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In recent years, steady progress has been made in synthesizing and characterizing engineered nanoparticles, resulting in several approved drugs and multiple promising candidates in clinical trials. Regulatory agencies such as the Food and Drug Administration and the European Medicines Agency released important guidance documents facilitating nanoparticle-based drug product development, particularly in the context of liposomes and lipid-based carriers. Even with the progress achieved, it is clear that many barriers must still be overcome to accelerate translation into the clinic. At the recent conference workshop "Mechanisms and Barriers in Nanomedicine" in May 2023 in Colorado, U.S.A., leading experts discussed the formulation, physiological, immunological, regulatory, clinical, and educational barriers. This position paper invites open, unrestricted, nonproprietary discussion among senior faculty, young investigators, and students to trigger ideas and concepts to move the field forward.

The COVID-19 pandemic exposed a global deficiency of systematic, data-driven guidance to identify high-risk individuals. Here, we illustrate the utility of routinely recorded medical history to predict the risk for 1883 diseases across clinical specialties and support the rapid response to emerging health threats such as COVID-19. We developed a neural network to learn from health records of 502,460 UK Biobank. Importantly, we observed discriminative improvements over basic demographic predictors for 1774 (94.3%) endpoints. After transferring the unmodified risk models to the All of US cohort, we replicated these improvements for 1347 (89.8%) of 1500 investigated endpoints, demonstrating generalizability across healthcare systems and historically underrepresented groups. Ultimately, we showed how this approach could have been used to identify individuals vulnerable to severe COVID-19. Our study demonstrates the potential of medical history to support guidance for emerging pandemics by systematically estimating risk for thousands of diseases at once at minimal cost., (© 2024. The Author(s).)

