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Background Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase (BTK) that is FDA-approved for several lymphoproliferative disorders and chronic GVHD. Objective To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor inhibitor (EGFRi)-induced dermatologic adverse events (dAEs). Methods Single-center retrospective cohort of patients referred to the Skin Toxicities Program for management of cutaneous eruptions while taking ibrutinib. Results Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. The majority of patients were able to continue ibrutinib therapy with focused management of their cutaneous toxicities. Limitations This study represents cases at a single tertiary care center and is limited to patients referred for toxicity. Conclusions With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Introduction Scalds from hot tap water can have devastating consequences and lifelong impact on survivors. The aims of this study were to (i) describe the frequency, demographic profile, injury event characteristics, and in-hospital outcomes for people with tap water scalds admitted to Australian and New Zealand burn centres; and (ii) determine whether there was variation in the frequency and epidemiological characteristics of tap water scalds between jurisdictions. Methods Data were extracted from the Burns Registry of Australia and New Zealand for people with tap water scalds admitted to Australian or New Zealand burn centres between January 1, 2010 and December 31, 2018. Demographic, injury severity and event characteristics, surgical intervention, and in-hospital outcomes were investigated. Results There were 650 people with tap water scalds admitted to Australian and New Zealand burn centres during the study period. Australians with tap water scalds (median [IQR] 29 [1–69] years) were older than New Zealanders (2 [1–36] years). Most tap water scalds occurred in the home, and 92% of these occurred in the bathroom. More than 55% of injuries occurred due to the accidental alteration of water temperature at the tap fixture. Two thirds of patients underwent a surgical wound procedure. The overall mortality rate was 3.7%, and the median hospital length of stay was 8.8 days. Conclusion Tap water scalds remain a public health problem in Australia and New Zealand. Our research highlights where gaps in current heated water regulations in residential homes perpetuate risks of tap water scalds, particularly in high-risk groups at the extremes of age. Extending current heated water regulations to include all Australia and New Zealand homes is required urgently, in conjunction with design safety improvements, and ongoing education of key stakeholders.

In this report, we present a case of successful long-term salvage of a patient with transfusion-related acute lung injury associated with acute respiratory distress syndrome immediately after a liver transplant. The patient was a 29-year-old man with end-stage liver disease due to sclerosing cholangitis who underwent liver transplant. After organ reperfusion, there was evidence of liver congestion, acidosis, coagulopathy, and acute kidney injury. He received 61 units of blood products. Continuous renal replacement therapy was initiated intraoperatively. On arrival to the intensive care unit, the patient was on high-dose pressors, and the patient developed respiratory failure and was immediately placed on veno-arterial extracorporeal membrane oxygenation via open femoral exposure. The patient presented with severe coagulopathy and early allograft dysfunction; therefore, no systemic heparin was administered and no thrombotic events occurred. He required extracorporeal membrane oxygenation support until posttransplant day 4, when resolution of the respiratory and cardiac dysfunction was noted. At 2 years after liver transplant, the patient has normal liver function, normal cognitive function, and stage V chronic kidney disease. We conclude that extracorporeal membrane oxygenation is a valuable therapeutic approach in patients with cardiorespiratory failure after liver transplant.

Over decades now, laparoscopic Nissen fundoplication represents the treatment of choice for symptomatic children with gastroesophageal reflux disease (GERD) unresponsive to medication. Although the basic principles of Nissen's technique are still essential today, academic studies of long-Term results, complications, and patients benefits have fostered distinct modifications. Identification of surgical factors for wrap migration, dysphagia, and recurrent GERD led to recommendations for "short and floppy"wraps with minimal dissection of the phrenoesophageal membranes. This report summarizes up-To-date information from experts in the field on "how to wrap it right"followed by a critical discussion about long-Term benefits for children with GERD and future developments of laparoscopic Nissen fundoplication.

Patients with pulmonary emphysema often develop locomotor muscle dysfunction, which is independently associated with disability and higher mortality in that population. Muscle dysfunction entails r...

Purpose Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging, due to the native lung contribution to pulmonary function tests (PFT). We aimed to assess the ISHLT CLAD classification and its prognostic performance in SLTX. Methods In this retrospective cohort of adult, first, SLTX from 2009 to 2017, patients with persistent drop in FEV1>20% were assessed by 2 independent reviewers to determine CLAD status and phenotype, specifically noting presence or absence of RAS-like opacities. Disagreements were resolved by a 3rd reviewer. Interobserver agreement (IOA) was calculated by Cohen's Kappa. Association of CLAD phenotypes with time to death/retransplant (ReTx), adjusted for age, sex, CMV mismatch and native lung condition, were assessed with Cox models. Results Out of 172 SLTX patients, 92 had a persistent drop in FEV1>20%, of whom 67 got a diagnosis of CLAD. We noted a moderate IOA for CLAD status (Kappa 0.69) and poor IOA for phenotype (Kappa 0.5). When applying the ISHLT criteria strictly (based on exact cut-offs for PFT, along with imaging), 34 patients had BOS (50.7%), 9 RAS/mixed (13.4%), 7 undefined (10.4%), and 17 unclassified (25.5%). We found no association of these strict phenotypes with death/ReTx (Fig A). When using adjudicated CLAD phenotypes, 31 patients had BOS (46.3%), 15 RAS/mixed (22.4%), 2 Undefined (3%), and 19 Unclassified (28.3%). Using these adjudicated phenotypes, RAS/mixed was significantly associated with higher risk of death/ReTx (HR 2.98, 95%CI [1.39-6.4]) (Fig B). Finally, the specific adjudication of RAS-like opacities had the best IOA (Kappa 0.73). Presence of RAS-like opacities was a strong predictor of death/ReTx (HR 2.3, 95%CI [1.2-4.5]) (Fig C). Conclusion PFT interpretation is challenging in SLTX. Using a classification relying more on imaging analysis that harboured good IOA, we obtained better prognostic performances than with a strict application of published physiologic cut-offs.

