Observational Cohort Of Patients Research Articles

SPONGE-assisted versus Trendelenburg position surgery in laparoscopic sigmoid and rectal cancer surgery (SPONGE trial): randomized clinical trial.

In minimally invasive surgery of the sigmoid colon and rectum a retractor sponge has been introduced as an alternative to the Trendelenburg position. This randomized clinical trial (RCT) compared postoperative duration of hospital stay and perioperative outcomes in patients with sigmoid or rectal cancer undergoing sponge-assisted versus Trendelenburg position surgery. The SPONGE trial is a single-centre RCT nested within the Dutch nationwide prospective observational cohort of patients with colorectal cancer, and follows the Trials within Cohorts (TwiCs) design. Patients with sigmoid or rectal cancer undergoing elective laparoscopic or robotic surgery were randomized to either sponge-assisted or Trendelenburg surgery on a 1:1 basis using block randomization. Duration of postoperative hospital stay was the primary outcome and was compared using the Mann-Whitney U test. Secondary endpoints included the proportion of complications, readmissions, or mortality versus the χ2 test in intention-to-treat and per-protocol analyses. This trial was not blinded for patients in the intervention arm or physicians. Between November 2015 and June 2021, 82 patients were randomized to sponge-assisted surgery and 81 to Trendelenburg surgery. After post-randomization exclusion, 150 patients remained for analyses (75 patients per arm). There was no statistically significant difference in median duration of hospital stay (5 days versus 4 days, respectively; P = 0.06), 30-day postoperative complications (30 per cent versus 31 per cent; P = 1.00), readmission rate (8 per cent versus 15 per cent; P = 0.30), or mortality (0 per cent versus 1 per cent, P = 1.00). The per-protocol analysis showed similar results. No adverse device events were seen. Sponge-assisted laparoscopic/robotic surgery does not reduce the duration of hospital stay, or perioperative morbidity or mortality. NCT02574013 (http://www.clinicaltrials.gov).

P-614 Predicting if or when ovarian activation occurs after Drug-Free in vitro Activation (IVA) in primary ovarian insufficiency (POI) patients

Abstract Study question Can we predict if or when ovarian activation resumption occurs after Drug-Free in vitro Activation (IVA) in primary ovarian insufficiency (POI) patients? Summary answer Duration of amenorrhea alone could predict if ovarian activity resumption occurs. Regarding to when: as early as 21 days until 330 days after surgery. What is known already Primary ovarian insufficiency occurs before age 40, leading patients to infertility. Although there are a few remaining follicles, their only chance to achieve pregnancy is through egg donation. Recently, studies have been focusing on the determinants and intracellular signaling pathways involved in the activation of primordial follicles, as the maintenance of a correct ovarian reserve. A new surgical technique known as Drug-Free IVA would activate ovarian function by mechanical fragmentation. For selected patients whose ovaries still contain residual secondary follicles, the fragmentation step alone, which implies a Hippo signaling pathway disruption, would be sufficient to promote follicle growth. Study design, size, duration Our study is a prospective observational cohort of patients recruited in a tertiary-care university hospital approved by the Ethics Research Committee from Hospital Clinic of Barcelona (HCB/2017/0856). The diagnostic criteria of POI followed the European Society of Human Reproduction and Embryology (ESHRE) Guideline from 2016. All patients provided written informed consent.Thirty-two women included in our study underwent Drug-Free IVA by laparoscopy between January 2018 and December 2019. After surgery, a year-long follow-up was carried out. Participants/materials, setting, methods All patients were younger than 40 years of age; presented oligomenorrhoea or amenorrhea for at least 4 months; and FSH level greater than 25 IU/mL . We also restrict inclusion criteria to low estradiol serum levels (<20 pg/ml) absence of antral follicles in transvaginal ultrasound; and anti-Müllerian hormone (AMH) levels less than 0.10 ng/mL. Regardless of the time from POI diagnosis, all patients had duration of amenorrhea greater than 1 year. Main results and the role of chance As for prediction of ovarian activation, duration of amenorrhea was the only factor that could significantly differentiate patients' response to Drug-Free IVA. Since a shorter time of amenorrhea (less than 2 years) was related with ovarian activation during a year follow-up. No differences were found in age at Drug-free IVA, age of menarche, baseline FSH or AMH levels; nor presence of follicles in ovarian tissue biopsy. Regarding to time to response, in 12 patients ovarian activation occurred in the first 6 months after surgery with a total of 5 pregnancies achieved (22.7%)- resulting in 4 heathy live births and, unfortunately, one miscarriage. The other 10 patients showed ovarian activation resumption once the 180 days passed, resulting in 3 pregnancies (pregnancy rate of 30%): 2 healthy live births and one neonatal death due to extreme prematurity. An important concept here is that activation before 6 months after surgery could mean an effect on primary and/or secondary follicles, while beyond 6 months the effect might occurred on primordial follicles. Sugesting that maybe the disruption of the Hippo pathway would not only be able to act in the activation of the secondary follicles but also act in the earlier phases of the folliculogenesis. Limitations, reasons for caution The lack of a control group is the main limitation of our study because it would be interesting to seek for the placebo effect or intensive medical attention/care consequences in those patients, whose reported pregnancy rate is as low as 4% in observational studies. Wider implications of the findings Our findings define the clinical profile of patients with POI in which Drug-Free IVA would be more effective and report late ovarian follicular resumption. Meaning that disruption of the Hippo signaling pathway by ovarian fragmentation could be capable of acting in the initial phases of folliculogenesis prior to secondary follicles. Trial registration number not applicable

