Search

This briefing provides a short introduction to a supplement of the Ciria Manual on Scour at Bridges and Other Hydraulic Structures published in 2021. The supplement captures additional knowledge since the scour manual was published in 2015. This note is intended for designers and asset managers of structures in the water environment that may be subject to scour.

Background: Scaphotrapeziotrapezoid (STT) arthrodesis is a procedure used for specific degenerative arthritis and instability patterns of the wrist. This study evaluates nonunion rate and risk factors for reoperation after STT arthrodesis in the Veterans Affairs Department patient population. The purpose of our study was to assess the long-term nonunion rate following STT arthrodesis and to identify factors associated with reoperation. Methods: The national Veterans Health Administration Corporate Data Warehouse and Current Procedural Terminology codes identified STT arthrodesis procedures from 1995 to 2016. Frequencies of total wrist arthrodesis (TWA) and secondary operations were determined. Univariate analyses provided odds ratios for risk factors associated with complications. Results: Fifty-eight STT arthrodeses were performed in 54 patients with a mean follow-up of 120 months. Kirschner wires (K-wires) were the most common fixation method (69%). Six wrists (10%) required secondary procedures: 5 TWAs and 1 revision STT arthrodesis. Four patients underwent additional procedures for nonunion (7%). Twenty-four patients required K-wire removal, 8 (14%) of these in the operating room, which were not included in regression analysis. Every increase in 1 year of age resulted in a 15% decrease in likelihood of reoperation (95% confidence interval: 0.77-0.93; P < .0001). Opioid use within 90 days before surgery ( P = 1.00), positive smoking history ( P = 1.00), race ( P = .30), comorbidity count ( P = .25), and body mass index ( P = .19) were not associated with increased risk of reoperation. Conclusions: At a mean follow-up of 10 years, patients undergoing STT arthrodesis have a 10% risk of reoperation, and this risk decreases with older patient age. There was a symptomatic nonunion rate of 7%, similar to prior published rates. Patient demographics, comorbidity, smoking history, and opioid use did not appear to increase risk of reoperation.

Objective To assess the initial clinical experience with a novel endograft system (NEXUS Aortic Arch Stent Graft System) designed to treat aortic arch pathologies and address the morphology and hemodynamic challenges of the aortic arch. Summary background data The aortic arch remains the most challenging part of the aorta for both open and endovascular repair. Transcatheter aortic arch repair has the potential to significantly reduce surgical risks. Methods Patients underwent transcatheter aortic arch repair with a single branch, two stent graft system, implanted over a through-and-through guidewire from the brachiocephalic trunk, to the descending aorta with an ascending aorta stent graft. The ascending aorta stent graft is deployed into a designated docking sleeve to connect the two stent grafts and isolate the aortic arch pathology. Proximal landing zone in all cases was in Zone 0. Anatomical inclusion criteria included adequate landing zone in the ascending aorta, brachiocephalic trunk and descending thoracic aorta. Preparatory debranching procedure was performed in all patients with carotid - carotid crossover bypass and left carotid to left subclavian bypass, or parallel graft from descending aorta to left subclavian artery. Safety and performance were evaluated through one year. Survival analysis used the Kaplan-Meier method. Results Twenty-eight patients, 79% males, with a mean age of 72.2 ± 6.2 years were treated with 100% procedural success. Isolated aortic arch aneurysm was the principle pathology in 17 (60.7%) of patients while chronic aortic dissection was the principle pathology in 6 (21.4%) of patients. The remaining 5(17.8%) had combined or other pathologies. At one month, the vascular pathology was excluded in 25 of 26 alive patients (96.1%). The 30 days mortality rate was 7.1%, stroke rate was 3.6% (all non-disabling) and combined mortality/stroke rate was 10.7%. One year mortality was 10.7%, without device or aneurysm related death. Two patients (7.1%) reported stroke or transient ischemic attack at one year that recovered completely. One year combined mortality/stroke rate was 17.8%. There were three patients (10.7%) that had device related unplanned reinterventions through one year. Conclusions The NEXUS Aortic Arch Stent Graft System, a novel single branch, two stent graft system used for endovascular aortic arch repair that requires landing in the ascending aorta, demonstrates a high success rate with excellent one year safety and performance.

Access to resources by users may need to be granted only upon certain conditions and contexts, perhaps particularly in cyber-physical settings. Unfortunately, creating and modifying context-sensitive access control solutions in dynamic environments creates ongoing challenges to manage the authorization contexts. This paper proposes RASA, a context-sensitive access authorization approach and mechanism leveraging unsupervised machine learning to automatically infer risk-based authorization decision boundaries. We explore RASA in a healthcare usage environment, wherein cyber and physical conditions create context-specific risks for protecting private health information. The risk levels are associated with access control decisions recommended by a security policy. A coupling method is introduced to track coexistence of the objects within context using frequency and duration of coexistence, and these are clustered to reveal sets of actions with common risk levels; these are used to create authorization decision boundaries. In addition, we propose a method for assessing the risk level and labelling the clusters with respect to their corresponding risk levels. We evaluate the promise of RASA-generated policies against a heuristic rule-based policy. By employing three different coupling features (frequency-based, duration-based, and combined features), the decisions of the unsupervised method and that of the policy are more than 99% consistent., ACM Digital Threats: Research and Practice, 2021 30 pages, 14 Figures, 14 Tables

Purpose To highlight a case of chorioretinitis sclopetaria, with concomitant macular hole formation and orbital emphysema, caused by a commercial-grade pressure washer. Patient A 19-year-old male presented to the emergency department with a left eye injury, incurred after being sprayed with a commercial-grade pressure washer. He endorsed ipsilateral blurred vision, pain, and linear floaters. Left eye visual acuity was 20/40. Dilated fundus exam showed inferior vitreous hemorrhage, retinal whitening, and pre-, intra-, and sub-retinal hemorrhages, consistent with chorioretinitis sclopetaria. Optical coherence tomography revealed a full-thickness macular hole. Computed tomography scan of the orbits showed subcutaneous and post-septal orbital emphysema. Two months following injury, vitreous and retinal hemorrhages and macular hole resolved. Five months following injury, visual acuity improved to 20/20. Discussion Chorioretinitis sclopetaria is defined as a full-thickness chorioretinal disruption resulting from a high-velocity projectile passing adjacent to or into the orbit without penetrating the globe. Chorioretinal deformation and ocular comorbidities are influenced by the velocity of the missile and its spatial relationship to the orbit. While this pattern of injury is typically associated with indirect trauma to the globe by a BB or a bullet, this is the first report of chorioretinitis sclopetaria precipitated by a high-velocity liquid missile.

