bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordances Between Factors Associated With Withholding Extubation and Extubation Failure After a Successful Spontaneous Breathing Trial*
Authors: Taran Shaurya , Angriman Federico , Pinto Ruxandra , Ferreyro Bruno L. , Amaral Andre Carlos Kajdacsy-Balla 
Published: July 2021

OBJECTIVES:
To identify whether factors associated with withholding extubation in the ICU also predict the risk of extubation failure.

DESIGN:
Retrospective cohort study.

SETTING:
Eight medical-surgical ICUs in Toronto.

Patients:
Adult patients receiving invasive mechanical ventilation, with a first successful spontaneous breathing trial within 28 days of initial ICU admission.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
The primary end point had three mutually exclusive levels, including: 1) withholding extubation after a successful spontaneous breathing trial, 2) extubation failure within 48 hours, and 3) successful extubation. Among 9,910 patients, 38% of patients were not extubated within 24 hours of their first successful spontaneous breathing trial. A total of 12.9% of patients who were promptly extubated failed within the next 48 hours. Several discrepancies were evident in the association of factors with risk of withholding extubation and extubation failure. Specifically, both age and female sex were associated with withholding extubation (odds ratio, 1.07; 95% CI, 1.03–1.11; and odds ratio, 1.13; 95% CI, 1.02–1.26, respectively) but not a higher risk of failed extubation (odds ratio, 0.99; 95% CI, 0.93–1.05; and odds ratio, 0.93; 95% CI, 0.77–1.11, respectively). Conversely, both acute cardiovascular conditions and intubation for hypoxemic respiratory failure were associated with a higher risk of failed extubation (odds ratio, 1.32; 95% CI, 1.06–1.66; and odds ratio, 1.46; 95% CI, 1.16–1.82, respectively) but not a higher odds of a withheld extubation attempt (odds ratio, 0.79; 95% CI, 0.68–0.91; and odds ratio, 1.07; 95% CI, 0.93–1.23, respectively).

CONCLUSIONS:
Several factors showed discordance between the decision to withhold extubation and the risk of extubation failure. This discordance may lead to longer duration of mechanical ventilation or higher reintubation rates. Improving the decision-making behind extubation may help to reduce both exposure to invasive mechanical ventilation and extubation failure.
Critically Ill Patients Treated for Chimeric Antigen Receptor-Related Toxicity: A Multicenter Study*
Authors: Gutierrez Cristina , Brown Anne Rain T. , May Heather P. , Beitinjaneh Amer , Stephens R. Scott , Rajendram Prabalini , Nates Joseph L. , Pastores Stephen M. , Dharshan Ananda , de Moraes Alice Gallo , Hensley Matthew K. , Feng Lei , Brudno Jennifer N. , Athale Janhavi , Ghosh Monalisa , Kochenderfer James N. , Arias Alejandro S. , Lin Yi , McEvoy Colleen , Mead Elena , Westin Jason , Kostelecky Natalie , Mian Agrima , Herr Megan M. 
Published: July 2021

OBJECTIVES:
To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.

DESIGN:
Retrospective cohort study

SETTING:
Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative.

PATIENTS:
Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019.

INTERVENTIONS:
Demographics, toxicities, specific interventions, and outcomes were collected.

RESULTS:
One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3–4 toxicities (66.7%); 15.2% had grade 3–4 cytokine release syndrome and 64% grade 3–4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64–not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival.

CONCLUSIONS:
This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.
Left Ventricular Function Changes Induced by Moderate Hypothermia Are Rapidly Reversed After Rewarming—A Clinical Study
Authors: Wisløff-Aase Kristin , Skulstad Helge , Beitnes Jan Otto , Lundblad Runar , Halvorsen Per Steinar , Fiane Arnt , Espinoza Andreas 
Published: July 2021

OBJECTIVES:
Targeted temperature management (32–36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts.

DESIGN:
Prospective clinical study, from June 2015 to May 2018.

SETTING:
Cardiothoracic surgery operation room, Oslo University Hospital.

PATIENTS:
Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included.

INTERVENTIONS:
Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions.

MEASUREMENTS AND MAIN RESULTS:
Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored.

CONCLUSIONS:
In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.
Union Burying Ground
Authors: Eisenberg-Guyot Jerzy , Mooney Stephen J. , Barrington Wendy E. , Hajat Anjum 
Published: July 2021

Background:
Over the last several decades in the United States, socioeconomic life-expectancy inequities have increased 1–2 years. Declining labor-union density has fueled growing income inequities across classes and exacerbated racial income inequities. Using Panel Study of Income Dynamics (PSID) data, we examined the longitudinal union–mortality relationship and estimated whether declining union density has also exacerbated mortality inequities.