Background and Overview Trigeminal neuralgia due to a metastatic lesion is a relatively rare occurrence. These cases pose a diagnostic challenge for the clinician due to a complex clinical presentation. Case Description The authors describe the case of a 65-year-old woman with left-sided facial pain and occasional numbness. The patient also reported autonomic features associated with facial pain, facial muscular weakness, and hearing and visual impairment. The patient's history of breast cancer, for which she was receiving treatment for bone metastasis, warranted diagnostic imaging. Magnetic resonance imaging with and without contrast was performed and revealed a possible metastatic lesion. Conclusions and Practical Implications Unusual clinical features must be identified, and prompt appropriate imaging is instrumental in making at an accurate diagnosis and management plan.

Purpose Determine associations between early residual fluid (ERF)-free status and improved long-term visual outcomes. Design Clinical cohort study from post hoc analysis of two phase 3 clinical trials’ data. Methods Independent of treatment allocation, patients from the multicenter, prospective, randomized, double-masked HAWK and HARRIER trials who received either brolucizumab 6 mg or aflibercept 2 mg were split into two cohorts dependent on presence or absence of ERF at week 12. Additionally, similar analyses were performed on presence or absence of early residual intraretinal fluid (IRF) and subretinal fluid (SRF) at week 12. The two groups, ERF-free (N=1051) and ERF (N=366) were compared. Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were determined. Results From week 12 to 96, patients who were ERF-free had greater least square (LS) mean increases from baseline for BCVA and CST compared to ERF patients. Greater LS mean differences in BCVA from week 12 to 96 were noted between ERF-free and ERF patients. A greater proportion of patients in the ERF-free cohort reported a ≥5, ≥10, or ≥15 letter improvement and a higher proportion reported BCVA ≥70 letters from baseline to week 96 compared to those with fluid. Conclusions Improvements in visual outcomes in ERF-free patients were greater than in ERF patients occurring as early as 4 weeks (week 12) following the last loading dose and continued to week 96. Therefore, ERF status may be a useful indicator of anti-vascular endothelial growth factor treatment response.

Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics.To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity.This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set.Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]1.5, FDR.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH1.3, FDR.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r.6; P .05).This study was limited by a small sample size and predominantly female FFA patients.Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition.

Background: Although estimates of suboptimal adherence to oral corticosteroids in asthma range from 30% to 50%, no ideal method for measurement exists; the impact of poor adherence in severe asthma is likely to be particularly high. Research Questions: What is the prevalence of suboptimal adherence detected by self-reporting and direct measures? Is suboptimal adherence associated with disease activity? Study Design and Methods: Data were included from individuals with severe asthma taking part in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) study and prescribed daily oral corticosteroids. Participants completed the Medication Adherence Report Scale, a five-item questionnaire used to grade adherence on a scale from 1 to 5, and provided a urine sample for analysis of prednisolone and metabolites by liquid chromatography-mass spectrometry. Results: Data from 166 participants were included in this study: mean (SD) age, 54.2 (± 11.9) years; FEV 1, 65.1% (± 20.5%) predicted; female, 58%; 37% completing the Medication Adherence Report Scale reported suboptimal adherence; and 43% with urinary corticosteroid data did not have detectable prednisolone or metabolites in their urine. Good adherence by both methods was detected in 49 of the 142 (35%) of participants in whom both methods were performed; adherence detection did not match between methods in 53%. Self-reported high adherers had better asthma control and quality of life, whereas directly measured high adherers had lower blood eosinophil levels. Interpretation: Low adherence is a common problem in severe asthma, whether measured directly or self-reported. We report poor agreement between the two methods, suggesting some disassociation between self-assessment of medication adherence and regular oral corticosteroid use, which suggests that each approach may provide complementary information in clinical practice.

Significance\ud \ud Communicating in ways that motivate engagement in social distancing remains a critical global public health priority during the COVID-19 pandemic. This study tested motivational qualities of messages about social distancing (those that promoted choice and agency vs. those that were forceful and shaming) in 25,718 people in 89 countries. The autonomy-supportive message decreased feelings of defying social distancing recommendations relative to the controlling message, and the controlling message increased controlled motivation, a less effective form of motivation, relative to no message. Message type did not impact intentions to socially distance, but people’s existing motivations were related to intentions. Findings were generalizable across a geographically diverse sample and may inform public health communication strategies in this and future global health emergencies.\ud \ud \ud \ud Abstract\ud \ud Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges.