We evaluated a protocolized endoscopic necrosectomy approach with a lumen-apposing metal stent (LAMS) in patients with large symptomatic walled-off pancreatic necrosis (WON) comprising significant necrotic content, with or without infection.Randomized trials have shown similar efficacy of endoscopic treatment compared to surgery for infected WON.We conducted a regulatory, prospective, multicenter single-arm clinical trial examining the efficacy and safety of endoscopic ultrasound (EUS)-guided LAMS with protocolized necrosectomy to treat symptomatic WON ≥ 6 cm in diameter with 30% solid necrosis. After LAMS placement, protocolized WON assessment was conducted and endoscopic necrosectomy was performed for insufficient WON size reduction and persistent symptoms. Patients with radiographic WON resolution to ≤ 3 cm and/or 60-day LAMS indwell had LAMS removal, then 6-month follow-up. Primary endpoints were probability of radiographic resolution by 60 days and procedure-related serious adverse events (SAEs).Forty consecutive patients were enrolled September 2018 - March 2020, of whom 27 (67.5%) were inpatients and 19 (47.5%) had clinical evidence of infection at their index procedure. Mean WON size was 15.0 ± 5.6 cm with mean 53.2% ± 16.7% solid necrosis. Radiographic WON resolution was seen in 97.5% (95% CI, 86.8%, 99.9%) by 60 days, without recurrence in 34 patients with 6-month follow-up data. Mean time to radiographic WON resolution was 34.1 ± 16.8 days. SAEs occurred in 3 patients (7.5%), including sepsis, vancomycin-resistant enterococcal bacteremia and shock, and upper gastrointestinal bleeding. There were no procedure-related deaths.EUS-guided drainage with protocolized endoscopic necrosectomy to treat large symptomatic or infected walled-off necrotic pancreatic collections was highly effective and safe. Clinicaltrials.gov no: NCT03525808.

Objective To compare the demographic, clinical, ancillary testing, and multimodal imaging characteristics of birdshot chorioretinopathy (BSCR) patients with late recurrence and birdshot patients with durable remission. Patients and Methods This was a retrospective observational case series. The above-mentioned parameters were studied in BSCR patients with late recurrence (group 1) and BSCR patients with durable remission (group 2). Results Fifty-five patients were included in this study. The average age of patients was 62.1 ± 11.1 years (range, 35–88 years). Groups 1 and 2 included 20 (36.4%) and 35 (63.6%) patients, respectively. In group 1, the average age of patients was 60.5 ± 10.39 years (range, 35–79 years). The female-to-male ratio was 16:4. In group 2, the average age of patients was 63.1 ± 11.6 years (range, 37–88 years). The female-to-male ratio was 22:13. None of the demographic, clinical, ancillary testing, and multimodal imaging parameters were statistically significantly different between the two groups. Using a receiver operating characteristics (ROC) curve, we found that the ideal duration of successful therapy to induce durable remission was 30 months with 70% sensitivity and 40% specificity (ideal point on the curve). A Kaplan–Meier survival curve demonstrated that late recurrence was seen within 30 months after stopping successful treatment of patients with BSCR. Conclusion There are no demographic, clinical, ancillary testing, or multimodal imaging characteristics that can predict late recurrence in BSCR patients. However, we found that 30 months of successful treatment may be ideal and recommended.

Purpose To describe an unusual case of unilateral, endogenous endophthalmitis in an otherwise healthy, term neonate. Methods A 3-week-old otherwise healthy, term male infant was referred to St. Louis Children's Hospital for a second opinion of presumed panuveitis of the right eye. Patients Single male infant. Results Diffusion weighted magnetic resonance imaging (MRI) demonstrating purulent intraocular contents facilitated the diagnosis of endophthalmitis. Examination of surgical vitreous samples by staining and cytology demonstrated Gram-positive bacterial cocci in short chains, thereby confirming endophthalmitis. Polymerase chain reaction testing of vitreous fluid identified Streptococcus agalactiae, despite an unremarkable systemic workup and a negative pre-partum maternal Group B streptococcal screen. Conclusions Endogenous endophthalmitis is a rare but devastating cause of vision loss in otherwise healthy, term neonates. Prompt diagnosis may be facilitated by MRI imaging and diagnostic vitreous biopsy.

Importance: Ninety-day mortality rates after esophagectomy are an indicator of the quality of surgical oncologic management. Accurate risk prediction based on large data sets may aid patients and surgeons in making informed decisions. Objective: To develop and validate a risk prediction model of death within 90 days after esophagectomy for cancer using the International Esodata Study Group (IESG) database, the largest existing prospective, multicenter cohort reporting standardized postoperative outcomes. Design, Setting, and Participants: In this diagnostic/prognostic study, we performed a retrospective analysis of patients from 39 institutions in 19 countries between January 1, 2015, and December 31, 2019. Patients with esophageal cancer were randomly assigned to development and validation cohorts. A scoring system that predicted death within 90 days based on logistic regression ß coefficients was conducted. A final prognostic score was determined and categorized into homogeneous risk groups that predicted death within 90 days. Calibration and discrimination tests were assessed between cohorts. Exposures: Esophageal resection for cancer of the esophagus and gastroesophageal junction. Main Outcomes and Measures: All-cause postoperative 90-day mortality. Results: A total of 8403 patients (mean [SD] age, 63.6 [9.0] years; 6641 [79.0%] male) were included. The 30-day mortality rate was 2.0% (n = 164), and the 90-day mortality rate was 4.2% (n = 353). Development (n = 4172) and validation (n = 4231) cohorts were randomly assigned. The multiple logistic regression model identified 10 weighted point variables factored into the prognostic score: age, sex, body mass index, performance status, myocardial infarction, connective tissue disease, peripheral vascular disease, liver disease, neoadjuvant treatment, and hospital volume. The prognostic scores were categorized into 5 risk groups: very low risk (score, =1; 90-day mortality, 1.8%), low risk (score, 0; 90-day mortality, 3.0%), medium risk (score, -1 to -2; 90-day mortality, 5.8%), high risk (score, -3 to -4: 90-day mortality, 8.9%), and very high risk (score, =-5; 90-day mortality, 18.2%). The model was supported by nonsignificance in the Hosmer-Lemeshow test. The discrimination (area under the receiver operating characteristic curve) was 0.68 (95% CI, 0.64-0.72) in the development cohort and 0.64 (95% CI, 0.60-0.69) in the validation cohort. Conclusions and Relevance: In this study, on the basis of preoperative variables, the IESG risk prediction model allowed stratification of an individual patient's risk of death within 90 days after esophagectomy. These data suggest that this model can help in the decision-making process when esophageal cancer surgery is being considered and in informed consent.

Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes. Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1e6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2

© 2020, The Author(s), under exclusive licence to Springer Nature Limited.Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

Iliopsoas abscesses (IPA) are uncommon, with an associated mortality rate of up to 20%. We describe the case of a 55-year-old man war veteran who presented with an unusual cause of IPA secondary to retained foreign body (FB). His initial trauma 30 years before was a result of a blast injury with shrapnel penetration suffered after inadvertently driving over a landmine as an ambulance driver in a conflict region. A CT scan was performed, revealing a 13 mmx8 mm radio-opaque FB within the right psoas at the level of the fifth lumbar vertebra with a surrounding collection. Subsequent open surgical exploration removed two gravel fragments. Given the knowledge of a traumatic blast injury with retained FB and repeated episodes of sepsis, surgical exploration is warranted. To our knowledge, this is the first case of recurrent IPA secondary to a retained FB from a historical trauma.

To describe longitudinal, anatomical, and functional alterations caused by inflammatory and neovascular lesions of idiopathic multifocal choroiditis/punctate inner choroidopathy using adaptive optics imaging and microperimetry.Longitudinal case study using multiple imaging modalities, including spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, optical coherence tomography angiography, flood illumination adaptive optics, and microperimetry.A 21-year-old myopic Asian man presented with blurred vision in the right eye. Clinical examination was notable for an isolated hypopigmented, perifoveal lesion in each eye. Multimodal imaging showed inflammatory lesions in the outer retina, retina pigment epithelium, and inner choroid lesions of both eyes. The right eye additionally exhibited active Type-2 macular neovascularization with loss of cone mosaic regularity that was associated with reduced sensitivity on microperimetry. The clinical picture was consistent with multifocal choroiditis/punctate inner choroidopathy. The patient was treated with oral steroids and three injections of intravitreal bevacizumab in the right eye. After therapy, imaging showed reestablishment of the cone mosaic on flood illumination adaptive optics and improvement in sensitivity on microperimetry.Adaptive optics imaging and microperimetry may detect biomarkers that help to characterize the nature and activity of multifocal choroiditis lesions and to help monitor response to therapy. With timely intervention, structural abnormalities in the outer retina and choroid can be treated, and anatomical improvements precede improvements in visual function.

A 49-year-old man with a structurally normal heart presented to the emergency department with pyelonephritis secondary to extended spectrum beta lactamase Escherichia coli , resulting in both septic shock and an acute kidney injury. He had a background history of a renal transplant for adult

Chronic pain is highly prevalent among persons with HIV (PWH), as is depression. Both comorbidities might contribute to, as well as be maintained by, avoidance-based coping. A promising alternative to avoidance-based coping is acceptance. Acceptance of pain is associated with improved functioning and quality of life in chronic pain patients, but this relationship has not been substantially explored among PWH. Cross-sectional data from 187 adult outpatients enrolled in a randomized trial for depressed PWH with chronic pain were analyzed. Controlling for pain severity and demographics, the relationships among pain acceptance and indicators of activity, functioning, and emotional distress (i.e., anxiety and anger) were assessed in seven regression models. No significant relationships were found between self-reported physical activity or objective measurement of mean steps/day with pain acceptance. Results revealed an inverse relationship between chronic pain acceptance and pain-related functional interference (b

Making public health data easier to access, understand, and use makes it more likely that the data will be influential. Throughout the COVID-19 pandemic, the New York City (NYC) Department of Health and Mental Hygiene’s Web-based data communication became a cornerstone of NYC’s response and allowed the public, journalists, and researchers to access and understand the data in a way that supported the pandemic response and brought attention to the deeply unequal patterns of COVID-19’s morbidity and mortality in NYC. (Am J Public Health. 2021;111(S3):S193–S196. https://doi.org/10.2105/AJPH.2021.306446 )

We report a case of a 74-year-old male patient who was referred to the respiratory clinic with an incidental finding of a left sided pleural effusion. He was initially being treated by the general practitioner for chest infection with productive cough that had limited resolution after course of oral antibiotics. At the pleural clinic, 1.5 L of serosanguineous fluid was drained and sent for diagnostics. However, the diagnosis only reached as far as idiopathic exudative effusion with lymphocytes and plasma cells. He was then referred for video-assisted thoracoscopic surgery pleural biopsy and pleurodesis. It revealed black pleura with abundant IgG4 positive cells. He is followed up in respiratory clinic where further discussion and treatment has commenced.

