and 122 (24.3%) had operations after 12 months. The median age at resection was 6.7 months (interquartile range, 3.6–11.4). Among 230 elective lobectomies performed in asymptomatic patients, thoracoscopy was successfully utilized in 102 (44.3%), but there was substantial variation across centers. The most common lesions were congenital pulmonary airway malformation (n = 234, 47.3%) and intralobar bronchopulmonary sequestration (n = 106, 21.4%). Conclusion This multicenter cohort study on operative CLMs highlights marked disease heterogeneity and substantial practice variation in preoperative evaluation and operative management. Future registry studies are planned to help establish evidence-based guidelines to optimize the care of these patients. Level of evidence Level II.

Desmoplastic small round cell tumor is a rare sarcoma with 5-year overall survival of 15%. An 8-year-old female presented with diffuse abdominal/pelvic desmoplastic small round cell tumor including numerous liver metastasis. She underwent neoadjuvant chemotherapy followed by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Residual disease was found shortly after CRS/HIPEC which was resected, followed by whole abdomen/pelvic radiation and autologous hematopoietic cell transplant. Previous papers have reported dismal survival in patients with liver metastasis and residual disease arguing against CRS/HIPEC. Our patient remains disease-free over 6 years after completing therapy indicating long-term survival is achievable with aggressive multimodal therapy.

OBJECTIVE To describe utilization and long-term outcomes of pneumonectomy in children and adolescents with cancer. SUMMARY BACKGROUND DATA Pneumonectomy in adults is associated with significant morbidity and mortality. Little is known about the indications and outcomes of pneumonectomy for pediatric tumors. METHODS The Pediatric Surgical Oncology Research Collaborative (PSORC) identified pediatric patients

Background Although literature exists regarding hip and knee arthroplasty outcomes in patients with skin allergy to metals, there is minimal information about skin allergy implications on shoulder arthroplasty outcomes. The purpose of this study was to determine the results, complications, and failure rate among patients with a self-reported metal allergy undergoing shoulder arthroplasty. Methods Fifty-two shoulder arthroplasties were performed at our Institution in 43 patients with self-reported metal allergies. Forty primary and 12 revision shoulder arthroplasties were performed using anatomic (30) and reverse (22) components. Retrospective chart review was performed to determine metal allergy history, implant composition, pain, motion, and complications. Radiographs were reviewed to determine mechanical failure rates. Average follow-up time was 65 months. Results Allergies reported included nickel (37), cobalt chrome (4), copper (2), zinc (1), titanium (1), gold (1), and nonspecific metal allergy (8); 8 patients reported multiple metal allergies. All components implanted in patients with nickel allergies contained nickel. At most recent follow-up, pain was rated as none or mild in 88% of shoulders. Active elevation improved from 80° to 141° and external rotation from 24° to 52°. Two revisions were performed for glenoid loosening (3.8%); both were revision cases with substantial glenoid bone loss. One patient with mild pain had a radiographically loose glenoid component 12 years after anatomic shoulder arthroplasty. Conclusion Results from this study suggest that shoulder arthroplasty in patients with self-reported metal allergy provides satisfactory pain relief and improved range of motion with low revision rates.

Purpose Chest tube (CT) management for pediatric primary spontaneous pneumothorax (PSP) is associated with long hospital stays and high recurrence rates. To streamline management, we explored simple aspiration as a test to predict need for surgery. Methods A multi-institution, prospective pilot study of patients with first presentation for PSP at 9 children’s hospitals was performed. Aspiration was performed through a pigtail catheter, followed by 6 h observation with CT clamped. If pneumothorax recurred during observation, the aspiration test failed and subsequent management was per surgeon discretion. Results Thirty-three patients were managed with simple aspiration. Aspiration was successful in 16 of 33 (48%), while 17 (52%) failed the aspiration test and required hospitalization. Twelve who failed aspiration underwent CT management, of which 10 (83%) failed CT management owing to either persistent air leak requiring VATS or subsequent PSP recurrence. Recurrence rate was significantly greater in the group that failed aspiration compared to the group that passed aspiration [10/12 (83%) vs 7/16 (44%), respectively, P = 0.028]. Conclusion Simple aspiration test upon presentation with PSP predicts chest tube failure with 83% positive predictive value. We recommend changing the PSP management algorithm to include an initial simple aspiration test, and if that fails, proceed directly to VATS. Type of study Prospective pilot study Level of evidence Level III.

