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Background Type I open distal radius fractures treated with open reduction internal fixation (ORIF) have demonstrated minimal risk of infection. For this reason, they may not require urgent surgical treatment. The purpose of this study was to evaluate the outcomes of patients with type I open distal radius fractures treated with delayed ORIF compared with urgent ORIF. Methods We identified all Gustilo-Anderson type I open distal radius fractures that had undergone ORIF using volar plating over a 5-year period. Patients were stratified into those treated urgently within 24 hours and those scheduled for delayed surgery. Outcomes including functional scores, complications, reoperations, and radiographic measures were compared. Results Twenty-four patients (17 treated urgently and 7 treated delayed) had open type I distal radius fractures. All patients were started on empiric antibiotics at initial presentation—patients in the delayed treatment group were prescribed oral antibiotics, whereas those admitted for urgent treatment received intravenous antibiotics. There were no infections in either group and a single reoperation in each group. The mean postoperative Quick Disabilities of the Arm, Shoulder, and Hand score was 29 (range = 0-77) and did not differ significantly between delayed (mean = 19) and urgent (mean = 38) treatment. Rate of complications and radiographic measures did not differ significantly between the groups. Conclusions Type I open distal radius fractures appear amenable to delayed outpatient ORIF provided that the wound is clean at the time of initial presentation and that antibiotics are initiated appropriately. Further prospective studies comparing delayed and urgent treatment strategies are warranted.

Background: Distal radius fractures (DRF) are the most common upper extremity fractures in adults. The purpose of this study was to determine the incidence, causes, and independent predictors for unplanned return to the operating room (URTO) in a single institution within 90 days following distal radius open reduction internal fixation (ORIF). Methods: A retrospective study of 2933 consecutive patients from January 2015 to December 2019 who underwent distal radius ORIF was undertaken. Patients who returned to the operating room within 90 days of the index procedure were identified. Patients with planned return to the operating room for staged procedures were excluded, yielding a patient cohort of those with URTO. Demographic data, causes for reoperation, and final Quick Disabilities of the Arm, Shoulder and Hand DASH (QuickDASH) scores were collected. Results: Overall, 45 patients had URTO (1.5%) occurring a mean of 44 (6-89) days from the index procedure. Reasons for reoperation included nerve complications (n = 14), loss of fixation (n = 11), hardware complications (n = 9), wound complications (n = 7), and tendon complications (n = 4). Neurologic reasons for return included carpal tunnel release (n = 13) and ulnar nerve decompression (n = 1). QuickDASH scores were higher for URTO compared with control cohort at the final follow-up (33 [range: 0-91] vs 14 [range: 0-100], P < .01). Conclusions: Mechanical hardware failure and neurologic symptoms were the most common reasons for URTO after distal fracture ORIF.

Seat belt breast deformity can result in significant aesthetic, functional and psychosocial sequelae. Although seat belt breast deformity is well documented, there is a lack of literature describing their reconstructive management. We describe the surgical management of a 63-year-old woman presenting with stage 2b seat belt breast deformity, who underwent scar revision, repositioning of the nipple–areola complex and contralateral breast reduction using Wise-pattern incisions based on superior pedicles. She made an excellent recovery with an improved aesthetic result.

We compare the ability of dictionary-based and machine-learning methods to capture disclosure sentiment at 10-K filing and conference-call dates. Like Loughran and McDonald [Loughran T, McDonald B (2011) When is a liability not a liability? Textual analysis, dictionaries, and 10-Ks. J. Finance 66(1):35–65.], we use returns to assess sentiment. We find that measures based on machine learning offer a significant improvement in explanatory power over dictionary-based measures. Specifically, machine-learning measures explain returns at 10-K filing dates, whereas measures based on the Loughran and McDonald dictionary only explain returns at 10-K filing dates during the time period of their study. Moreover, at conference-call dates, machine-learning methods offer an improvement over the Loughran and McDonald dictionary method of a greater magnitude than the improvement of the Loughran and McDonald dictionary over the Harvard Psychosociological Dictionary. We further find that the random-forest-regression-tree method better captures disclosure sentiment than alternative algorithms, simplifying the application of the machine-learning approach. Overall, our results suggest that machine-learning methods offer an easily implementable, more powerful, and reliable measure of disclosure sentiment than dictionary-based methods. This paper was accepted by Brian Bushee, accounting.

Background In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association of anti-hypertensive drug initiation and outcomes in patients with HFrEF. Methods In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in matched cohort. Results Matched patients (n=1374) had a mean age of 74 years, 41% were women, 17% were African American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83–1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80–1.07). Similar associations were observed during 30 days and 12 months of follow-up. Conclusions Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

We have developed “Microscope-Cockpit” (Cockpit), a highly adaptable open source user-friendly Python-based GUI environment for precision control of both simple and elaborate bespoke microscope systems. The user environment allows next-generation near-instantaneous navigation of the entire slide landscape for efficient selection of specimens of interest and automated acquisition without the use of eyepieces. Cockpit uses “Python-Microscope” (Microscope) for high-performance coordinated control of a wide range of hardware devices using open source software. Microscope also controls complex hardware devices such as deformable mirrors for aberration correction and spatial light modulators for structured illumination via abstracted device models. We demonstrate the advantages of the Cockpit platform using several bespoke microscopes, including a simple widefield system and a complex system with adaptive optics and structured illumination. A key strength of Cockpit is its use of Python, which means that any microscope built with Cockpit is ready for future customisation by simply adding new libraries, for example machine learning algorithms to enable automated microscopy decision making while imaging.HighlightsUser-friendly setup and use for simple to complex bespoke microscopes.Facilitates collaborations between biomedical scientists and microscope technologists.Touchscreen for near-instantaneous navigation of specimen landscape.Uses Python-Microscope, for abstracted open source hardware device control.Well-suited for user training of AI-algorithms for automated microscopy.

