bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Time to Intervention on Catheter-Directed Therapy for Pulmonary Embolism
Authors: Lehr Andrew , Guichet Phillip , Garimella Bhaskara , Krolikowski Kelsey , Amoroso Nancy , Sista Akhilesh , Brosnahan Shari B. 
Published: January 2023

OBJECTIVES:
Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality.

DESIGN:
Retrospective cohort study.

SETTING:
Single academic center.

PATIENTS:
We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late).

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1–20.3 hr) in the early group versus 33.4 (27.9–41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6–20 mm Hg] vs 6 mm Hg [1–10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523).

CONCLUSIONS:
Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.
Impact of Antibiotic Time-Outs in Multidisciplinary ICU Rounds for Antimicrobial Stewardship Program on Patient Survival: A Controlled Before-and-After Study
Authors: Mishima Yuka , Nawa Nobutoshi , Asada Mizuho , Nagashima Michio , Aiso Yoshibumi , Nukui Yoko , Fujiwara Takeo , Shigemitsu Hidenobu 
Published: January 2023

OBJECTIVES:
The antimicrobial stewardship program (ASP) is an important quality improvement initiative that is recommended in the ICU. However, the shortage of infectious disease physicians in Japan has led to the need for simpler methods for implementing ASPs. We investigated whether antibiotic time-outs (ATOs) during multidisciplinary rounds as part of an ASP can improve patient survival and reduce the number of days of therapy (DOT) with antibiotics.

DESIGN:
Single-center controlled before-and-after study.

SETTING:
Medical/surgical ICU in a tertiary university medical center in Tokyo, Japan.

PATIENTS:
All patients 16 years old or older admitted consecutively in the ICU between October 2016 and March 2020.

INTERVENTIONS:
An intensivist-driven ICU multidisciplinary round was introduced in October 2016, and ATOs with ICU rounds were implemented in June 2018. ATOs were conducted 3, 7, and 14 days after initiation of antibiotics.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was the subdistribution hazard ratio (SHR) of survival to hospital discharge compared between multidisciplinary rounds (phase 1) and ATO during multidisciplinary rounds (phase 2) using the multivariable Fine-Gray model. The secondary outcomes were the SHR of survival to ICU discharge and the trends in the DOT with IV antibiotics per 1,000 patient-days between October 2016 and March 2020 by using interrupted time-series analysis. The number of patients in phases 1 and 2 was 777 and 796, respectively. The group that underwent ATO during multidisciplinary rounds showed a significant increase in the survival to hospital discharge in comparison with the multidisciplinary round-only group (SHR, 1.13; 95% CI, 1.02–1.25); however, the SHR of survival to ICU discharge showed no significant intergroup difference. The DOT with total IV antibiotics decreased after ATO implementation (change in intercept, –178.26; 95% CI, –317.74 to –38.78; change in slope, –7.00; 95% CI, –15.77 to 1.78).

CONCLUSIONS:
ATOs during multidisciplinary rounds are associated with improved patient survival and reduced DOT.
Impact of Hospital Safety-Net Burden on Outcomes of In-Hospital Cardiac Arrest in the United States
Authors: Olanipekun Titilope , Abe Temidayo , Chris-Olaiya Abimbola , Effoe Valery S. , Bhardwaj Abhishek , Harrison Michael F. , Moreno Franco Pablo , Guru Pramod , Sanghavi Devang 
Published: January 2023

IMPORTANCE:
High safety-net burden hospitals (HBHs) treating large numbers of uninsured or Medicaid-insured patients have generally been linked to worse clinical outcomes. However, limited data exist on the impact of the hospitals’ safety-net burden on in-hospital cardiac arrest (IHCA) outcomes in the United States.

OBJECTIVES:
To compare the differences in survival to discharge, routine discharge home, and healthcare resource utilization between patients at HBH with those treated at low safety-net burden hospital (LBH).

