bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Type of Immunosuppression and the Incidence, Microbiology, and Outcomes of Bacterial Ventilator-Associated Lower Respiratory Tract Infections: A Retrospective Multicenter Study
Authors: Kreitmann Louis , Bayon Constance , Martin-Loeches Ignacio , Póvoa Pedro , Salluh Jorge , Rouzé Anahita , Moreau Anne-Sophie , Duhamel Alain , Labreuche Julien , Nseir Saad ,   for the Type of iMmunosuppression and the Incidence, Microbiology, and OutcomeS of ventilator-Associated lower respiratory tract infections (MIMOSA) Study Group
Published: February 2025

Objectives:
Ventilator-associated lower respiratory tract infections (VALRTIs) are among the most common ICU-acquired infections in patients receiving invasive mechanical ventilation (IMV). Immunocompromised patients may have a lower incidence of VALRTI when compared with nonimmunocompromised patients, but the influence of the type of immunosuppression on the epidemiology of VALRTI has not been investigated. The study objectives were to assess the association of the type of immunosuppression with the incidence, microbiology, and outcomes (ICU mortality, ICU length of stay, and duration of IMV) of VALRTI related to bacterial pathogens.

Design:
Multicenter, international retrospective cohort study.

Setting:
One hundred eighteen ICUs (118) in nine countries.

Patients:
Eight hundred fifty-four immunocompromised adult patients (median age, 65 yr; 57.6% males) requiring IMV for greater than 48 hours, including 162 with hematologic malignancies.

Interventions:
None.

Measurements and Main Results:
Patients with hematologic malignancies had a lower 28-day cumulative incidence of bacterial VALRTI than patients with other types of immunosuppression (13.6% vs. 20.1%; adjusted cause-specific hazard ratio, 0.61; 95% CI, 0.37–0.97), mostly due to a lower incidence of ventilator-associated pneumonia (9.3% vs. 13.9%). The proportion of VALRTI cases related to multidrug-resistant bacteria was similar between groups. Occurrence of bacterial VALRTI was associated with an increased mortality and a longer ICU length of stay, but this effect was independent of the type of immunosuppression.

Conclusions:
Patients with hematologic malignancies had a lower 28-day cumulative incidence of bacterial VALRTI than patients with other types of immunosuppression, mainly due to a lower incidence of ventilator-associated pneumonia.
Outcome Following Surgical Treatment for Chronic Pilonidal Sinus Disease: A Systematic Review of Common Surgical Techniques
Authors: Wiinblad Ida-Marie Myron , Ulrichsen Johan , Brandstrup Birgitte 
Published: February 2025

BACKGROUND:
The choice of operation for chronic pilonidal sinus disease remains controversial.

OBJECTIVE:
To compare the outcomes of common operations for chronic pilonidal disease.

DATA SOURCES:
We searched PubMed, Embase, and Cochrane Library.

STUDY SELECTION:
We included randomized trials in English or Danish language, published 2002-2024 comparing operations treating chronic pilonidal disease in adults and teenagers.

INTERVENTIONS:
We compared the outcomes of secondary healing, primary midline closure, Bascom’s-, Limberg’s- and Karydakis' flap operations.

MAIN OUTCOME MEASURES:
The primary outcome was recurrence; secondary outcomes were infection, healing time, and length-of-stay. We compared recurrence and infection rates in meta-analyses for all techniques. We assessed the risk-of-bias and the quality of all trials.

RESULTS:
Fifty trials included a total of 5762 participants. In a meta-analysis, the flap-operations had fewer recurrences than primary midline closure (OR 0.31 (95% CI, 0.19 to 0.51, p < 0.01). The trials comparing Flap-operations with secondary healing were heterogeneous and did not reach significance (OR 0.38 (95% CI, 0.13 to 1.13, p = 0.08). Recurrence was similar between Limberg’s- and Karydakis' operations. Infection rates were lower for the flap-operations compared with primary closure (OR 0.33 (95% CI, 0.23 to 0.48, p < 0.01) and with secondary healing (OR 0.48 (95% CI, 0.30 to 0.77, p < 0.01). Two trials tested Bascom's procedure against Limberg’s operation without significant differences. All trials found secondary healing to have significantly longer healing times than any other operation.