IMPORTANCE: This study identifies the diagnostic errors leading to misdiagnosis of 3(rd) nerve palsy in order to aid clinicians in making this diagnosis. OBJECTIVE: To determine the incidence of misdiagnosis of third cranial nerve palsy (3(rd) nerve palsy) amongst providers referring to a tertiary care neuro-ophthalmology clinic and to characterize diagnostic errors that led to an incorrect diagnosis. DESIGN: Retrospective clinic-based cross-sectional study of office encounters at two institutions from 1/2014 to 1/2017. All encounters with scheduling comments containing variations of “3(rd) nerve palsy” were reviewed. Patients with a documented referral diagnosis of new 3(rd) neve palsy were included in the study. Examination findings including extraocular movement exam, external lid exam, and pupil exam were collected. The final diagnosis was determined by a neuro-ophthalmologist. The Diagnosis Error Evaluation and Research (DEER) taxonomy tool was used to categorize the causes of misdiagnosis. SETTING: Multicenter study describing patients at two neuro-ophthalmology referral centers. PARTICIPANTS: 78 patients referred for a new diagnosis of 3(rd) nerve palsy. MAIN OUTCOMES AND MEASURES: The main outcome measure was the type of diagnostic error that led to incorrect diagnoses using the DEER criteria as determined by two independent reviewers. Secondary outcomes were rates of misdiagnosis, misdiagnosis rate by referring specialty, and examination findings associated with incorrect diagnoses. RESULTS: Out of 78 patients referred with a suspected diagnosis of 3(rd) nerve palsy, 21.8% were determined to have an alternate diagnosis. The most common error in misdiagnosed cases was failure to correctly interpret the physical exam. Ophthalmologists were the most common referring provider for third nerve palsy, and optometrists had the highest overdiagnosis rate of 3(rd) nerve palsy. CONCLUSIONS: Misdiagnosis of 3(rd) nerve palsy was common. Performance and interpretation of the physical exam were the most common factors leading to misdiagnosis of 3(rd) nerve palsy.

Background: Beta-blockers improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their role in older nursing home residents with HFrEF. Methods: From the combined OPTIMIZE-HF and Alabama Heart Failure Project datasets, we assembled a propensity score-matched balanced cohort of 6494 hospitalized patients ≥65 years with HFrEF (ejection fraction ≤40%). In our primary approach, hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with discharge prescriptions for beta-blockers were estimated, examining for heterogeneity by admission from nursing homes. In our sensitivity approach, we examined these associations in a separately assembled propensity score-matched cohort of 122 patients admitted from nursing homes. Results: In the matched primary cohort of 6494 patients, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.80 (0.74–0.87) and 0.94 (0.86–1.02), respectively. Respective HRs (95% CIs) in the nursing home and non-nursing home subgroups were 0.77 (0.51–1.16) and 0.81 (0.74–0.87) for all-cause mortality (interaction p, 0.653) and 1.06 (0.53–2.12) and 0.89 (0.82–0.96) for heart failure readmission (interaction p, 0.753). In the matched sensitivity cohort of 122 patients admitted from nursing homes, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.86 (0.55–1.35) and 1.07 (0.52–2.22), respectively. Similar associations were observed for 30-day outcomes. Conclusions: Beta-blocker use was associated with a lower risk of all-cause mortality but not of heart failure readmission in older patients with HFrEF, which were similar for patients admitted and not admitted from nursing homes.

Drug deposition into the intrapericardial space is favourable for achieving localised effects and targeted cardiac delivery owing to its proximity to the myocardium as well as facilitating optimised pharmacokinetic profiles and a reduction in systemic side effects. Access to the pericardium requires invasive procedures but the risks associated with this have been reduced with technological advances, such as combining transatrial and subxiphoid access with different guidance methods. A variety of introducer devices, ranging from needles to loop-catheters, have also been developed and validated in pre-clinical studies investigating intrapericardial delivery of therapeutic agents. Access techniques are generally well-tolerated, self-limiting and safe, although some rare complications associated with certain approaches have been reported. This review covers these access techniques and how they have been applied to the delivery of drugs, cells, and biologicals, demonstrating the potential of intrapericardial delivery for treatments in cardiac arrhythmia, vascular damage, and myocardial infarction.

Positron emission tomography (PET) imaging is used to track biochemical processes in the human body. PET image quality is limited by noise and several methods have been implemented to improve the quality. Kernel-based image reconstruction is among the methods implemented to increase PET image quality and commonly uses a Gaussian kernel to include spatial correlations from image priors into the forward projection model of PET. Unfortunately, the Gaussian kernel tends to smooth details in the reconstructed image. To reduce noise without losing contrast details, a different kernel is needed. Wavelet kernels can be more efficient than the Gaussian kernel in reducing noise while keeping contrast details 1 by better separating signal from noise and thus it does not over smooth peak values in the final reconstructed images. In this work, we evaluate a wavelet kernel for kernel-based PET image reconstruction. For this goal, a wavelet kernel approach has been tested using simulated brain data, physical phantom data and patient data. Reconstruction results are presented and discussed in detail comparing the wavelet kernel method with the Gaussian kernel method. Our results suggest that a wavelet kernel performs better in contrast recovery for phantoms and also results in higher signal-to-noise ratio (SNR) for real patient data.