Methods:
Our sample included respondents ages 25–66 to the 1979–2015 PSID with mortality follow-up through age 68 and year 2017. To address healthy-worker bias, we used the parametric g-formula. First, we estimated how a scenario setting all (versus none) of respondents’ employed-person–years to union-member employed-person–years would have affected mortality incidence. Next, we examined gender, racial, and educational effect modification. Finally, we estimated how racial and educational mortality inequities would have changed if union-membership prevalence had remained at 1979 (vs. 2015) levels throughout follow-up.

Results:
In the full sample (respondents = 23,022, observations = 146,681), the union scenario was associated with lower mortality incidence than the nonunion scenario (RR = 0.90, 95% CI = 0.80, 0.99; RD per 1,000 = −19, 95% CI = −37, −1). This protective association generally held across subgroups, although it was stronger among the more-educated. However, we found little evidence mortality inequities would have lessened if union membership had remained at 1979 levels.

Conclusions:
To our knowledge, this was the first individual-level US-based study with repeated union-membership measurements to analyze the union–mortality relationship. We estimated a protective union–mortality association, but found little evidence declining union density has exacerbated mortality inequities; importantly, we did not incorporate contextual-level effects. See video abstract at, http://links.lww.com/EDE/B839.
Infectious Scleritis: Pathophysiology, Diagnosis, and Management
Authors: Yu Julia , Syed Zeba A. , Rapuano Christopher J. 
Published: July 2021

Abstract:
Infectious scleritis (IS) is a rare and severe ocular disorder responsible for approximately 5%–15% of all scleritis cases. It is often associated with a poor prognosis due to its similar clinical presentation to autoimmune scleritis, resulting in a delayed diagnosis and treatment. Therefore, differentiating between infectious and noninfectious entities is critical. Several details extracted from the patient's history and clinical examination can raise suspicion for infection. The most common predisposing factor is previous ocular surgery, especially pterygium, cataract, and vitreoretinal surgeries. Ocular trauma, poor contact lens hygiene, “eye-whitening” procedures, and subtenon triamcinolone injections have also been implicated. Clinical features of infection include the presence of scleral necrosis, hypopyon, unifocal or multifocal scleral abscesses, and mucopurulent discharge. Thorough diagnostic testing is essential before excluding infection as a possibility. Empiric broad-spectrum topical and systemic antibiotic therapy should be initiated while awaiting laboratory results and adjusted accordingly. Most IS cases require both aggressive medical and surgical treatment, and various studies have reported favorable outcomes with this combination. At this time, there is no consensus on the management of this severe ocular condition, and future studies are needed to establish clear treatment guidelines.
Online Vs In-person Education: Evaluating the Potential Influence of Teaching Modality on Dry Eye Symptoms and Risk Factors During the COVID-19 Pandemic
Authors: Talens-Estarelles Cristian , García-Marqués José Vicente , Cervino Alejandro , García-Lázaro Santiago 
Published: July 2021

Objectives:
To assess the potential effects of switching to online lecture format on dry eye symptoms and dry eye disease (DED) risk factors.

Methods:
An anonymous cross-sectional online survey was conducted in 812 university students (mean age, 21.5±4.0 years). Participants were classified according to the number of hours the participants took online lectures into online students or in-person students. Respondents completed a total of three DED questionnaires (Ocular Surface Disease Index [OSDI]; 5-item Dry Eye Questionnaire; 8-item Contact Lens Dry Eye Questionnaire) and were surveyed on dry eye risk factors contemplated by the Tear Film and Ocular Surface Society Dry Eye Workshop II in addition to other factors potentially linked to dry eye.

Results:
Five hundred twenty-three subjects (64.4%) were classified into the online group and 289 (35.6%) into the in-person group. No statistically significant age (P=0.266) or sex (P=0.423) differences were found between groups. Students taking online lectures used the computer more, spent less time outdoors, practised more exercise, wore a face mask for less time, experienced fewer allergies and fewer psoriasis episodes, and obtained a higher OSDI score (P<0.029 for all). Multivariate logistic regression analysis revealed that the hours of online lectures taken per week was independently associated with having a positive OSDI score (P=0.022).

Conclusions:
Taking online lectures is independently associated with having dry eye symptoms. Despite a lower prevalence of DED risk factors, a higher computer use is probably behind the greater ocular dryness reported by online students.
Effect of longitudinal and torsional ultrasound on corneal endothelial cells: experimental study in rabbit eyes
Authors: Ungricht Emilie L. , Culp Catherine , Qu Phillip , Jensen Nathan , Harris Jacob T. , Brintz Ben J. , Mamalis Nick , Olson Randall J. , Werner Liliana 
Published: July 2021

Purpose:
To compare corneal endothelial damage from longitudinal and torsional ultrasound during phacoemulsification.