A female in her 40s was referred to our institution having undergone right-sided percutaneous sacroiliac (SI) screw fixation of a pelvic fracture 28 years prior, following a road traffic collision. She had made a complete recovery and was engaging in an active lifestyle. She presented to her local

CLINICAL RELEVANCE This study identifies key signs and symptoms of acute conjunctivitis, that when combined with a point-of-care test, can improve clinician accuracy of diagnosing adenoviral conjunctivitis. BACKGROUND Adenoviral conjunctivitis is a common ocular infection with the potential for high economic impact due to widespread outbreaks and subsequent furloughs from work and school. In this report, we describe clinical signs and participant-reported symptoms that most accurately identify polymerase chain reaction (PCR)-confirmed adenoviral conjunctivitis. METHODS Adults with 'red eye' symptoms of four days or less were enrolled. Participants rated 10 ocular symptoms from 0 (not bothersome) to 10 (very bothersome), and indicated the presence or absence of systemic flu-like symptoms. Clinicians determined the presence or absence of swollen lymph nodes and rated the severity of eight ocular signs using a 5-point scale. An immunoassay targeting adenovirus antigen was utilised for the point-of-care test, and conjunctival swab samples were obtained for subsequent adenovirus detection by PCR analyses. Univariate and multivariate logistic regression models were used to identify symptoms and signs associated with PCR-confirmed adenoviral conjunctivitis. The diagnostic accuracy of these clinical findings, and the potential benefit of incorporating point-of-care test results, was assessed by calculating areas under the receiver operating characteristic curves (AUC). RESULTS Clinician-rated bulbar conjunctival redness, participant-rated eyelid swelling and overall ocular discomfort had the best predictive value in the multivariate logistic regression model with an AUC of 0.83. The addition of the point-of-care test results to these three clinical sign/symptom scores improved diagnostic accuracy, increasing the AUC to 0.94. CONCLUSIONS Conjunctival redness severity and participant-reported eyelid swelling and overall discomfort, along with adenoviral point-of-care test results, were highly predictive in identifying individuals with PCR-confirmed adenoviral conjunctivitis. Improved diagnostic accuracy by clinicians at the initial presenting visit could prevent unnecessary work furloughs and facilitate earlier treatment decisions.

Breast implant anaplastic large cell lymphoma (ALCL) is a T-cell neoplasm arising around textured breast implants that was recognized recently as a distinct entity by the World Health Organization. Rarely, other types of lymphoma have been reported in patients with breast implants, raising the possibility of a pathogenetic relationship between breast implants and other types of lymphoma. We report eight cases of Epstein-Barr virus (EBV)-positive large B-cell lymphoma associated with breast implants. One of these cases was invasive, and the other seven neoplasms were noninvasive and showed morphologic overlap with breast implant ALCL. All eight cases expressed B-cell markers, had a non-germinal center B-cell immunophenotype, and were EBV+ with a latency type III pattern of infection. We compared the noninvasive EBV+ large B-cell lymphoma cases with a cohort of breast implant ALCL cases matched for clinical and pathologic stage. The EBV+ large B-cell lymphoma cases more frequently showed a thicker capsule, and more often were associated with calcification and prominent lymphoid aggregates outside of the capsule. The EBV+ B-cell lymphoma cells were more often arranged within necrotic fibrinoid material in a layered pattern. We believe that this case series highlights many morphologic similarities between EBV+ large B-cell lymphoma and breast implant ALCL. The data presented suggest a pathogenetic role for breast implants (as well as EBV) in the pathogenesis of EBV+ large B-cell lymphoma. We also provide some histologic findings useful for distinguishing EBV+ large B-cell lymphoma from breast implant ALCL in this clinical setting.

The 0 to 10 numeric rating scale (NRS) of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between “observed” pain intensity (the NRS, irrespective of concurrent analgesic use), and “underlying” pain intensity (what the NRS would be had concurrent analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections (LESI). The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to observed pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs.

Background: The long-term outcomes following surgical resection for pancreatic ductal adenocarcinoma (PDAC) remains poor, with only 20% of patients surviving 5 years after pancreatectomy. Patient selection for surgery remains sub-optimal largely due to the absence of consideration of aggressive tumor biology. Objective: The aim of this study was to evaluate traditional staging criteria for PDAC in the setting of molecular subtypes. Methods: Clinicopathological data were obtained for 5 independent cohorts of consecutive unselected patients, totaling n = 1298, including n = 442 that underwent molecular subtyping. The main outcome measure was disease-specific survival following surgical resection for PDAC stratified according to the American Joint Commission for Cancer (TNM) staging criteria, margin status, and molecular subtype. Results: TNM staging criteria and margin status confers prognostic value only in tumors with classical pancreatic subtype. Patients with tumors that are of squamous subtype, have a poor outcome irrespective of favorable traditional pathological staging [hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04–2.28, P = 0.032]. Margin status has no impact on survival in the squamous subtype (16.0 vs 12.1 months, P = 0.374). There were no differences in molecular subtype or gene expression of tumors with positive resection margin status. Conclusions: Aggressive tumor biology as measured by molecular subtype predicts poor outcome following pancreatectomy for PDAC and should be utilized to inform patient selection for surgery.

Beta-blockers (βB) are a frequently used class of medications. Although βB have many indications, those related to cardiovascular disease are among the most common and important. However, in patients with chronic obstructive pulmonary disease (COPD), βB are used less often due to concerns about an unfavorable impact on respiratory morbidity and mortality. a need for well-designed randomized controlled trials to examine their safety and efficacy, particularly in patients with comorbid heart disease who otherwise have strong indications for βB.

Rare variants in JPH2 have been associated with a range of cardiac disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, and sudden cardiac death (SCD); however, our understanding of how variants in JPH2 correspond to specific modes of inheritance and correlate clinical phenotypes has not been comprehensively explored. In this systematic review, we assess current case reports and series that describe patients with JPH2 variants and cardiac disease. We identified a total of 61 variant-positive individuals, approximately 80% of whom had some form of cardiac disease, including 47% HCM, 18% DCM, and 14% arrhythmia/SCD. In analyzing the 24 probands described in the studies, we found that autosomal recessive, loss-of-function variants are associated with severe, early onset DCM, while autosomal dominant missense variants are associated with a wider range of cardiac disease, including HCM, arrhythmia, SCD, and cardiac conduction disease.