Myositis-specific antibodies (MSAs) facilitate grouping children with juvenile dermatomyositis (DM) into distinct phenotypes. The first aim of this study was to investigate the link between anti-p155/140 and lipodystrophy as determined by dual x-ray absorptiometry (DXA) assessment of fat distribution. The second aim was to examine the relationship between anti-p155/140 and damage to the nailfold capillary system.Children with juvenile DM followed for a minimum of 5 years were included. The study population was divided into 3 groups (anti-p155/140, other MSA, and MSA negative). Lipodystrophy was assessed by physician assessment and DXA fat distribution (trunk-to-leg fat ratio). Documentation of nailfold capillary end row loops (ERLs) was obtained at diagnosis.A total of 96 subjects (44% anti-p155/140, 23% other MSA, 33% MSA negative) were included. There was no significant difference in age, disease activity scores, or lipodystrophy between the 3 groups. The trunk-to-leg fat ratios were similar among the 3 groups at different time points. However, the anti-p155/140 group had significantly decreased ERL counts (P = 0.006) at baseline as well as a prolonged duration of untreated disease at diagnosis (P = 0.027). Also, the anti-p155/140 group had fewer patients with a monophasic disease course than the other 2 groups (P = 0.008).Generalized lipodystrophy frequency was equivalent in all 3 groups based on physician assessments and trunk-to-leg fat ratios. The anti-p155/140 group had a greater loss of ERLs, suggesting that this MSA may impact the vascular component of juvenile DM.

To examine the association between income and cardiovascular disease (CVD) in community-dwelling older adults.Of the 5795 Medicare-eligible community-dwelling older Americans aged 65-100 years in the Cardiovascular Health Study (CHS), 4518 (78%) were free of baseline CVD, defined as heart failure, acute myocardial infarction, stroke, or peripheral arterial disease. Of them, 1846 (41%) had lower income, defined as a total annual household income$16,000. Using propensity scores for lower income, estimated for each of the 4518 participants, we assembled a matched cohort of 1078 pairs balanced on 42 baseline characteristics. Outcomes included centrally adjudicated incident CVD and mortality.Matched participants (n = 2156) had a mean age of 73 years, 63% were women, and 13% African American. During an overall follow-up of 23 years, incident CVD, all-cause mortality and the combined endpoint of incident CVD or mortality occurred in 1094 (51%), 1726 (80%) and 1867 (87%) individuals, respectively. Compared with the higher income group, hazard ratio (HR) for time to the first occurrence of incident CVD in the lower income group was 1.16 with a 95% confidence interval (CI) of 1.03 to 1.31. A lower income was also associated with a significantly higher risk of all-cause mortality (HR, 1.19; 95% CI, 1.08-1.30), and consequently a higher risk of the combined endpoint of incident CVD or death (HR, 1.20; 95% CI, 1.09-1.31).Among community-dwelling older Americans free of baseline CVD, an annual household income$16,000 is independently associated with significantly higher risks of new-onset CVD and death.

Since 2009, ESA has been conducting R&D activities leading towards the development of a European capability in radioisotope power systems for space. The programme is focused on the use of americium-241 as an innovative alternative to the plutonium-238 currently used by the USA and Russia. Two different technologies are being developed by the University of Leicester in the UK: radioisotope thermoelectric generators and radioisotope heater units. The development of the fuel containment architectures, known as heat sources, has recently evolved from the design stage to more representative prototypic systems. Multiple containment layers ensure that the heat sources can survive accident conditions from launch failures to Earth re-entry, minimising the risk of inadvertently releasing radioactive material into the environment. Validated accident models are necessary for the design iteration process of these systems, and for the creation of a safety case for their launch. The research project here presented was a collaboration, supported by ESA , between the University of Leicester in the UK and ArianeGroup in France. The goals of this activity were to perform the first-ever impact tests for the European Am-based heat sources, and to start developing computer models to simulate the behaviour of the containment systems under different impact conditions in accident scenarios. Tested samples were then characterized both at ESA/ESTEC and at the University of Leicester, in order to understand the behaviour of the fuel containment materials under the most relevant accident conditions.

When patients are unsuitable for deep inferior epigastric perforator (DIEP) flap breast reconstruction, the inferior gluteal artery perforator (IGAP) flap has been used as an alternative option. However, the profunda artery perforator (PAP) flap is also gaining popularity as an alternative to the DIEP flap for several reasons. This retrospective cohort study compares baseline characteristics, peri- and post-operative outcomes following IGAP flap and PAP flap breast reconstructions after mastectomy for cancer.In a single center in the UK, from September 2008 through December 2016, 43 women underwent IGAP Flap(s) breast reconstruction and 51 received PAP flap(s) breast reconstructions. Statistical analysis was performed to compare baseline, peri-operative and post-operative variables between the two reconstruction methods.Perioperative complications requiring reoperation were experienced in women undergoing IGAP flap breast reconstructions only (21% versus 0%, p = 0.001), principally due to the risk of total flap failure (12% versus 0%, p = 0.01). Women undergoing IGAP flap breast reconstructions were at significantly higher odds of revision surgery (OR 17 [95% CI: 5.5-53], p 0.001), which was unchanged after adjusting for bilateral reconstructions (adjusted OR 18 [95% CI: 5.3-58], p 0.001).PAP flaps appear to be associated with significantly fewer complications and revision surgeries than IGAP flaps for breast reconstruction in women undergoing mastectomy for cancer and who are unsuitable for a DIEP flap breast reconstruction.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes., Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