DESIGN, SETTING, AND PARTICIPANTS:
Retrospective cohort study across hospitals in the United States: Hospitalized patients greater than or equal to 18 years that underwent cardiopulmonary resuscitation (CPR) between 2008 and 2018 identified from the Nationwide Inpatient Database. Data analysis was conducted in January 2022.

EXPOSURE:
IHCA.

MAIN OUTCOMES AND MEASURES:
The primary outcome is survival to hospital discharge. Other outcomes are routine discharge home among survivors, length of hospital stay, and total hospitalization cost

RESULTS:
From 2008 to 2018, an estimated 555,016 patients were hospitalized with IHCA, of which 19.2% occurred at LBH and 55.2% at HBH. Compared with LBH, patients at HBH were younger (62 ± 20 yr vs 67 ± 17 yr) and predominantly in the lowest median household income (< 25th percentile). In multivariate analysis, HBH was associated with lower chances of survival to hospital discharge (adjusted odds ratio [aOR], 0.88; 95% CI, 0.85–0.96) and lower odds of routine discharge (aOR, 0.6; 95% CI, 0.47–0.75), compared with LBH. In addition, IHCA patients at publicly owned hospitals and those with medium and large hospital bed size were less likely to survive to hospital discharge, while patients with median household income greater than 25th percentile had better odds of hospital survival.

CONCLUSIONS AND RELEVANCE:
Our study suggests that patients who experience IHCA at HBH may have lower rates and odds of in-hospital survival and are less likely to be routinely discharged home after CPR. Median household income and hospital-level characteristics appear to contribute to survival.
Electrical Impedance Tomography As a Bedside Diagnostic Tool for Pulmonary Embolism
Authors: Prins Susanne A. , Weller Dolf , Labout Joost A. M. , den Uil Corstiaan A. 
Published: January 2023

BACKGROUND:
Electrical impedance tomography (EIT) has been shown to be of value in evaluating the distribution of ventilation. In addition, several studies, particularly case reports, have demonstrated the use of EIT in the assessment of lung perfusion. EIT may be a potential diagnostic bedside tool in the diagnosis and follow-up of acute pulmonary embolism.

CASE SUMMARY:
We present one case of a patient with COVID-19 who likely had pulmonary thromboembolism where perfusion scans were made before and after thrombolytic therapy. Perfusion scans showed improvement after thrombolytic therapy. This article should therefore be seen as a first step in proving the validity of EIT-derived perfusion scans as a diagnostic for pulmonary embolism.

CONCLUSION:
The hypertonic saline bolus EIT method as a diagnostic tool for pulmonary embolism is a promising new technique, which can be particularly meaningful for critically ill patients. Further study is required to evaluate the sensitivity and specificity of this technique and the impact on decision-making and outcomes of critically ill patients.
Assessment of Opioid-Induced Immunomodulation in Experimental and Clinical Sepsis
Authors: Bissell Brittany D. , Sturgill Jamie L. , Bruno Maria E. C. , Lewis Erick D. , Starr Marlene E. 
Published: January 2023

CONTEXT:
Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS:
We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS:
This was a two-phase preclinical and clinical study. The clinical phase included a subgroup of patients with sepsis from an existing randomized controlled trial while the preclinical phase used a murine model of sepsis with C57BL/6 mice. In the clinical phase, a post hoc analysis was performed in subjects receiving fentanyl versus no opioid receipt. In the preclinical phase, a murine cecal slurry-induced sepsis model followed by secondary infection was used. Mice were randomized to fentanyl versus no fentanyl concomitantly.

RESULTS:
In clinical sepsis, a significant decrease in interleukin-23 (IL-23) level in patients with fentanyl exposure was observed and lower IL-23 was associated with mortality (p < 0.001). Other measured cytokines showed no significant differences. Concomitant fentanyl exposure during murine sepsis was associated with a significantly higher bacterial burden (p < 0.001) after secondary infection; however, immune cell counts and plasma cytokine levels were largely unaffected by fentanyl.

