bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacologic prevention and therapy of postoperative paralytic ileus after gastrointestinal cancer surgery: systematic review and meta-analysis
Authors: Reichert Martin , Willis Franziska , Post Stefan , Schneider Martin , Vilz Tim , Willis Maria , Hecker Andreas 
Published: March 2024

Background:
Postoperative paralytic ileus (POI) is a significant concern following gastrointestinal tumor surgery. Effective preventive and therapeutic strategies are crucial but remain elusive. Current evidence from randomized-controlled trials on pharmacological interventions for prevention or treatment of POI are systematically reviewed to guide clinical practice and future research.

Materials and methods:
Literature was systematically searched for prospective randomized-controlled trials testing pharmacological interventions for prevention or treatment of POI after gastrointestinal tumor surgery. Meta-analysis was performed using a random effects model to determine risk ratios and mean differences with 95% CI. Risk of bias and evidence quality were assessed.

Results:
Results from 55 studies, involving 5078 patients who received experimental interventions, indicate that approaches of opioid-sparing analgesia, peripheral opioid antagonism, reduction of sympathetic hyperreactivity, and early use of laxatives effectively prevent POI. Perioperative oral Alvimopan or intravenous administration of Lidocaine or Dexmedetomidine, while safe regarding cardio-pulmonary complications, demonstrated effectiveness concerning various aspects of postoperative bowel recovery [Lidocaine: −5.97 (−7.20 to −4.74)h, P<0.0001; Dexmedetomidine: −13.00 (−24.87 to −1.14)h, P=0.03 for time to first defecation; Alvimopan: −15.33 (−21.22 to −9.44)h, P<0.0001 for time to GI-2] and length of hospitalization [Lidocaine: −0.67 (−1.24 to −0.09)d, P=0.02; Dexmedetomidine: −1.28 (−1.96 to −0.60)d, P=0.0002; Alvimopan: −0.58 (−0.84 to −0.32)d, P<0.0001] across wide ranges of evidence quality. Perioperative nonopioid analgesic use showed efficacy concerning bowel recovery as well as length of hospitalization [−1.29 (−1.95 to −0.62)d, P=0.0001]. Laxatives showed efficacy regarding bowel movements, but not food tolerance and hospitalization. Evidence supporting pharmacological treatment for clinically evident POI is limited. Results from one single study suggest that Neostigmine reduces time to flatus and accelerates bowel movements [−37.06 (−40.26 to −33.87)h, P<0.0001 and −42.97 (−47.60 to −38.35)h, P<0.0001, respectively] with low evidence quality.

Conclusion:
Current evidence concerning pharmacological prevention and treatment of POI following gastrointestinal tumor surgery is limited. Opioid-sparing concepts, reduction of sympathetic hyperreactivity, and laxatives should be implemented into multimodal perioperative approaches.
Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption
Authors: Iwasa Motoh , Sugimoto Ryosuke , Eguchi Akiko , Tamai Yasuyuki , Shigefuku Ryuta , Fujiwara Naoto , Tanaka Hideaki , Kobayashi Yoshinao , Ikoma Jiro , Kaito Masahiko , Nakagawa Hayato 
Published: March 2024

Background/aims
Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. We previously reported that pemafibrate significantly improves liver function, serum triglyceride (TG) levels and liver stiffness in non-alcoholic fatty liver disease patients, however the influence of alcohol consumption was not considered. Therefore, we explored pemafibrate efficacy in patients with steatotic liver disease (SLD) and alcohol-associated liver disease (ALD).

Methods
We retrospectively evaluated pemafibrate efficacy on liver enzymes and lipids in metabolic dysfunction-associated SLD (MASLD) (n = 93), MASLD plus increased alcohol intake (MetALD; n = 23) and ALD (n = 22) patients who had taken pemafibrate for at least 48 weeks. Liver shear wave velocity (SWV, n = 75) was also evaluated.

Results
In MASLD group, ALT, aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and TG values were significantly decreased from baseline to week 24 and week 48 (P < 0.0001). ALT and TG values in MetALD group and ALT and AST values in ALD group were also significantly decreased from baseline to week 24 and week 48. Study participant SWV values decreased from baseline to week 48. We observed no significant difference in changes to ALT, AST, γ-GTP and TG (value at week 24 or week 48 minus value at baseline) among the three groups.

