bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long term outcomes in the critically ill: Investigating the association between frailty and survival. LONG a SWARM regional observational study
Authors: Garland Adam , Womersley James , Clark Thomas 
Published: January 2024

Background: Frailty is common and is present in up to 30% of patients admitted to the ICU. We do not yet understand the true impact of ICU admission on this population, certainly in terms of longer-term outcomes. Method: Random selection of patients admitted to each general ICU within the SWARM network between October 1st 2012 and January 31st 2013. To be eligible, patients had to be over the age of 18 and admitted to the ICU with either a medical diagnosis or following emergency gastrointestinal/vascular surgery. Results: 1888 patients were eligible for random selection. 560 patients were selected for the final analysis. Three hundred and eighteen patients had an estimated frailty score between 1 and 3 (classified as not frail, 56.8%), whilst 112 had a score of 4 (classified as vulnerable, 20%) and 130 patients had a score of between 5 and 7 (classified as frail, 23.2%). The median survival for patients with an estimated frailty score of four (vulnerable) was lower than those with an estimated score of 5 or greater (331.5 vs 594 days, p < 0.0001). One-year survival was 79% (75, 84), whilst 5-year survival was 69% (65, 75). Hazard ratios for ‘vulnerable’ and ‘frail’ sub-groups were estimated as 2.6 and 2.4 respectively. Conclusion: There is significant evidence to suggest a strong causal association between frailty and survival after ICU admission. ‘Vulnerable’ status may well be associated with similar effect on long-term survival to that of ‘frailty’.
Evaluating histone modification analysis of individual preimplantation embryos
Authors: Zeng Yiren , Hoshino Yoichiro , Susami Kazuki , Honda Shinnosuke , Minami Naojiro , Ikeda Shuntaro 
Published: January 2024

Abstract
Background
We previously reported a modification of the CUT&Tag method (NTU-CAT) that allows genome-wide histone modification analysis in individual preimplantation embryos. In the present study, NTU-CAT was further simplified by taking advantage of the Well-of-the-Well (WOW) system, which enables the processing of multiple embryos in a shorter time with less reagent and cell loss during the procedure (WOW-CUT&Tag, WOW-CAT).

Results
WOW-CAT allowed histone modification profiling from not only a single blastocyst but also from a portion of it. WOW-CAT generated similar H3K4me3 profiles as NTU-CAT, but they were closer to the profiles produced by chromatin immunoprecipitation-sequencing, such as a valley-like trend and relatively lower false positive rates, indicating that WOW-CAT may attenuate the bias of Tn5 transposase to cut open chromatin regions. Simultaneous WOW-CAT of two halves of single blastocysts was conducted to analyze two different histone modifications (H3K4me3 and H3K27ac) within the same embryo. Furthermore, trophectoderm cells were biopsied and subjected to WOW-CAT in anticipation of preimplantation diagnosis of histone modifications. WOW-CAT allowed the monitoring of epigenetic modifications in the main body of the embryo. For example, analysis of H3K4me3 modifications of XIST and DDX3Y in trophectoderm biopsies could be used to sex embryos in combination with quantitative PCR, but without the need for deep sequencing.

Conclusions
These results suggest the applicability of WOW-CAT for flexible epigenetic analysis of individual embryos in preimplantation epigenetic diagnosis.
Impact of intraoperative fluid management on postoperative complications in patients undergoing minimally invasive esophagectomy for esophageal cancer: a retrospective single-center study
Authors: Takahashi Misaki , Toyama Hiroaki , Takahashi Kazuhiro , Kaiho Yu , Ejima Yutaka , Yamauchi Masanori 
Published: January 2024

Abstract
Background
Esophagectomy is a high-risk procedure that can involve serious postoperative complications. There has been an increase in the number of minimally invasive esophagectomies (MIEs) being performed. However, the relationship between intraoperative management and postoperative complications in MIE remains unclear.

Methods
After the institutional review board approval, we enrolled 300 patients who underwent MIE at Tohoku University Hospital between April 2016 and March 2021. The relationships among patient characteristics, intraoperative and perioperative factors, and postoperative complications were retrospectively analyzed. The primary outcome was the relationship between intraoperative fluid volume and anastomotic leakage, and the secondary outcomes included the associations between other perioperative factors and postoperative complications.