The biological functions of cholesterol are diverse, ranging from cell membrane integrity, cell membrane signaling, and immunity to the synthesis of steroid and sex hormones, vitamin D, bile acids, and oxysterols. Multiple studies have demonstrated hypocholesterolemia in sepsis, the degree of which is an excellent prognosticator of poor outcomes. However, the clinical significance of hypocholesterolemia has been largely unrecognized. We undertook a detailed review of the biological roles of cholesterol, the impact of sepsis, its reliability as a prognosticator in sepsis, and the potential utility of cholesterol as a treatment. Sepsis affects cholesterol synthesis, transport, and metabolism. This likely impacts its biological functions, including immunity, hormone and vitamin production, and cell membrane receptor sensitivity. Early preclinical studies show promise for cholesterol as a pleiotropic therapeutic agent. Hypocholesterolemia is a frequent condition in sepsis and an important early prognosticator. Low plasma concentrations are associated with wider changes in cholesterol metabolism and its functional roles, and these appear to play a significant role in sepsis pathophysiology. The therapeutic impact of cholesterol elevation warrants further investigation.

Purpose This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials. Design Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. Participants Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. Methods Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. Main Outcome Measures Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE. Results Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0–29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were −0.84 ± 20.6 , −16.31 ± 17.6, and −0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and −7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of −10.4 ± 25.5 ETDRS letters from baseline to EOS. Conclusions Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.

Non-invasive respiratory support (NIRS) has increasingly been used in the management of COVID-19-associated acute respiratory failure, but questions remain about the utility, safety, and outcome benefit of NIRS strategies. We identified two randomised controlled trials and 83 observational studies, compromising 13 931 patients, that examined the effects of NIRS modalities-high-flow nasal oxygen, continuous positive airway pressure, and bilevel positive airway pressure-on patients with COVID-19. Of 5120 patients who were candidates for full treatment escalation, 1880 (37%) progressed to invasive mechanical ventilation and 3658 of 4669 (78%) survived to study end. Survival was 30% among the 1050 patients for whom NIRS was the stated ceiling of treatment. The two randomised controlled trials indicate superiority of non-invasive ventilation over high-flow nasal oxygen in reducing the need for intubation. Reported complication rates were low. Overall, the studies indicate that NIRS in patients with COVID-19 is safe, improves resource utilisation, and might be associated with better outcomes. To guide clinical decision making, prospective, randomised studies are needed to address timing of intervention, optimal use of NIRS modalities-alone or in combination-and validation of tools such as oxygenation indices, response to a trial of NIRS, and inflammatory markers as predictors of treatment success.

Objective Seropositive rheumatoid arthritis (RA) is a chronic autoimmune disease that is rarely "cured." Human mesenchymal stem cells (hMSCs) are known to reduce inflammation and restore immune homeostasis. However, methods for predicting therapeutic hMSC potency have not been established. The goal of these studies was to use and refine an ex vivo functional assay that determines potency of hMSCs and can then be validated in clinical trials as a potency measure of hMSCs used therapeutically to treat RA. Methods Allogeneic hMSCs were cytokine-stimulated, and a conditioned medium (CM) was harvested. The CM was tested for the potential to attenuate RA CD4+ T cell proliferation using suppression assays. Indoleamine 2, 3-dioxygenase (IDO) mRNA, and protein were quantified in hMSCs as a measure to compare hMSCs across (prior) studies. Results To mimic a proinflammatory environment that resembles that in RA, interleukin-1(IL1β), tumor necrosis factor α (TNFα) , and interferon γ (IFNγ) (alone or in combination) were used to precondition hMSCs. Treating hMSCs with a combination of these cytokines generated a CM "secretome" that suppressed T cell proliferation between 70 and 83%. Forty-eight hours of cytokine preconditioning hMSCs was required to maximize this effect. T cell suppression positively correlated with increases in hMSC cellular IDO mRNA and protein. Conclusion By standardizing assays to measure hMSC effects, their potency on T cell suppression can be quantified. These studies demonstrate that hMSCs can be compared functionally to identify optimal preparation(s) for therapeutic use in RA and that the potency of hMSC-dependent T cell suppression may differ between hMSC donors. Clinical studies are warranted to validate the hypothesis that ex vivo potency in suppressing T cells will positively correlate with a reduction in RA disease activity and increase in immunological quiescence.

