Acute versus non-acute targeted muscle reinnervation for pain control following major limb amputation: A comparative study.

BACKGROUND: Targeted muscle reinnervation (TMR) has been shown to reduce phantom limb pain (PLP) and residual limb pain (RLP) after major limb amputation. However, the effect of the timing of surgery on pain control and quality of life outcomes is controversial. We conducted a retrospective study to compare the outcomes of acute TMR for pain prevention with non-acute TMR for the treatment of established pain. METHODS: All patients treated with TMR in our institution between January 2018 and December 2021 were evaluated at 6, 12, 18 and 24 months post-operatively. Pain intensity and quality of life outcomes were assessed using the Brief Pain Inventory (Pain Severity and Pain Interference scales) and Pain Catastrophizing Scale. Outcomes were compared between acute and non-acute TMR using the Wilcoxon ranked-sum test or Fisher's exact test as appropriate. Multilevel mixed-effects linear regression was used to account for repeat measures and potential pain confounders. RESULTS: Thirty-two patients with 38 major limb amputations were included. Acute TMR patients reported significantly lower RLP and PLP scores, pain interference and pain catastrophisation at all time points (p < 0.05). Acute TMR was significantly associated with lower pain severity and pain interference in a linear mixed-effects model accounting for patient age, gender, amputation indication, amputation site, time post-TMR and repeated surveys (p < 0.05). There was no significant difference in the complication rate (p = 0.51). CONCLUSION: Acute TMR was associated with clinically and statistically significant pain outcomes that were better than that in non-acute TMR. This suggests that TMR should be performed with preventative intent, when possible, as part of a multidisciplinary approach to pain management, rather than deferred until the development of chronic pain.

Utility of the Endoscopic Healing Index in Identifying Active Inflammation in Patients with Crohn's Disease: Real World Data from a Tertiary Center.

BACKGROUND: The Endoscopic Healing Index (EHI) analyzes biomarkers in a patient's peripheral blood to assess mucosal healing. We aimed to characterize the effectiveness of the EHI as a predictor of disease activity in a real world clinical setting. METHODS: This retrospective study looked at patients treated and followed up at the University of Chicago Medicine IBD center who had EHI tests done as part of routine clinical care. The results of the EHI were compared with radiological imaging or endoscopy performed within 3 months of the EHI in order to determine accuracy at diagnosing active inflammation. RESULTS: Fifty-five patients with CD and with an available EHI were included in this study. Four (50%) patients with an EHI of < 20 (n = 8) had evidence of objective inflammation. A cutoff of ≤ 20 had a sensitivity of 89% and specificity of 23.5% for predicting no evidence of any objective inflammation with an AUROC of 0.69. This score had a negative predictive value (NPV) of 50% and positive predictive value (PPV) of 72.3%. A cutoff EHI of 30 tended to classify patients as either having objective evidence of inflammation or not more often than FCAL (Correctly classifying inflammation: 89% vs 64%, respectively; p = 0.32). CONCLUSION: In this real world analysis, the EHI showed poor predictive value for the absence of active inflammation as assessed by imaging or endoscopy, has limited utility in confirming deep remission and should be used with another objective modality.

Faculty and Resident Perspectives on the Implementation of Entrustable Professional Activities in General Surgery Residency.

OBJECTIVE: This study aimed to identify what best practices facilitate implementation of Entrustable Professional Activities (EPAs) into surgical training programs. DESIGN: This is a mixed methods study utilizing both survey data as well as semi-structured interviews of faculty and residents involved in the American Board of Surgery (ABS) EPA pilot study. SETTING: From 2018 to 2020, the ABS conducted a pilot that introduced five EPAs across 28 general surgery training programs. PARTICIPANTS: All faculty members and residents at the 28 pilot programs were invited to participate in the study. RESULTS: About 117 faculty members and 79 residents responded to the survey. The majority of faculty (81%) and residents (66%) felt that EPAs were useful and were a valuable addition to training. While neither group felt that EPAs were overly time consuming to complete, residents did report difficulty incorporating them into their daily workflow (44%). Semi-structured interviews found that programs that focused on faculty and resident -development and utilized frequent reminders about the importance and necessity of EPAs tended to perform better. CONCLUSIONS: EPA implementation is feasible in general surgery training programs but requires significant effort and engagement from all levels of program personnel. As EPAs are implemented by the ABS nationally a focus on resident and faculty development will be critical to success.

Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

BACKGROUND: Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS: Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS: A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS: We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

This work establishes the clinical utility of perspiration as a noninvasive, continuous marker for gut inflammation and demonstrates the ability to distinguish between active and inactive inflammatory bowel disease across perspiration, serum, and stool.

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches.

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.

Impact of medical technologies may be predicted using constructed graph bibliometrics.

Scientific research is driven by allocation of funding to different research projects based in part on the predicted scientific impact of the work. Data-driven algorithms can inform decision-making of scarce funding resources by identifying likely high-impact studies using bibliometrics. Compared to standardized citation-based metrics alone, we utilize a machine learning pipeline that analyzes high-dimensional relationships among a range of bibliometric features to improve the accuracy of predicting high-impact research. Random forest classification models were trained using 28 bibliometric features calculated from a dataset of 1,485,958 publications in medicine to retrospectively predict whether a publication would become high-impact. For each random forest model, the balanced accuracy score was above 0.95 and the area under the receiver operating characteristic curve was above 0.99. The high performance of high impact research prediction using our proposed models show that machine learning technologies are promising algorithms that can support funding decision-making for medical research.

Real World Clinical Effectiveness and Safety of Ozanimod in the Treatment of Ulcerative Colitis: 1-Year Follow-Up from a Tertiary Center.

BACKGROUND: Ozanimod is a first-in-class Sphingosine-1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. AIM: To provide 1-year follow-up results of our UC patient cohort treated with ozanimod. METHODS: This prospective, observational cohort study includes consecutive patients who initiated ozanimod at the University of Chicago IBD Center between 5/2021 and 12/2022. We collected demographic, clinical, and laboratory data. Clinical disease activity was prospectively assessed using the Simple Clinical Colitis Activity Index. RESULTS: Forty-five patients with UC initiated ozanimod therapy and were included in the effectiveness analysis. The median age was 35 years (interquartile range (IQR) 28-52), median disease duration of 6 years (IQR 3-13), 26 (58%) were male, 23 (51%) had extensive colitis, 34 (76%) had previous advanced therapy exposure. Thirty-four patients had clinically active UC at the time of ozanimod initiation; week 10 clinical response and remission rates were 58% and 53%, respectively. By week 52, the rates were 25% for both clinical response and remission. In the 12 (39%) patients with a > 75% reduction in absolute lymphocyte count, numerically greater induction clinical response and remission rates were observed (80% vs 54%, p = 0.4 and 75% vs 53%, p = 0.4, respectively). There were no episodes of symptomatic bradycardia and no other new safety signals. CONCLUSION: Ozanimod effectively induced clinical response and remission patients with largely treatment refractory UC, however, had modest long-term effectiveness. The safety profile was favorable with no new signals.

Complex decision making in an intensive care environment: Perceived practice versus observed reality.

RATIONALE: Advancing our understanding of how decisions are made in cognitively, socially and technologically complex hospital environments may reveal opportunities to improve healthcare delivery, medical education and the experience of patients, families and clinicians. AIMS AND OBJECTIVES: Explore factors impacting clinician decision making in the Boston Children's Hospital Cardiac Intensive Care Unit. METHODS: A convergent mixed methods design was used. Quantitative and qualitative data sources consisted of a faculty survey, direct observations of clinical rounds in a specific patient population identified by a clinical decision support system (CDSS) and semistructured interviews (SSIs). Deductive and inductive coding was used for qualitative data. Qualitative data were translated into images using social network analysis which illustrate the frequency and connectivity of the codes in each data set. RESULTS: A total of 25 observations of eight faculty-led interprofessional teams were performed between 12 February and 31 March 2021. Individual patient characteristics were noted by faculty in SSIs to be the most important factor in their decision making, yet ethnographic observations suggested faculty cognitive traits, team expertise and value-based decisions were more heavily weighted. The development of expertise was impacted by role modeling. Decisions were perceived to be influenced by the system and environment. CONCLUSIONS: Clinician perception of decision making was not congruent with the observed behaviours in a complicated and dynamic system. This study identifies important considerations in clinical curricula as well as the design and implementation of CDSS. Our method of using social network analysis to visualize components of decision making could be adopted to explore other complex environments.