Results
Among 300 patients, 28 were excluded because of missing data; accordingly, 272 patients were included in the final analysis. The median [interquartile range] operative duration was 599 [545–682] minutes; total intraoperative infusion volume was 3,747 [3,038–4,399] mL; total infusion volume per body weight per hour was 5.48 [4.42–6.73] mL/kg/h; and fluid balance was + 2,648 [2,015–3,263] mL. The postoperative complications included anastomotic leakage in 68 (25%) patients, recurrent nerve palsy in 91 (33%) patients, pneumonia in 62 (23%) patients, cardiac arrhythmia in 13 (5%) patients, acute kidney injury in 5 (2%) patients, and heart failure in 5 (2%) patients. The Cochrane-Armitage trend test indicated significantly increased anastomotic leakage among patients with a relatively high total infusion volume (P = 0.0085). Moreover, anastomotic leakage was associated with male sex but not with peak serum lactate levels. Patients with a longer anesthesia duration or recurrent nerve palsy had a significantly higher incidence of postoperative pneumonia than those without. Further, the incidence of postoperative pneumonia was not associated with the operative duration, total infusion volume, or fluid balance. The operative duration and blood loss were related to the total infusion volume. Acute kidney injury was not associated with the total infusion volume or serum lactate levels.

Conclusions
Among patients who underwent MIE, the total infusion volume was positively correlated with the incidence of anastomotic leakage. Further, postoperative pneumonia was associated with recurrent nerve palsy but not total infusion volume or fluid balance.
Multisite spontaneous hematomas and bleeding in critically ill Chinese patients with COVID-19: two case reports and a literature review
Authors: Sha Sha , Qi Sun , Qindong Shi 
Published: January 2024

Abstract
Background
Anticoagulation is recommended as a standardized therapy for COVID-19 patients according to the WHO guidelines. However, bleeding events have also been reported. Hemorrhage or hematoma was observed in sites including the retroperitoneum, brain, alimentary tract, muscles, and soft tissues. Reduction or suspension of anticoagulants is a common intervention. Transfusion, endoscopic hemostasis, and vascular interventional therapy have been used to improve the condition.

Case presentation
In this article, we present two cases of concurrent multisite hematomas and bleeding at other sites in patients with SARS-CoV-2 infection. Both patients were treated with heparins and experienced bleeding after the anticoagulation therapy. Both patients were older with more than two comorbidities, and critical COVID-19. Laboratory tests revealed a considerable decrease in hemoglobin levels and alterations in the coagulation system. In the first patient, the main intervention was embolization using angiography. However, we only adjusted the anticoagulation strategy in the second case. The first patient recovered and was discharged; however, the second died of other causes. This study provides a retrospective review of typical hemorrhagic cases during anticoagulation in COVID-19 patients over the course of four years. A relatively comprehensive search was performed in Pubmed by constructing MeSH subject terms on limiting the search period and specific contents. It summarizes and synthesizes the research related to heparins and other novel anticoagulants in the context of COVID-19 from the onset of the pandemic to the present disseminated phase. This study aimed to offer valuable insights and reference points for developing anticoagulation treatment strategies for patients with COVID-19.

Conclusions
Anticoagulation is a crucial treatment option for patients with COVID-19. The difference in anticoagulant effects is related to the severity of COVID-19. Nafamostat can reduce thrombosis in the extracorporeal circuits in critically ill patients with COVID-19. The efficacy and safety of novel anticoagulants require further clinical data. Routine bedside assessments and real-time laboratory monitoring are essential for early identification of bleeding events during anticoagulant therapy and administering intervention.
Efficacy of treatment patterns based on concurrent chemoradiotherapy in patients with stage IIB cervical squamous cell carcinoma
Authors: Pan Xin-Bin , Lu Yan , Wei You-Sheng , Yao De-Sheng 
Published: January 2024

Abstract
Purpose
To assess survival of treatment patterns based on concurrent chemoradiotherapy (CCRT) in patients with stage IIB cervical squamous cell carcinoma (CSCC).

