bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of Procalcitonin Value on Hospital Admission and Its Subsequent Change in Value Is Associated With the Prognosis of Sepsis
Authors: Muratsu Arisa , Muroya Takashi , Katayama Yusuke , Shimizu Kentaro , Ogura Hiroshi , Kuwagata Yasuyuki , Shimazu Takeshi 
Published: February 2021

Objectives:
To evaluate the relationship between the procalcitonin value in blood on hospital admission and its subsequent change and prognosis among sepsis patients.

Design:
A single-center, retrospective, observational study.

Setting:
Critical care center in Japan.

Patients:
Sepsis patients 18 years old or older admitted from January 1, 2015, to March 31, 2018.

Interventions:
None.

Measurement and Main Results:
Among 173 sepsis patients enrolled, the median age was 74 years old (interquartile range, 64–79 yr old), and there were 102 men. The median value of procalcitonin in blood on hospital admission was 14.8 ng/mL (interquartile range, 3.5–78.4 ng/mL), and the median change in serum procalcitonin value between hospital admission and the next day was 0 ng/mL (interquartile range, –4.5 to 5.2 ng/mL). Mortality at 28 days after hospital admission was 5.8% (10/173). In univariate logistic regression analysis, elderly (crude odds ratio, 5.314; 95% CI, 1.094–25.806; p = 0.044), procalcitonin value of less than 33.2 ng/mL on hospital admission (p = 0.007), and change in serum procalcitonin of less than 0.0 ng/mL (crude odds ratio, 5.056; 95% CI, 1.041–24.545; p = 0.046) were associated with mortality at 28 days after hospital admission. The mortality of patients with a procalcitonin value of less than 33.2 ng/mL on hospital admission and change in serum procalcitonin of less than 0.0 ng/mL was 18.6% (8/43) and was significantly higher than that of other patients (p < 0.001).

Conclusions:
Our study showed the sepsis patients with a procalcitonin value in blood of less than 33.2 ng/mL on hospital admission and change in serum procalcitonin of less than 0.0 ng/mL had high mortality at 28 days after hospital admission.
SURvival PRediction In SEverely Ill Patients Study—The Prediction of Survival in Critically Ill Patients by ICU Physicians
Authors: Ros Marijke M. , van der Zaag-Loonen Hester J. , Hofhuis José G.M. , Spronk Peter E. 
Published: February 2021

Objectives:
The surprise question, “Would I be surprised if this patient died in the next 12 months?” is a tool to identify patients at high risk of death in the next year. Especially in the situation of an ICU admission, it is important to recognize patients who could and could not have the benefits of an intensive treatment in the ICU department.

Design and Setting:
A single-center, prospective, observational cohort study was conducted between April 2013 and April 2018, in ICU Gelre hospitals, location Apeldoorn.

Patients:
A total of 3,140 patients were included (57% male) with a mean age of 63.5 years. Seven-hundred thirteen patients (23%) died within 1 year.

Interventions:
The physician answered three different surprise question’s with either “yes” or “no”: “I expect that the patient is going to survive the ICU admission” (surprise question 1), “I expect that the patient is going to survive the hospital stay” (surprise question 2), and “I expect that the patient is going to survive one year after ICU admission” (surprise question 3). We tested positive and negative predicted values of the surprise questions, the mean accuracy of the surprise questions, and kappa statistics.

Measurements and Main Results:
The positive and negative predictive values of the surprise questions for ICU admission, hospital admission, and 1-year survival were, respectively, 64%/94%, 59%/92%, and 60%/86%. Accordingly, the mean accuracy and kappa statistics were 93% (95% CI, 92–94%), κ equals to 0.43, 89% (95% CI, 88–90%), κ equals to 0.40, and 81% (95% CI, 80–82%), κ equals to 0.43.

Conclusions:
The frequently overlooked simple and cheap surprise question is probably an useful tool to evaluate the prognosis of acutely admitted critically ill patients.
Presence of Spontaneous Echo Contrast on Point-of-Care Vascular Ultrasound and the Development of Major Clotting Events in Coronavirus Disease 2019 Patients
Authors: Connor-Schuler Randi , Daniels Lisa , Coleman Caroline , Harris Danny , Herbst Nicole , Fiza Babar 
Published: February 2021

Objectives:
The presence of spontaneous echo contrast on ultrasonography is a predisposition to increased thromboembolic risk. The purpose of this study was to assess for the prevalence and consequences of spontaneous echo contrast on point-of-care vascular ultrasound in coronavirus disease 2019.