Graft-Host Interaction and Its Effect on Wound Repair Using Mouse Models.

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-ß1 levels in days 1-21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-ß1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.

Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histologic Changes.

INTRODUCTION: Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on ozanimod is unknown. MATERIALS AND METHODS: This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who received ozanimod and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens was reviewed and multiple features were scored by experienced pathologists. RESULTS: Six (13%) ozanimod-treated patients with UC required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were examined. Histologic examination of lymph nodes showed that patients treated with ozanimod had significantly greater extent of dilated sinuses (p=0.03) and greater degrees of sinus histiocytosis (p=0.03) compared with control patients. In addition, there was a trend towards more Castleman-like angiotrophic hyperplasia, plasma cell infiltration and subcortical interfollicular expansion in ozanimod treated patients. CONCLUSION: This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. The presence of sinus histiocytosis and dilated sinuses is in keeping with the known mechanism of action of ozanimod and suggests that blocking lymphocyte egression from lymph nodes was insufficient to ameliorate disease severity in these patients. The possibility of Castleman-like features identified in several of the cases, needs to be further investigated.

Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease.

BACKGROUND: Studies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD). METHODS: A retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure. RESULTS: The discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL <10th percentile of normal. fHP and uILD patients with LTL <10th percentile experienced reduced survival when exposed to either mycophenolate or azathioprine in the discovery cohort (mortality hazard ratio (HR) 4.97, 95% CI 2.26-10.92; p<0.001) and replication cohort (mortality HR 4.90, 95% CI 1.74-13.77; p=0.003). Immunosuppressant exposure was not associated with differential survival in patients with LTL ≥10th percentile. There was a significant interaction between LTL <10th percentile and immunosuppressant exposure (discovery pinteraction=0.013; replication pinteraction=0.011). Low event rate and prevalence of LTL <10th percentile precluded subgroup analyses for CTD-ILD. CONCLUSION: Similar to IPF, fHP and uILD patients with age-adjusted LTL <10th percentile may experience reduced survival when exposed to immunosuppression.

Unusual photophysics of geranic acid deep eutectic solvents.

The photophysics of natural deep eutectic solvents (NADESs) remains unexplored. Here, we report that a class of NADESs aggregates in water, enabling through-space interaction as evidenced by an unusual emission and redshifted UV absorption band. The NADESs enhanced fluorescence excitation and emission of fluorogenic proteins for improved bioimaging.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

Patterns of Platelet Mapping Thromboelastography Abnormalities in Trauma.

OBJECTIVES: Platelet mapping thromboelastography (TEG-PM) to evaluate trauma induced coagulopathy has become more prevalent. The objective of this study was to evaluate associations between TEG-PM and outcomes in trauma patients, including patients with TBI. METHODS: A retrospective review was conducted utilizing the American College of Surgeons National Trauma Database. Chart review was conducted to obtain specific TEG-PM parameters. Patients were excluded if they were on anti-platelets, anticoagulation, or received blood products prior to arrival. TEG-PM values and their associations with outcomes were evaluated using generalized linear model and Cox cause-specific hazards model. Outcomes included in-hospital death, hospital and ICU length of stay (LOS). Relative risk (RR) and hazard ratio (HR) and their 95% confidence intervals (CIs) are provided. RESULTS: A total of 1066 patients were included, with 151 (14%) diagnosed with isolated TBI. ADP inhibition was associated with significant increase rate of hospital LOS and ICU LOS (RR per % increase = 1.002 and RR = 1.006 per % increase, respectively) while increased MA(AA) and MA(ADP) were significantly associated with decrease rate of hospital LOS and ICU LOS (RR = .993 per mm increase and RR = .989 per mm increase, respectively, and RR = .986 per mm increase and RR = .989 per mm increase). R (per minute increase) and LY30 (per % increase) were associated with increased risk of in-hospital mortality (HR = 1.567 and HR = 1.057, respectively). No TEG-PM values significantly correlated with ISS. CONCLUSION: Specific TEG-PM abnormalities are associated with worse outcomes in trauma patients, including TBI patients. These results require further investigation to understand associations between traumatic injury and coagulopathy.

Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts.

Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran-Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = -0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79-2.72; Black, HR = 2.22, 95% CI = 1.05-4.66; Hispanic, HR = 3.40, 95% CI = 1.88-6.14; and Asian, HR = 2.11, 95% CI = 0.55-8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.

Evaluation of Pulmonary Fibrosis Outcomes by Race and Ethnicity in US Adults.

Importance: Pulmonary fibrosis (PF) is characterized by progressive scarring of lung tissue and poor survival. Racial and ethnic minority populations face the greatest risk of morbidity and mortality from disparities impacting respiratory health, but the pattern of age at clinically relevant outcomes across diverse racial and ethnic populations with PF is unknown. Objective: To compare the age at PF-related outcomes and the heterogeneity in survival patterns among Hispanic, non-Hispanic Black, and non-Hispanic White participants. Design, Setting, and Participants: This cohort study included adult patients with a PF diagnosis and used data from prospective clinical registries: the Pulmonary Fibrosis Foundation Registry (PFFR) for the primary cohort and registries from 4 geographically distinct tertiary hospitals in the US for the external multicenter validation (EMV) cohort. Patients were followed between January 2003 and April 2021. Exposures: Race and ethnicity comparisons between Black, Hispanic, and White participants with PF. Main Outcomes and Measures: Age and sex distribution of participants were measured at the time of study enrollment. All-cause mortality and age at PF diagnosis, hospitalization, lung transplant, and death were assessed in participants over 14 389 person-years. Differences between racial and ethnic groups were compared using Wilcoxon rank sum tests, Bartlett 1-way analysis of variance, and χ2 tests, and crude mortality rates and rate ratios were assessed across racial and ethnic categories using Cox proportional hazards regression models. Results: In total, 4792 participants with PF were assessed (mean [SD] age, 66.1 [11.2] years; 2779 [58.0%] male; 488 [10.2%] Black, 319 [6.7%] Hispanic, and 3985 [83.2%] White); 1904 were in the PFFR and 2888 in the EMV cohort. Black patients with PF were consistently younger than White patients (mean [SD] age at baseline, 57.9 [12.0] vs 68.6 [9.6] years; P < .001). Hispanic and White patients were predominantly male (Hispanic: PFFR, 73 of 124 [58.9%] and EMV, 109 of 195 [55.9%]; and White: PFFR, 1090 of 1675 [65.1%] and EMV, 1373 of 2310 [59.4%]), while Black patients were less likely to be male (PFFR, 32 of 105 [30.5%] and EMV, 102 of 383 [26.6%]). Compared with White patients, Black patients had a lower crude mortality rate ratio (0.57 [95% CI, 0.31-0.97), but for Hispanic patients, the mortality rate ratio was similar to that of White patients (0.89; 95% CI, 0.57-1.35). Mean (SD) hospitalization events per person were highest among Black patients compared with Hispanic and White patients (Black: 3.6 [5.0]; Hispanic, 1.8 [1.4]; and White, 1.7 [1.3]; P < .001). Black patients were consistently younger than Hispanic and White patients at first hospitalization (mean [SD] age: Black, 59.4 [11.7] years; Hispanic, 67.5 [9.8] years; and White, 70.0 [9.3] years; P < .001), lung transplant (Black, 58.6 [8.6] years; Hispanic, 60.5 [6.1] years; and White, 66.9 [6.7] years; P < .001), and death (Black, 68.7 [8.4] years; Hispanic, 72.9 [7.6] years; and White, 73.5 [8.7] years; P < .001). These findings remained consistent in the replication cohort and in sensitivity analyses within prespecified deciles of age groups. Conclusions and Relevance: In this cohort study of participants with PF, racial and ethnic disparities, especially among Black patients, were found in PF-related outcomes, including earlier onset of death. Further research is essential to identify and mitigate the underlying responsible factors.

