bluuebunny/crossref_metadata_2025 huggingface dataset:
A221 GENERALIZABILITY OF RANDOMIZED CONTROLLED TRIALS TO ROUTINE CLINICAL CARE IN ULCERATIVE COLITIS
Authors: Chhibba T , Frolkis A , Stein L , Lee S , Schill K , Mitseva E , Judge A , Martin M , Martin M , Novak K , Lu C , Chan M , Shukla T , Seow C , Kaplan G G , Ananthakrishnan A , Panaccione R , Ma C
Published: February 2025

Background

Historically, randomized controlled trials (RCTs) have been criticized for being poorly generalizable to patients with ulcerative colitis (UC) evaluated in routine care.

Aims

We aimed to evaluate the proportion of patients with UC starting an advanced therapy who would be eligible to participate in phase 3 registrational UC RCTs.

Methods

We conducted a retrospective cohort analysis of UC patients starting vedolizumab, ustekinumab, or tofacitinib at two IBD clinics at the University of Calgary. Patient charts, endoscopy reports, and laboratory results were reviewed, and compared against the inclusion and exclusion criteria from five RCTs (GEMINI-I, UNIFI, OCTAVE, ELEVATE, and LUCENT). The proportion of patients who would have been deemed eligible vs. ineligible for trial participation at the time of starting a new advanced therapy was determined.

Results

A total of 125 patients with UC were included: 78 (62.4%) would have been eligible for at least one of the considered RCTs (Table 1). Trial-eligible patients were younger, less likely to be exposed to prior immunosuppressants, and had higher C-reactive protein and fecal calprotectin. The most common reason for trial ineligibility was having inadequate disease activity at baseline (Mayo endoscopy subscore <2 or absence of rectal bleeding). A significantly greater proportion of patients would have been eligible for LUCENT (44.9%) compared to GEMINI-I (24.8%), OCTAVE (35.2%), or ELEVATE (35.2%) (p<0.01 for all comparisons) (Figure 1).

Conclusions

Half of patients with UC starting advanced therapy in routine care may be eligible for participation in phase 3 RCTs. Disease activity is the primary reason for trial exclusion.

Funding Agencies

None
A223 ORBITAL MYOSITIS AS THE INITIAL PRESENTING SIGN OF CROHN’S DISEASE IN AN ADOLESCENT FEMALE
Authors: AlAyedh N , alhadab a , Cellucci T , Batthish M , Heede S , Zachos M
Published: February 2025

Background

Ocular extraintestinal manifestations (O-EIM) of inflammatory bowel disease (IBD) are rare, with most being attributed to scleritis, episcleritis and uveitis. Orbital myositis, however, is an exceedingly rare manifestation that is described as acute or chronic inflammation of one or more extraocular muscles leading to symptoms related to the mass effect including orbital pain, swelling, ophthalmoplegia, proptosis, and diplopia. To date, 3 reports of varying ocular myositis preceding IBD diagnosis have been described in pediatrics.

Aims

This report describes a case of unilateral orbital myositis, which was the initial and only symptom of newly diagnosed adolescent with Crohn’s disease (CD).

Methods

A chart review was conducted and placed into the context of this rare presentation.

Results

15-year-old female presented with acute 6th cranial nerve palsy with ipsilateral optic disc edema, raising concern for raised intracranial pressure. Magnetic resonance imaging (MRI) revealed a retro-orbital mass on the left lateral rectus muscle, consistent with orbital pseudo tumor and myositis, no intracranial tumor or vascular lesion. She was treated with 3-month course of prednisone. An inflammatory condition was suspected based on the unusual presentation of orbital myositis which responded well to prednisone. Alternative infectious or rheumatologic causes of orbital pseudotumor were excluded and the patient was treated with corticosteroids prior to gastroenterology (GI) consultation. She was found to have elevated C-reactive protein (CRP), hypoalbuminemia and anemia at presentation. Fecal calprotectin (649)) was subsequently found to be positive at GI consultation after corticosteroid treatment initiation. Given the patient did not exhibit any GI signs or symptoms at the time of the evaluation, further GI investigations were deferred to after completion of steroids. Fecal calprotectin was persistently elevated (1463) after resolution of ocular symptoms and completion of steroids. Magnetic resonance enterography (MRE) identified inflammation of the terminal ileum. A definitive diagnosis of CD was established following upper GI endoscopy and colonoscopy with biopsies.