The complement system is critical to human health owing to its central role in host defense and innate immunity. During pregnancy, the complement system must be appropriately regulated to allow for immunologic tolerance to the developing fetus and placenta. Although some degree of complement activation can be seen in normal pregnancy, the fetus seems to be protected in part through the placental expression of complement regulatory proteins, which inhibit complement activation at different steps along the complement activation cascade. In women who develop preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, there is a shift toward increased complement activation and decreased complement regulation. There is an increase in placental deposition of C5b-9, which is the terminal effector of classical, lectin, and alternative complement pathways. C5b-9 deposition stimulates trophoblasts to secrete soluble fms-like tyrosine kinase-1, which sequesters vascular endothelial growth factor and placental growth factor. Pathogenic mutations or deletions in complement regulatory genes, which predispose to increased complement activation, have been detected in women with preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Before the disease, biomarkers of alternative complement pathway activation are increased; during active disease, biomarkers of terminal complement pathway activation are increased. Urinary excretion of C5b-9 is associated with preeclampsia with severe features and distinguishes it from other hypertensive disorders of pregnancy. Taken together, existing data link preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome with increased activation of the terminal complement pathway that, in some cases, may be influenced by genetic alterations in complement regulators. These findings suggest that the inhibition of the terminal complement pathway, possibly through C5 blockade, may be an effective strategy to treat preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, but this strategy warrants further evaluation in clinical trials.

Preclinical studies have demonstrated a complex cross-talk between Notch and estrogen signaling in ERα-positive breast cancer. Gamma-secretase inhibitors (GSIs) are investigational agents that block the cleavage and activation of Notch receptors. In animal models of endocrine-resistant breast cancer, combinations of tamoxifen and GSIs produce additive or synergistic efficacy, while decreasing the intestinal toxicity of GSIs. However, results of a clinical trial of a GSI-endocrine therapy combination in the metastatic setting have not been published to date, nor had the safety of such combinations been investigated with longer term treatment. We conducted a phase 1b dose escalation trial (NCT01149356) of GSI RO4929097 with exemestane in patients with ERα+, metastatic breast cancer (MBC) Study objectives: to determine the safety, tolerability and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of RO4929097 when administered in combination with exemestane in patients with estrogen receptor positive metastatic breast cancer Results: We enrolled 15 patients with MBC. Of 14 evaluable patients, one had a partial response, 6 had stable disease and 7 progressive disease. Twenty % of patients had stable disease for ≥ 6 months. Common toxicities included nausea (73.3%), anorexia (60%), hyperglycemia (53.3%), hypophosphatemia (46.7%), fatigue (66.7%) and cough (33.0%). Grade 3 toxicities were uncommon, and included hypophosphatemia (13%) and rash (6.3%). Rash was the only DLT observed at 140 mg/d. Results suggest a possible recommended phase 2 dose of 90 mg/d. Ten patients with evaluable archival tissue showed expression of PKCα, which correlated with expression of Notch4. Mammospheres from a PKCα-expressing, endocrine-resistant T47D cell line were inhibited by a GSI-fulvestrant combination Conclusions: Our data indicate that combinations including endocrine therapy and Notch inhibitors deserve further investigation in endocrine-resistant ERα-positive breast cancer.

Vehicle control by humans is possible because the central nervous system is capable of using visual information to produce complex sensorimotor actions. Drivers must monitor errors and initiate steering corrections of appropriate magnitude and timing to maintain a safe lane position. The perceptual mechanisms determining how a driver processes visual information and initiates steering corrections remain unclear. Previous research suggests 2 potential alternative mechanisms for responding to errors: (a) perceptual evidence (error) satisficing fixed constant thresholds (Threshold), or (b) the integration of perceptual evidence over time (Accumulator). To distinguish between these mechanisms, an experiment was conducted using a computer-generated steering correction paradigm. Drivers (N = 20) steered toward an intermittently appearing "road-line" that varied in position and orientation with respect to the driver's position and trajectory. One key prediction from a Threshold framework is a fixed absolute error response across conditions regardless of the rate of error development, whereas the Accumulator framework predicts that drivers would respond to larger absolute errors when the error signal develops at a faster rate. Results were consistent with an Accumulator framework; thus we propose that models of steering should integrate perceived control error over time in order to accurately capture human perceptual performance. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

BACKGROUND The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score

Background There is currently no formal prostate cancer screening programme in the UK. Early detection using age-based prostate-specific antigen (PSA) testing is unlikely to be cost-effective due to limited mortality benefit and harms associated with overdetection. However, the discovery of new prostate cancer specific biomarkers and more accurate diagnostic strategies (e.g. magnetic resonance imaging (MRI)) could improve the outcomes of screening. A systematic review was conducted to assess the evidence base on cost-effectiveness of such innovations and areas for further development. Methods To identify model-based economic evaluations of screening and diagnostic tests for prostate cancer, a systematic review of the literature using the NHS Economic Evaluation Database, Medline, EMBASE, HTA databases, NICE guidelines, and UK National Screening Committee guidance was carried out, between 2009 and 2019. Relevant data were extracted on study type, model inputs, modelling methods and cost-effectiveness conclusions and the results narratively synthesized. Results Sixteen studies were included in the review. Seven studies compared the cost-effectiveness of new urinary or blood biomarkers compared to each other or the PSA test and found the biomarkers e.g. the Prostate Health Index (PHI) and SelectMDx, to be the most cost-effective. Seven studies compared newer prostate biopsy methods, including MRI-guided, to TRUS guided biopsy and found MRI-guided methods to be most cost-effective. The newer detection methods showed a reduction in unnecessary biopsies and overtreatment. However, there was uncertainty around the most cost-effective pathway of follow-up strategies (MRI/biomarkers) in men who have a negative initial biopsy. Many studies did not model stage or grade of cancer, cancer progression or the entire testing, screening and treatment pathway. Very few studies fully accounted for uncertainty in their analysis. Conclusions This review brings together the cost-effectiveness literature for novel screening and testing methods used in the diagnosis of prostate cancer. Several limitations of the published models were identified. The models generally either compared new biomarkers or new imaging techniques which highlights the importance of future work in this area, as biomarkers and imaging are likely to be used in combination.