INTERPRETATION AND CONCLUSIONS:
Minimal alterations in cytokines were seen with opioid exposure during clinical sepsis. In a preclinical model, opioid exposure during sepsis was associated with ineffective bacterial clearance upon secondary infection. Further studies are warranted to evaluate the immunomodulatory role of opioids and their implications, especially in the post-sepsis period.
Characteristics of Mid-Term Post-Intensive Care Syndrome in Patients Attending a Follow-Up Clinic: A Prospective Comparison Between COVID-19 and Non-COVID-19 Survivors
Authors: Rousseau Anne-Françoise , Colson Camille , Minguet Pauline , Kellens Isabelle , Collard Maxine , Vancraybex Camille , Guiot Julien , Lambermont Bernard , Misset Benoit 
Published: January 2023

IMPORTANCE:
At present, it is not clear if critically ill COVID-19 survivors have different needs in terms of follow-up compared with other critically ill survivors, and thus if duplicated post-ICU trajectories are mandatory.

OBJECTIVES:
To compare the post-intensive care syndrome (PICS) of COVID-19 acute respiratory distress syndrome and non-COVID-19 (NC) survivors referred to a follow-up clinic at 3 months (M3) after ICU discharge.

DESIGN, SETTING, AND PARTICIPANTS:
Adults who survived an ICU stay greater than or equal to 7 days and attended the M3 consultation were included in this observational study performed in a post-ICU follow-up clinic of a single tertiary hospital.

MAIN OUTCOMES AND MEASURES:
Patients underwent a standardized assessment, addressing health-related quality of life (3-level version of EQ-5D), sleep disorders (Pittsburgh Sleep Quality Index [PSQI]), physical status (Barthel index, handgrip and quadriceps strengths), mental health disorders (Hospital Anxiety and Depression Scale and Impact of Event Scale-Revised [IES-R]), and cognitive impairment (Montreal Cognitive Assessment [MoCA]).

RESULTS:
A total of 143 survivors (86 COVID and 57 NC) attended the M3 consultation. Their median age and severity scores were similar. NC patients had a shorter ICU stay (10 d [8–17.2 d]) compared with COVID group (18 d [10.8–30 d]) (p = 0.001). M3 outcomes were similar in the two groups, except for a higher PSQI (p = 0.038) in the COVID group (6 [3–9.5]) versus NC group (4 [2–7]), and a slightly lower Barthel index in the NC group (100 [100–100]) than in the COVID group (100 [85–100]) (p = 0.026). However, the proportion of patients with abnormal values at each score was similar in the two groups. Health-related quality of life was similar in the two groups. The three MoCA (≥ 26), IES-R (<33), and Barthel (=100) were normal in 58 of 143 patients (40.6%). In contrast, 68.5% (98/143) had not returned to their baseline level of daily activities.

CONCLUSIONS AND RELEVANCE:
In our follow-up clinic at 3 months after discharge, the proportion of patients presenting alterations in the main PICS domains was similar whether they survived a COVID-19 or another critical illness, despite longer ICU stay in COVID group. Cognition and sleep were the two most affected PICS domains.
Relationship Among Clinically Obtained Biomarkers of Inflammation, Hypercoagulability, and Macrophage Activation, and Delirium in Critically Ill Patients With COVID-19
Authors: Khan Sikandar H. , Perkins Anthony J. , Chi Rosalyn , Seyffert Sarah , Conrad Peter , Lindroth Heidi , Wang Sophia , Mulkey Malissa , Gao Sujuan , Khan Babar 
Published: January 2023

OBJECTIVES:
Critically ill patients with COVID-19 experience high rates of delirium and coma. Whether delirium occurs through novel mechanisms in COVID-19 is not known. We analyzed the relationship among biomarkers of inflammation (C-reactive protein [CRP]), hypercoagulability (d-dimer), and lung macrophage activation (ferritin), and the primary composite outcome of delirium/coma next day. We also measured associations between biomarkers and next day delirium and coma independently, and delirium severity.

DESIGN:
Retrospective, observational cohort study.

SETTING:
ICUs at two large, urban, academic referral hospitals.