Contamination of planktonic food webs in the Mediterranean Sea: Setting the frame for the MERITE-HIPPOCAMPE oceanographic cruise (spring 2019).

This paper looks at experiential feedback and the technical and scientific challenges tied to the MERITE-HIPPOCAMPE cruise that took place in the Mediterranean Sea in spring 2019. This cruise proposes an innovative approach to investigate the accumulation and transfer of inorganic and organic contaminants within the planktonic food webs. We present detailed information on how the cruise worked, including 1) the cruise track and sampling stations, 2) the overall strategy, based mainly on the collection of plankton, suspended particles and water at the deep chlorophyll maximum, and the separation of these particles and planktonic organisms into various size fractions, as well as the collection of atmospheric deposition, 3) the operations performed and material used at each station, and 4) the sequence of operations and main parameters analysed. The paper also provides the main environmental conditions that were prevailing during the campaign. Lastly, we present the types of articles produced based on work completed by the cruise that are part of this special issue.

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience.

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).

Understanding the mechanisms of spontaneous and skin-grafted wound repair: the path to engineered skin grafts.

Spontaneous wound repair is a complex process that involves overlapping phases of inflammation, proliferation and remodelling, co-ordinated by growth factors and proteases. In extensive wounds such as burns, the repair process would not be achieved in a timely fashion unless grafted. Although spontaneous wound repair has been extensively described, the processes by which wound repair mechanisms mediate graft take are yet to be fully explored. This review describes engraftment stages and summarises current understanding of molecular mechanisms which regulate autologous skin graft healing, with the goal of directing innovation in permanent wound closure with skin substitutes. Graftability and vascularisation of various skin substitutes that are either in the market or in development phase are discussed. In doing so, we cast a spotlight on the paucity of scientific information available as to how skin grafts (both autologous and engineered) heal a wound bed. Better understanding of these processes may assist in developing novel methods of wound management and treatments.

Trajectories of nutrients concentrations and ratios in the French coastal ecosystems: 20 years of changes in relation with large-scale and local drivers.

Along with their important diversity, coastal ecosystems receive various amounts of nutrients, principally arising from the continent and from the related human activities (mainly industrial and agricultural activities). During the 20th century, nutrients loads have increased following the increase of both the global population and need of services. Alongside, climate change including temperature increase or atmospheric circulation change has occurred. These processes, Ecosystem state changes are hard to monitor and predict. To study the long-term changes of nutrients concentrations in coastal ecosystems, eleven French coastal ecosystems were studied over 20 years as they encompass large climatic and land pressures, representative of temperate ecosystems, over a rather small geographical area. Both univariate (time series decomposition) and multivariate (relationships between ecosystems and drivers) statistical analyses were used to determine ecosystem trajectories as well as typologies of ecosystem trajectories. It appeared that most of the French coastal ecosystems exhibited trajectories towards a decrease in nutrients concentrations. Differences in trajectories mainly depended on continental and human influences, as well as on climatic regimes. One single ecosystem exhibited very different trajectories, the Arcachon Bay with an increase in nutrients concentrations. Ecosystem trajectories based on ordination techniques were proven to be useful tools to monitor ecosystem changes. This study highlighted the importance of local environments and the need to couple uni- and multi-ecosystem studies. Although the studied ecosystems were influenced by both local and large-scale climate, by anthropogenic activities loads, and that their trajectories were mostly similar based on their continental influence, non-negligible variations resulted from their internal functioning.