The prevalence of homologous recombination–DNA damage response (HR-DDR) genetic alterations is of therapeutic interest in gastroesophageal cancers. This study is a comprehensive assessment of HR-DDR mutation prevalence across gastroesophageal adenocarcinomas and squamous cell carcinomas. Here we investigate the association of HR-DDR mutations with known predictors for immune-checkpoint inhibition [deficiency in mismatch-repair (dMMRP), tumor mutational burden (TMB), and programmed death ligand 1 (PD-L1)]. We confirmed HR-DDR mutations are present in a subset of gastroesophageal adenocarcinomas (23%) and gastroesophageal squamous cell carcinomas (20%). Biomarker expression of dMMRP (18% vs. 1%) and TMB-high with a cutoff of ≥10 mt/MB (27% vs. 9%) was significantly more prevalent in the DDR-mutated cohort compared with the non-DDR-mutated cohort. Mean combined positive score for PD-L1 in the total adenocarcinoma cohort was significantly higher in the DDR-mutated cohort compared with the non–DDR-mutated cohort (10.1 vs. 5.8). We demonstrated that alterations in ARID1A, BRCA2, PTEN, and ATM are correlated with dMMRP, TMB-high, and increased PD-L1 expression in gastroesophageal adenocarcinomas. Our findings show that a subset of gastroesophageal tumors harbor HR-DDR mutations correlated with established immune biomarkers. By better understanding the relationship between HR-DDR mutations and immune biomarkers, we may be able to develop better immunotherapy combination strategies to target these tumors.

Objective B cells can become activated in germinal center (GC) reactions in secondary lymphoid tissue and ectopic GCs in synovium in RA that may be TNF and lymphotoxin (LT) dependent. Here we characterized the peripheral B cell compartment longitudinally during anti-TNF therapy in RA. Methods Participants were randomized in a 2:1 ratio to receive standard dosing regimens of etanercept (n=43) or adalimumab (n=20) for 24 weeks. Eligible participants met the 1987 ACR criteria for RA, clinically active (DAS28>4.4), and on stable doses of methotrexate. The primary mechanistic endpoint was the change in switched memory B cell fraction from baseline to week 12 in each treatment group. Results B cell subsets remained surprisingly stable over the course of the study regardless of treatment group, with no significant change in memory B cells. Blockade of TNF and LT with etanercept compared to TNF blockade alone with adalimumab did not translate into significant differences in clinical response. Multiple activated B cell populations including CD21- double negative memory and activated naive were higher in RA non-responders (NR) at all time points, and CD95+ activated B cells increased with anti-TNF in the NR group. In contrast, transitional B cells- a putative regulatory subset- were lower in the NRs. Conclusions Overall, our results support that peripheral blood B cell subsets are remarkably stable in RA and not differentially impacted by dual blockade of TNF and LT with etanercept or single blockade of TNF with adalimumab. Activated B cells do associate with a less robust response.

Background: The purpose of this study was to collect 1 year of real-world data from individuals with type 1 diabetes (T1D) initiating the Medtronic 670G hybrid closed-loop insulin delivery system a...

Background: Automated insulin delivery systems are associated with improved glycemic outcomes for patients with diabetes. Ultra rapid lispro (URLi), which has an accelerated pharmacokinetic profile...

Objective To provide an understanding of important aspects of the participant recruitment and data collection, become aware of any potential problems, and obtain necessary information in order to design a large-scale randomized controlled trial (RCT) for lung cancer and colorectal cancer (CRC) screening in China. Methods This feasibility study was a multicentered, open-label, pilot randomized trial. A total of 2696 participants who were at high risk of lung cancer were recruited from three screening centers and randomly allocated to arm 1 (n=894), annual low-dose computed tomography (LDCT) plus a baseline colonoscopy; arm 2 (n=902), biennial LDCT plus annual fecal immunochemical test (FIT) with OC-Sensor (OC-FIT); and arm 3 (n=900), annual Insure-FIT plus Septin 9 blood test. Information on randomization, compliance, positivity rate, cancer case detection, and contamination with screening for lung cancer and CRC were collected. Results Participant characteristics were similar across study arms. The compliance rate of annual LDCT screening in arm 1 was 86.4% (95% CI: 83.9%, 88.5%) at baseline (T0), and 69.0% (95% CI: 65.8%, 72.0%) and 70.7% (95% CI: 67.6%, 73.7%) are at the following two rounds (T1 and T2). The compliance rates of biennial LDCT screening in arm 2 were similar to those in arm 1 in the corresponding rounds. The compliance rate was 55.5% (95% CI: 52.2%, 58.8%) for colonoscopy in arm 1, while the compliance rates of OC-FIT, Insure-FIT, and the Septin 9 test in arms 2 and 3 were all approximately 90% at T0, decreasing to 65%–80% at T1 and T2. The positivity rate, cancer case detection rate, and contamination rate of screening for lung cancer and CRC were also reported. Conclusion In this pilot study, the feasibility of an RCT in China of lung cancer and CRC screening was demonstrated.