Conclusion
Pemafibrate improves liver function and liver stiffness thus making it a promising therapeutic agent for SLD, even in patients with excess alcohol consumption (MetALD and ALD groups).
The Construction of Peer Support Among Recently Diagnosed Breast Cancer Patients
Authors: Toija Anu , Kettunen Tarja , Kasila Kirsti 
Published: March 2024

Background
Breast cancer (BC) and its treatments decrease patients’ psychological well-being. Peer support is one form of social support, but little is known about what gives rise to peer support.

Objective
The purpose of this study was to examine how peer support is constructed among recently diagnosed BC patients.

Methods
Eighteen women were randomly picked from 130 women who had received phone calls from a trained peer supporter and were invited to group interviews. In the interviews, patients discussed their cancer, peer support experiences, and social support. The transcribed data were analyzed using Braun and Clarke’s thematic analysis approach.

Results
The construction of peer support among newly diagnosed BC patients was complex. It depended on the needs of the patient and the success of interactions. Once they had received a diagnosis, the lives of the patients changed suddenly, and patients dove into the I-we-others consideration and had a need to talk. Interaction with peer supporters gave them a chance to share their stories. At their best, interactions led to belonging, caring, and a sense of security.

Conclusions
The need to be heard and seen is strong in a patient’s changing health situation. Peer support plays an important role in high-standard care and in strengthening patients’ self-determination.

Implications for Practice
Hospitals should create chances for supportive communication, and the supportive communication should be easily accessible and successful. The training of peer supporters should ensure that they have reflected on their own BC process and know how to consider the needs of newly diagnosed patients.
Primary NTRK-rearranged Spindle Cell Neoplasm of the Gastrointestinal Tract: A Clinicopathological and Molecular Analysis of 8 Cases
Authors: Gao Xiaojiao , Xu Song , Zhu Peipei , Lao I. Weng , Yu Lin , Wang Jian 
Published: March 2024

NTRK-rearranged spindle cell neoplasm occurs predominantly in the superficial or deep soft tissues of extremities or trunk. Occurrence in the visceral organs is extremely rare. Herein, we describe 8 cases of NTRK-rearranged spindle cell neoplasm that arose primarily in the gastrointestinal tract. Patients included 5 males and 3 females with age at presentation ranging from 6 to 63 years (median: 29.5 years). Tumors occurred in the colon (n=3), small intestine (n=2), rectum (n=2), and stomach (n=1). Tumor size ranged from 3.5 to 9 cm (median: 5 cm). Morphologically, 4 tumors were low-grade, composed of haphazard or intertwining fascicles of spindle cells, with prominent interstitial collagen fibers and ring-like perivascular hyalinization being present in 2 tumors. The other 4 tumors were histologically high-grade sarcomas, consisting of sweeping fascicles of atypical spindle cells showing increased cellularity and brisk mitotic activity. Immunohistochemically, 6/6 cases (100%) showed diffuse and strong cytoplasmic staining of pan-TRK. Variable expression of TrkA, CD34, and S100 was noted in 5/5 (100%), 5/8 (62.5%), and 4/7 (57.1%) cases, respectively. Fluorescence in situ hybridization analysis showed NTRK1 rearrangement (n=7) and NTRK2 rearrangement (n=1). In cases with available materials, RNA sequencing identified LMNA::NTRK1 (n=3), TPM3::NTRK1 (n=2), and STRN::NTRK2 (n=1) fusions. At follow-up (range: 4 to 30 months; median: 12.5 months), 6 of 7 patients who underwent surgery had no evidence of disease at last follow-up. One patient was succumbed to the disease at 12 months despite adjunctive treatment with TRK inhibitor larotrectinib after surgery. One patient was treated with larotrectinib alone. He showed significant response at 7 months after treatment. NTRK-rearranged spindle cell neoplasm represents an exceptionally rare entity in the gastrointestinal tract. The presence of interstitial collagen fibers and ring-like perivascular hyalinization and co-expression of CD34 and S100 are diagnostic clues to low-grade neoplasms. However, high-grade sarcomas pose a considerable diagnostic challenge to pathologists owing to the lack of specific features. The final diagnosis relies on molecular assays. Patients with advanced disease may benefit from TRK inhibitor treatment.
Metastatic Melanoma Treatment in Special Populations
Authors: Miceli Madeline , Boatwright Christina , Mehnert Janice M. 
Published: March 2024