Background: Comorbidity, frailty, and decreased cognitive function lead to a higher risk of death in elderly patients (more than 65 years of age) during acute medical events. Early and accurate illness severity assessment can support appropriate decision making for clinicians caring for these patients. We aimed to develop ELDER-ICU, a machine learning model to assess the illness severity of older adults admitted to the intensive care unit (ICU) with cohort-specific calibration and evaluation for potential model bias., Methods: In this retrospective, international multicentre study, the ELDER-ICU model was developed using data from 14 US hospitals, and validated in 171 hospitals from the USA and Netherlands. Data were extracted from the Medical Information Mart for Intensive Care database, electronic ICU Collaborative Research Database, and Amsterdam University Medical Centers Database. We used six categories of data as predictors, including demographics and comorbidities, physical frailty, laboratory tests, vital signs, treatments, and urine output. Patient data from the first day of ICU stay were used to predict in-hospital mortality. We used the eXtreme Gradient Boosting algorithm (XGBoost) to develop models and the SHapley Additive exPlanations method to explain model prediction. The trained model was calibrated before internal, external, and temporal validation. The final XGBoost model was compared against three other machine learning algorithms and five clinical scores. We performed subgroup analysis based on age, sex, and race. We assessed the discrimination and calibration of models using the area under receiver operating characteristic (AUROC) and standardised mortality ratio (SMR) with 95% CIs., Findings: Using the development dataset (n=50 366) and predictive model building process, the XGBoost algorithm performed the best in all types of validations compared with other machine learning algorithms and clinical scores (internal validation with 5037 patients from 14 US hospitals, AUROC=0·866 [95% CI 0·851-0·880]; external validation in the US population with 20 541 patients from 169 hospitals, AUROC=0·838 [0·829-0·847]; external validation in European population with 2411 patients from one hospital, AUROC=0·833 [0·812-0·853]; temporal validation with 4311 patients from one hospital, AUROC=0·884 [0·869-0·897]). In the external validation set (US population), the median AUROCs of bias evaluations covering eight subgroups were above 0·81, and the overall SMR was 0·99 (0·96-1·03). The top ten risk predictors were the minimum Glasgow Coma Scale score, total urine output, average respiratory rate, mechanical ventilation use, best state of activity, Charlson Comorbidity Index score, geriatric nutritional risk index, code status, age, and maximum blood urea nitrogen. A simplified model containing only the top 20 features (ELDER-ICU-20) had similar predictive performance to the full model., Interpretation: The ELDER-ICU model reliably predicts the risk of in-hospital mortality using routinely collected clinical features. The predictions could inform clinicians about patients who are at elevated risk of deterioration. Prospective validation of this model in clinical practice and a process for continuous performance monitoring and model recalibration are needed., Funding: National Institutes of Health, National Natural Science Foundation of China, National Special Health Science Program, Health Science and Technology Plan of Zhejiang Province, Fundamental Research Funds for the Central Universities, Drug Clinical Evaluate Research of Chinese Pharmaceutical Association, and National Key R&D Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Multiple myeloma (MM), a hematologic malignancy that preferentially colonizes the bone marrow, remains incurable with a survival rate of 3 to 6 mo for those with advanced disease despite great efforts to develop effective therapies. Thus, there is an urgent clinical need for innovative and more effective MM therapeutics. Insights suggest that endothelial cells within the bone marrow microenvironment play a critical role. Specifically, cyclophilin A (CyPA), a homing factor secreted by bone marrow endothelial cells (BMECs), is critical to MM homing, progression, survival, and chemotherapeutic resistance. Thus, inhibition of CyPA provides a potential strategy to simultaneously inhibit MM progression and sensitize MM to chemotherapeutics, improving therapeutic response. However, inhibiting factors from the bone marrow endothelium remains challenging due to delivery barriers. Here, we utilize both RNA interference (RNAi) and lipid-polymer nanoparticles to engineer a potential MM therapy, which targets CyPA within blood vessels of the bone marrow. We used combinatorial chemistry and high-throughput in vivo screening methods to engineer a nanoparticle platform for small interfering RNA (siRNA) delivery to bone marrow endothelium. We demonstrate that our strategy inhibits CyPA in BMECs, preventing MM cell extravasation in vitro. Finally, we show that siRNA-based silencing of CyPA in a murine xenograft model of MM, either alone or in combination with the Food and Drug Administration (FDA)-approved MM therapeutic bortezomib, reduces tumor burden and extends survival. This nanoparticle platform may provide a broadly enabling technology to deliver nucleic acid therapeutics to other malignancies that home to bone marrow.

Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient's cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients' hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD) associated with AS. Through a combination of echocardiographic and catheterization techniques, this system is shown to recreate clinical metrics of AS with greater controllability compared with methods based on image-guided aortic root reconstruction and parameters of cardiac function that rigid systems fail to mimic physiologically. Last, we leverage this model to evaluate the hemodynamic benefit of transcatheter aortic valves in a subset of patients with diverse anatomies, etiologies, and disease states. Through the development of a high-fidelity model of AS and DD, this work demonstrates the use of soft robotics to recreate cardiovascular disease, with potential applications in device development, procedural planning, and outcome prediction in industrial and clinical settings.

Background To analyze the quantity and impact of cardiovascular research done in Africa or coauthored by researchers based in Africa, their determinants, and the patterns of research collaboration. Methods and Results We retrieved data from Web of Science and additional sources. We analyzed temporal trends from 1971 to 2021 and geographical distribution, research impact using country-level h-index, international research cooperation, and associations of research quantity and quality using linear regression. The annual volume of cardiovascular research from Africa has increased from 4 publications in 1971 to 3867 in 2020 and currently represents ~3% of the global cardiovascular research output. Authors from South Africa (28.1%) and Egypt (24.1%) accounted for more than half of all publications from African countries, and they had the highest h-index (209 and 111, respectively). Important collaborators outside Africa included the United States, United Kingdom, France, Germany, and Australia. The country's publication count was associated with larger population size ( P <0.001), whereas the country's h-index was associated with larger population size ( P =0.001) and higher human development index ( P =0.023). International collaboration was dominated by the United States, South Africa, United Kingdom, Egypt, and Canada. The level of collaboration between African countries was lower than their collaboration with non-African countries. Conclusions Cardiovascular research output from African authors remains low, despite marked progress over the past 5 decades. These findings highlight the urgent need to improve the quantity and quality of cardiovascular research in Africa through increased investments, training of human resources, improved infrastructures, and expansion of collaborative research networks, particularly within Africa.