Setting:
John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.

Design:
Experimental study.

Methods:
9 New Zealand white rabbits underwent bilateral surgery. After incision, the Intrepid Balanced Tip of the Centurion Ozil handpiece was inserted into the anterior chamber, and the following settings were used: 50 mL/min flow, 70 mm Hg intraocular pressure, 600 mm Hg vacuum, and 60% longitudinal (1 eye) or torsional (contralateral eye) ultrasound for 30 seconds. Cumulative dissipated energy (CDE) was noted. After euthanasia and enucleation, the corneas were removed, stained with trypan blue/alizarin red, and photographed (400× photographs from 5 specific areas and 1 overview photograph from each corneal button). The ImageJ program was used to evaluate cell damage and loss in the photographs obtained from each cornea.

Results:
Cavitation bubbles around the phacoemulsification tip were generally observed in the longitudinal group. CDE was 17.4 ± 0.58 and 6.93 ± 0.15 in the longitudinal and torsional groups, respectively (P = .003). The percentage of intact cells was statistically higher in the torsional group (94.22% ± 5.99% vs 56.85% ± 22.29%), and the percentage of lost cells was statistically higher in the longitudinal group (42.10% ± 22.02% vs 4.97% ± 6.23%) (P = .003). This was observed in the analysis of the 400× photographs and the overview photographs.

Conclusions:
This study suggests that torsional ultrasound was associated with significantly less corneal endothelial cell damage than classical longitudinal tip motion, providing further insight on mechanisms of corneal endothelial damage during phacoemulsification.
Pain is common after sexual assault and posttraumatic arousal/reactivity symptoms mediate the development of new or worsening persistent pain
Authors: Short Nicole A. , Tungate Andrew S. , Bollen Kenneth A. , Sullivan Jenyth , D'Anza Teresa , Lechner Megan , Bell Kathy , Black Jenny , Buchanan Jennie , Reese Rhiannon , Ho Jeffrey D. , Reed Gordon D. , Platt Melissa A. , Riviello Ralph J. , Rossi Catherine H. , Martin Sandra L. , Liberzon Israel , Rauch Sheila A.M. , Kessler Ronald C. , Nugent Nicole , McLean Samuel A. 
Published: July 2021

Abstract
Clinically significant new or worsening pain (CSNWP) is a common, yet often overlooked, sequelae of sexual assault. Little is known regarding factors influencing the development of CSNWP in sexual assault survivors. The current study used data from a recently completed prospective study to evaluate whether posttraumatic alterations in arousal and reactivity in the early aftermath of sexual assault influence the transition from acute to clinically significant new or worsening persistent pain. Women ≥ 18 years of age (n = 706) presenting for emergency care after sexual assault to 13 emergency care sites were enrolled in the study. Women completed assessments at the time of presentation as well as at 1 week (n = 706, 100%) and 6 weeks (n = 630, 91%). Nearly 70% of women reported CSNWP at the time of emergency care (n = 475, 69%), which persisted to 6 weeks in approximately 2 in 5 survivors (n = 248, 41%). A structural equation model adjusted for age, race, past trauma exposure, and preassault pain levels suggested that posttraumatic alterations in arousal/reactivity symptoms 1 week after assault partially mediated the transition from acute to persistent CSNWP. A significant portion (41%) of women sexual assault survivors develop CSNWP 6 weeks postassault. Posttraumatic arousal/reactivity symptoms in the early aftermath of assault contribute to CSNWP development; such symptoms are potential targets for secondary preventive interventions to reduce chronic postassault pain.
Effects of combined chemotherapy and anti-programmed cell death protein 1 treatment on peripheral neuropathy and neuroinflammation in mice
Authors: Livni Lital , Keating Brooke A. , Fiore Nathan T. , Lees Justin G. , Goldstein David , Moalem-Taylor Gila 
Published: July 2021