To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic nonresponder phenotype.Phase 2b, randomized, double-blind, placebo-controlled pilot trial.HIV-positive individuals with blood CD4+ T-cell counts350/mm3 despite viral suppression were randomized to 2:1 to receive De Simone Formulation Probiotic (DSFP; "Visbiome" commercially) or placebo for 48 weeks; target enrollment was 36 patients. The primary endpoint was the change in blood CD8+ T-cell coexpression of human leukocyte antigen-DR isotype and CD38 ("CD8 activation"). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed regression methods evaluated the differences between study arms from baseline to week 48. Study monitoring was performed by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee.Nineteen patients received DSFP, whereas 10 received placebo. One probiotic arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval: -1.23 to 2.87;) and decreased by 2.06 pp in the placebo arm (-4.81 to 0.70; between arms P = 0.097). CD4+ T-cell activation (%HLA-DR+) decreased in the placebo arm [-3.79 pp (-7.32 to -0.26)] but increased in the probiotic arm [1.64 (-0.98 to 4.26); between arms P = 0.018]. No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation.Blood immune activation markers in immunologic nonresponder individuals on effective antiretroviral treatment were not reduced by supplementation with DSFP; CD4+ T-cell activation may have been increased.

Background Neoadjuvant chemotherapy (NAC) in combination with anti-HER2 treatment is standard of care in patients with early HER2 positive breast cancer. Preoperative radiological evaluation is mandatory for defining the extent of surgery. In this study, we evaluated the correlation between preoperative radiological and postoperative pathological tumor size in early HER2 positive patients after neoadjuvant chemotherapy in combination with trastuzumab and pertuzumab. In a patient population with HER2 positive breast cancer, who received neoadjuvant chemotherapy and anti-HER2 treatment, the correlation between preoperative radiological and postoperative pathological tumor size was performed. Concordance of radiological and pathological tumor size was found in 55.7%, leading to more extensive breast surgery as required in 7 cases and to the underestimation of 6 neoplastic lesions before surgery, respectively. Patients and Methods Seventy early HER2 positive breast cancer patients were included and retrospectively analysed. All preoperative radiological assessments as well as the tumor board decision on surgical extent and pathological evaluation were completed at the Medical University of Vienna. Preoperative radiological assessment of tumor size and lymph node status were compared with final histopathological findings. The correlation between different radiological modalities regarding tumor size was investigated. Results Concordance of radiological and pathological tumor size was found in 55.7 % (50% by sonography and 66.7% by MRI, respectively) of patients with a nonsignificant correlation of r = 0.31 (P = .08). Of the 39 patients with pathologic complete remission (pCR), 16 were also classified as radiological complete response (rCR) while 23 of those showed a radiological stable disease or partial response. In 6 patients, radiological assessment showed a CR but invasive cancer with a tumor size range from 7 to 36 mm was found in histopathological examination. Neither menopausal status (P= .69) nor BMI (P = .60) and age (P = .50) had an impact on the correlation between radiological and histopathological tumor size. Regarding lymph node status, a statistically significant association and clinically relevant correlation between radiological and histopathological evaluation was found (r = 0.66, P Conclusion Concordance between radiology and histopathology was low regarding tumor size after NAC in combination with trastuzumab and pertuzumab, but significant regarding lymph node status.

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

OBJECTIVE: To describe the impact of social determinants on the experience of the coronavirus disease 2019 (COVID-19) pandemic within the pediatric population, how this impact may influence the long-term health and security of children, and what measures can be taken to ameliorate this impact moving forward. DATA SOURCES: Nonsystematic review of relevant literature and news sources. STUDY SELECTIONS: Relevant literature and news sources. RESULTS: There have been increases in housing insecurity and food insecurity during the pandemic, including global increases in poverty. Public policies such as school closures have had a disproportionate impact on those facing adverse social determinants. There has been a dramatic increase in reports of abuse-related injuries and other injuries indicative of child abuse during the pandemic. In addition, there are disproportionate impacts of COVID-19 based on race and ethnicity within the United States. It is clear that children are facing more adverse determinants as a result of this pandemic and that there are both short-term and long-term implications associated. For those living in poverty or with other adverse social determinants of health, the pandemic has made a bad situation worse. Ongoing studies are required to measure the impact of COVID-19 on those with adverse social determinants, in particular among children. CONCLUSION: Social determinants of health must be part of pandemic research priorities, public health and vaccination goals, and economic policy implementation. The impact of the COVID-19 pandemic has further served to shed a light on the broad disparities that exist within our society and their direct and indirect impacts on health outcomes.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

Background: Palliative care (PC) services expanded rapidly to meet the needs of coronavirus disease 2019 (COVID-19) patients, yet little is known about which patients were referred for PC consultation during the pandemic. Objective: Examine factors predictive of PC consultation for COVID-19 patients. Design: Retrospective cohort study of COVID-19 patients discharged from four hospitals (March 1–June 30, 2020). Exposures: Patient demographic, socioeconomic, and clinical factors and hospital-level characteristics. Outcome Measurement: Inpatient PC consultation. Results: Of 4319 hospitalized COVID-19 patients, 581 (14%) received PC consultation. Increasing age, serious illness (cancer, chronic obstructive pulmonary disease, and dementia), greater illness severity, and admission to the quaternary hospital were associated with receipt of PC consultation. There was no association between PC consultation and race/ethnicity, household crowding, insurance status, or hospital-factors, including inpatient, emergency department, and intensive care unit census. Conclusions: Although site variation existed, the highest acuity patients were most likely to receive PC consultation without racial/ethnic or socioeconomic disparities.

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene–environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: “young” individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider “young” patients with COPD those patients in the age range of 20–50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age.