Background: Injury patterns are well-documented for taekwondo competitions prior to the use of an electronic chest protector for scoring tabulation. To see if injury rates and types changed following this rule change that transformed the fighting style in taekwondo, we investigated injuries in collegiate taekwondo competitions in the USA., Methods: Data were collected at eight collegiate taekwondo tournaments from April 2018 to December 2019. All injured athletes seen at the first-aid station were invited to complete a survey that included injury location, type, and mechanism of injury. Injury rates were calculated per 1000 athlete-exposures (A-Es) and minute-exposures (M-Es). Risk factors were modeled using logistic regression and χ 2 analysis., Results: Out of 1096 athletes, 194 athletes reported 275 acute injuries. We found an injury risk of 17.7/100 athletes (95% CI: 15.4, 20.0) and injury rate of 68.9/1000 A-E (95% CI: 60.7, 77.0) which was comparable to previous studies. The most common injuries were contusions to the lower limbs. In contrast to prior reports, men were injured more frequently from delivering a kick and women from receiving a kick. Populations at higher risk for injury included those with low belt rank and middle weight class for women., Conclusions: It appears that the new fighting style did not affect injury rates. Injury locations and types remain similar, but the mechanisms of injury have reversed as men are more injured from attacking and women from defending. There remains a strong need for research to improve protective equipment and safety rules in taekwondo.

While serum lactate level is a predictor of poor clinical outcomes among critically ill patients with sepsis, many have normal serum lactate. A better understanding of this discordance may help differentiate sepsis phenotypes and offer clues to sepsis pathophysiology. Three intensive care unit datasets were utilized. Adult sepsis patients in the highest quartile of illness severity scores were identified. Logistic regression, random forests, and partial least square models were built for each data set. Features differentiating patients with normal/high serum lactate on day 1 were reported. To exclude that differences between the groups were due to potential confounding by pre-resuscitation hyperlactatemia, the analyses were repeated for day 2. Of 4861 patients included, 47% had normal lactate levels. Patients with normal serum lactate levels had lower 28-day mortality rates than those with high lactate levels (17% versus 40%) despite comparable physiologic phenotypes. While performance varied between datasets, logistic regression consistently performed best (area under the receiver operator curve 87-99%). The variables most strongly associated with normal serum lactate were serum bicarbonate, chloride, and pulmonary disease, while serum sodium, AST and liver disease were associated with high serum lactate. Future studies should confirm these findings and establish the underlying pathophysiological mechanisms, thus disentangling association and causation., (© 2021. The Author(s).)

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.

Background: Despite having high comorbidity rates and shortened life expectancy, patients with ESKD may harbor unrealistically optimistic expectations about their prognoses. Whether this affects resuscitation orders is unknown., Methods: To determine whether do-not-resuscitate (DNR) orders differ among patients with ESKD compared with other critically ill patients, including those with diseases of other major organs, we investigated DNR orders on admission to intensive care units (ICUs) among 106,873 patients in the United States., Results: Major organ disease uniformly associated with increased risk of hospital mortality, particularly for cirrhosis (adjusted odds ratio [aOR], 2.67; 95% confidence interval [95% CI], 2.30 to 3.08), and ESKD (aOR, 1.47; 95% CI, 1.31 to 1.65). Compared with critically ill patients without major organ disease, patients with stroke, cancer, heart failure, dementia, chronic obstructive pulmonary disease, and cirrhosis were statistically more likely to have a DNR order on ICU admission; those with ESKD were not. Findings were similar when comparing patients with a single organ disease with those without organ disease. The disconnect between prognosis and DNR use was most notable among Black patients, for whom ESKD (compared with no major organ disease) was associated with a 62% (aOR, 1.62; 95% CI, 1.27 to 2.04) higher odds of hospital mortality, but no appreciable difference in DNR utilization (aOR, 1.06; 95% CI, 0.66 to 1.62)., Conclusions: Unlike patients with diseases of other major organs, critically ill patients with ESKD were not more likely to have a DNR order than patients without ESKD. Whether this reflects a greater lack of advance care planning in the nephrology community, as well as a missed opportunity to minimize potentially needless patient suffering, requires further study., (Copyright © 2020 by the American Society of Nephrology.)

Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications., Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749., Findings: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months., Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications., Funding: Medtronic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective : To compare the characteristics, use of invasive ventilation and outcomes of patients admitted with critical asthma syndrome (CAS) to ICUs in Australia and New Zealand (ANZ), and a large cohort of ICUs in the United States (US). Methods : We examined two large databases of ICU for patients admitted with CAS in 2014 and 2015. We obtained, analyzed, and compared information on demographic and physiological characteristics, use of invasive mechanical ventilation, and clinical outcome and derived predictive models. Results : Overall, 2202 and 762 patients were admitted with a primary diagnosis of CAS in the ANZ and US databases respectively (0.73% vs. 0.46% of all ICU admissions, P  < 0.001). A similar percentage of patients received invasive mechanical ventilation in the first 24 h (24.7% vs. 24.4%, P  = 0.87) but ANZ patients had lower respiratory rates and higher PaCO 2 levels. Overall mortality was low (1.23 for ANZ and 1.71 for USA; P  = 0.36) and even among invasively ventilated patients (2.4% for ANZ vs. 1.1% for USA; P  = 0.38). However, ANZ patients also had longer length of stay in ICU (43 vs. 37 h, P  = 0.001) and hospital (105 vs. 78 h, P  = 0.003). Conclusions : Patients admitted to ANZ and USA ICU with CAS are broadly similar and have a low and similar rate of invasive ventilation and mortality. However, ANZ patients made up a greater proportion of ICU patients and had longer ICU and hospital stays. These findings provide a modern invasive ventilation and mortality rates benchmark for future studies of CAS.

Rationale: Whether critical care improvements over the last 10 years extend to all hospitals has not been described. Objectives: To examine the temporal trends of critical care outcomes in minority and non-minority-serving hospitals using an inception cohort of critically ill patients. Measurements and Main Results: Using the Philips Health Care electronic ICU Research Institute Database, we identified minority-serving hospitals as those with an African American or Hispanic ICU census more than twice its regional mean. We examined almost 1.1 million critical illness admissions among 208 ICUs from across the United States admitted between 2006 and 2016. Adjusted hospital mortality (primary) and length of hospitalization (secondary) were the main outcomes. Large pluralities of African American (25%, n  = 27,242) and Hispanic individuals (48%, n  = 26,743) were cared for in minority-serving hospitals, compared with only 5.2% ( n  = 42,941) of white individuals. Over the last 10 years, although the risk of critical illness mortality steadily decreased by 2% per year (95% confidence interval [CI], 0.97-0.98) in non-minority-serving hospitals, outcomes within minority-serving hospitals did not improve comparably. This disparity in temporal trends was particularly noticeable among African American individuals, where each additional calendar year was associated with a 3% (95% CI, 0.96-0.97) lower adjusted critical illness mortality within a non-minority-serving hospital, but no change within minority-serving hospitals (hazard ratio, 0.99; 95% CI, 0.97-1.01). Similarly, although ICU and hospital lengths of stay decreased by 0.08 (95% CI, -0.08 to -0.07) and 0.16 (95% CI, -0.16 to -0.15) days per additional calendar year, respectively, in non-minority-serving hospitals, there was little temporal change for African American individuals in minority-serving hospitals. Conclusions: Critically ill African American individuals are disproportionately cared for in minority-serving hospitals, which have shown significantly less improvement than non-minority-serving hospitals over the last 10 years.