Materials and methods
Patients with stage IIB CSCC receiving CCRT were investigated from June 2012 to June 2019 in Guangxi Medical University Cancer Hospital. Baseline characteristics and treatment patterns were described. Survival between treatment patterns were compared using Kaplan-Meier methods.

Results
A total of 232 patients were included: 39.7% of patients received CCRT alone, 6.5% of patients received neoadjuvant chemotherapy (NACT) + CCRT, 45.6% of patients received CCRT + adjuvant chemotherapy (AC), and 8.2% of patients received NACT + CCRT + AC. CCRT + AC showed similar overall survival (OS; hazard ratio [HR] = 0.95, 95% confidence interval [CI]: 0.41–2.17; P = 0.894) and locoregional-free survival (LRFS; HR = 2.39, 95% CI: 0.45–12.63; P = 0.303) compared with CCRT. However, CCRT + AC had a worse distant metastasis-free survival (DMFS; HR = 5.39, 95% CI: 1.14–25.57; P = 0.034). After propensity score matching, CCRT + AC had comparable OS (HR = 0.89, 95% CI: 0.29–2.70; P = 0.833), LRFS (HR = 3.26, 95% CI: 0.30-35.38; P = 0.331), and DMFS (HR = 4.80, 95% CI: 0.55–42.26; P = 0.157) compared to CCRT.

Conclusion
AC did not improve survival in patients with stage IIB CSCC receiving CCRT.
Paclitaxel liposome (Lipusu) based chemotherapy combined with immunotherapy for advanced non-small cell lung cancer: a multicenter, retrospective real-world study
Authors: Li Ran , Liang Hongge , Li Jun , Shao Zhenyu , Yang Donghong , Bao Jing , Wang Keqiang , Xi Wen , Gao Zhancheng , Guo Renhua , Mu Xinlin 
Published: January 2024

Abstract
Background
Paclitaxel liposome (Lipusu) is known to be effective in non-small cell lung cancer (NSCLC) as first-line treatment. This study aimed to evaluate the effectiveness and safety of paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in patients with advanced NSCLC.

Methods
In this multicenter, retrospective, real-world study, patients with advanced NSCLC who were administered paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor in three centers (Peking University People’s Hospital as the lead center) in China between 2016 and 2022 were included. Progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate, and adverse events (AEs) were evaluated.

Results
A total of 49 patients were included, with 33 (67.3%) receiving paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor as first-line treatment. There were 34 patients (69.4%) diagnosed with squamous cell carcinoma and 15 (30.6%) with adenocarcinoma. The median follow-up was 20.5 (range: 3.1–41.1) months. The median PFS and OS of all patients were 9.7 months (95% confidence interval [CI], 7.0-12.4) and 30.5 months (95% CI, not evaluable-not evaluable), respectively. Patients with squamous cell carcinoma and adenocarcinoma had median PFS of 11 months (95%CI, 6.5–15.5) and 9.3 months (95%CI, 7.0-12.4), respectively. The median PFS was 9.9 months (95%CI, 7.1–12.7) in patients who received the combined regimen as first-line treatment. Treatment-related AEs of any grade were observed in 25 (51.0%) patients, and AEs of grade 3 or worse were observed in nine patients (18.4%). The most common treatment-related AEs were myelosuppression (14.3%) and fever (10.2%).

Conclusions
Paclitaxel liposome based chemotherapy plus PD-1/PD-L1 inhibitor prolonged the PFS in advanced NSCLC with acceptable safety, which was worthy of clinical application.
Digital protractor as an intraoperative guide to cup anteversion in total hip arthroplasty
Authors: Yi Ning , Yuan Hang , Xu Nanwei , Liu Ruiping , Wang Yuji , Zhuang Chao 
Published: January 2024

Abstract
Introduction
To explore if digital protractor could guide the anteversion of acetabular cup during primary THA and make it consistent with preoperative.