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Rationale COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. Objectives To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in “usual” (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Methods Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. Results COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm−3·min−1, respectively, p, FDG PET/CT has potential utility to noninvasively evaluate pulmonary inflammation in COPD. Pulmonary FDG uptake is increased in COPD patients, positively associated with systemic inflammatory markers and shows low inter-occasion variability. https://bit.ly/3dELYAW

Background & aims: The year 2019 marked the centenary of the publication of the Harris and Benedict equations for estimation of energy expenditure. In October 2019 a Scientific Symposium was organized by the European Society for Clinical Nutrition and Metabolism (ESPEN) in Vienna, Austria, to celebrate this historical landmark, looking at what is currently known about the estimation and measurement of energy expenditure. Methods: Current evidence was discussed during the symposium, including the scientific basis and clinical knowledge, and is summarized here to assist with the estimation and measurement of energy requirements that later translate into energy prescription. Results: In most clinical settings, the majority of predictive equations have low to moderate performance, with the best generally reaching an accuracy of no more than 70%, and often lead to large errors in estimating the true needs of patients. Generally speaking, the addition of body composition measurements did not add to the accuracy of predictive equations. Indirect calorimetry is the most reliable method to measure energy expenditure and guide energy prescription, but carries inherent limitations, greatly restricting its use in real life clinical practice. Conclusions: While the limitations of predictive equations are clear, their use is still the mainstay in clinical practice. It is imperative to recognize specific patient populations for whom a specific equation should be preferred. When available, the use of indirect calorimetry is advised in a variety of clinical settings, aiming to avoid under-as well as overfeeding. (C)2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The current ST-elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI) paradigm prevents some NSTEMI patients with acute coronary occlusion from receiving emergent reperfusion, in spite of their known increased mortality compared with NSTEMI without occlusion. We have proposed a new paradigm known as occlusion MI vs. nonocclusion MI (OMI vs. NOMI).We aimed to compare the two paradigms within a single population. We hypothesized that STEMI(-) OMI would have characteristics similar to STEMI(+) OMI but longer time to catheterization.We performed a retrospective review of a prospectively collected acute coronary syndrome population. OMI was defined as an acute culprit and either TIMI 0-2 flow or TIMI 3 flow plus peak troponin T 1.0 ng/mL. We collected electrocardiograms, demographic characteristics, laboratory results, angiographic data, and outcomes.Among 467 patients, there were 108 OMIs, with only 60% (67 of 108) meeting STEMI criteria. Median peak troponin T for the STEMI(+) OMI, STEMI(-) OMI, and no occlusion groups were 3.78 (interquartile range [IQR] 2.18-7.63), 1.87 (IQR 1.12-5.48), and 0.00 (IQR 0.00-0.08). Median time from arrival to catheterization was 41 min (IQR 23-86 min) for STEMI(+) OMI compared with 437 min (IQR 85-1590 min) for STEMI(-) OMI (p 0.001). STEMI(+) OMI was more likely than STEMI(-) OMI to undergo catheterization within 90 min (76% vs. 28%; p 0.001).STEMI(-) OMI patients had significant delays to catheterization but adverse outcomes more similar to STEMI(+) OMI than those with no occlusion. These data support the OMI/NOMI paradigm and the importance of further research into emergent reperfusion for STEMI(-) OMI.

Background This post hoc analysis compared the efficacy and safety of CLS-TA to other commonly available treatments for noninfectious uveitis (NIU). Methods Results from the PEACHTREE study were compared between subjects randomized to CLS-TA not requiring rescue therapy and those subjects randomized to control and subsequently requiring rescue therapy. Endpoints included best corrected visual acuity (BCVA), central subfield thickness (CST), treatment emergent adverse events (TEAEs), and intraocular pressure (IOP) related safety findings. Results In this analysis, there were 83 unrescued CLS-TA subjects and 46 rescued control subjects. At Week 24, 51.9% of the unrescued CLS-TA subjects gained ≥15 letters in BCVA, compared to 37.0% of the rescued control subjects (P = 0.115). Unrescued CLS-TA subjects showed a mean gain of 15.7 versus 10.9 letters in rescued control subjects (P = 0.080). A significantly greater mean reduction in CST was observed for unrescued CLS-TA subjects versus rescued control subjects (174.0 and 148.5 μm; P = 0.040). Of unrescued CLS-TA subjects, 4.9% experienced IOP elevations ≥ 30 mm Hg at any visit versus 10.9% of rescued control subjects. Further, use of IOP-lowering medications appeared lower in unrescued CLS-TA subjects versus rescued control subjects (7.2% versus 13.0%). There were no IOP-related surgical interventions in either group. Conclusion CLS-TA subjects experienced significantly greater reduction in CST and tended towards greater improvement in BCVA, compared with rescued control subjects. Suprachoroidally administered CLS-TA showed a lower incidence of IOP-related safety findings. This article is protected by copyright. All rights reserved.

Purpose: Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. Experimental Design: We profiled 93 genes in tissue from 193 patients with early breast cancer. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. Results: At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR = 0.062; 95% CI, 0.01–0.48; P = 0.0077). Of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were nonresponders (RCB II, n = 8; RCB III, n = 22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, whereas 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. Conclusions: Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III.