Design, Setting and Patients:
This was a retrospective cohort study of 39 adult patients admitted to the ICU with a confirmed coronavirus disease 2019 diagnosis at a large tertiary-care academic medical center. Patients were included if they had undergone a vascular ultrasound examination during their ICU admission. Overall, 48 venous ultrasound studies among the 39 patients were reviewed in blinded fashion by two reviewers for the presence of venous spontaneous echo contrast, and charts were analyzed for laboratory data and outcomes.

Measurements and Main Results: S
pontaneous echo contrast correlated with serum viscosity (mean values of 2.64, 2.54, and 2.04 cP for dense spontaneous echo contrast, spontaneous echo contrast , and no spontaneous echo contrast, respectively, with a p value of 0.0056 for spontaneous echo contrast compared with negative spontaneous echo contrast) and hyperfibrinogenemia (mean values of 726.6, 668.5, and 566.6 mg/dL for dense spontaneous echo contrast, positive spontaneous echo contrast, and negative spontaneous echo contrast, respectively, with a p value of 0.0045 for dense spontaneous echo contrast compared with negative spontaneous echo contrast). About 36% of patients with dense spontaneous echo contrast and 33% of individuals with positive spontaneous echo contrast experienced significant clotting events compared with 17% of those with negative spontaneous echo contrast. A total of 19% of patients with spontaneous echo contrast suffered a cardiac arrest following a major clotting event, and there were no cardiac arrests from clotting events in the negative spontaneous echo contrast group. There was no association with the presence of spontaneous echo contrast and right or left cardiac function or other laboratory values such as d-dimer, external thromboelastometry - maximum lysis, platelet counts, C-reactive protein, or interleukin-6.

Conclusions:
Point-of-care venous ultrasonography is easily performed and reliably interpreted for visualization of spontaneous echo contrast. The presence of spontaneous echo contrast in patients with coronavirus disease 2019 is associated with hyperviscosity and increased rates of thrombotic events and complications.
Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness
Authors: Rengel Kimberly F. , Hayhurst Christina J. , Jackson James C. , Boncyk Christina S. , Patel Mayur B. , Brummel Nathan E. , Shi Yaping , Shotwell Matthew S. , Ely E. Wesley , Pandharipande Pratik P. , Hughes Christopher G. 
Published: February 2021

OBJECTIVES:
Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors.

DESIGN:
Secondary analysis of a prospective multicenter cohort study.

SETTING:
Academic, community, and Veteran Affairs hospitals.

PATIENTS:
Adult ICU survivors of respiratory failure and/or shock.

INTERVENTIONS:
We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes.

MEASUREMENTS AND MAIN RESULTS:
In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07–0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder.

CONCLUSIONS:
Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.
Evolution Over Time of Ventilatory Management and Outcome of Patients With Neurologic Disease*
Authors: Tejerina Eva E. , Pelosi Paolo , Robba Chiara , Peñuelas Oscar , Muriel Alfonso , Barrios Deisy , Frutos-Vivar Fernando , Raymondos Konstantinos , Du Bin , Thille Arnaud W. , Ríos Fernando , González Marco , del-Sorbo Lorenzo , Marín Maria del Carmen , Valle Pinheiro Bruno , Soares Marco Antonio , Nin Nicolas , Maggiore Salvatore M. , Bersten Andrew , Amin Pravin , Cakar Nahit , Young Suh Gee , Abroug Fekri , Jibaja Manuel , Matamis Dimitros , Ali Zeggwagh Amine , Sutherasan Yuda , Anzueto Antonio , Esteban Andrés 
Published: February 2021

OBJECTIVES:
To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality.

DESIGN:
Secondary analysis of three prospective, observational, multicenter studies.

SETTING:
Cohort studies conducted in 2004, 2010, and 2016.