Abstract
A modern approach for cancer treatment is the use of immunotherapy, and particularly immune checkpoint inhibitors, such as anti-programmed cell death protein 1 (PD-1), alone and in combination with chemotherapy. The PD-1 pathway plays a crucial role in inhibiting immune responses and recently has been shown to modulate neuronal activity. However, the impact of PD-1 blockade on the development of chemotherapy-induced peripheral neuropathy is currently unknown. In this study, we show that C57BL/6 mice treated with the chemotherapeutic drug paclitaxel or cotherapy (paclitaxel and anti–PD-1), but not with anti–PD-1 alone, exhibited increased mechanical sensitivity of the hind paw. Both chemotherapy and immunotherapy caused a reduction in neurite outgrowth of dorsal root ganglion (DRG) explants derived from treated mice, whereas only paclitaxel reduced the neurite outgrowth after direct in vitro treatment. Mice treated with anti–PD-1 or cotherapy exhibited distinct T-cell changes in the lymph nodes and increased T-cell infiltration into the DRG. Mice treated with paclitaxel or cotherapy had increased macrophage presence in the DRG, and all treated groups presented an altered expression of microglia markers in the dorsal horn of the spinal cord. We conclude that combining anti–PD-1 immunotherapy with paclitaxel does not increase the severity of paclitaxel-induced peripheral neuropathy. However, because anti–PD-1 treatment caused significant changes in DRG and spinal cord immunity, caution is warranted when considering immune checkpoint inhibitors therapy in patients with a high risk of developing neuropathy.
Predictive value of quantitative sensory testing for acute and chronic postsurgical pain after total joint arthroplasty: a systematic review
Authors: Paredes Ana Cristina , Pinto Joana Milhazes , Almeida Armando , Pinto Patrícia R. 
Published: July 2021

Abstract
Quantitative sensory testing (QST) can be useful to identify high-risk patients for the development of chronic postsurgical pain. This systematic review aims to assess if presurgical sensory sensitivity measured using QST is associated with acute and chronic postsurgical pain after total joint arthroplasty. A systematic search was performed in September 2020 in PubMed, EMBASE, Web of Science, and Scopus, using terms related to total joint arthroplasty and QST. Prospective studies were included if they reported an association between presurgical QST and postsurgical pain in adults with osteoarthritis undergoing primary unilateral total joint arthroplasty. From 2994 identified studies, 18 met the inclusion criteria (1869 patients). Total knee arthroplasty was the most common surgery (16 studies), and pressure pain threshold was the most common test (11 studies), followed by dynamic measures (9 studies). Postsurgical pain was assessed at acute (5 studies), subacute (2 studies), and chronic (13 studies) time points. Risk of bias was assessed using the Quality in Prognosis Studies tool and evaluated as low to moderate in most domains. Fourteen studies reported at least one statistically significant association between QST and pain (acute: 4 studies, subacute: 1 study, and chronic: 9 studies). Pressure pain threshold was associated with postsurgical pain in 6 studies (of 11, 55%), heat pain threshold in 2 studies (of 6, 33%), conditioned pain modulation in 1 study (of 6, 17%), and temporal summation of pain in 5 studies (of 8, 63%). The predictive role of presurgical QST for postarthroplasty pain remains unclear, mainly because of heterogeneous methodologies and inconsistent results.
Systemic inflammatory markers in neuropathic pain, nerve injury, and recovery
Authors: Sandy-Hindmarch Oliver , Bennett David L. , Wiberg Akira , Furniss Dominic , Baskozos Georgios , Schmid Annina B. 
Published: July 2021

Abstract
The role that inflammation plays in human nerve injury and neuropathic pain is incompletely understood. Previous studies highlight the role of inflammation in the generation and maintenance of neuropathic pain, but the emerging evidence from the preclinical literature for its role in the resolution of neuropathic pain remains to be explored in humans. Here, we use carpal tunnel syndrome (CTS) as a human model system of nerve injury and neuropathic pain to determine changes in serum cytokine protein levels and gene expression levels before (active stage of disease) and after carpal tunnel decompression surgery (recovery). Fifty-five patients with CTS were studied, and 21 healthy age-matched and gender-matched participants served as controls. In the active stage of the disease (CTS before surgery vs healthy controls), PTGES2 mRNA was decreased in patients (adjusted P = 0.013), while transforming growth factor-β and C-C motif chemokine ligand 5 protein levels were increased (adjusted P = 0.016 and P = 0.047, respectively). In the resolution phase (CTS before surgery vs after surgery), IL-9 mRNA was increased after surgery (adjusted P = 0.014) and expression of IL-6 mRNA and IL-4 protein levels were increased before surgery (adjusted P = 0.034 and P = 0.002, respectively). IL-9 mRNA expression negatively correlated with several (neuropathic) pain scores. By contrast, protein levels of IL-4 positively correlated with pain scores. In conclusion, we demonstrate specific dysregulation of systemic cytokine expression in both the active and resolution phases of nerve injury and neuropathic pain. IL-9 represents an interesting candidate associated with resolution of nerve injury and neuropathic pain.