Abstract
This review outlines the most up-to-date metastatic melanoma treatment recommendations and relevant risks for patients with solid organ transplants, patients with renal dysfunction, and patients with preexisting autoimmune conditions. These specific treatment populations were excluded from the original clinical trials, which studied immune checkpoint inhibitors and BRAF/MEK inhibitors in the advanced melanoma setting. We have synthesized the current body of literature, mainly case series and retrospective analyses, to reflect the evidence for the treatment of these special patient populations at present.
Tumor-Infiltrating Lymphocyte and Other Cell Therapies for Metastatic Melanoma
Authors: Los Christy , Klobuch Sebastian , Haanen John B. A. G. 
Published: March 2024

Abstract
Major progress in prolonging survival of patients with advanced melanoma has been made in the past decade because of the development and approval of immune checkpoint inhibitor and targeted therapies. However, for nonresponding or relapsing patients, their prognosis is still dismal. Based on clinical trial data, treatment with adoptive cell therapies holds great promise. In patients with metastatic melanoma progressing on or nonresponsive to single-agent anti–programmed cell death 1, infusion of tumor-infiltrating lymphocytes can produce responses in up to half of patients, with durable complete responses in up to 20%. Genetic modification of peripheral blood T cells with T-cell receptors derived from tumor-specific T cells, or with chimeric antigen receptors, has the potential to further improve treatment outcomes in this refractory population. In this review, we will discuss the historical development, current status, and future perspectives of adoptive T-cell therapies in melanoma.
Treatment of Stage III Resectable Melanoma—Adjuvant and Neoadjuvant Approaches
Authors: Tarhini Ahmad A. , Castellano Ella , Eljilany Islam 
Published: March 2024

Abstract
Patients with stage III resectable melanoma carry a high risk of melanoma recurrence that ranges from approximately 40% to 90% at 5 years following surgical management alone. Postoperative systemic adjuvant therapy targets residual micrometastatic disease that could be the source of future recurrence and death from melanoma. Randomized phase III adjuvant trials reported significant improvements in overall survival with high-dose interferon α in 2 of 3 studies (compared with observation and GMK ganglioside vaccine) and with anti–cytotoxic T-lymphocyte antigen 4 ipilimumab at 10 mg/kg compared with placebo and ipilimumab 3 mg/kg compared with high-dose interferon α. In the modern era, more recent phase III trials demonstrated significant recurrence-free survival improvements with anti–programmed cell death protein 1, pembrolizumab, and BRAF-MEK inhibitor combination dabrafenib-trametinib (for BRAF mutant melanoma) versus placebo. Furthermore, anti–programmed cell death protein 1, nivolumab and pembrolizumab have both been shown to significantly improve recurrence-free survival as compared with ipilimumab 10 mg/kg. For melanoma patients with clinically or radiologically detectable locoregionally advanced disease, emerging data support an important role for preoperative systemic neoadjuvant therapy. Importantly, a recent cooperative group trial (S1801) reported superior event-free survival rates with neoadjuvant versus adjuvant therapy. Collectively, current data from neoadjuvant immunotherapy and targeted therapy trials support a future change in clinical practice in favor of neoadjuvant therapy for eligible melanoma patients.
Current Role and Status for Intratumoral Injection Therapies in Metastatic Melanoma
Authors: Haugh Alexandra M. , Daud Adil I. 
Published: March 2024

Abstract
Intratumoral therapies represent a unique avenue for drug development in melanoma as patients often have accessible lesions that are particularly amenable to these approaches. In addition, a majority of intratumoral therapies have focused on stimulating antitumor immune responses, making them a particularly attractive option for use in melanoma. In this review, we describe applications for talimogene laherparepvec, a US Food and Drug Administration–approved intratumoral therapy in melanoma, as well as several classes of intratumoral therapies in development including novel oncolytic viruses, mRNA-based intratumoral injections, and cytokines and other signaling molecules.
What Is the Timing and Role of Targeted Therapy in Metastatic Melanoma?
Authors: Hadfield Matthew J. , Sullivan Ryan J. 
Published: March 2024