When multiple retailers hold inventory to satisfy random demand, retailer inventory-sharing strategies can potentially reduce the supply-demand mismatch and increase overall supply chain performance. In this paper, we experimentally investigate alternative inventory-sharing strategies in a two-tier supply chain with an upstream manufacturer and two downstream retailers. In one setting, retailers act as if they are centralized and use a single quantity to fulfill joint demand. In the other, retailers are decentralized and face separate demands, but they can transfer inventory after demands are realized. In this latter decentralized scenario, we also consider whether the manufacturer or retailers have decision authority over the inventory transfer price. One key result is that when the retailers are decentralized and the manufacturer sets the transfer price, both retailers and the manufacturer earn higher profits than in the centralized retailer strategy, which runs counter to theory. We also find that when retailers are decentralized and set their own transfer price, the most equitable distribution of profits is achieved. In an effort to account for these results, we find that a model of fairness captures decisions well. Overall, by investigating how different inventory-sharing strategies affect the distribution of profits in a two-tier supply chain, our results provide guidance to firms considering how, if at all, they should enter such arrangements. This paper was accepted by Jay Swaminathan, operations management. Funding: The authors acknowledge financial support from Cornell University and the University of Virginia. Supplemental Material: The data files and electronic companion are available at https://doi.org/10.1287/mnsc.2022.4323 .

Sleep impairment is a common comorbid and debilitating symptom for persons with opioid use disorder (OUD). Research into underlying mechanisms and efficacious treatment interventions for OUD-related sleep problems requires both precise and physiologic measurements of sleep-related outcomes and impairment. This pilot examined the feasibility of a wireless sleep electroencephalography (EEG) monitor (Sleep Profiler™) to measure sleep outcomes and architecture among participants undergoing supervised opioid withdrawal. Sleep outcomes were compared to a self-reported sleep diary and opioid withdrawal ratings. Participants (n = 8, 100% male) wore the wireless EEG 85.6% of scheduled nights. Wireless EEG detected measures of sleep architecture including changes in total, NREM and REM sleep time during study phases, whereas the diary detected changes in wakefulness only. Direct comparisons of five overlapping outcomes revealed lower sleep efficiency and sleep onset latency and higher awakenings and time spent awake from the wireless EEG versus sleep diary. Associations were evident between wireless EEG and increased withdrawal severity, lower sleep efficiency, less time in REM and non-REM stages 1 and 2, and more hydroxyzine treatment; sleep diary was associated with total sleep time and withdrawal only. Data provide initial evidence that a wireless EEG is a feasible and useful tool for objective monitoring of sleep in persons experiencing acute opioid withdrawal. Data are limited by the small and exclusively male sample, but provide a foundation for using wireless EEG sleep monitors for objective evaluation of sleep-related impairment in persons with OUD in support of mechanistic and treatment intervention research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: The objective of this study was to evaluate England's Best Practice Tariff (BPT) and consider potential implications for Medicare patients should the US adopt a similar plan.Summary Background Data: Since the beginning of the Affordable Care Act, Medicare has renewed efforts to improve the outcomes of older adults through introduction of an expanding set of alternative-payment models. Among trauma patients, recommended arrangements met with mixed success given concerns about the heterogeneous nature of trauma patients and resulting outcome variation. A novel approach taken for hip fractures in England could offer a viable alternative.Methods: Linear regression, interrupted time-series, difference-in-difference, and counterfactual models of 2000–2016 Medicare (US), HES-APC (England) death certificate-linked claims (≥65y) were used to: track US hip fracture trends, look at changes in English hip fracture trends before-and-after BPT implementation, compare changes in US-versus-English mortality, and estimate total/theoretical lives saved.Results: 806,036 English and 3,221,109 US hospitalizations were included. Following BPT implementation, England's 30-day mortality decreased by 2.6 percentage-points (95%CI: 1.7–3.5) from a baseline of 9.9% (relative reduction 26.3%). 90- and 365-day mortality decreased by 5.6 and 5.4 percentage-points. 30/90/365-day readmissions also declined with a concurrent shortening of hospital length-of-stay. From 2000–2016, US outcomes were stagnant (p > 0.05), resulting in an inversion of the countries’ mortality and > 38,000 potential annual US lives saved.Conclusions: Process measure pay-for-performance led to significant improvements in English hip fracture outcomes. As efforts to improve US older adult health continue to increase, there are important lessons to be learned from a successful initiative like the BPT.

Intensive care medicine 47(10), 1115-1129 (2021). doi:10.1007/s00134-021-06484-1, Published by Springer, Berlin

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.

Stereotactic body radiation therapy (SBRT) is a recognized treatment for low- and intermediate-risk prostate cancer, with 36.25 Gy in 5 fractions the most commonly used regimen. We explored the preliminary efficacy, patient recorded toxicity, and decision regret in intermediate- and high-risk prostate cancer receiving SBRT with prostate-specific membrane antigen (PSMA)/magnetic resonance imaging (MRI) guided focal gross tumor volume boost to 45 Gy.Between July 2015 and June 2019, 120 patients received SBRT across 2 institutions with a uniform protocol. All patients had fiducial markers and hydrogel, MRI and PSMA positron emission tomography (PET) scan. All patients received a questionnaire asking the degree of urinary, bowel, and sexual bother experienced at set time points, including questions about treatment choice and decision regret.One hundred twelve of 120 patients consented. Their median age was 72 years and median follow-up was 2.3 years. As per National Comprehensive Cancer Network guidelines, 78% had intermediate risk and 20% high risk. Androgen deprivation was combined with radiation in 6 patients. Most patients (74%) reported that receiving SBRT significantly influenced their choice of treatment. Five men (4%) expressed "quite a lot" (n = 4) or "very much" regret (n = 1) regarding their choice of treatment, while 89% expressed "no regret." Similar to pretreatment levels, "quite a lot" or "very much" urinary or bowel bother was expressed in 8% and 6% of patients, respectively. Two patients experienced nadir +2 biochemical failure, both found to have bone metastases. A third patient underwent PSMA PET at nadir +1.7 and had disease at the penile bulb, which was out of field. Three year estimated freedom from biochemical failure was 99% for intermediate and 85% for high-risk groups.We have demonstrated promising efficacy and low toxicity with PSMA/MRI-guided SBRT focal boost. Less than 5% of patients expressed significant decision regret for their choice of treatment.