Conclusions

Orbital myositis is a rare ocular manifestation of CD. Early recognition and treatment are critical as they may precede the development of overt gastrointestinal symptoms, potentially delaying diagnosis if not considered. Given the rarity of this presentation, further studies are needed to better understand the pathophysiological link between CD and orbital myositis.

Funding Agencies

None
A235 DETERMINANTS AND OUTCOMES OF EARLY CHOLECYSTECTOMY FOR GALLSTONE PANCREATITIS IN BRITISH COLUMBIA.
Authors: Arif A A , Sasson S , Aboalfaraj N , Telford J
Published: February 2025

Background

Gallstone pancreatitis is the most common cause of pancreatitis, with early cholecystectomy reducing recurrence and improving outcomes compared to delayed surgery or ERCP alone. However, the use of early cholecystectomy in British Columbia (BC) and its long-term effects are not well understood.

Aims

This study will evaluate the prevalence and outcomes of early cholecystectomy in BC, potentially contributing to improved management guidelines.

Methods

A retrospective multicenter analysis of patients with gallstone pancreatitis admitted from 2018 to 2023 to four hospitals within BC. Patients with prior cholecystectomy or pancreatic cancer were excluded from the analysis. Patients with moderate or severe pancreatitis as determined by the revised Atlanta criteria were excluded. Patients who received a cholecystectomy in under 4 weeks were labelled as early, whereas over 4 weeks or not at all were labelled as late. Baseline characteristics, details of cholecystectomy and outcomes were recorded.

Results

A total of 193 patients with a mean age of 58.5 years (SD 18.4) and 60.1% female were included. 84 patients underwent early cholecystectomy (43.5%) including during the index admission (36.3%). Patients who received early cholecystectomy were younger (52.6 years vs 62.9 years, P<0.001) with fewer comorbidities (Charlson comorbidity index 1.5 vs 2.8, P<0.001). Patient gender, body mass index or hospital type were not associated with early cholecystectomy. Early cholecystectomy patients were more likely admitted by a surgeon (OR 11.7, 95% CI 4.6 to 29.6, P<0.001), offered cholecystectomy at index admission (OR 59.8, 95% CI 24.5 to 146.0, P<0.001), and receive cholecystectomy at index admission (OR 497, 95% CI 64.1 to 3848, P<0.001). There was no difference in the symptom onset to admission time interval or length of stay. ERCP was equally likely in both groups (OR 0.62, 95% CI 0.34 to 1.1, P=0.12). Patients who received early cholecystectomy were less likely to have a recurrent biliary event (HR 0.26, 95% CI 0.15 to 0.45, P<0.001). Pancreatitis was the most common (81.1%) recurrent biliary event. Reasons for not undergoing early cholecystectomy included: referral to outpatient cholecystectomy as the most common (29.7%), age and/or comorbidities (25.0%) and patient declining surgery (21.9%).

Conclusions

Early cholecystectomy reduces recurrent rates of biliary events. Admission under surgery and offering surgery at the index admission were much more likely in the early group. Early surgical involvement may be an important factor in achieving higher rates of index admission cholecystectomy.