Abstract
Melanoma is the most lethal cutaneous malignancy worldwide. The last 15 years have ushered in several regulatory approvals that have dramatically altered the landscape of treatment options for patients with melanoma. Many patients with melanoma harbor activating mutations in the BRAF proto-oncogene, a key component of the mitogen-activated protein kinase (MAPK) intracellular signaling pathway. Therapies targeting BRAF have led to remarkable improvements in both response rates and survival in patients with metastatic disease. In parallel with these developments in MAPK-targeted therapy has been the clinical development of immune checkpoint inhibitors, which also have improved response rates and survival in patients with metastatic disease including randomized trials compared with MAPK-targeted therapy in patients with advanced, BRAF-mutant melanoma. Immune checkpoint inhibitors have become the preferred first-line standard-of-care treatment for patients with newly diagnosed metastatic disease in patients irrespective of BRAF mutational status. Given these developments, it is now less clear how to optimize the use of MAPK-targeted therapy regarding treatment setting and in sequence with immune checkpoint inhibitor.
An Executive Summary of the National Trauma Research Action Plan (NTRAP)
Authors: Bulger Eileen M. , Bixby Pamela J. , Price Michelle A. , Villarreal Cynthia Lizette , Moreno Ashley N. , Herrera-Escobar Juan Pablo , Bailey Jeffrey A. , Brasel Karen J. , Cooper Zara R. , Costantini Todd W. , Gibran Nicole S. , Groner Jonathan I. , Joseph Bellal A. , Newgard Craig D. , Stein Deborah M. 
Published: March 2024

AbstractThe National Trauma Research Action Plan (NTRAP) project successfully engaged multidisciplinary experts to define opportunities to advance trauma research and has fulfilled the recommendations related to trauma research from the National Academies of Sciences, Engineering and Medicine (NASEM) report. These panels identified more than 4,800 gaps in our knowledge regarding injury prevention and the optimal care of injured patients and laid out a priority framework and tools to support researchers to advance this field. Trauma research funding agencies and researchers can use this executive summary and supporting manuscripts to strategically address and close the highest priority research gaps. Given that this is the most significant public health threat facing our children, young adults, and military service personnel, we must do better in prioritizing these research projects for funding and providing grant support to advance this work. Through the Coalition for National Trauma Research (CNTR), the trauma community is committed to a coordinated, collaborative approach to address these critical knowledge gaps and ultimately reduce the burden of morbidity and mortality faced by our patients.
Reducing low-value interhospital transfers for mild traumatic brain injury
Authors: Shen Aricia , Mizraki Nathaniel , Maya Marcel , Torbati Sam , Lahiri Shouri , Chu Ray , Margulies Daniel R. , Barmparas Galinos 
Published: March 2024

BACKGROUND
The modified Brain Injury Guidelines (mBIG) were developed to stratify traumatic brain injuries (TBIs) and improve health care utilization by selectively requiring repeat imaging, intensive care unit admission, and neurosurgical (NSG) consultation. The goal of this study is to assess safety and potential resource savings associated with the application of mBIG on interhospital patient transfers for TBI.

METHODS
Adult patients with TBI transferred to our Level I trauma center from January 2017 to December 2022 meeting mBIG inclusion criteria were retrospectively stratified into mBIG1, mBIG2, and mBIG3 based on initial clinicoradiological factors. At the time, our institution routinely admitted patients with TBI and intracranial hemorrhage (ICH) to the intensive care unit and obtained a repeat head computed tomography with NSG consultation, independent of TBI severity or changes in neurological examination. The primary outcome was progression of ICH on repeat imaging and/or NSG intervention. Secondary outcomes included length of stay and financial charges. Subgroup analysis on isolated TBI without significant extracranial injury was performed.

RESULTS
Over the 6-year study period, 289 patients were classified into mBIG1 (61; 21.1%), mBIG2 (69; 23.9%), and mBIG3 (159; 55.0%). Of mBIG1 patients, 2 (2.9%) had radiological progression to mBIG2 without clinical decline, and none required NSG intervention. Of mBIG2, 2 patients (3.3%) progressed to mBIG3, and both required NSG intervention. More than 35% of transferred patients had minor isolated TBI. For mBIG1 and mBIG2, the median hospitalization charges per patient were $152,296 and $149,550, respectively, and the median length of stay was 4 and 5 days, respectively, with the majority downgraded from the intensive care unit within 48 hours.