LIMITATIONS:
Most studies had a high or medium risk-of-bias, resulting in very-low to low certainty of evidence. The trials generally had small numbers, short follow-ups, and no reported primary outcomes or power calculations.

CONCLUSIONS:
Primary closure and secondary healing performed poorly compared with the flap techniques. Most trials tested Limberg’s operation; only 2 tested Bascom's operation. The literature suggests the surgeon's expertise determines the choice of flap technique.
Changes in Relationship Dynamics in Men and Women After Receiving the Diagnosis of Breast Versus Prostate Cancer: A Population-based Study
Authors: Heath Frederick , Ockerman Kyle , Wiesemann Gayle S. , Safeek Rachel , Heath Marie , Momeni Arash , Spiguel Lisa R. , Kovach Stephen , Sorice-Virk Sarah 
Published: February 2025

Background:
Relationship changes after cancer are prevalent yet underexplored. This investigation aimed to assess factors influencing relationship changes between participants receiving the 2 most common gender-specific cancer diagnoses: breast and prostate.

Methods:
Anonymous surveys were administered via Amazon Mechanical Turk. Eligible participants were 18 years or older and diagnosed with breast or prostate cancer. Relationship satisfaction and mental health were assessed via Personal Health Questionnaire Depression Scale (PHQ-8), General Anxiety Disorder (GAD-7), and Self-Esteem and Relationship Questionnaire.

Results:
Of the 186 study respondents, 85.4% (159) had breast cancer and 14.5% (27) had prostate cancer. More breast cancer participants reported that their relationship worsened after cancer diagnosis (breast: 40.9%, prostate: 11.1%), whereas a majority of prostate cancer patients reported improved relationships (breast: 17%, prostate: 66.7%; P < 0.001). However, most participants reported no relationship status change (breast: 66.7%, prostate: 77.8%; P = 0.508) and remained with the same partner postdiagnosis (breast: 84.9%; prostate: 77.8%). Breast cancer participants reported higher self-esteem compared with prostate cancer participants (P = 0.019). There was no significant difference in overall Self-Esteem and Relationship Questionnaire (P = 0.140), PHQ-8 (P = 0.689), and GAD-7 (P = 0.871) scores. Average PHQ-8 and GAD-7 scores indicated moderate depression (breast: 12.62, prostate: 12.88) and moderate anxiety (breast: 10.96, prostate: 11.06).

Conclusions:
Breast cancer participants reported greater perceived changes in their relationship postdiagnosis. This study supports routine, active, and pre-emptive involvement of a mental health provider for patients with cancer to improve mental health outcomes.
The Impact of a High Sensitivity Troponin HEART Pathway-Based Clinical Decision Protocol on Observation Visits
Authors: Hughes George B. , Emeli Iyesatta , Wheatley Matthew A. , Goyal Abhinav , Bryksin Janetta , Moran Timothy P. , Keadey Matthew T. , Ross Michael A. 
Published: February 2025

Background:
Use of high-sensitivity troponin (hs-cTn) might lead to an increase in hospital observation visits due to a higher number of abnormal troponin levels.

Study objective(s):
To determine the impact of incorporating hs-cTn into a chest pain clinical decision protocol (CDP) on observation visits in a large academic health system.

Methods:
This is a retrospective observational cohort study of all chest pain observation patients in 4 hospitals in an academic health system over 24 months. All hospitals used the Beckman Coulter Unicel Dxi instrument, and all shared the same emergency department (ED) chest pain protocol, which used the HEART pathway and serial troponins and directed ED dispositions to either an observation stay, ED discharge, or inpatient admission. Outcomes studied before and after the introduction of an hs-cTn protocol included daily chest pain observation census, cost, observation hours, and inpatient admit rate. Census was reported as the daily chest pain observation census and as a proportion of all observation visits. Data were retrieved from a health system data warehouse and a cost accounting program.