One of the most common fetal complications in pregnant women with cardiovascular disease is a small for gestational age (SGA) neonate, which is associated with a higher risk of perinatal morbidity/mortality and poor long-term health outcomes. The objective of this study was to identify cardiac determinants and derive a risk score for clinically relevant SGA5th percentile (SGA-5th).A prospective cohort of 1812 pregnancies in women with heart disease were studied. SGA-5th was the outcome of interest, defined as birth weight5th percentile for gestational age and sex. Multivariable logistic regression analysis was used to identify predictors for SGA-5th. Based on the regression coefficients, a weighted risk score was created.SGA-5th complicated 10% of pregnancies, 11 predictors of SGA-5th were identified, and each was assigned a weighted score: maternal cyanosis (8), Fontan palliation (7), smoking (3), moderate or severe valvular regurgitation (3), β-blocker use throughout pregnancy (4) or only in the 2nd and 3rd trimesters (2), high baseline β-blocker dose (4), body mass index18.5 kg/mThere are a number of cardiac predictors that are associated with increased risk of SGA-5th. This is a prognostically important outcome, and consideration should be given to routinely predicting and modifying the risk whenever possible.

BackgroundTrimodality therapy (TMT) with preoperative chemoradiation followed by surgical resection is used for locally-advanced non-small-cell lung cancer (LA-NSCLC). Traditionally, preoperative radiation doses ≤54Gy are used due to concerns regarding excess morbidity, but little is known about outcomes and toxicities after TMT with intensity-modulated radiotherapy (IMRT) to higher doses.MethodsA retrospective analysis of patients who received planned TMT with IMRT for LA-NSCLC at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2008 and 2017 was performed. Clinical and treatment characteristics, pathologic response, and surgical toxicity were assessed. Kaplan-Meier method and log-rank test was used for survival outcomes. Cox proportional-hazards regression was used for multivariable analysis.ResultsForty-six patients received less than definitive doses of 7days were associated with OS.ConclusionsWith IMRT, there was no increased rate of surgical complications in patients receiving higher doses of radiation. Survival outcomes or LOS did not differ based on radiation dose, but increased LOS was associated with worse OS. Larger prospective studies are needed to further examine outcomes after IMRT in patients with LA-NSCLC receiving TMT.

Background . A major, prolonged measles outbreak occurred in Israel during 2018-19, despite vaccination coverage rates of 97% and 96% for the first and second doses, respectively, of measles containing vaccine (MCV). Aim . To study the causes and patterns of the outbreak through analysis of the epidemiological data, review the control measures taken, and identify lessons learned and efforts needed to prevent recurrences. Methods . All reported cases of measles in Israel from 1 March 2018 through 30 September 2019 were analysed using the epidemiological, clinical, laboratory, and demographic data that are systematically reported to the Division of Epidemiology of the Ministry of Health. Results . A total of 4,311 measles cases were reported. 75% of case patients were children and 25% were adults. Pockets of undervaccination and delayed vaccination were identified: 72.6% of measles patients whose vaccination histories were known had not received any doses of MCV. Case importation was also a key factor, with a majority being adults coming from European countries and over half from Ukraine, a major locus of measles cases during the recent measles resurgence in Europe. Control measures were implemented at the local, district, and national levels. Conclusions . Similarities were noted between the 2018-19 outbreak and the prior one in 2007-08, principally pockets of undervaccination in the Jewish ultra-orthodox community, and case importation. Efforts to improve timeliness and coverage in pockets of undervaccination, and compliance with travel immunization guidelines, will be continued.

Introduction Thrombotic events are potentially devastating complications of coronavirus disease 2019 (COVID-19) infection. Although less common than venous thromboembolism, arterial thrombosis has been reported in COVID-19 cohorts in almost 3% of patients. We describe a patient with COVID-19 infection and concurrent cerebral and noncerebral infarction. Case report A 53-year-old man with history of COVID-19 pneumonia was admitted to a primary stroke center for speech disturbances and left hemiplegia. Urgent laboratory tests showed a great increase of inflammatory and coagulation parameters as D-dimer, ferritin, interleukin-6 and C-reactive protein. Neuroimaging found occlusion of the M1 segment of the right middle cerebral artery with early signs of ischemic stroke. He received intravenous thrombolysis and mechanical thrombectomy. Abdominal computed tomography discovered a splenic infarction with hemorrhagic transformation and bilateral renal infarction. Urgent angiography showed an associated splenic pseudoaneurysm, which was embolized without complications. He was treated with intermediate-dose anticoagulation (1 mg subcutaneous enoxaparin/kg/24 h), acetylsalicylic acid 100 mg and 5 days of intravenous corticosteroids. In the following days, inflammatory markers decreased so anticoagulant treatment was stopped and acetylsalicylic acid 300 mg was prescribed. His condition improved and he was discharged to a rehabilitation facility on hospital day 30. Conclusion In this case, a patient with multiple thrombotic events in the acute phase of COVID-19 infection, the delimitation of the inflammatory state through analytical markers as D-dimer helped to individualize the antithrombotic treatment (full anticoagulation or anticoagulation at intermediate doses plus antiplatelet treatment as used in our patient) and its duration. However, more data are needed to better understand the mechanisms and treatment of stroke in patients with COVID-19 infection.