INTRODUCTION AND OBJECTIVES Conventional renal stone dusting is challenging; the holmium laser (Ho:YAG) and holmium with MOSES Effect (Ho:YAG-MOSES) fail to uniformly produce fragments

Background Takotsubo syndrome (TS) is often triggered by an acute physical or emotional stressor. We hypothesised that medium-term prognosis may be better for TS patients with an associated emotional stressor than for those with an acute physical illness. Methods We identified consecutive TS patients presenting in New Zealand (2006–2018). The clinical presentation and outcomes of TS patients according to types of stressor (physical, emotional or no stressor) were assessed. Post-discharge survival after TS was compared with age- and gender-matched patients after myocardial infarction (MI) and people in the community without known cardiovascular disease (CVD). Results Of 632 TS patients (95.9% women, mean age 65.0±11.1 years), 27.4% had an associated acute physical stressor, 46.4% an emotional stressor and 26.2% no evident stressor. In-hospital mortality was similar for each group (1.7%, 1.2%, 0.3% respectively, p=0.29). In a median 4.4 years post-discharge there were 54 deaths (53 non-cardiac). Compared with patients without known CVD, TS patients with physical stress and those with MI were less likely to survive (HR 4.46, 95%CI 3.10–6.42; HR 4.23, 95%CI 3.81–4.70 respectively) but survival for TS patients associated with emotional stress or no stressor was similar (HR 1.11, 95%CI 0.66–1.85; HR 1.08, 95%CI 0.54–2.18, respectively). Recurrence was similar among the three groups (p=0.14). Conclusion Takotsubo syndrome associated with physical stressor has a post-discharge mortality risk as high as after MI. In contrast, prognosis for TS triggered by an emotional stressor is excellent, and similar to that of those without known CVD.

Wind turbines in wind farms often operate in waked or partially waked conditions, which can greatly increase the fatigue damage. Some fatigue considerations may be included, but currently a full fidelity analysis of the increased damage a turbine experiences in a wind farm is not considered in wind farm layout optimization because existing models are too computationally expensive. In this paper, we present a model to calculate fatigue damage caused by partial waking on a wind turbine that is computationally efficient and can be included in wind farm layout optimization. The model relies on analytic velocity, turbulence, and loads models commonly used in farm research and design, and captures some of the effects of turbulence on the fatigue loading. Compared to high-fidelity simulation data, our model accurately predicts the damage trends of various waking conditions. We also perform example wind farm layout optimizations with our presented model in which we maximize the annual energy production (AEP) of a wind farm while constraining the damage of the turbines in the farm. The results of our optimization show that the turbine damage can be significantly reduced, more than 10 %, with only a small sacrifice of around 0.07 % to the AEP, or the damage can be reduced by 20 % with an AEP sacrifice of 0.6 %.

Background Individuals with COPD have increased sensitivity to traffic-related air pollution (TRAP) such as diesel exhaust (DE), but little is known about the acute effects of TRAP on exercise responses in COPD. Research question Does pre-exercise exposure to TRAP (DE300, PM2.5=300 μg/m3) have greater adverse effects on exercise endurance, exertional dyspnea, and cardiorespiratory responses to exercise in participants with mild-to-moderate COPD compared to former smokers with normal spirometry and healthy controls? Study design and Methods In this double-blind, randomized, placebo-controlled, crossover study, 11 healthy never-smokers, 9 ex-smokers without COPD and 9 ex-smokers with COPD were separately exposed to filtered air (FA) and DE300 for 2 hours separated by a minimum of 4 weeks. Participants performed symptom limited constant load cycling tests within 2.5 hours of exposure with detailed cardiorespiratory and exertional symptom measurements. Results There was a significant negative effect of TRAP on exercise endurance time in healthy controls (DE300 vs. FA: 10.2±8.2 vs. 12.9±9.5 min, respectively; p=0.03), but not in ex-smokers without COPD (10.1±6.9 vs. 12.2±8.0 min; respectively, p=0.57) or ex-smokers with COPD (9.8±6.4 vs. 8.4±6.6 min, respectively, p=0.31). Furthermore, significant increases in inspiratory duty cycle and absolute end-expiratory and end-inspiratory lung volumes were observed, and dyspnea ratings were elevated at select submaximal measurement times only in healthy controls. Interpretation Contrary to our hypothesis, it was the healthy controls rather than the ex-smokers with and without COPD that were negatively impacted by TRAP during exercise.

Summary Background The pathophysiology of COVID-19 includes immune-mediated hyperinflammation, which could potentially lead to respiratory failure and death. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is among cytokines that contribute to the inflammatory processes. Lenzilumab, a GM-CSF neutralising monoclonal antibody, was investigated in the LIVE-AIR trial to assess its efficacy and safety in treating COVID-19 beyond available treatments. Methods In LIVE-AIR, a phase 3, randomised, double-blind, placebo-controlled trial, hospitalised adult patients with COVID-19 pneumonia not requiring invasive mechanical ventilation were recruited from 29 sites in the USA and Brazil and were randomly assigned (1:1) to receive three intravenous doses of lenzilumab (600 mg per dose) or placebo delivered 8 h apart. All patients received standard supportive care, including the use of remdesivir and corticosteroids. Patients were stratified at randomisation by age and disease severity. The primary endpoint was survival without invasive mechanical ventilation to day 28 in the modified intention-to-treat population (mITT), comprising all randomised participants who received at least one dose of study drug under the documented supervision of the principal investigator or sub-investigator. Adverse events were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov , NCT04351152 , and is completed. Findings Patients were enrolled from May 5, 2020, until Jan 27, 2021. 528 patients were screened, of whom 520 were randomly assigned and included in the intention-to-treat population. 479 of these patients (n=236, lenzilumab; n=243, placebo) were included in the mITT analysis for the primary outcome. Baseline demographics were similar between groups. 311 (65%) participants were males, mean age was 61 (SD 14) years at baseline, and median C-reactive protein concentration was 79 (IQR 41–137) mg/L. Steroids were administered to 449 (94%) patients and remdesivir to 347 (72%) patients; 331 (69%) patients received both treatments. Survival without invasive mechanical ventilation to day 28 was achieved in 198 (84%; 95% CI 79–89) participants in the lenzilumab group and in 190 (78%; 72–83) patients in the placebo group, and the likelihood of survival was greater with lenzilumab than placebo (hazard ratio 1·54; 95% CI 1·02–2·32; p=0·040). 68 (27%) of 255 patients in the lenzilumab group and 84 (33%) of 257 patients in the placebo group experienced at least one adverse event that was at least grade 3 in severity based on CTCAE criteria. The most common treatment-emergent adverse events of grade 3 or higher were related to respiratory disorders (26%) and cardiac disorders (6%) and none led to death. Interpretation Lenzilumab significantly improved survival without invasive mechanical ventilation in hospitalised patients with COVID-19, with a safety profile similar to that of placebo. The added value of lenzilumab beyond other immunomodulators used to treat COVID-19 alongside steroids remains unknown. Funding Humanigen.