Results:
There were 6712 chest pain observation visits over 24 months, with 4087 visits before and 2634 visits after the hs-cTn protocol implementation. Comparison groups were similar in terms of age, gender, and type of insurance. There were 10.59 (95% CI, 10.24-10.95) daily chest pain observation visits before and 7.66 (95% CI, 7.34-7.97) visits after implementation, with a 28% (95% CI, 35%-20%) decrease in the total daily census. As a portion of all observation visits, there was a 22% drop in the proportion that were observed for chest pain. The daily number of chest pain patients requiring inpatient admission was unchanged. The daily total direct cost for chest pain observation decreased with an effective daily cost savings of $4313 USD (95% CI, $1534-$6998). The total daily number of chest pain observation bed hours also decreased by 41.5 hours (95% CI, 13.4–96.4 hours).

Conclusions:
Implementation of a hs-cTn chest pain protocol was associated with a significant decrease in the number and proportion of observation visits, a decrease in total daily cost and bed hours used, and no increase in inpatient admissions.
The Phoenix Sepsis Score in Pediatric Oncology Patients With Sepsis at PICU Admission: Test of Performance in a European Multicenter Cohort, 2018–2020
Authors: Wösten-van Asperen Roelie M. , la Roi-Teeuw Hannah M. , Tissing Wim J.E. , Jordan Iolanda , Dohna-Schwake Christian , Bottari Gabriella , Pappachan John , Crazzolara Roman , Amigoni Angela , Mizia-Malarz Agnieszka , Moscatelli Andrea , Sánchez-Martín María , Willems Jef , Schlapbach Luregn J. ,   on behalf of PICU Oncology Kids in Europe Research (POKER) group research consortium of European Society for Paediatric and Neonatal Intensive Care (ESPNIC)
Published: February 2025

Objectives:
The Pediatric Sepsis Definition Task Force developed and validated a new organ dysfunction score, the Phoenix Sepsis Score (PSS), as a predictor of mortality in children with suspected or confirmed infection. The PSS showed improved performance compared with prior scores. However, the criteria were derived in a general pediatric population, in which only 10% had cancer. Given that pediatric cancer patients with sepsis have higher mortality compared with noncancer patients with sepsis, we aimed to assess the PSS in PICU patients with cancer and sepsis.

Design:
Retrospective multicenter cohort study.

Setting:
Twelve PICUs across Europe.

Patients:
Each PICU identified patients 18 years young or younger, with underlying malignancy and suspected or proven sepsis, and admission between January 1, 2018, and January 1, 2020.

Interventions:
None.

Measurements and Main Results:
The PSS and three other scores, including Phoenix-8, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, and pediatric Sequential Organ Failure Assessment (pSOFA) score, were calculated for comparison. The primary outcome was 90-day all-cause mortality. We compared score performance using area under the receiver operating characteristic curve (AUROC) and area under the precision-recall curve (AUPRC) analyses. Among 383 patients with proven or suspected sepsis, 90-day mortality was 19.3% (74/383). We failed to identify an association between a particular score and performance for 90-day mortality. The mean (95% CI) values for the AUROC of each score was: PSS 0.66 (0.59–0.72), Phoenix-8 0.65 (0.58–0.72), PELOD-2 0.64 (0.57–0.71), and pSOFA 0.67 (0.60–0.74) and for the AUPRC of each score: PSS 0.32 (0.23–0.42), Phoenix-8 0.32 (0.23–0.42), PELOD-2 0.32 (0.22–0.43), and pSOFA 0.36 (0.26–0.46). Similar results were obtained for PICU mortality or sepsis-related PICU mortality.

Conclusions:
Contrary to the general PICU population, our retrospective test of the PSS in a PICU oncology dataset with suspected or proved sepsis from European PICUs, 2018–2020, failed to identify improved performance in association with mortality. This unique patient population deserves development of organ dysfunction scores that reflect organ dysfunction and mortality data specifically from these patients and will require prospective validation in future studies.
Molecular Classification of Endometrial Carcinoma: Insights From a Teaching Hospital
Authors: Saharti Samah , Altaf Fadwa 
Published: February 2025