Purpose: This study assessed the relationship of core muscle sarcopenia, myosteatosis, and L1 attenuation to the 5-factor modified frailty index (mFI-5), discharge disposition, and post-admission complications in orthopedic and general trauma patients. It was hypothesized that reduced sarcopenia, L1 attenuation, and increased myosteatosis is associated with higher mFI-5 scores (≥ 0.3), discharge into care, and increased post-admission complications.Methods: This prospective cohort study was performed at a Level 1 trauma center. Patients were surveyed and metrics of the mFI-5 were used. Frail was categorized as a mFI-5 score ≥ 0.3. Recent abdominal computed tomography (CT) scans were used to extract radiographical information of total psoas cross-sectional area, psoas myosteatosis, and L1 vertebrae attenuation.Results: There were 140 patients who consented to the study, of which 83 had available abdomen and pelvis CT scans. The mean age was 43.19 (± 17.36), and 65% were male (n = 52). When comparing the frail (16%, n = 13) and not frail (84%, n = 70) patients, there was a significant difference in mean psoas myosteatosis (p < 0.0001) and the attenuation of the L1 vertebrae (p < 0.001). On multivariate analysis when accounting for age, myosteatosis of the psoas muscles was predictive of an mFI-5 score ≥ 0.3.Conclusion: The findings suggest that myosteatosis and L1 attenuation are associated with frailty indices (mFI-5) after traumatic injury. Future studies are needed to prospectively assess the validity of both radiographical and index-based markers of frailty in predicting post-traumatic complications, mortality, and hospital utilization.

Definitions for chronic lung allograft dysfunction (CLAD) phenotypes were recently revised (2019 ISHLT consensus). Post-CLAD onset phenotype transition may occur as a result of change in obstruction, restriction, or RAS-like opacities (RLO). We aimed to assess the prevalence and prognostic implications of these transitions. This was a single-center, retrospective cohort study of bilateral lung transplants performed in 2009-2015. CLAD phenotypes were determined per ISHLT guidelines. CLAD phenotype transition was defined as a sustained change in obstruction, restriction or RLO. We specifically focused on phenotype changes based on RLO emergence. Association of RLO development with time to death or retransplant were assessed using Kaplan-Meier and Cox proportional hazards models. Among 211 patients with CLAD, 47 (22.2%) experienced a phenotype transition. Nineteen patients developed RLO. Development of RLO phenotype after CLAD onset was associated with a shorter time to death/retransplant when considering the entire CLAD patient cohort (HR = 4.00, CI 2.74-5.83, P

Background Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. Methods A prospective, double-blinded, randomized placebo-control study was conducted at a Level 1 trauma center as an FDA investigational new drug study. Enrollment criteria included patients ≥18 years admitted to the ICU with blunt chest wall trauma who could not achieve >50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to 6 intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. Results 100 patients were enrolled, 50 per cohort, with similar demographics (ISS 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and ICU lengths of stay were similar and there were no differences in post-injection pneumonia, use of epidural catheters or adverse events bet ween groups. Conclusions While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia.Clinical Trial Registration: "Intercostal Liposomal Bupivacaine for the Management of Blunt Chest Wall Trauma" NCT02749968. Level of evidence Level 2 ; Therapeutic/Care Management.

Background Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. Methods We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators’ physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. Results The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating. Conclusion The simulator physiology deviated significantly from preterm infants’ reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. Impact Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators.

OBJECTIVES Inclusion of Prolonged Grief Disorder (PGD) in the ICD-11 warrants examination of risk factors using diagnostic criteria as there is a paucity of research that has examined risk factors of PGD using the diagnostic criteria. This study examines if the identified risk factors for prolonged grief predict PGD using the diagnostic criteria across three samples. METHODS A cross-sectional survey design was used to assess risk factors and PG-13 in three distinct samples of bereaved adults. The PG-13 was either parsed dichotomously using the ICD-11 diagnostic criteria to indicate presence of PGD or summed to index general grief severity.Results: When using ICD-11 diagnostic criteria, only female gender and high levels of pre-loss contact were identified in separate samples as increasing risk of diagnosis. The most replicable results across samples were found when using the summed PG-13 symptom scores. When using the PG-13 total score, younger age and more pre-loss contact with the deceased were associated with higher symptom levels, which replicated in all three studies.Conclusions: This study provided evidence that the extant literature using summed scores to explore risk factors might not generalize to the ICD-11 diagnostic criteria.