Purpose: Mechanical power (MP) may unify variables known to be related to development of ventilator-induced lung injury. The aim of this study is to examine the association between MP and mortality in critically ill patients receiving invasive ventilation for at least 48 h., Methods: This is an analysis of data stored in the databases of the MIMIC-III and eICU. Critically ill patients receiving invasive ventilation for at least 48 h were included. The exposure of interest was MP. The primary outcome was in-hospital mortality., Results: Data from 8207 patients were analyzed. Median MP during the second 24 h was 21.4 (16.2-28.1) J/min in MIMIC-III and 16.0 (11.7-22.1) J/min in eICU. MP was independently associated with in-hospital mortality [odds ratio per 5 J/min increase (OR) 1.06 (95% confidence interval (CI) 1.01-1.11); p = 0.021 in MIMIC-III, and 1.10 (1.02-1.18); p = 0.010 in eICU]. MP was also associated with ICU mortality, 30-day mortality, and with ventilator-free days, ICU and hospital length of stay. Even at low tidal volume, high MP was associated with in-hospital mortality [OR 1.70 (1.32-2.18); p < 0.001] and other secondary outcomes. Finally, there is a consistent increase in the risk of death with MP higher than 17.0 J/min., Conclusion: High MP of ventilation is independently associated with higher in-hospital mortality and several other outcomes in ICU patients receiving invasive ventilation for at least 48 h.

Objectives: Presenting symptoms in patients with sepsis may influence rapidity of diagnosis, time-to-antibiotics, and outcome. We tested the hypothesis that vague presenting symptoms are associated with delayed antibiotics and increased mortality. We further characterized individual presenting symptoms and their association with mortality., Design: Retrospective cohort study., Setting: Emergency department of large, urban, academic U.S. hospital., Patients: All adult patients with septic shock treated in the emergency department between April 2014 and March 2016., Interventions: None., Measurements and Main Results: Of 654 septic shock cases, 245 (37%) presented with vague symptoms. Time-to-antibiotics from first hypotension or elevated lactate was significantly longer for those with vague symptoms versus those with explicit symptoms of infection (1.6 vs 0.8 hr; p < 0.01), and in-hospital mortality was also substantially higher (34% vs 16%; p < 0.01). Patients with vague symptoms were older and sicker as evidenced by triage hypotension, Sequential Organ Failure Assessment score, initial serum lactate, and need for intubation. In multivariate analysis, vague symptoms were independently associated with mortality (adjusted odds ratio, 2.12; 95% CI, 1.32-3.40; p < 0.01), whereas time-to-antibiotics was not associated with mortality (adjusted odds ratio, 1.01; 95% CI, 0.94-1.08; p = 0.78). Of individual symptoms, only the absence of fever, chills, or rigors (odds ratio, 2.70; 95% CI, 1.63-4.47; p < 0.01) and presence of shortness of breath (odds ratio, 1.97; 95% CI, 1.23-3.15; p < 0.01) were independently associated with mortality., Conclusions: More than one third of patients with septic shock presented to the emergency department with vague symptoms that were not specific to infection. These patients had delayed antibiotic administration and higher risk of mortality even after controlling for demographics, illness acuity, and time-to-antibiotics in multivariate analysis. These findings suggest that the nature of presenting symptoms is an important component of sepsis clinical phenotyping and may be an important confounder in sepsis epidemiologic studies.

Critical care patients are monitored closely through the course of their illness. As a result of this monitoring, large amounts of data are routinely collected for these patients. Philips Healthcare has developed a telehealth system, the eICU Program, which leverages these data to support management of critically ill patients. Here we describe the eICU Collaborative Research Database, a multi-center intensive care unit (ICU)database with high granularity data for over 200,000 admissions to ICUs monitored by eICU Programs across the United States. The database is deidentified, and includes vital sign measurements, care plan documentation, severity of illness measures, diagnosis information, treatment information, and more. Data are publicly available after registration, including completion of a training course in research with human subjects and signing of a data use agreement mandating responsible handling of the data and adhering to the principle of collaborative research. The freely available nature of the data will support a number of applications including the development of machine learning algorithms, decision support tools, and clinical research.