Abstract:
Endometrial carcinoma is a heterogeneous disease with distinct molecular subtypes that have varied prognosis and therapeutic implications. Since the development of molecular signatures of malignancy is prominent, we are trying to implement this development in our cases of previously diagnosed endometrial cancer. The aim was to determine the prevalence of specific molecular alterations and correlate the genetic profile with the pathologic features and clinical characteristics. We identified 100 cases of endometrial carcinoma, which were eventually classified using immunostains for mismatch repair (MMR) and p53 proteins, in addition to Sanger analysis for POLE gene (Ex, 9, 13, 14). Our findings showed a high prevalence of nonspecific molecular profile (NSMP) in 46 cases (46%), and MMR deficiency in 30 cases (30%). The worst prognosis was observed in the p53 mutant pattern expressed tumors. No statistical difference in pathologic characteristics was observed when the molecular classification was applied. Of note, mutual molecular grouping assignment appears to be present in 5 (5%) of cases of endometrial carcinoma. This is the first study conducted in Saudi Arabia that investigated the prevalence and implications of these molecular subtypes in endometrial carcinoma. The percentage of cases in our result is similar to what had been published globally.
Sclerosis in Metastatic Uterine Tumor Resembling Ovarian Sex Cord Tumor: Diagnostic Dilemma Presented by Unusual Morphology
Authors: Lei Li , Aisagbonhi Omonigho 
Published: February 2025

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare neoplasms that typically follow a benign course. However, metastasis occurs in rare cases and features associated with poor outcomes are only recently being described. These include: size >5 cm, at least moderate cytologic atypia, >3 mitosis per 10 high-powered fields, infiltrative borders, necrosis, GREB1 rearrangements, ESR1 rearrangements, and NCOA2/3 fusions. To our knowledge, prominent sclerosis has not been described in UTROSCT, nor has it been associated with an increased risk of metastasis. We present the case of a 51-yr-old woman with UTROSCT with corded/trabecular growth and sclerosis. The presence of sclerosis resulted in the misdiagnosis of her uterine tumor as leiomyoma and her lung metastasis as sclerosing epithelioid fibrosarcoma. The correct diagnosis of UTROSCT with lung metastasis was reached upon a morphologic comparison of the primary and metastatic tumors and the performance of a broad panel of immunohistochemical stains revealing the tumor to be CD99, CD56, ER, and inhibin positive and negative for rearrangements in 138 targeted genes, including genes commonly described as rearranged in endometrial stromal sarcomas, Ewing sarcoma and sclerosing epithelioid fibrosarcoma. The panel did not include GREB1 or ESR or NCOA3, but NCOA1/2 rearrangements were not detected. Our case highlights the diagnostic dilemma introduced by the presence of sclerosis in UTROSCT. We suspect prominent sclerosis may be another feature predictive of malignant potential in UTROSCT.
Radio-Guided Monitoring of Systemic Leakage With 99mTc-MAA Uptake in a Patient With Melanoma During Isolated Limb Perfusion
Authors: Samadi Mohammad Hadi , Hadad Ehsan Hasanzadeh , Khezri Susan , Sadeghi Ramin , Aghaee Atena 
Published: February 2025

Abstract
We present a case of a 65-year-old woman with a history of melanoma of the left foot who underwent tumor resection with inguinal lymph nodes dissection and received external beam radiation therapy. After some time, she developed nodular lesions in the same region that were confirmed to be due to involvement of the dermis. She was selected as a candidate for isolated limb perfusion procedure. The isolated limb perfusion was performed with the aid of radioguided monitoring of systemic leakage by injecting 99mTc-labeled macroaggregated albumin, and whole-body acquisition was also performed, which confirmed compartmental localization of the tracer. Our case is the first one in which 99mTc-labeled macroaggregated albumin injection has been used.
Implementation and Validation of Decision Aid Tool to Reduce Unnecessary Testing Before Thoracic Surgery
Authors: Odeh Ayham M , Verm Raymond , Kwak Jenny , Baker Marshall S , Lozanoski Madison , Helenowski Irene , Vigneswaran Wickii , Lubawski James , Raad Wissam , Freeman Richard K , Abdelsattar Zaid M 
Published: February 2025

Background:
To implement and prospectively validate a previously published decision-aid tool to guide ordering of preoperative type and screen tests (preT&S).

Study Design:
In this interrupted time-series quasi-experimental study, we implemented a decision-aid tool for patients undergoing elective thoracic surgery at a single academic institution. Data was collected 6 months before and prospectively after implementation. The tool, a previously published nomogram, predicts the need for a preT&S using age, body mass index (BMI), planned operation, approach, and preoperative hemoglobin. We excluded patients who had prior transfusions, neoadjuvant therapy, redo operations and/or inpatient consults. We validated the tool using multivariable logistic regression, regression discontinuity, c-index, sensitivity, predictive values, and cost savings.