Funding Agencies

None
The relationship between pathogenic bacteria and different stages of colorectal cancer
Authors: Nezhadi Javad , Kafil Hossein Samadi , Sadrkabir Mohammad , Mahdavi Farshad , Moaddab Seyed Yaghoub , Nouri Roghayeh , Mohammadzadeh-Asl Yalda , Sattarpour Simin , Rezaee Mohammad Ahangarzadeh
Published: February 2025

Colorectal cancer (CRC) involves uncontrolled cell growth in the colon and rectum. This study aims to explore the prevalence of key pathogenic bacteria and their role in the progression of CRC, focusing on microbial dysbiosis. This study analyzed 52 stool and tissue samples through polymerase chain reaction (PCR), real-time PCR, and bioinformatics to identify associations between pathogenic bacteria and CRC progression. PCR results revealed a significant association between the Bacteroides fragilis toxin (bft) gene and CRC progression (P = 0.001, r = 0.570). Furthermore, Real-time PCR showed significant differences in the frequency of pks+Escherichia coli in CRC stages 1 (P = 0.03), 2 (P = 0.004), and 3 (P = 0.0002) compared to the control group. Additionally, the frequency of Fusobacterium nucleatum in stage 3 CRC patients was significantly higher than in the control group (P = 0.004) and stage 1 patients (P = 0.01). Furthermore, Streptococcus gallolyticus showed similar significant differences in stage 3 patients (P = 0.004). Bioinformatics analyses using KEGG, Reactome, STRING, and dbSNP highlighted bacteria’s roles in colorectal carcinogenesis, emphasizing the need for early identification and management in CRC treatment and prevention strategies. Finally, due to the limitations of the study, the use of more advanced methods and the validation of results through more reliable techniques are essential for future research.
A dynamic equilibrium theory for zonal circulation in the solar convection zone
Authors: Hester Richard , Zhang J , Dikpati M
Published: February 2025

This work proposes a new theoretical model for the observed differential zonal motion in the solar convection zone. It is based on a dynamic equilibrium among three fundamental forces: pressure gradient forces, centrifugal forces, and Coriolis forces. Existing models, many achieving substantial success, require convection as a key mechanism to drive the zonal motion. Generally these models have a geostrophic balance as their lowest order balance. In the new approach presented here, an even lower order balance is derived and convection is not required. The precise observed shape of the Sun is treated as a fixed boundary condition. Recent observations characterize solar shape in terms of a surface radius function composed of Legendre polynomials P0, P2, P4, and their amplitudes a0, a2, a4. In the present work it is assumed the a2 and a4 shape anomaly amplitudes are determined a priori as an energy minimum configuration of the body. The model calculates the poleward pressure gradient forces caused by the shape anomaly. It separately calculates the equatorward centrifugal forces caused by the rotation of the reference frame. Contrary to expectations, these two forces do not exactly cancel. The residual is identified as the Coriolis force. The fluid velocity required to close the force budget is the observed zonal circulation. This dynamic equilibrium model offers a new paradigm to explain the zonal circulation of the Sun.
Abiotic stress-regulated LEA gene mediates the response to drought, salinity, and cold stress in Medicago sativa L.
Authors: Wang Xiaoyu , Hu Yulu , Dong Ying , Zhang Linsheng , Wang Bo
Published: February 2025

Late embryogenesis abundant (LEA) proteins are typical stress-related proteins widely distributed across various organisms. Their anti-stress functions in higher plants have garnered significant attention and have been extensively studied; however, no such studies have been reported on the entire protein family in Medicago sativa. In this study, we identified a total of 83 MsLEA proteins in M. sativa and conducted a comprehensive analysis to elucidate their functions in response to abiotic stresses. The results indicated that these proteins could be classified into seven groups and were distributed across eight chromosomes. Collineation analysis revealed that segmental duplication primarily drove the expansion of MsLEA genes. Furthermore, the promoters of MsLEA genes were found to be enriched with cis-elements associated with various stress responses. Through transcriptome and qRT-PCR analysis, nine MsLEA genes related to drought, salinity, and cold stress were identified, with MsLEA69 selected for further validation. The ectopic expression of MsLEA69 improves osmotic and extreme temperature tolerance by increasing the activity of stress-related enzymes in both prokaryotic and eukaryotic cells. These comprehensive analyses and identifications lay the groundwork for future research into the functional mechanisms of MsLEA proteins and offer potential candidate genes for enhancing resistance breeding in M. sativa.
Maize COMPACT PLANT 3 regulates plant architecture and facilitates high-density planting
Authors: Sheng Huangjun , Zhang Han , Deng Hua , Zhang Zuxin , Qiu Fazhan , Yang Fang
Published: February 2025