This work was completed as part of a Scottish Funding Council (SFC) Global Challenges Research Fund (GCRF) pump-priming project at Heriot Watt University (PI Nicholson). We would like to thank our partners at Bandung Institute of Technology, and the members of the Indonesian Marine Geological Institute and Geological Survey of Indonesia for their discussion and contribution to this research. We thank TGS and Multiclient Geophysical for permission to publish seismic and multibeam data respectively. D.R. Tappin publishes with the permission of the Executive Director of the BGS (United Kingdom Research and Innovation).

Wilms tumor (WT) is the most common renal malignancy in children. Children with favorable histology WT achieve survival rates of over 90%. Twelve percent of patients present with metastatic disease, most commonly to the lungs. The presence of a pleural effusion at the time of diagnosis of WT may be noted on staging imaging; however, minimal data exist regarding the significance and prognostic importance of this finding. The objectives of our study are to identify the incidence of pleural effusions in patients with WT, and to determine the potential impact on oncologic outcomes. A multi-institutional retrospective review was performed from January 2009 to December 2019, including children with WT and a pleural effusion on diagnostic imaging treated at Pediatric Surgical Oncology Research Collaborative (PSORC) participating institutions. Of 1259 children with a new WT diagnosis, 94 (7.5%) had a pleural effusion. Patients with a pleural effusion were older than those without (median 4.3 vs 3.5 years; P = .004), and advanced stages were more common (local stage III 85.9% vs 51.9%; P .0001). Only 14 patients underwent a thoracentesis for fluid evaluation; 3 had cytopathologic evidence of malignant cells. Event-free and overall survival of all children with WT and pleural effusions was 86.2% and 91.5%, respectively. The rate and significance of malignant cells present in pleural fluid is unknown due to low incidence of cytopathologic analysis in our cohort; therefore, the presence of an effusion does not appear to necessitate a change in therapy. Excellent survival can be expected with current stage-specific treatment regimens.

Hepatocellular carcinoma (HCC) is a rare cancer in children, with various histologic subtypes and a paucity of data to guide clinical management and predict prognosis.A multi-institutional review of children with hepatocellular neoplasms was performed, including demographic, staging, treatment, and outcomes data. Patients were categorized as having conventional HCC (cHCC) with or without underlying liver disease, fibrolamellar carcinoma (FLC), and hepatoblastoma with HCC features (HB-HCC). Univariate and multivariate analyses identified predictors of mortality and relapse.In total, 262 children were identified; and an institutional histologic review revealed 110 cHCCs (42%; 69 normal background liver, 34 inflammatory/cirrhotic, 7 unknown), 119 FLCs (45%), and 33 HB-HCCs (12%). The authors observed notable differences in presentation and behavior among tumor subtypes, including increased lymph node involvement in FLC and higher stage in cHCC. Factors associated with mortality included cHCC (hazard ratio [HR], 1.63; P = .038), elevated α-fetoprotein (HR, 3.1; P = .014), multifocality (HR, 2.4; P.001), and PRETEXT (pretreatment extent of disease) stage IV (HR, 5.76; P.001). Multivariate analysis identified increased mortality in cHCC versus FLC (HR, 2.2; P = .004) and in unresectable tumors (HR, 3.4; P.001). Disease-free status at any point predicted survival.This multi-institutional, detailed data set allowed a comprehensive analysis of outcomes for children with these rare hepatocellular neoplasms. The current data demonstrated that pediatric HCC subtypes are not equivalent entities because FLC and cHCC have distinct anatomic patterns and outcomes in concert with their known molecular differences. This data set will be further used to elucidate the impact of histology on specific treatment responses, with the goal of designing risk-stratified algorithms for children with HCC.This is the largest reported granular data set on children with hepatocellular carcinoma. The study evaluates different subtypes of hepatocellular carcinoma and identifies key differences between subtypes. This information is pivotal in improving understanding of these rare cancers and may be used to improve clinical management and subsequent outcome in children with these rare malignancies.

Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients.A retrospective review was performed on patients 21 years of age undergoing localization of pulmonary nodules at 15 institutions. Localization and resection success, time in interventional radiology (IR), operating room (OR) and total anesthesia time, complications, and technical problems were compared between techniques.225 patients were included with an average of 1.3 lesions (range 1-5). Median nodule size and depth were 4 mm (range 0-30) and 5.4 mm (0-61), respectively. The most common localization techniques were: wire + methylene blue dye (MBD) (28%), MBD only (25%), wire only (14%), technetium-99 only (11%), coil + MBD (7%) and coil only (5%). Localization technique was associated with institution (p 0.01); technique and institution were significantly associated with mean IR, OR, and anesthesia time (all p 0.05). Comparing techniques, there was no difference in successful IR localization (range 92-100%, p = 0.75), successful resection (94-100%, p = 0.98), IR technical problems (p = 0.22), or operative complications (p = 0.16).Many IR localization techniques for small pulmonary nodules in children can be successful, but there is wide variability in application by institution and in procedure time.Retrospective review, Level 3.

Sediment microbial communities drive the biogeochemical cycles that make rivers globally important sources and sinks of carbon (C) and nitrogen (N). The structure of these communities is strongly determined by the local physico-chemical environment. However, we currently lack an understanding of the factors that determine microbial community structures at the catchment scale. Here, we show that the contribution of groundwater to total river flow (quantified as base flow index; BFI) predicts the structure and diversity of the different microbial functional groups that cycle N and C across nine UK rivers, spanning a geological BFI gradient from 0.23 (clay sediment) to 0.95 (chalk gravel sediment). Furthermore, the GC-content (percentage of guanine-cytosine bases in a DNA sequence) and codon-usage bias of ammonia monooxygenase DNA sequences, and the hydrophobicity and net-charge of the corresponding amino acid sequences, were all strongly correlated with BFI, likely reflecting physiological adaptations to different riverbed sediment structure along the BFI gradient. Our results offer an opportunity to overcome the “paradox of scales” that has seen microbial ecologists focus on small- rather than large-scale environmental variables, enabling us to scale-up our understanding of microbial biogeochemistry to the catchment and beyond.

Additional file 1. Supplementary Figures.

Additional file 1. Clinical endpoints in Pronmed and Biobanque Québécoise de la COVID-19 (BQC19) for outcomes of acute COVID-19 and Long COVID-19 clustered as physical or mental symptoms.

Background We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19. Methods The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental. Results Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern. Conclusions Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID. Trial registration: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29). Graphical abstract

Background Scalp arteriovenous malformation (AVM) is a rare congenital disease that may present with massive bleeding. To date, surgical excision remains the definitive management. However, the procedure could lead to intraoperative bleeding due to the tumor’s high blood flow and complex vascularity. Case Report A 49-year old Filipino male presented with a bleeding giant scalp AVM. Computed tomographic scan and duplex studies showed multiple feeding vessels with turbulent flow arising primarily from the right superficial temporal, right posterior auricular, and occipital vessels. Prior to surgery, the patient underwent transfusion due to preoperative hemoglobin of 6 g/dL. Proximal control of the right external carotid artery was performed through a supine position and left in place to reduce the majority of blood flow to the AVM. The patient was turned to a prone position for surgical planning to achieve maximal skin-sparing dissection prior to excision. First, ligation of bilateral superficial temporal and posterior auricular arteries was performed. Next, excision above the periosteum with segmental ligation of feeding vessels around the AVM was carried out. Reconstruction of the defect was done via scalp advancement flap and split-thickness skin grafting. Intraoperative blood loss was 1.6 L. On the sixth postoperative day, the patient was discharged with 100% graft take. Conclusion Management of scalp AV malformation is challenging, and despite measures to decrease intraoperative bleeding, blood loss is still high. While preoperative embolization has been reported to decrease the risk of bleeding, this procedure is not currently available in our setting. Our case highlights the complexity of giant scalp AV malformation management in a limited-resource setting. Even in the absence of endovascular intervention, outright surgical excision of AVM can be performed, albeit with higher levels of blood loss.