CONCLUSION
Clinically significant progression of ICH occurred infrequently in 1.5% of patients with mBIG1 and mBIG2 injuries. More than 35% of interfacility transfers for minor isolated TBI meeting mBIG1 and 2 criteria are low value and may potentially be safely deferred in an urban health care setting.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level IV.
To close or not to close? Wound management in emergent colorectal surgery, an EAST multicenter prospective cohort study
Authors: Feather Cristina B. , Rehrig Scott , Allen Rebecca , Barth Nadine , Kugler Emmalee M. , Cullinane Daniel C. , Falank Carolyne R. , Bhattacharya Bishwajit , Maung Adrian A. , Seng Sirivan , Ratnasekera Asanthi , Bass Gary Alan , Butler Dale , Pascual Jose L. , Srikureja Daniel , Winicki Nolan , Lynde Jennifer , Nowak Brittany , Azar Faris , Thompson Lauren A. , Nahmias Jeffry , Manasa Morgan , Tesoriero Ronald , Kumar Sandhya B. , Collom Morgan , Kincaid Michelle , Sperwer Kimberly , Santos Ariel P. , Klune J. Robert , Turcotte Justin 
Published: March 2024

BACKGROUND
This study aimed to determine the clinical impact of wound management technique on surgical site infection (SSI), hospital length of stay (LOS), and mortality in emergent colorectal surgery.

METHODS
A prospective observational study (2021–2023) of urgent or emergent colorectal surgery patients at 15 institutions was conducted. Pediatric patients and traumatic colorectal injuries were excluded. Patients were classified by wound closure technique: skin closed (SC), skin loosely closed (SLC), or skin open (SO). Primary outcomes were SSI, hospital LOS, and in-hospital mortality rates. Multivariable regression was used to assess the effect of wound closure on outcomes after controlling for demographics, patient characteristics, intensive care unit admission, vasopressor use, procedure details, and wound class. A priori power analysis indicated that 138 patients per group were required to detect a 10% difference in mortality rates.

RESULTS
In total, 557 patients were included (SC, n = 262; SLC, n = 124; SO, n = 171). Statistically significant differences in body mass index, race/ethnicity, American Society of Anesthesiologist scores, EBL, intensive care unit admission, vasopressor therapy, procedure details, and wound class were observed across groups. Overall, average LOS was 16.9 ± 16.4 days, and rates of in-hospital mortality and SSI were 7.9% and 18.5%, respectively, with the lowest rates observed in the SC group. After risk adjustment, SO was associated with increased risk of mortality (OR, 3.003; p = 0.028) in comparison with the SC group. Skin loosely closed was associated with increased risk of superficial SSI (OR, 3.439; p = 0.014), after risk adjustment.

CONCLUSION
When compared with the SC group, the SO group was associated with mortality but comparable when considering all other outcomes, while the SLC was associated with increased superficial SSI. Complete skin closure may be a viable wound management technique in emergent colorectal surgery.

LEVEL OF EVIDENCE
Therapeutic/Care Management; Level III.
Opportunities and limits of lunar gravitational-wave detection
Authors: Cozzumbo Andrea , Mestichelli Benedetta , Mirabile Marco , Paiella Lavinia , Tissino Jacopo , Harms Jan 
Published: March 2024

A new era of lunar exploration has begun with participation of all major space agencies. This activity brings opportunities for revolutionary science experiments and observatories on the Moon. The idea of a lunar gravitational-wave detector was already proposed during the Apollo programme. The key characteristic of the Moon is that it is seismically extremely quiet. It was also pointed out that the permanently shadowed regions at the lunar poles provide ideal conditions for gravitational-wave detection. In recent years, three different detector concepts were proposed with varying levels of technological complexity and science potential. In this paper, we confront the three concepts in terms of their observational capabilities based on a first more detailed modelling of instrumental noise. We identify important technological challenges and potential show-stoppers.
This article is part of a discussion meeting issue ‘Astronomy from the Moon: the next decades (part 2)’.