Background Understanding COVID-19 epidemiology is crucial to clinical care and to clinical trial design and interpretation. Objective To describe characteristics, treatment, and outcomes among patients hospitalized with COVID-19 early in the pandemic. Methods A retrospective cohort study of consecutive adult patients with laboratory-confirmed, symptomatic SARS-CoV-2 infection admitted to 57 US hospitals from March 1 to April 1, 2020. Results Of 1480 inpatients with COVID-19, median (IQR) age was 62.0 (49.4-72.9) years, 649 (43.9%) were female, and 822 of 1338 (61.4%) were non-White or Hispanic/Latino. Intensive care unit admission occurred in 575 patients (38.9%), mostly within 4 days of hospital presentation. Respiratory failure affected 583 patients (39.4%), including 284 (19.2%) within 24 hours of hospital presentation and 413 (27.9%) who received invasive mechanical ventilation. Median (IQR) hospital stay was 8 (5-15) days overall and 15 (9-24) days among intensive care unit patients. Hospital mortality was 17.7% (n = 262). Risk factors for hospital death identified by penalized multivariable regression included older age; male sex; comorbidity burden; symptoms-to-admission interval; hypotension; hypoxemia; and higher white blood cell count, creatinine level, respiratory rate, and heart rate. Of 1218 survivors, 221 (18.1%) required new respiratory support at discharge and 259 of 1153 (22.5%) admitted from home required new health care services. Conclusions In a geographically diverse early-pandemic COVID-19 cohort with complete hospital folllow-up, hospital mortality was associated with older age, comorbidity burden, and male sex. Intensive care unit admissions occurred early and were associated with protracted hospital stays. Survivors often required new health care services or respiratory support at discharge.

Liver transplantation (LT) from donors-with-HIV to recipients-with-HIV (HIV D+/R+) is permitted under the HOPE Act. There are only three international single-case reports of HIV D+/R+ LT, each with limited follow-up. We performed a prospective multicenter pilot study comparing HIV D+/R+ to donors-without-HIV to recipients-with-HIV (HIV D-/R+) LT. We quantified patient survival, graft survival, rejection, serious adverse events (SAEs), human immunodeficiency virus (HIV) breakthrough, infections, and malignancies, using Cox and negative binomial regression with inverse probability of treatment weighting. Between March 2016-July 2019, there were 45 LTs (8 simultaneous liver-kidney) at 9 centers: 24 HIV D+/R+, 21 HIV D-/R+ (10 D- were false-positive). The median follow-up time was 23 months. Median recipient CD4 was 287 cells/µL with 100% on antiretroviral therapy; 56% were hepatitis C virus (HCV)-seropositive, 13% HCV-viremic. Weighted 1-year survival was 83.3% versus 100.0% in D+ versus D- groups (p = .04). There were no differences in one-year graft survival (96.0% vs. 100.0%), rejection (10.8% vs. 18.2%), HIV breakthrough (8% vs. 10%), or SAEs (all p .05). HIV D+/R+ had more opportunistic infections, infectious hospitalizations, and cancer. In this multicenter pilot study of HIV D+/R+ LT, patient and graft survival were better than historical cohorts, however, a potential increase in infections and cancer merits further investigation.

BACKGROUND Civilians are often first-line responders in hemorrhage control; however, windlass tourniquets are not intuitive. Untrained users reading enclosed instructions failed in 38.2% of tourniquet applications. This prospective follow-up study replicated testing following Stop the Bleed (STB) training. MATERIALS AND METHODS One and six months following STB, first-year medical students were randomly assigned a windlass tourniquet with enclosed instructions. Each was given one minute to read instructions and two minutes to apply the windlass tourniquet on the TraumaFX HEMO trainer. Demographics, time to read instructions and stop bleeding, blood loss, and simulation success were analyzed. RESULTS 100 students received STB training. 31 and 34 students completed tourniquet testing at one month and six months, respectively. At both intervals, 38% of students were unable to control hemorrhage (P = 0.97). When compared to the pilot study without STB training (median 48 sec, IQR 33-60 sec), the time taken to read the instructions was shorter one month following STB (P

Foot ulceration in diabetes mellitus is common. Foot problems remain the commonest cause of hospital admission amongst patients with diabetes in Western countries. The lifetime risk of a patient with diabetes developing an ulcer is 25%, and up to 85% of all lower limb amputations in diabetes are preceded by foot ulcers. As many as 50% of older patients with type 2 diabetes have risk factors for foot problems and regular screening by careful clinical examination is essential; those found to be at risk should attend more regular follow-up together with education in foot self-care. The key to management of diabetic neuropathic foot ulceration is aggressive debridement with removal of callus and dead tissue, followed by application of some form of cast to offload the ulcer area. Most ulcers will heal if pressure is removed from the ulcer site, if the arterial circulation is sufficient and if infection is managed and treated aggressively. Any patient with a warm swollen foot without ulceration should be presumed to have acute Charcot neuroarthropathy (CN) until proven otherwise. The optimal approach to reducing ulceration requires regular screening, patient education and a team approach to management, both in the community and in hospital.