PATIENTS:
All consecutive adult patients admitted to the ICU from March 1, 2020, to June 7, 2020, with COVID-19 with clinical biomarkers and delirium assessments performed.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Daily concentrations of CRP, d-dimer, and ferritin were obtained. Coma (assessed by Richmond Agitation-Sedation Scale) and delirium (assessed by Confusion Assessment Method for the ICU/Confusion Assessment Method for the ICU-7) were measured bid. A cohort of 197 ICU patients with COVID-19 were included. Higher d-dimer (odds ratio [OR], 1.57; 95% CI, 1.17–2.12; p < 0.01) and ferritin quartiles (OR, 1.36; 95% CI, 1.02–1.81; p < 0.01) were associated with greater odds of the composite outcome of delirium/coma next day. d-dimer was associated with greater odds of next day delirium (OR, 1.49; 95% CI, 1.14–1.94; p < 0.01) and coma independently (OR, 1.52; 95% CI, 1.08–2.14; p = 0.017). Higher ferritin quartiles were associated with greater odds of next day delirium (OR, 1.33; 95% CI, 1.04–1.70; p = 0.026) and coma independently (OR, 1.59; 95% CI, 1.14–2.23; p < 0.01). Higher CRP quartiles were associated with coma (OR, 1.36; 95% CI, 1.03–1.79; p = 0.030) and delirium severity the next day (β = 0.30; se, 0.07; p ≤ 0.01).

CONCLUSIONS:
Our hypothesis-generating study found d-dimer and ferritin were associated with delirium/coma the following day, as well as delirium and coma independently. CRP was associated with next day coma and delirium severity. Larger studies to validate these results are needed.
Therapeutic cancer vaccination against telomerase: clinical developments in melanoma
Authors: Ellingsen Espen Basmo , Bjørheim Jens , Gaudernack Gustav 
Published: January 2023

Purpose of review
Checkpoint inhibitors (CPIs) have revolutionized treatment outcomes for patients with malignant melanoma. Long-term follow-up shows that a substantial subset of patients who exhibit clinical responses achieve extended overall survival. Nevertheless, most patients do not achieve durable benefit from CPIs, and improvements are urgently needed. The clinical efficacy of CPIs depends on highly variable preexisting spontaneous T-cell immune responses. Cancer vaccines represent an independent treatment modality uniquely capable of expanding the repertoire of tumor-specific T cells in cancer patients and thus have the capacity to compensate for the variability in spontaneous T-cell responses. Vaccines are, therefore, considered attractive components in a CPI-combination strategy.

Recent findings
Here we discuss recent results obtained through therapeutic vaccination against telomerase human telomerase reverse transcriptase (hTERT). Recent publications on translational research and clinical results from phase I trials indicate that vaccination against telomerase in combination with CPIs provides relevant immune responses, negligible added toxicity, and signals of clinical efficacy.

Conclusion
In the near future, randomized data from clinical trials involving therapeutic cancer vaccines and checkpoint inhibitors will be available. Positive readout may spark broad development and allow cancer vaccines to find their place in the clinic as an important component in multiple future CPI combinations.
Prognostic Value of the Cutoffs for HALP in Endometrial Cancer
Authors: Wang Jinyu , Jiang Peng , Huang Yuzhen , Tu Yuan , Zhou Qian , Li Ning , Kong Wei , Yuan Rui 
Published: January 2023

Objectives:
Using preoperative hemoglobin, albumin, lymphocyte, and platelet (HALP) scores, a cutoff value of HALP in endometrial cancer was identified, and the significance of HALP value in endometrial cancer prognosis was evaluated to guide the management of patients.

Materials and Methods:
This study included 626 patients with endometrial cancer who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between June 2015 and June 2020. A Cox regression model was used to analyze the correlation between HALP endometrial cancer recurrence and death, and the receiver operating characteristic curve was used to determine the optimal cutoff value of HALP for predicting the lymph node metastasis (LNM), recurrence, and death of endometrial cancer. Survival analysis was performed using the Kaplan-Meier method and log-rank test.