PATIENTS:
Adult patients who received mechanical ventilation for more than 12 hours.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma.

CONCLUSIONS:
More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease.
Plasma Nucleosomes Are Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome
Authors: Yehya Nadir , Fazelinia Hossein , Lawrence Gladys G. , Spruce Lynn A. , Mai Mark V. , Worthen G. Scott , Christie Jason D. 
Published: February 2021

OBJECTIVES:
Circulating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown.

DESIGN:
We performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome.

SETTING:
Large academic tertiary-care PICU.

PATIENTS:
Intubated children meeting Berlin criteria for acute respiratory distress syndrome.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20–0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04–0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38–2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63–0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome.

CONCLUSIONS:
Plasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.
The Effect of Early Sedation With Dexmedetomidine on Body Temperature in Critically Ill Patients*
Authors: Grayson Kim E. , Bailey Michael , Balachandran Mayurathan , Banneheke Piyusha P. , Belletti Alessandro , Bellomo Rinaldo , Naorungroj Thummaporn , Serpa-Neto Ary , Wright Jason D. , Yanase Fumitaka , Young Paul J. , Shehabi Yahya 
Published: February 2021

OBJECTIVES:
Previous case series reported an association between dexmedetomidine use and hyperthermia. Temperature data have not been systematically reported in previous randomized controlled trials evaluating dexmedetomidine. A causal link between dexmedetomidine administration and elevated temperature has not been demonstrated.

DESIGN:
Post hoc analysis.

SETTING:
Four ICUs in Australia and New Zealand.

PATIENTS:
About 703 mechanically ventilated ICU patients.

INTERVENTIONS:
Early sedation with dexmedetomidine versus usual care.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was mean daily body temperature. Secondary outcomes included the proportions of patients with body temperatures greater than or equal to 38.3°C and greater than or equal to 39°C, respectively. Outcomes were recorded for 5 days postrandomization in the ICU. The mean daily temperature was not different between the dexmedetomidine (n = 351) and usual care (n = 352) groups (36.84°C ± sd vs 36.78°C ± sd; p = 0.16). Over the first 5 ICU days, more dexmedetomidine group (vs usual care) patients had a temperature greater than or equal to 38.3°C (43.3% vs 32.7%, p = 0.004; absolute difference 10.6 percentage points) and greater than or equal to 39.0°C (19.4% vs 12.5%, p = 0.013; absolute difference 6.9 percentage points). Results were similar after adjusting for diagnosis, admitting temperature, age, weight, study site, sepsis occurrence, and the time from dexmedetomidine initiation to first hyperthermia recorded. There was a significant dose response relationship with temperature increasing by 0.30°C ±0.08 for every additional 1 μg/kg/hr of dexmedetomidine received p < 0.0002.

CONCLUSIONS:
Our study suggests potentially important elevations in body temperature are associated with early dexmedetomidine sedation, in adults who are mechanically ventilated in the ICU.
Early Seizures Are Predictive of Worse Health-Related Quality of Life at Follow-Up After Intracerebral Hemorrhage
Authors: Naidech Andrew M. , Weaver Bradley , Maas Matthew , Bleck Thomas P. , VanHaerents Stephen , Schuele Stephan U. 
Published: February 2021

OBJECTIVES:
Early seizures are a common complication of intracerebral hemorrhage, occurring in ~10% of patients. However, the independent effect of early seizures on patient outcomes, particularly health-related quality of life, is unclear. Without a potential benefit to patient outcomes, the widespread use (~40%) of prophylactic seizure medications has no reasonable chance of improving patient outcomes. We tested the hypothesis that health-related quality of life at follow-up is different between patients with and without early seizures (and secondarily, with nonconvulsive status epilepticus) after intracerebral hemorrhage.

DESIGN:
Patients with intracerebral hemorrhage were enrolled in an observational cohort study that prospectively collected clinical data and health-related quality of life at follow-up.

SETTING:
Academic medical center.

PATIENTS:
One-hundred thirty-three patients whose health-related quality of life was assessed 3 months after intracerebral hemorrhage onset.