Results:
177 consecutive patients met inclusion criteria. 88 were after implementation, and 89 patients before. There were no differences between the groups in terms of age, sex, BMI, comorbidities, approach, nor preoperative hemoglobin (all p>0.05). Overall transfusion rates were similar (6.8% vs 6.7%; p>0.99); however, the rate of ordering preT&S was reduced significantly (94.4% vs 60.2%; p<0.001). At our institution, the decision aid tool resulted in cost savings of $25,048 over 6 months alone. With a c-index of 0.977, our validation demonstrated 100% sensitivity, 90.3% specificity, and 100% negative predictive value.

Conclusions:
Implementation and validation of the preT&S nomogram proved feasible, accurate, and resulted in reducing unnecessary testing and costs before elective non-cardiac thoracic surgery. Wider implementation has the potential for substantial cost savings.
Rationally Designed PKD1 Activator Protects Against Neurodegeneration in Pre-clinical Models of Parkinson’s Disease
Authors: Asaithambi Arunkumar , Jang Ahyoung , Ghosh Anamitra , Ay Muhammet , Jin Huajun , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G. 
Published: February 2025

AbstractOxidative stress leads to degeneration in Parkinson’s disease (PD). The key signal transduction and regulatory networks that are involved during this degenerative process in PD are currently being investigated for novel neuro-protective strategies. We recently discovered that the activation of Protein Kinase D1 (PKD1) acts as a novel compensatory mechanism in PD models and positive modulation of PKD1 can be a therapeutic strategy. Therefore, the purpose of the present study was to take a translational approach by developing a PKD1 activator and characterizing the protective function in pre-clinical models of PD. Positive genetic modulation of PKD1 by overexpression of constitutively active PKD1 protected against MPP+induced dopaminergic neurotoxicity. Pharmacological activation by Rosiglitazone protected, whereas inhibition by kb NB 142-70 exacerbated against MPP+and 6-OHDA toxicity in cell culture PD models. Importantly, peptides were rationally designed and screened for their ability to activate PKD1 using our screening methods. Peptide AK-P4 was identified to activate PKD1 specifically and protect against MPP+and 6-OHDA in both N27 cells and primary mesencephalic neurons. Further AK-P4 tagged with TAT sequence (AK-P4T) delivered using intra-venous injections activated PKD1 in mice. The neuro-protective effects of AK-P4T were tested using the sub-chronic MPTP mice model. Co-treatment with AK-P4T significantly restored the neurotransmitter levels and the behavioral and locomotory activities of the MPTP mouse model of PD. Collectively, our results demonstrate that rationally designed PKD1 activator peptide AK-P4T positively modulated PKD1 and protected against neurodegeneration in the pre-clinical models of PD. Our results suggest that positive modulation of the PKD1 using AK-P4T shows promise as a potential therapeutic agent against PD.
N-Glycan Fingerprinting of the NIST monoclonal antibody (NISTmAb)
Authors: Wu Zhengliang L 
Published: February 2025

AbstractGlycosylation on therapeutic antibodies is critically important for their drug efficacies. Here, using NISTmAb and Humira® as examples, we present methods of glycan fingerprinting for these antibodies. Glycans are first released with PNGase F or Endo S2, and then labeled by specific glycosyltransferases, including sialyltransferase ST6Gal1, fucosyltransferase FUT9, N-acetyl-glucosaminyltransferase MGAT3 and fucosyltransferase FUT8, with respective fluorophore-conjugated donor sugars. The labeled glycans are then separated by gel electrophoresis (SDS-PAGE). A fluorophore-labeled hyaluronan ladder is run along with the samples to reveal the relative mobility of each glycan band. Pretreatment of the samples with specific glycosidase or glycosyltransferase results in additional mobility shift of specific glycan bands, which allows identification of some of these bands. Particularly, we report the identification of α-Gal epitopes, core-6 fucosylated glycans, paucimannose glycans and likely some bisecting/tri-antennary glycans on NISTmAb. Overall, our methods could serve as quick assessments of glycosylation on therapeutic antibodies.