Zusammenfassung Hintergrund und Fragestellung Die Psychotherapiestrukturreform im Jahr 2017 verfolgte u. a. das Ziel, die Wartezeiten auf Psychotherapien zu verringern. Diese Studie ging der Frage nach, ob dieses Ziel erreicht wurde. Methoden Psychotherapiepraxen aus 7 Bundesländern entnahmen ihren Akten die Daten für Erstkontakt, Erstgespräch und Behandlungsbeginn. Der Vergleich der Wartezeiten auf ein Erstgespräch und auf den Beginn der Behandlung vor vs. nach der Reform erfolgte mithilfe von Kaplan-Meier-Kurven und stratifizierten Log-Rank-Tests. Ergebnis Akten von 1548 Patienten aus 9 Praxen wurden ausgewertet. Die durchschnittliche Wartezeit auf ein Erstgespräch lag sowohl vor als auch nach der Reform bei 3 Wochen (p = 0,20). Die Zeit zwischen der Anmeldung und dem Behandlungsbeginn erhöhte sich von durchschnittlich 18 auf 20 Wochen, wobei nach der Reform v. a. die sehr kurzen Wartezeiten (p = 0,0004). Diskussion Die in den Praxen dokumentierten Daten liefern keine Anhaltspunkte dafür, dass sich die Wartezeit auf Erstgespräche bei Psychotherapeuten verkürzt hat. Das Warten auf einen Psychotherapieplatz scheint insgesamt etwas länger geworden zu sein, sodass in dieser Hinsicht keine Verbesserung der Versorgung durch die Reform festgestellt werden konnte.

Introduction:The COVID-19 pandemic starkly affected all aspects of health care, forcing many to divert resources towards emergent patient needs while decreasing emphasis on routine cancer c...

Overdiagnosis of anaphylaxis risk is an underappreciated aspect of anaphylaxis prevention. Whereas the benefits of anaphylaxis-risk prevention are well known, potential harms resulting from preemptive approaches to mitigate anaphylaxis-risk are not insignificant. Still, great progress has been made in recent years to avoid the unintended consequences of anaphylaxis-risk overdiagnosis. Reflection on recent advances in the use of diagnostic testing, as well as the application of diagnostic labels, provides an important perspective to understand how far the specialty of allergy and immunology has come in improving the lives of patients and families. Examples of recent paradigm shifts in anaphylaxis-risk management include approaches to peanut allergy prevention without screening, deferral of corticosteroids to prevent biphasic anaphylaxis reactions, reevaluation of reflex use of emergency medical services for resolved community anaphylaxis, and an approach to penicillin allergy delabeling with direct oral challenge. Routine medical practices to decrease anaphylaxis risk can have lifelong impacts for patients-beyond just preventing anaphylaxis. As our understanding of these trade-offs evolves, it becomes necessary to weigh both the benefits and the harms of past management approaches. Because medicine remains a science of uncertainty and an art of probability, a critical approach to risk mitigation remains necessary to find the often-elusive balance in anaphylaxis prevention.

BACKGROUND Donor-recipient size-matching has been repeatedly reported to improve outcomes following lung transplantation (LTx). However, there is significant variability in practice and the optimal strategy for size-matching is yet to be defined. For recipients with ILD, size-matching decisions are complicated by concerns regarding the potential impact of pre-LTx pulmonary restriction. We evaluate whether a specific donor-to-recipient size-matching strategy, based on predicted total lung capacity, benefits this patient group. METHODS This retrospective, single-centre, cohort study describes the post-LTx outcomes of adults who underwent LTx for ILD between 1983 and 2020. Only patients with restrictive physiology, based on pre-LTx pulmonary function testing were included. Post-LTx outcomes were compared based on donor-recipient predicted TLC (D-R pTLC) ratio. A D-R pTLC ratio of ≥0.8 or

In eyes with neovascular AMD, early persistent retinal dryness response to anti-VEGFs was associated with clinically relevant improvements in vision-related function and a greater visual acuity gain compared with when intraretinal fluid was present.

World COPD Day raises awareness about chronic obstructive pulmonary disease (COPD). COPD accounts for over 150,000 US deaths per year. A major challenge is that COPD receives only a fraction of the research funding provided to other major diseases. Control of COPD is dependent on developing new approaches to diagnose the disease earlier with a recognition of either pre-COPD or established COPD based on symptoms, lung structural change and/or loss of lung function that occurs before meeting long established criteria for a population-based definition of obstruction. Optimization of current therapies improves lung function, exercise capacity, quality of life, and survival. New pathways of disease progression are being identified creating new opportunities for development of therapies that could stop or cure this disease.

Since 2004, multiple blockbuster drugs have been approved for men with metastatic prostate cancer. Nevertheless, it has been reported that no improvement in survival was observed between 2004 and 2009. Herein, we have analyzed the SEER database to assess the survival outcome of metastatic prostate cancer patients since 2000. The results demonstrated that there was an improvement in both overall and prostate cancer‐specific survival for 4 months among men diagnosed with metastatic prostate cancer from 2010 to 2016 when compared to those in the pre‐2010 period. Interestingly, this survival benefit was limited to patients with bone and visceral metastasis (M1b and M1c stages). Collectively, our observation suggests that despite the new treatment agents such as second‐line antiandrogen therapies introduced in the modern era, the improvement in survival of metastatic prostate cancer patients has been surprisingly small., Since 2000–2003, there has been an improvement in both overall and cancer‐specific survival of only 4 months in men diagnosed with metastatic prostate cancer.