Objectives: Interhospital transfer, a common intervention, may be subject to healthcare disparities. In mechanically ventilated patients with sepsis, we hypothesize that disparities not disease related would be found between patients who were and were not transferred., Design: Retrospective cohort study., Setting: Nationwide Inpatient Sample, 2006-2012., Patients: Patients over 18 years old with a primary diagnosis of sepsis who underwent mechanical ventilation., Interventions: None., Measurements and Main Results: We obtained age, gender, length of stay, race, insurance coverage, do not resuscitate status, and Elixhauser comorbidities. The outcome used was interhospital transfer from a small- or medium-sized hospital to a larger acute care hospital. Of 55,208,382 hospitalizations, 46,406 patients met inclusion criteria. In the multivariate model, patients were less likely to be transferred if the following were present: older age (odds ratio, 0.98; 95% CI, 0.978-0.982), black race (odds ratio, 0.79; 95% CI, 0.70-0.89), Hispanic race (odds ratio, 0.79; 95% CI, 0.69-0.90), South region hospital (odds ratio, 0.79; 95% CI, 0.72-0.88), teaching hospital (odds ratio, 0.31; 95% CI, 0.28-0.33), and do not resuscitate status (odds ratio, 0.19; 95% CI, 0.15-0.25)., Conclusions: In mechanically ventilated patients with sepsis, we found significant disparities in race and geographic location not explained by medical diagnoses or illness severity.

Objectives: The outcomes of critically ill patients who undergo interhospital transfer are not well understood. Physicians assume that patients who undergo interhospital transfer will receive more advanced care that may translate into decreased morbidity or mortality relative to a similar patient who is not transferred. However, there is little empirical evidence to support this assumption. We examined country-level U.S. data from the Nationwide Readmissions Database to examine whether, in mechanically ventilated patients with sepsis, interhospital transfer is associated with a mortality benefit., Design: Retrospective data analysis using complex survey design regression methods with propensity score matching., Setting: The Nationwide Readmissions Database contains information about hospital admissions from 22 States, accounting for roughly half of U.S. hospitalizations; the database contains linkage numbers so that admissions and transfers for the same patient can be linked across 1 year of follow-up., Patients: From the 2013 Nationwide Readmission Database Sample, 14,325,172 hospital admissions were analyzed. There were 61,493 patients with sepsis and on mechanical ventilation. Of these, 1,630 patients (2.7%) were transferred during their hospitalization. A propensity-matched cohort of 1,630 patients who did not undergo interhospital transfer was identified., Interventions: None., Measurements and Main Results: The exposure of interest was interhospital transfer to an acute care facility. The primary outcome was hospital mortality; the secondary outcome was hospital length of stay. The propensity score included age, gender, insurance coverage, do not resuscitate status, use of renal replacement therapy, presence of shock, and Elixhauser comorbidities index. After propensity matching, interhospital transfer was not associated with a difference in in-hospital mortality (12.3% interhospital transfer vs 12.7% non-interhospital transfer; p = 0.74). However, interhospital transfer was associated with a longer total hospital length of stay (12.8 d interquartile range, 7.7-21.6 for interhospital transfer vs 9.1 d interquartile range, 5.1-17.0 for non-interhospital transfer; p < 0.01)., Conclusions: Patients with sepsis requiring mechanical ventilation who underwent interhospital transfer did not have improved outcomes compared with a cohort with matched characteristics who were not transferred. The study raises questions about the risk-benefit profile of interhospital transfer as an intervention.

Beginning with the 18th-century physician-scientist William Heberden, the elder, Science Translational Medicine introduces a new article series about historical figures whose transformational contributions to science, medicine, and society remain relevant today., (Copyright © 2015, American Association for the Advancement of Science.)