Study objective When using a standard geometry laryngoscope, experts recommend engaging the hyoepiglottic ligament—a ligament deep to the vallecula not visible to the intubator. The median glossoepiglottic fold (hereafter termed midline vallecular fold) is a superficial mucosal structure, visible to the intubator, that lies in the midline of the vallecula. We aimed to determine whether engaging the midline vallecular fold with a standard geometry blade tip during orotracheal intubation improved laryngeal visualization. Methods We reviewed laryngoscopic videos from intubations by emergency physicians using standard geometry video laryngoscopes over a 2-year period. Two reviewers watched each video and recorded whether the blade tip engaged the midline vallecular fold (obscured the fold with the blade tip) and the best modified Cormack-Lehane grade and percent of glottic opening obtained. We compared laryngeal views in the presence and absence of fold engagement. Results We analyzed 183 discrete laryngoscopic episodes, including 113 instances in which the midline vallecular fold was engaged and 70 instances in which the fold was not engaged. The proportion with a Cormack-Lehane grade 1 or 2a was higher with fold engagement (96%) than without (87%) (absolute difference 9% [95% confidence interval (CI) 1 to 18%]). Ordinal logistic regression demonstrated that midline vallecular fold engagement was associated with a more favorable Cormack-Lehane grade (odds ratio 2.1 [95% CI 1.1 to 4.2]). The median percent of glottic opening score was 95% (interquartile range 90 to 100%) with fold engagement and 95% (65 to 100%) without engagement (median difference 0% [95% CI 0 to 5%]). Conclusion Engaging the midline vallecular fold with the laryngoscope blade tip during orotracheal intubation when using a standard geometry blade was associated with improved laryngeal visualization.

Logistics supply chains with nodes at critical locations such as the Earth’s surface, Earth’s orbit, cis-lunar space, Mars orbit and the surface of Mars are crucial to enable sustainable human exploration of Mars. The concept of a Mars orbital logistics node is envisaged to have at least aggregation, refueling, resupply and refurbishing capabilities is defined in this paper. Its elements are analogous to platforms like the International Space Station and Lunar Gateway. The stationing orbit of the logistics node is one of the primary design drivers in determining the associated propellant requirement. We evaluate Δ V requirements across four phases of the mission—interplanetary transfer, capture and departure, deorbit and entry, and launch and orbit transfer. A comprehensive data base of interplanetary trajectories is analyzed. Perturbations due to Mars’ gravity are considered and multiple options for maneuver are considered herein. Three mission scenarios – long stay crewed, short stay crewed and cargo transfer – are evaluated along with three deorbit concepts. A broad range of Low Mars Orbits (LMO) with periods between 0.4 and 0.6 sols and Highly Elliptical Mars Orbits (HEMO) with periods between 2 and 4 sols is found to fall on the trade-off curve of total Δ V and orbital periods across seven synodic periods. Final orbit selection can be made using this data and a desired criteria and mission timeline. For example, HEMO minimizes propellant to access the stationing orbit from interplanetary trajectory whereas LMO minimizes propellant requirement to access the surface from the stationing orbit. HMO is also favorable for short stay and cargo missions.

Background Vaginoplasty is a crucial part of genital gender-affirming surgery with the number of trans women undergoing this intervention steadily, however, up to date, there is still no standardized vaginoplasty technique. Aim This retrospective single-center study compares single-stage vs two-stage penile skin inversion vaginoplasty techniques and their long-term outcomes. Methods Medical records of 63 consecutive patients who underwent single-stage vaginoplasty, as described by Dr Preecha Tiewtranon, and 62 consecutive patients who underwent 2-stage vaginoplasty were reviewed. Results The mean postoperative hospital stay was 7 days for patients who underwent single-stage vaginoplasty vs 16 days for patients who underwent 2-stage vaginoplasty. Neovaginal depth proved constant in patients who underwent single-stage vaginoplasty, whereas a loss of more than 30% was observed in patients who underwent 2-stage vaginoplasty during the first postoperative year. Early complications were more common than late-onset complications in both groups. The most common complication in the single-stage group was wound dehiscence (4.8%). There were significantly more complications in 2-stage collective, among which wound dehiscence (33.9%), unsatisfactory cosmetic outcome (25.8%), and urethral stenosis (14.5%) were the most common. In the single-stage cohort, 4 (6.4%) patients needed one revision surgery, whereas 35 (56.5%) patients in the 2-stage cohort necessitated one or more reoperations with up to 10 quaternary revisions. All patients reported to have sensitivity to neoclitoris in the single-stage group, whereas 3 (4.8%) patients in the 2-stage group were deprived of it because of neoclitoral necrosis. Clinical Implications Optimizing a vaginoplasty surgical technique and its postoperative protocol. Strengths & Limitations The present retrospective study with a mean follow-up of more than 3.5 years offers the first ever comparison of 2 different PSI vaginoplasty surgical techniques performed in the same center. Conclusion Significantly lower complication and revision rates, shorter recovery time, and superior esthetic and functional outcomes were observed in the single-stage than in the two-stage penile skin inversion vaginoplasty surgical technique. Fakin RM, Giovanoli P. A Single-Center Study Comparison of Two Different Male-to-Female Penile Skin Inversion Vaginoplasty Techniques and Their 3.5-Year Outcomes. J Sex Med 2021;18:391–399.

Objectives: the primary objective of this study was to train and test machine learning algorithms to be able to detect accurately whether EEG data contains an auditory brainstem response (ABR) or not and recommend suitable machine learning methods. In addition, the performance of the best machine learning algorithm was compared with that of prominent statistical detection methods.Design: four machine learning algorithms were trained and evaluated using nested k-fold cross-validation: a random forest, a convolutional long short-term memory network, a stacked ensemble, and a multilayer perceptron. The best method was evaluated on a separate test set and compared with conventional detection methods: Fsp, Fmp, q-sample uniform scores test, and Hotelling’s T2 test. The models were trained and tested on simulated data that were generated based on recorded ABRs collected from 12 normal-hearing participants and no-stimulus EEG data from 15 participants. Simulation allowed the ground truth of the data (“response present” or “response absent”) to be known.Results: the sensitivity of the best machine learning algorithm, a stacked ensemble, was significantly greater than that of the conventional detection methods evaluated. The stacked ensemble, evaluated using a bootstrap approach, consistently achieved a high and stable level of specificity across ensemble sizes.Conclusions: the stacked ensemble model presented was more effective than conventional statistical ABR detection methods and the alternative machine learning approaches tested. The stacked ensemble detection method may have potential both in automated ABR screening devices as well as in evoked potential software, assisting clinicians in making decisions regarding a patient’s ABR threshold. Further assessment of the model’s generalizability using a large cohort of subject recorded data, including participants of different ages and hearing status, is a recommended next step.