MEASUREMENTS AND MAIN RESULTS:
Health-related quality of life was obtained at 3 months after intracerebral hemorrhage onset. T Scores of health-related quality of life were modeled with multivariable linear models accounting for severity with the intracerebral hemorrhage Score and hematoma location. Health-related quality of life was measured with National Institutes of Health Patient Reported Outcomes Measurement Information System/Neuroquality of life, expressed in T Scores (U.S. normal 50 ± 10). The modified Rankin Scale (a global measure) was a secondary outcome. There were 12 patients (9%) with early seizures. T Scores of health-related quality of life at follow-up were lower (worse) in patients with early seizure compared with patients without an early seizure (44 [32.75–51.85] vs 30.25 [18.9–39.15]; p = 0.04); results for other domains of health-related quality of life were similar. The association persisted in multivariable models. There was no association between early seizures and prophylactic seizure medications (p = 0.4). Results for patients with nonconvulsive status epilepticus were similar. There was no association between early seizures and the modified Rankin Scale at 3 months.

CONCLUSIONS:
Early seizures and nonconvulsive status epilepticus were associated with lower health-related quality of life at follow-up in survivors of intracerebral hemorrhage.
Understanding the tumor-immune microenvironment in prostate cancer
Authors: Dong Liang , Myers Kayla V. , Pienta Kenneth J. 
Published: February 2021

Purpose of review
This review aims to highlight recent advances in prostate cancer tumor-immune microenvironment research and summarize the state-of-the-art knowledge of immune checkpoint inhibitors in prostate cancer.

Recent findings
Immune checkpoint inhibitors are the cornerstone of modern immunotherapy which have shown encouraging results across a spectrum of cancers. However, only limited survival benefit has been seen in patients with prostate cancer. Prostate cancer progression and its response to immunotherapies are strongly influenced by the tumor-immune microenvironment, whose feature can be summarized as low amounts of tumor-specific antigens, low frequency of tumor-infiltrating lymphocytes and high frequency of tumor-associated macrophages. To improve the therapeutic effect of immunotherapies, in recent years, many strategies have been applied, of which the most promising ones include the combination of multiple immunotherapeutic agents, the combination of an immunotherapeutic agent with other modalities in parallel or in sequential, and the development of biomarkers to find a subgroup of patients who may benefit the most from immunotherapeutic agents.

Summary
The impact of immune content and specific immune cell types on prostate cancer biology is highly complex. Recent clinical trials have shed light on the optimal use of immunotherapies for prostate cancer.
Prolonged recombinant pregnancy hormone use in BRCA1 and BRCA2 mutation carriers
Authors: Depypere Herman , Su Yanrong , Dang Nhi , Poppe Bruce , Stanczyk Frank , Janssens Jaak , Russo Jose 
Published: February 2021

Background
An early first full-time pregnancy substantially reduces the risk of developing breast cancer later in life. Extensive studies indicate that this protective effect is mediated by the pregnancy hormone human chorionic gonadotrophin (hCG).

Methods
In this proof-of-concept study 33 women with a BRCA mutation received recombinant-hCG (r-hCG). A 4-mm breast biopsy was obtained before (T1) and after 12 weeks of r-hCG injections (T2), as well as 6 months later (T3). The tissue was examined using RNA-sequencing methodology to determine if the ‘high-risk’ transcriptomic signature was converted to a ‘low-risk’ signature as in an early first full-time pregnancy. A stringent clinical safety monitoring was performed.

Results
The r-hCG administration was well tolerated in all participants. No clinically relevant changes were observed. In 25 women, the RNA quality was good for RNA sequencing in all three breast tissue biopsies. In response to the r-hCG, we observed 1907 differentially expressed genes (DEGs) (1032 up, 875 down) at T2 vs. T1 and 1065 DEGs (897 up, 168 down) at T3 vs. T1 in the group of women (n = 11) not using any hormonal contraceptives during the study. There was no response at T2 vs. T1 and a small number of DEGs, 260 (214 up, 46 down) at T3 vs. T1 in the group of 14 women using contraceptives.

Conclusions
In summary, r-hCG has a remarkable effect on the gene expression profile of breast tissues from BRCA1/2 carriers who did not use any contraception. This opens an opportunity for a novel preventive strategy to reduce the incidence of breast cancer.