Methods
We retrospectively reviewed 172 cases of primary THA with direct anterior approach (DAA) over 2 years. The anteversion of acetabular cup were measured from computed tomography (CT) scan preoperative and de-identified plain radiographs postoperative by two blinded investigators who were not involved in the surgery. The effect of the digital protractor on the anteversion was determined using regression analysis.

Results
The mean anteversion for the THAs in digital protractor group was 15.5°and 21.4°in control group (P < 0.01). The mean anteversion bias for the THAs in digital protractor group was 1.59° and 6.63° in control group (P < 0.01).Regression analysis identified a 10.7% difference in anteversion due to the use of digital protractor (P < 0.01), and THAs performed without digital protractor were six times more likely to result in anteversion of > 25°. The correlation coefficient for the interobserver reliability of the measurement of the two investigators was 0.94.

Conclusion
The digital protractor is a practical tool in the DAA for THA to determine the anteversion of the acetabular prosthesis.
Time-Controlled Adaptive Ventilation (TCAV): a personalized strategy for lung protection
Authors: Al-Khalisy Hassan , Nieman Gary F. , Kollisch-Singule Michaela , Andrews Penny , Camporota Luigi , Shiber Joseph , Manougian Toni , Satalin Joshua , Blair Sarah , Ghosh Auyon , Herrmann Jacob , Kaczka David W. , Gaver Donald P. , Bates Jason H. T. , Habashi Nader M. 
Published: January 2024

AbstractAcute respiratory distress syndrome (ARDS) alters the dynamics of lung inflation during mechanical ventilation. Repetitive alveolar collapse and expansion (RACE) predisposes the lung to ventilator-induced lung injury (VILI). Two broad approaches are currently used to minimize VILI: (1) low tidal volume (LVT) with low-moderate positive end-expiratory pressure (PEEP); and (2) open lung approach (OLA). The LVT approach attempts to protect already open lung tissue from overdistension, while simultaneously resting collapsed tissue by excluding it from the cycle of mechanical ventilation. By contrast, the OLA attempts to reinflate potentially recruitable lung, usually over a period of seconds to minutes using higher PEEP used to prevent progressive loss of end-expiratory lung volume (EELV) and RACE. However, even with these protective strategies, clinical studies have shown that ARDS-related mortality remains unacceptably high with a scarcity of effective interventions over the last two decades. One of the main limitations these varied interventions demonstrate to benefit is the observed clinical and pathologic heterogeneity in ARDS. We have developed an alternative ventilation strategy known as the Time Controlled Adaptive Ventilation (TCAV) method of applying the Airway Pressure Release Ventilation (APRV) mode, which takes advantage of the heterogeneous time- and pressure-dependent collapse and reopening of lung units. The TCAV method is a closed-loop system where the expiratory duration personalizes VT and EELV. Personalization of TCAV is informed and tuned with changes in respiratory system compliance (CRS) measured by the slope of the expiratory flow curve during passive exhalation. Two potentially beneficial features of TCAV are: (i) the expiratory duration is personalized to a given patient’s lung physiology, which promotes alveolar stabilization by halting the progressive collapse of alveoli, thereby minimizing the time for the reopened lung to collapse again in the next expiration, and (ii) an extended inspiratory phase at a fixed inflation pressure after alveolar stabilization gradually reopens a small amount of tissue with each breath. Subsequently, densely collapsed regions are slowly ratcheted open over a period of hours, or even days. Thus, TCAV has the potential to minimize VILI, reducing ARDS-related morbidity and mortality.
Graphical Abstract
Increased regulatory activity of intestinal innate lymphoid cells type 3 (ILC3) prevents experimental autoimmune encephalomyelitis severity
Authors: Lazarević Milica , Stegnjaić Goran , Jevtić Bojan , Despotović Sanja , Ignjatović Đurđica , Stanisavljević Suzana , Nikolovski Neda , Momčilović Miljana , Fraser Graeme L. , Dimitrijević Mirjana , Miljković Đorđe 
Published: January 2024

AbstractExperimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice
Authors: Wakatsuki Koji , Kiryu-Seo Sumiko , Yasui Masaya , Yokota Hiroki , Kida Haruku , Konishi Hiroyuki , Kiyama Hiroshi 
Published: January 2024

Abstract
Background
Fibromyalgia is characterized by chronic pain, fatigue, and other somatic symptoms. We have recently revealed that proprioceptor hyperactivation induces chronic pain in a rat model of myalgic encephalomyelitis. The present study explores whether similar proprioceptor-induced pain is elicited in a mouse model of fibromyalgia.