Diffuse Myocardial Fibrosis and Cardiomyocyte Diameter Are Associated With Heart Failure Symptoms in Chagas Cardiomyopathy.

BackgroundChronic Chagas cardiomyopathy (CCC) constitutes the most life-threatening consequence of the Trypanosoma cruzi infection. Our goal was to test in CCC the associations of the myocardial tissue phenotype with cardiac dysfunction, and heart failure (HF) severity, using cardiac magnetic resonance (CMR).MethodsWe performed a prospective observational cohort of patients with consecutive CCC with a CMR protocol, including ventricular function, myocardial T1, and late gadolinium enhancement (LGE). Extracellular volume (ECV), and intracellular water lifetime, τic, a measure of cardiomyocyte diameter, were compared to CCC disease progression, including Rassi score and New York Heart Association (NYHA) class. An exploratory prognostic analysis was performed to investigate the association of both ECV and τic with CV death.ResultsA total of 37 patients with intermediate-to-high-risk CCC were enrolled (Chagas Rassi score ≥7, mean left ventricle (LV) ejection fraction (EF) 32 ± 16%). Myocardial ECV (0.40 ± 0.07) was correlated with Rassi score (r = 0.43; P = 0.009), higher NYHA class, and LV EF (r = −0.51; P = 0.0015). τic decreased linearly with NYHA class (P = 0.007 for non-parametric test of linear trend) and showed a positive association with LV EF (r = 0.47; P = 0.004). Over a median follow-up of 734 days (range: 6–2,943 days), CV death or cardiac transplantation occurred in 10 patients. The Rassi score (heart rate [HR] = 1.3; 95% CI = [1.0, 1.8]; P = 0.028) and ECV (HR = 3.4 for 0.1 change, 95% CI = [1.1, 11.0], P = 0.039) were simultaneously associated with CV death.ConclusionIn patients with intermediate-to-high-risk CCC, an expanded ECV and regression of cardiomyocyte diameter were associated with worsening systolic function and HF severity, respectively. The exploratory analysis indicates that ECV may have a prognostic value to identify patients with CCC at a higher risk for cardiovascular events.

Impact of Pruritus on Quality of Life and Current Treatment Patterns in Patients with Primary Biliary Cholangitis

Background and AimsPatients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort.MethodsTARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal–Wallis tests were used to compare differences in symptoms between groups.ResultsA total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%).ConclusionsThe prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus.

Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction.

BackgroundHydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment.Methods and ResultsA total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2‐year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all‐cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity‐score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all‐cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity‐score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55–0.90]), all‐cause mortality (HR, 0.67 [95% CI, 0.49–0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21–0.73]), but not for revascularization and ischemic stroke.ConclusionsHydrophilic statin treatment was associated with lower risk of MACEs and all‐cause mortality than lipophilic statin in a propensity‐score matched observational cohort of patients with renal impairment following acute myocardial infarction.

MALIGNANT HYPERTENSION HAMA COHORT: WHERE DO WE STAND IN 2021?

Objective: Malignant hypertension still exists. It is the deadliest form of hypertension, and has been forgotten. Guidelines are mainly based on consensus, without strong evidence supporting it. French cohort HAMA is the first multicentric nationwide Describe the characteristics of the 300 first patients included in the HAMA cohort, the substudies started and in preparation and the perspectives. Design and method: We set up a prospective, multicentre, observational cohort of patients with malignant hypertension. We collected at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension crisis in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients. Results: We included 245 patients between September of 2019 and November of 2021, mainly men (66%), mean age 51,4 +/- 13,3 years, BMI 28 +/- 5,7, systolic and diastolic blood pressure at admission 228 +/- 23 and 124 +/- 25. Target organs damage included severe hypetensive retinopathy (87%), cardiac damage (52%), acute kidney injury (62%), cerebral damage (34%), thrombotic microangiopathy (15%). Conclusions: The findings of this cohort should help increasing the medical community awareness and disease screening. It should provide an up-to-date picture of the epidemiology of the disease, and help physician building guidelines based on high quality evidence, to improve the management of patients with malignant hypertension crisis. Subsequently, the knowledge gained from the HAMA cohort may be used to design controlled intervention and pathophysiological studies through biobank implementation. Next big step ahead is the inclusion of european centers.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS. Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort. We tested the contribution of respiratory variables (oxygenation index, ventilatory ratio [VR], and the radiographic assessment of lung edema score) to logistic regression models of 28-d mortality adjusted for indicators of systemic illness severity (the Acute Physiology and Chronic Health Evaluation [APACHE] III score or severity of shock as measured by the number of vasopressors required at baseline) using likelihood ratio testing. We also compared a model utilizing APACHE III with one including baseline number of vasopressors by comparing the area under the receiver operating curve (AUROC). VR significantly improved model performance by likelihood ratio testing when added to APACHE III (P = .036) or the number of vasopressors at baseline (P = .01). Number of vasopressors required at baseline had similar prognostic discrimination to the APACHE III. A model including the number of vasopressors and VR (AUROC 0.77 [95% CI 0.64-0.90]) was comparable to a model including APACHE III and VR (AUROC 0.81 [95% CI 0.68-0.93]; P for comparison = .58.). In this observational cohort of subjects with ARDS, the VR significantly improved discrimination for mortality when combined with indicators of severe systemic illness. The number of vasopressors required at baseline and APACHE III had similar discrimination for mortality when combined with VR. VR is easily obtained at the bedside and offers promise for clinical prognostication.

Similar response to biologic therapy across racial and ethnic groups among patients with psoriasis enrolled in the CorEvitas Psoriasis Registry

To the Editor: Psoriasis impacts 7 million Americans of all ethnoracial backgrounds. Racial/ethnic differences in response to biologic therapy for psoriasis have been described in clinical trials1; yet, these findings do not reflect real-world outcomes.2 Data from clinical practice are needed to further our understanding of potential variability in the effectiveness of biologics. We used data from the CorEvitas Psoriasis Registry,3 an observational cohort of patients evaluated in dermatology clinics, to better understand the response to biologics across racial/ethnic groups.

Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome

BackgroundA higher-than-usual resistance to standard sedation regimens in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) has led to the frequent use of the second-line anaesthetic agent ketamine. Simultaneously, an increased incidence of cholangiopathies in mechanically ventilated patients receiving prolonged infusion of high-dose ketamine has been noted. Therefore, the objective of this study was to investigate a potential dose–response relationship between ketamine and bilirubin levels.MethodsPost hoc analysis of a prospective observational cohort of patients suffering from COVID-19-associated ARDS between March 2020 and August 2021. A time-varying, multivariable adjusted, cumulative weighted exposure mixed-effects model was employed to analyse the exposure–effect relationship between ketamine infusion and total bilirubin levels.ResultsTwo-hundred forty-three critically ill patients were included into the analysis. Ketamine was infused to 170 (70%) patients at a rate of 1.4 [0.9–2.0] mg/kg/h for 9 [4–18] days. The mixed-effects model revealed a positively correlated infusion duration–effect as well as dose–effect relationship between ketamine infusion and rising bilirubin levels (p < 0.0001). In comparison, long-term infusion of propofol and sufentanil, even at high doses, was not associated with increasing bilirubin levels (p = 0.421, p = 0.258). Patients having received ketamine infusion had a multivariable adjusted competing risk hazard of developing a cholestatic liver injury during their ICU stay of 3.2 [95% confidence interval, 1.3–7.8] (p = 0.01).ConclusionsA causally plausible, dose–effect relationship between long-term infusion of ketamine and rising total bilirubin levels, as well as an augmented, ketamine-associated, hazard of cholestatic liver injury in critically ill COVID-19 patients could be shown. High-dose ketamine should be refrained from whenever possible for the long-term analgosedation of mechanically ventilated COVID-19 patients.

Variation in Alanine Aminotransferase in Children with Non-Alcoholic Fatty Liver Disease.

Background: Pediatric non-alcoholic fatty liver disease (NAFLD) is a major public health concern. Aminotransferase (ALT) is frequently used for screening and monitoring, but few studies have reported typical patterns of ALT elevation in children. Methods: TARGET-NASH is a real-world longitudinal observational cohort of patients with NAFLD receiving care across the United States. Analyses included children enrolled between 1 August 2016, and 12 October 2020, with at least one ALT measurement after enrollment. Peak ALT was based on the first and last available record and categorized into clinical cut points: <70 IU/L, >70–<250 IU/L, and >250 IU/L. A chi-squared test was used to compare differences in proportions, and a Kruskal–Wallis test was used to compare the medians and distributions of continuous responses. Results: Analyses included 660 children with a median age of 13 years. Of the 660, a total of 187 had undergone a biopsy and were more likely to be Hispanic or Latino (67% vs. 57%, p = 0.02) and to have cirrhosis (10% vs. 1%, p < 0.001). The highest ALT scores ranged from 28 U/L to 929 U/L; however, these scores varied across time. The prevalence of cirrhosis or any liver fibrosis stage was most common among children with a peak ALT > 70 U/L. Conclusions: Large variability was seen in ALT among children, including many values > 250 U/L. Higher levels of ALT were associated with increased prevalence of comorbidities and more advanced stages of NAFLD. These findings support an increased need for therapeutics and disease severity assessment in children with peak ALT > 70 U/L.

Individualized Provider Feedback Increased HIV and HCV Screening and Identification in a New York City Emergency Department.

Efforts to end the HIV and hepatitis C virus (HCV) epidemics begin with ascertainment of a person's infection status through screening. Despite its importance as a site of testing, missed opportunities for screening in the Emergency Department (ED) are common. We describe the impact of implementing an individualized provider feedback intervention on HIV and HCV testing in a quaternary ED. We conducted an interrupted time series analysis to evaluate the impact of the intervention on weekly HIV and HCV screening in an observational cohort of patients seeking care in the ED. The intervention included a physician champion individualized feedback with peer comparisons to all providers in the ED and an existing HIV/HCV testing and response team. Data were abstracted from the electronic medical record (EMR) for 30 weeks before, during, and after implementing the intervention. We used Poisson regression analysis to estimate changes in the weekly counts and rates of HIV and HCV testing. The incidence rate ratios (IRRs) of HIV testing were 1.94 [95% confidence interval (CI) 1.85-2.04] and 1.38 (95% CI 1.31-1.45) times higher for the intervention and post-intervention period compared with the pre-intervention period. The IRRs of HCV testing was 6.96 (95% CI 6.40-7.58) and 4.70 (95% CI 4.31-5.13) for the intervention and post-intervention periods. There were no meaningful differences in demographic characteristics during the observation period. The intervention meaningfully increased HIV and HCV testing volume and positive case detection, including testing in high-risk groups like young adults and individuals without prior testing. Although diminished, the intervention effect sustained in the 30-week period following implementation.