PURPOSE OF REVIEW: While limited to case reports or small case series, emerging evidence advocates the inclusion of smartphone-interfacing mobile platforms and wearable technologies, consisting of internet-powered mobile and wearable devices that interface with smartphones, in the orthopaedic surgery practice. The purpose of this review is to investigate the relevance and impact of this technology in orthopaedic surgery. RECENT FINDINGS: Smartphone-interfacing mobile platforms and wearable technologies are capable of improving the patients’ quality of life as well as the extent of their therapeutic engagement, while promoting the orthopaedic surgeons’ abilities and level of care. Offered advantages include improvements in diagnosis and examination, preoperative templating and planning, and intraoperative assistance, as well as postoperative monitoring and rehabilitation. Supplemental surgical exposure, through haptic feedback and realism of audio and video, may add another perspective to these innovations by simulating the operative environment and potentially adding a virtual tactile feature to the operator’s visual experience. SUMMARY: Although encouraging in the field of orthopaedic surgery, surgeons should be cautious when using smartphone-interfacing mobile platforms and wearable technologies, given the lack of a current academic governing board certification and clinical practice validation processes.

Epigastric pain can have multiple etiologies including myocardial infarction, pancreatitis, acute aortic syndromes, gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, and hiatal hernia. This document focuses on the scenarios in which epigastric pain is accompanied by symptoms such as heartburn, regurgitation, dysphagia, nausea, vomiting, and hematemesis, which raise suspicion for gastroesophageal reflux disease, esophagitis, peptic ulcer disease, gastritis, duodenal ulcer disease, gastric cancer, or hiatal hernia. Although endoscopy may be the test of choice for diagnosing these entities, patients may present with nonspecific or overlapping symptoms, necessitating the use of imaging prior to or instead of endoscopy. The utility of fluoroscopic imaging, CT, MRI, and FDG-PET for these indications are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.

Objectives To examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed.DesignParticipants from UKB with a left hip dual-energy x-ray absorptiometry (DXA) scan had alpha angle (AA), lateral centre-edge angle (LCEA) and joint space narrowing (JSN) derived automatically. Cam and pincer morphology, and AD were defined using AA and LCEA. Osteophytes were measured manually and rHOA grades were calculated from JSN and osteophyte measures. Logistic regression was used to examine the relationships between these hip morphologies and rHOA, osteophytes, JSN, and hip pain.Results6,807 individuals were selected (mean age: 62.7; 3382/3425 males/females). Cam morphology was more prevalent in males than females (15.4% and 1.8% respectively). In males, cam morphology was associated with rHOA [OR 3.20 (95% CI 2.41-4.25)], JSN [1.53 (1.24-1.88)], and acetabular [1.87 (1.48-2.36)], superior [1.94 (1.45-2.57)] and inferior [4.75 (3.44-6.57)] femoral osteophytes, and hip pain [1.48 (1.05-2.09)]. Broadly similar associations were seen in females, but with weaker statistical evidence. Neither pincer morphology nor AD showed any associations with rHOA or hip pain.ConclusionsCam morphology was predominantly seen in males in whom it was associated with rHOA and hip pain. In males and females, cam morphology was associated with inferior femoral head osteophytes more strongly than those at the superior femoral head and acetabulum. Further studies are justified to characterise the biomechanical disturbances associated with cam morphology, underlying the observed osteophyte distribution.

PURPOSE Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed < 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

Meniscal tears in adolescent patients are commonly treated with repair to preserve meniscal tissue and prevent future degenerative changes. Historically, meniscal tears best suited for repair are acute vertical tears in patients aged 1 cm and, Technique Video Video 1 This video demonstrates the use of an accessory anteromedial (AAM) portal to facilitate the repair of mid-body radial tears of the lateral meniscus in children and adolescents. Once tear is identified and a diagnostic arthroscopy is completed through standard anteromedial (AM) and anterolateral (AL) portals, the AAM portal is established just medial to the AM portal. The leg is brought into a figure four position for access into the lateral compartment of the knee. The tear is debrided to create confluent edges to facilitate edge-to-edge repair and enhance healing. The tear is then assessed for the feasibility of successful repair, which can be done with a blunted instrument or probe. It is important to identify the popliteus tendon to ensure it will not become entrapped within the repair. For all 3 mattress sutures passed, the AAM portal is used for viewing, whereas the zone-specific cannula (ZSC) and portal skid are located within the AM portal. With the arthroscope in the AAM, the portal skid is placed into the AM portal to protect the cartilage, followed by the ZSC. The desired trajectory is determined, and the 2-0 mini suture tape meniscus repair needle is passed through the ZSC into the meniscus, and subsequently outside the knee. The other end of the repair needle is passed on the contralateral side of the meniscus tear to create a single horizontal mattress stitch. The slack is taken out of the suture, which should confirm a successful reduction. A second 2-0 mini suture tape meniscus repair needle is introduced through the ZSC in the AM portal, and a second horizontal mattress is completed identically to that previously described. A third 2-0 mini suture tape meniscus repair needle is introduced through the ZSC. In this instance, an oblique type mattress stitch was created by obliquely crossing the tear on the second pass of the 2-0 suture. Customarily at least 3 sutures are placed; however, the number of sutures and orientation is determined by doing what is required to achieve a successful reduction. After all, sutures are passed, they will be located along with the lateral knee. Soft-tissue dissection is carried down through the skin and subcutaneous tissue along the trajectory of the sutures to the capsule where they are tied. It is important to note that all slack must be taken out of each suture before tying, and the maintenance of reduction should be checked arthroscopically prior to tying each suture sequentially. The final repair consists of 2 horizontal mattresses, and a single oblique type mattress. The case is completed with the injection of platelet-rich plasma into the joint. You can appreciate in this video the ease of instrumentation when an accessory medial portal is used for viewing, which in turn allows the standard anteromedial portal to be used for instrumentation which altogether allows for improved suture trajectory and enhanced visualization