Methods
Repeated cold stress (RCS) was used as a fibromyalgia model. Pain behavior was examined using the von Frey test, and neuronal activation was examined immunohistochemically as activating transcription factor (ATF)3 expression. The Atf3:BAC transgenic mouse, in which mitochondria in hyperactivated neurons are specifically labeled by green fluorescent protein, was used to trace the activated neuronal circuit. PLX3397 (pexidartinib) was used for microglial suppression.

Results
RCS elicited long-lasting pain in mice. ATF3, a marker of cellular hyperactivity and injury, was expressed in the lumbar dorsal root ganglion (DRG) 2 days after RCS initiation; the majority of ATF3-expressing DRG neurons were tropomyosin receptor kinase C- and/or vesicular glutamate transporter 1-positive proprioceptors. Microglial activation and increased numbers of microglia were observed in the medial part of the nucleus proprius 5 days after RCS initiation, and in the dorsal region of the ventral horn 7 days after RCS. In the ventral horn, only a subset of motor neurons was positive for ATF3; these neurons were surrounded by activated microglia. A retrograde tracer study revealed that ATF3-positive motor neurons projected to the intrinsic muscles of the foot (IMF). Using Atf3:BAC transgenic mice, we traced hyperactivated neuronal circuits along the reflex arc. Green fluorescent protein labeling was observed in proprioceptive DRG neurons and their processes originating from the IMF, as well as in motor neurons projecting to the IMF. Microglial activation was observed along this reflex arc, and PLX3397-induced microglial ablation significantly suppressed pain behavior.

Conclusion
Proprioceptor hyperactivation leads to local microglial activation along the reflex arc; this prolonged microglial activation may be responsible for chronic pain in the present model. Proprioceptor-induced microglial activation might be the common cause of chronic pain in both the fibromyalgia and myalgic encephalomyelitis models, although the experimental models are different.
Efficacy of direct-to-operating room trauma resuscitation: a systematic review
Authors: Seo Dongmin , Heo Inhae , Choi Donghwan , Jung Kyoungwon , Jung Hohyung 
Published: January 2024

Abstract
Background
Hemorrhage control is a time-critical task, and recent studies have demonstrated that a shorter time to definitive care is positively associated with patient survival and functional outcomes. The concept of direct transport to the operating room was proposed in the 1960s to reduce treatment time. Some trauma centers have developed protocols for direct-to-operating room resuscitation (DOR) programs. Moreover, few studies have reported the clinical outcomes of DOR in patients with trauma; however, their clinical effect in improving the efficiency and quality of care remains unclear. In this systematic review, we aimed to consolidate all published studies reporting the effect of DOR on severe trauma and evaluate its utility.

Methods
The PubMed, EMBASE, and Cochrane databases were searched from inception to April 2023, to identify all articles published in English that reported the effect of direct-to-operating room trauma resuscitation for severe trauma. The articles were reviewed as references of interest.

Results
We reviewed six studies reporting the clinical effect of operating room trauma resuscitation. A total of 3232 patients were identified. Five studies compared the actual mortality with the predicted mortality using the trauma score and injury severity score, while one study compared mortality using propensity matching. Four studies reported that the actual survival rate for overall injuries was better than the predicted survival rate, whereas two studies reported no difference. Some studies performed subgroup analyses. Two studies showed that the survival rate for penetrating injuries was better than the predicted survival rate, and one showed that the survival rate for blunt injuries was better than the predicted survival rate. Five studies reported the time to surgical intervention, which was within 30 min. Two studies time-compared surgical intervention, which was shorter in patients who underwent DOR.

Conclusion
Implementing DOR is likely to have a beneficial effect on mortality and can facilitate rapid intervention in patients with severe shock. Future studies, possibly clinical trials, are needed to ensure a proper comparison of the efficiency.