A Scalable Quality Assurance Process for Curating Oncology Electronic Health Records: The Project GENIE Biopharma Collaborative Approach.

PURPOSEThe American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative is a multi-institution effort to build a pan-cancer repository of genomic and clinical data curated from the electronic health record. For the research community to be confident that data extracted from electronic health record text are reliable, transparency of the approach used to ensure data quality is essential.MATERIALS AND METHODSFour institutions participating in AACR's Project GENIE created an observational cohort of patients with cancer for whom tumor molecular profiling data, therapeutic exposures, and treatment outcomes are available and will be shared publicly with the research community. A comprehensive approach to quality assurance included assessments of (1) feasibility of the curation model through pressure test cases; (2) accuracy through programmatic queries and comparison with source data; and (3) reproducibility via double curation and code review.RESULTSAssessments of feasibility resulted in critical modifications to the curation directives. Queries and comparison with source data identified errors that were rectified via data correction and curator retraining. Assessment of intercurator reliability indicated a reliable curation model.CONCLUSIONThe transparent quality assurance processes for the GENIE BPC data ensure that the data can be used for analyses that support clinical decision making and advances in precision oncology.

SASC: A simple approach to synthetic cohorts for generating longitudinal observational patient cohorts from COVID-19 clinical data

SummaryOne of the impacts of the coronavirus disease 2019 (COVID-19) pandemic has been a push for researchers to better exploit synthetic data and accelerate the design, analysis, and modeling of clinical trials. The unprecedented clinical efforts caused by COVID-19’s emergence will certainly boost future robust and innovative approaches of statistical sciences applied to clinical fields. Here, we report the development of SASC, a simple but efficient approach to generate COVID-19-related synthetic clinical data through a web application. SASC takes basic summary statistics for each group of patients and attempts to generate single variables according to internal correlations. To assess the “reliability” of the results, statistical comparisons with Synthea, a known synthetic patient generator tool, and, more importantly, with clinical data of real COVID-19 patients are provided. The source code and web application are available on GitHub, Zenodo, and Mendeley Data.

Ruxolitinib as a treatment strategy for SARS-CoV-2 pneumonia: clinical experience in a real-world setting.

Severe acute respiratory syndrome-related coronavirus (SARS-CoV-2) infection is characterised by a viral phase and a severe pro-inflammatory phase. The inhibition of the JAK/STAT pathway limits the pro-inflammatory state in moderate to severe COVID-19. We analysed the data obtained by an observational cohort of patients with SARS-CoV-2 pneumonia treated with ruxolitinib in 22 hospitals of Mexico. The applied dose was determined based on physician's criteria. The benefit of ruxolitinib was evaluated using the 8-points ordinal scale developed by the NIH in the ACTT1 trial. Duration of hospital stay, changes in pro-inflammatory laboratory values, mortality, and toxicity were also measured. A total of 287 patients were reported at 22 sites in Mexico from March to June 2020; 80.8% received ruxolitinib 5 mg BID and 19.16% received ruxolitinib 10 mg BID plus standard of care. At beginning of treatment, 223 patients were on oxygen support and 59 on invasive ventilation. The percentage of patients on invasive ventilation was 53% in the 10 mg and 13% in the 5 mg cohort. A statistically significant improvement measured as a reduction by 2 points on the 8-point ordinal scale was described (baseline 5.39 ± 0.93, final 3.67± 2.98, p = 0.0001). There were 74 deaths. Serious adverse events were presented in 6.9% of the patients. Ruxolitinib appears to be safe in COVID-19 patients, with clinical benefits observed in terms of decrease in the 8-point ordinal scale and pro-inflammatory state. Further studies must be done to ensure efficacy against mortality.