The Western Canadian Gastrointestinal Cancer Consensus Conference (WC-5) convened virtually on 10 February 2021. The WC-5 is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of hepatocellular cancer (HCC). Recommendations have been made for the transition from local to systemic therapy and the optimal sequencing of systemic regimens in the management of HCC.

Statistical modeling of ecological data is often faced with a large number of variables as well as possible nonlinear relationships and higher-order interaction effects. Gradient boosted trees (GBT) have been successful in addressing these issues and have shown a good predictive performance in modeling nonlinear relationships, in particular in classification settings with a categorical response variable. They also tend to be robust against outliers. However, their black-box nature makes it difficult to interpret these models. We introduce several recently developed statistical tools to the environmental research community in order to advance interpretation of these black-box models. To analyze the properties of the tools, we applied gradient boosted trees to investigate biological health of streams within the contiguous USA, as measured by a benthic macroinvertebrate biotic index. Based on these data and a simulation study, we demonstrate the advantages and limitations of partial dependence plots (PDP), individual conditional expectation (ICE) curves and accumulated local effects (ALE) in their ability to identify covariate–response relationships. Additionally, interaction effects were quantified according to interaction strength (IAS) and Friedman’s $$H^2$$ H 2 statistic. Interpretable machine learning techniques are useful tools to open the black-box of gradient boosted trees in the environmental sciences. This finding is supported by our case study on the effect of impervious surface on the benthic condition, which agrees with previous results in the literature. Overall, the most important variables were ecoregion, bed stability, watershed area, riparian vegetation and catchment slope. These variables were also present in most identified interaction effects. In conclusion, graphical tools (PDP, ICE, ALE) enable visualization and easier interpretation of GBT but should be supported by analytical statistical measures. Future methodological research is needed to investigate the properties of interaction tests. Supplementary materials accompanying this paper appear on-line.

Objectives/hypothesis Hashimoto's Thyroiditis (HT) is a common cause of hypothyroidism. Among adults with differentiated thyroid cancer (DTC), HT appears to be associated with less severe disease burden. In the absence of information regarding HT and disease burden among children with DTC, we assessed the relationship between pediatric DTC severity and HT. Study design Retrospective cohort. Methods Charts from 90 pediatric patients who underwent surgical removal of DTC from 2002 to 2017 at tertiary-care children's hospital were reviewed. Demographic, clinical, surgical, pathology, and outcome details were compared between patients with and without HT. Consistency among diagnostic modalities of HT was also evaluated. Results Median age at presentation was 16.0 years (range 4.2-18.9 years). Twenty-two patients were male (24%). Forty-five patients (50%) had HT based on presence of thyroid autoantibodies and/or surgical pathology findings and 45 patients did not have HT. Patients with HT had increased odds of microcalcifications (odds ratio [OR]: 3.01, P = .031) and decreased odds of palpable nodules (OR: 0.212, P = .024) and T2 lesions (vs. T1) (OR: 0.261, P = .015) compared with non-HT. No significant differences in demographics and the incidence of multifocality, extrathyroidal extension, lymphovascular invasion, lymph node or pulmonary metastases, disease recurrence, or radioactive iodine treatment were found between the two groups. Thyroglobulin/thyroid peroxidase autoantibodies and surgical pathology indicative of HT were concordant in 82.4% (κ = 0.635, P Conclusion HT was present in 50% of children with DTC. Patients with DTC and HT presented with smaller tumors compared to non-HT patients. No significant differences in other markers of disease aggressiveness were found between the two groups. Level of evidence 3 Laryngoscope, 2021.

BackgroundThe incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC).MethodsWe studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided.ResultsOf 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93).ConclusionIn this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older.

This article is the work product of the Continuous Ketone Monitoring Consensus Panel, which was organized by Diabetes Technology Society and met virtually on April 20, 2021. The panel consisted of 20 US-based experts in the use of diabetes technology, representing adult endocrinology, pediatric endocrinology, advanced practice nursing, diabetes care and education, clinical chemistry, and bioengineering. The panelists were from universities, hospitals, freestanding research institutes, government, and private practice. Panelists reviewed the medical literature pertaining to ten topics: (1) physiology of ketone production, (2) measurement of ketones, (3) performance of the first continuous ketone monitor (CKM) reported to be used in human trials, (4) demographics and epidemiology of diabetic ketoacidosis (DKA), (5) atypical hyperketonemia, (6) prevention of DKA, (7) non-DKA states of fasting ketonemia and ketonuria, (8) potential integration of CKMs with pumps and automated insulin delivery systems to prevent DKA, (9) clinical trials of CKMs, and (10) the future of CKMs. The panelists summarized the medical literature for each of the ten topics in this report. They also developed 30 conclusions (amounting to three conclusions for each topic) about CKMs and voted unanimously to adopt the 30 conclusions. This report is intended to support the development of safe and effective continuous ketone monitoring and to apply this technology in ways that will benefit people with diabetes.