Background The incidence of orthopedic disorders amongst patients with Prader–Willi Syndrome (PWS) is high when compared to the general pediatric population. The purpose of this retrospective study was to define the most commonly performed orthopedic procedures in pediatric patients with PWS and to characterize the peri-operative outcomes of these patients. Methods The Kids Inpatient Database (KID) was queried to collect data and identify all pediatric patients with PWS who underwent orthopedic procedures from 2001 to 2012. A total of 3684 patients with PWS were identified, 334 of who underwent an orthopedic procedure. Population demographics, comorbidities, and specific procedures undergone were defined. The incidences of postoperative complications and length of associated hospital stay were additionally evaluated. Results Mean age of patients in this sample was 10.33 years (SD 4.5). The most common comorbidities included obesity (18.1%), chronic pulmonary disease (14.1%), hypothyroidism (5.1%), hypertension (5.1%), and uncomplicated diabetes (4%). Common procedures were spinal fusion (165/334, 49%) and lower extremity procedures (50/334, 15%). Complications included acute blood loss anemia, device related complications, pneumonia, sepsis, and urinary tract infections. The overall complication rate was 35.6%. Average hospital lengths of stay for patients undergoing spinal fusion was 6.68 days (SD 4.13), lower extremity orthopedic procedure was 5.65 days (SD 7.4), and all other orthopedic procedures was 7.74 days (SD 16.3). Conclusions Orthopedic disorders are common in patients with PWS. Consequently, spinal fusions and lower extremity procedures are commonly performed in this patient population. Associated comorbid conditions may negatively impact surgical outcomes in these patients. This information should prove useful in the peri-operative management of patients with PWS undergoing orthopedic surgery and for shared decision making with families.

In social groups, such as school-based peer networks, youth often vie for power and dominance over others. Different strategies may be used to gain power (i.e., coercive and/or cooperative strategies), and with varying levels of success. Using a social networks approach, we examined whether and how social network centrality and social network prestige were associated with social strategies, social power, and peer reputation. Participants were fifth- to eighth-grade elementary school students (N = 466, 51% girls, 63% White) in southern Ontario, Canada. Peer nominations were used to assess social network centrality and prestige (via friendship nominations), social power strategies (coercive and cooperative strategies), social power, and peer reputation (popularity and likeability). Results indicated that coercive and cooperative strategies were used by youth high in both centrality and prestige, but that only high prestige related to power, popularity, and likeability. Results have implications for the usefulness of a social networks approach to understanding the structure of youths' social relationships and power in school settings, as well as practical implications for teachers and other school staff. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To characterize the progression of structural and functional changes in the retinas of a small cohort of unrelated patients with early late-onset retinal degeneration and evaluate these changes as potential biomarkers for future treatment trials.Best-corrected visual acuity, contrast sensitivity, Goldman visual fields, retinal sensitivity measurement by mesopic microperimetry, extent of ellipsoid zone disruption using spectral domain optical coherence tomography, and fundus autofluorescence imaging were performed at each biennial visit.Three unrelated patients with molecularly confirmed late-onset retinal degeneration (S163R mutation in C1QTNF5 ) were prospectively followed for 4 years.The patient's ages were 44, 54, and 62 at baseline. Over the 4-year follow-up period, one patient demonstrated a significant reduction in best-corrected visual acuity (6 Early Treatment of Diabetic Retinopathy Study letters), whereas two patients suffered a significant reduction in contrast sensitivity. Early in the disease, there was a close relationship between ellipsoid zone disruption and a loss in retinal sensitivity. Later in the course of the disease, there were areas outside the zones of ellipsoid zone disruption that also suffered progressive loss of retinal sensitivity, suggesting that ellipsoid zone loss was not the only factor responsible for the loss of retinal sensitivity. Changes in fundus autofluorescence and Goldman visual field loss were not closely related to changes in ellipsoid zone disruption or retinal sensitivity loss.This study has found that the monitoring of the progression of ellipsoid zone disruption and changes in mesopic microperimetry may be useful biomarkers in future clinical trials in patients with late-onset retinal degeneration.

Background: Gender-affirming hormone therapy is critical to the management of transgender persons. Cyproterone acetate (CPA) is a synthetic, progesterone-like compound commonly used in high doses a...

Saliency methods, which “explain” deep neural networks by producing heat maps that highlight the areas of the medical image that influence model prediction, are often presented to clinicians as an aid in diagnostic decision-making. Although many saliency methods have been proposed for medical imaging interpretation, rigorous investigation of the accuracy and reliability of these strategies is necessary before they are integrated into the clinical setting. In this work, we quantitatively evaluate seven saliency methods—including Grad-CAM, Grad-CAM++, and Integrated Gradients—across multiple neural network architectures using two evaluation metrics. We establish the first human benchmark for chest X-ray segmentation in a multilabel classification set up, and examine under what clinical conditions saliency maps might be more prone to failure in localizing important pathologies compared to a human expert benchmark. We find that (i) while Grad-CAM generally localized pathologies better than the other evaluated saliency methods, all seven performed significantly worse compared with the human benchmark; (ii) the gap in localization performance between Grad-CAM and the human benchmark was largest for pathologies that were smaller in size and had shapes that were more complex; (iii) model confidence was positively correlated with Grad-CAM localization performance. While it is difficult to know whether poor localization performance is attributable to the model or to the saliency method, our work demonstrates that several important limitations of saliency methods must be addressed before we can rely on them for deep learning explainability in medical imaging.

Background Concerns regarding long-term durability of surgical repair for functional mitral regurgitation are based on short-term data, with few comparisons of ischemic (IMR) versus non-ischemic (NIFMR) etiology. Methods 788 consecutive patients receiving mitral repair for functional mitral regurgitation were evaluated from a prospectively maintained database. Patients with other surgical procedures were included. Propensity score matching was used to compare outcomes in IMR versus NIFMR. Results Unmatched IMR patients tended to be older men with greater comorbidities. 198 matched pairs of IMR versus NIFMR patients had similar demographics with relatively preserved ejection fraction 40±13% and end-systolic diameter 4.3±1.1cm. Concomitant coronary revascularization occurred in 70% of matched IMR patients. All patients received an annuloplasty ring, usually 24-26 mm. Heart failure class improved from 2.8 preop to 1.5 at 5 years (P =2+) mitral regurgitation (27±4% v 26±4%, P=0.4), severe regurgitation (10±3% v 8±2%, P=0.5), and mitral reoperation (3±1% v 3±1%, P=0.4) were not different between IMR v NIFMR. Recurrent moderate regurgitation was associated with heart failure readmission but not with mortality. Conclusions In propensity-matched patients, IMR versus NIFMR had worse survival but similar repair durability, with moderate regurgitation in 27% at 10 years and rare severe regurgitation or mitral reoperation. In selected patients with relatively preserved function, mitral repair for IMR or NIFMR can improve symptoms with durable mild regurgitation in most patients out to 10 years.