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90-0·95) in EARLI and 0·88 (0·84-0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81-0·94] vs 0·92 [0·88-0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. US National Institutes of Health and European Society of Intensive Care Medicine.

Impact of Natural Killer (NK) Cells on Immune Reconstitution, and Their Potential as a Biomarker of Disease Activity, in Alemtuzumab-Treated Patients with Relapsing Remitting Multiple Sclerosis: An Observational Study.

Defining immune mechanisms leading to multiple sclerosis (MS) is difficult, due to the great inter-individual difference in immune system responses. The anti-CD52 antibody alemtuzumab transiently abolishes differences in immune parameters among individuals, allowing analysis of subsequent immune cell repopulation patterns, and their possible role in MS. To evaluate the correlation between innate and adaptive immune cell subsets and disease activity in MS in the context of treatment with alemtuzumab. A two-center observational cohort of patients treated with alemtuzumab underwent immune profiling of T, B, and natural killer (NK) cells, biomarker, clinical and radiological follow-up. After treatment, the percentage of NK and B cells increased; NK, T- and B-cell populations underwent a profound rearrangement. Within the effector T-cell compartment, treatment led to a transient decrease, followed by an increase, of T-helper 1 cells, and to a transient decrease of T-helper 17 cells. Within the T-regulatory compartment, naïve T-regulatory cells increased. Within the B-cell compartment, memory B cells and mature B cells decreased, whereas transitional B cells increased. Within the NK cell compartment, CD56bright NK cells increased. Subjects without disease activity had a greater decrease in serum NfL and greater NK cell/CD3+ T cell ratio. NK cell numbers at baseline and after treatment influenced reconstitution of T and B cells, being inversely correlated with the reconstitution of proinflammatory CD3+ T cells and mature B cells, and directly correlated to the increase in transitional B cells. The results of this study provide novel evidence that NK cells influence reconstitution of adaptive immune cells upon alemtuzumab and that patients with a successful response to alemtuzumab have an early immune reconstitution dominated by NK cells.

Real-world corticosteroid use in severe pneumonia: a propensity-score-matched study

BackgroundCommunity-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses.Study design and methodsWe analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone.ResultsOf the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29–0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32–2.36).ConclusionsCorticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.

Disease Control After Hypofractionation Versus Conventional Fractionation for Triple Negative Breast Cancer: Comparative Effectiveness in a Large Observational Cohort

Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer. Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups. The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P=.89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P=.95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P=.28). Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease.

Impact of Facility Treatment Volume on Stereotactic Ablative Radiotherapy (SABR) Outcomes in Early-Stage Non-Small Cell Lung Cancer (NSCLC)