Results:
Univariate analysis revealed that HALP was associated with a lower risk of recurrence and death of endometrial cancer. Multivariate analysis indicated that HALP was an independent protective factor for predicting recurrence and death in endometrial cancer. The thresholds of HALP for predicting LNM, recurrence, and death in endometrial cancer patients are around 33.8. Kaplan-Meier survival curves showed that the recurrence-free and the overall survival rates were significantly lower in the low-HALP group than that in the high-HALP group (P<0.001).

Conclusions:
Preoperative HALP values in patients with endometrial cancer are important in predicting LNM, recurrence, and death of patients. HALP scores combined with traditional pathologic factors can better guide the prognostic management of patients.
A Review of Midface Aging
Authors: Ugradar Shoaib , Kim Jane S. , Massry Guy 
Published: January 2023

Purpose:
To review and summarize studies on the anatomy and involutional changes of the midface.

Methods:
A PubMed search was performed searching for studies on the anatomy and involutional changes concerning the midface.

Results:
The anatomy of the midface is complex. Studies of involutional change vary in scientific quality and have conflicting results. However, it appears that among the more common changes, there is a decrease in the maxillary and pyriform angle, with changes to the orbital floor position. Further, there appears to be an inferior migration of the fat compartments of the midface during aging, exacerbating the hollow of the palpebromalar groove and causing a deepening of the nasojugal groove. Changes to the volume of the buccal extension of the buccal fat pad exacerbate these changes and contribute to the gestalt changes associated with facial aging. Here, we review the major characteristics of soft tissue and bony changes on the midface, with special reference to their anatomic relationships.

Conclusions:
The major findings characterizing midface aging are related largely to the soft tissue. However, more robust studies are required to quantify these changes and to appraise their impact on the overall manifestation of aging.
Prevalence and Predictors of Hering’s Response in Müller’s Muscle-conjunctival Resection
Authors: Lussier Charlotte , Leung Victoria C. , El-Khazen Dupuis Jessica , Ashraf Davin C. , Idowu Oluwatobi O. , Massicotte Erika , Vagefi M. Reza , Kersten Robert C. , Kalin-Hajdu Evan 
Published: January 2023

Purpose:
Determine the prevalence and predictors of Hering’s response following Muller’s muscle-conjunctival resection (MMCR).

Methods:
Seventy-five consecutive patients undergoing unilateral MMCR were recruited in this prospective, multicenter, cohort study. Margin-reflex distance-1 (MRD1) of both eyelids was recorded preoperatively and postoperatively. One hundred forty-three variables were investigated as potential predictors of a late postoperative (≥3 months) Hering’s response using regression analyses. Main outcome measures were Hering’s response (≥0.5 mm descent of the unoperated eyelid from baseline), and a clinically relevant Hering’s response (descent of the unoperated from baseline to a MRD1 ≤ 2.0 mm, or descent from baseline such that the MRD1 of the unoperated eyelid became >1 mm lower than the operated eyelid).

Results:
Twenty-four (32.0%) patients had a late postoperative Hering’s response, but only 6 (8.0%) responses were clinically relevant. A Hering’s response at the immediate (OR 16.24, p = 0.02) and 1-week postoperative (OR 8.94, p = 0.04) timepoints predicted a late postoperative response. However, the presence (OR 7.84, p = 0.07) and amplitude (OR 8.13, p = 0.06) of a preoperative phenylephrine Hering’s response did not predict a late postoperative response. Of the 10 patients with a clinically relevant phenylephrine Hering’s response, only 1 demonstrated a clinically relevant response late postoperatively.

Conclusion:
Unilateral MMCR induces a clinically relevant Hering’s response in 8% of patients. A preoperative phenylephrine Hering’s response does not predict a late postoperative Hering’s response. Therefore, when unilateral phenylephrine testing unmasks contralateral blepharoptosis, only the side with blepharoptosis at baseline should be operated.