Prior research suggests that radiation oncologist provider experience may influence outcomes for radiation treatment modalities requiring greater technical expertise for given disease sites. We investigated whether institution treatment volume (TV) for SABR technique impacted survival outcomes for patients with NSCLC.We conducted a retrospective cohort study using the Veteran's Affairs Informatics and Computing Infrastructure (VINCI) database to identify patients who underwent treatment for NSCLC between 2012 and 2017 at Veteran's Health Administration Medical Centers (VHAMCs). Patients were included in the cohort if they had tumor (T) stage 1 or 2 disease, node negative (N0) disease, and underwent SABR radiation treatment based on associated Current Procedural Terminology codes. We conducted univariate and multivariate analyses for overall survival (OS) and cause-specific survival (CSS) using Cox regression models accounting for age, sex, race, histology, T stage, tobacco history, ECOG status, and VHAMC facility TV. TV was calculated as the total number of SABR treatments performed per facility over the study period and was categorized into high and low volume groups based on a median TV cutoff.The observational cohort included N = 433 patients with early-stage NSCLC who underwent treatment with SABR across 25 VHAMC facilities. Most patients (83.1%) had T stage 1 disease, and nearly equal proportions had SCC (31.2%) and adenocarcinoma (32.5%) histologies, with the remaining having clinical diagnoses of NSCLC. Median facility TV was 29 SABR treatments (interquartile range 19-33). Median follow up was 657 days. Estimated 2-year overall and cause-specific survival rates were 78.4% (95% CI: 73.9% - 82.1%) and 87.0% (95% CI: 83.2% - 90.0%), respectively. On univariate analysis, high versus low facility TV was not significantly associated with OS (hazard ratio (HR) 1.08, 95% CI: 0.74-1.58) or CSS (HR 1.06, 95% CI: 0.65 - 1.73). Similarly, facility volume was not associated with OS or CSS on multivariate analysis. In a sensitivity analysis, facility volume was not associated with survival outcomes when treated as a continuous variable. Covariates associated with decreased OS included male sex (HR 4.5, P < 0.05), age over 65 (HR 1.77, P < 0.05), ECOG status 2 or greater (HR 1.94, P < 0.05), SCC histology (HR 1.66, P < 0.05), and T stage 2 disease (HR 1.68, P < 0.05).In this observational cohort of patients treated at VHAMCs, facility TV was not associated with survival outcomes for early-stage NSCLC radiation treatment using SABR technique. Research is ongoing to account for factors including baseline pulmonary function, comorbidities, and variations in institutional treatment patterns such as propensity for treatment with surgery versus radiation.

Clinical outcomes in revision lumbar spine fusions: an observational cohort study.

The authors compared primary lumbar spine fusions with revision fusions by using patient Oswestry Disability Index (ODI) scores to evaluate the impact of the North American Spine Society (NASS) evidence-based medicine (EBM) lumbar fusion indications on patient-reported outcome measures of revision surgeries. This study was a retrospective analysis of a prospective observational cohort of patients who underwent elective lumbar fusion between January 2018 and December 2019 at a single quaternary spine surgery service and had a minimum of 6 months of follow-up. A prospective quality improvement database was constructed that included the data from all elective lumbar spine surgeries, which were categorized prospectively as primary or revision surgeries and EBM-concordant or EBM-discordant revision surgeries based on the NASS coverage EBM policy. In total, 309 patients who met the inclusion criteria were included in the study. The ODIs of all groups (primary, revision, revision EBM concordant, and revision EBM discordant) were statistically compared. Differences in frequencies between cohorts were evaluated using chi-square and Fisher's exact tests. The unpaired 2-tailed Student t-test and the Mann-Whitney U-test for nonparametric data were used to compare continuous variables. Logistic regression was performed to determine the associations between independent variables (surgery status and NASS criteria indications) and functional outcomes. Primary lumbar fusions were significantly associated with improved functional outcomes compared with revisions, as evidenced by ODI scores (OR 1.85, 95% CI 1.16-2.95 to achieve a minimal clinically important difference, p = 0.01). The percentage of patients whose functional status had declined at the 6-month postoperative evaluation was significantly higher in patients who had undergone a revision surgery than in those who underwent a primary surgery (23% vs 12.3%, respectively). An increase in ODI score, indicating worse clinical outcome after surgery, was greater in patients who underwent revision procedures (OR 2.14, 95% CI 1.17-3.91, p = 0.0014). Patients who underwent EBM-concordant revision surgery had significantly improved mean ODI scores compared with those who underwent EBM-discordant revision surgery (7.02 ± 5.57 vs -4.6 ± 6.54, p < 0.01). The results of this prospective quality improvement program investigation illustrate that outcomes of primary lumbar fusions were superior to outcomes of revisions. However, revision procedures that met EBM guidelines were associated with greater improvements in ODI scores, which indicates that the use of defined EBM guideline criteria for reoperation can improve clinical outcomes of revision lumbar fusions.