Compact plant architecture allows more efficient light capture under higher planting density. Thus, it is a crucial strategy for improving crop yield, particularly in maize (Zea mays L.) Here, we isolated a maize gene, COMPACT PLANT 3 (CT3), regulating plant architecture, using map-based cloning. CT3, encoding a GRAS protein, interacts with an AP2 transcription factor (TF), DWARF AND IRREGULAR LEAF 1 (DIL1). The genetic analysis showed that CT3 and DIL1 regulate leaf angle and plant height via the same pathway, supporting the biological role of their interaction by forming a complex. Transcriptome and DNA profiling analyses revealed that these two TFs share many common target genes. We further observed that CT3 functions as a co-regulator to enhance the DNA affinity and transcriptional activity of DIL1. This finding was further supported by the direct binding of DIL1 to two cell wall-related genes, ZmEXO1 and ZmXTH14, which were downregulated in the ct3 mutant. Furthermore, ZmEXO1 regulated plant architecture in a manner similar to CT3- and DIL1-mediated regulation. Zmexo1, ct3, and dil1 mutants showed defective cell wall integrity and had reduced cell wall-related components. The introduction of the ct3 or dil1 mutant allele into elite maize hybrids led to a more compact architecture and increased yield under high planting density. Our findings reveal a regulatory pathway of maize plant architecture and provided targets to increase yield under high planting density.
Enhancing Speech Perception in Noise Through Home-Based Competing Talker Training
Authors: Van Wilderode Mira , Van Humbeeck Nathan , Krampe Ralf T. , van Wieringen Astrid
Published: February 2025

Objectives:

This study aimed to evaluate the effectiveness of a competing talker training paradigm (2TT-Flemish). The primary objectives were the assessment of on-task learning and the transfer to untrained tasks.

Design:

A total of 60 participants (54–84 years, mean age = 69.4) with speech-in-noise problems participated in the study. The study used a randomized controlled design with three groups: an immediate training group, a delayed training group, and an active control group. The immediate training group trained from the very beginning, while delayed training started after 4 weeks. The active control group listened to audiobooks for the first 4 weeks. All participants underwent 4 weeks of competing talker training. Outcome measures included speech perception in noise, analytical tasks (modulation detection and phoneme perception in noise), and inhibitory control. In addition, a listening-posture dual task assessed whether training freed up cognitive resources for a concurrently performed task. Finally, we assessed whether training induced self-reported benefits regarding hearing, listening effort, communication strategies, emotional consequences, knowledge, and acceptance of hearing loss. Outcome measures were assessed every 4 weeks over a 12-week period. The present study aimed to investigate the effectiveness of competing talker training in a stratified randomized controlled trial.

Results:

Overall compliance to the training was good and increased with age. We observed on-task improvements during the 4 weeks of training in all groups. Results showed generalization toward speech-in-noise perception, persisting for at least 4 weeks after the end of training. No transfer toward more analytical tasks or inhibitory control was observed. Initial dual-task costs in postural control were reliably reduced after competing talker training suggesting a link between improved listening skills and cognitive resource allocation in multitask settings. Our results show that listeners report better knowledge about their hearing after training.

Conclusions:

After training with the 2TT-Flemish, results showed on-task improvements and generalization toward speech-in-noise. Improvements did not generalize toward basic analytical tasks. Results suggest that competing talker training enables listeners to free up cognitive resources, which can be used for another concurrent task.
The Association between Postoperative Ketorolac Administration and Pseudoarthrosis Following Anterior Cervical Discectomy and Fusion
Authors: Baumann Anthony N. , Trager Robert J. , Anaspure Omkar S. , Metcalf Tyler , Cottrill Ethan J. , Hoffmann Cassandra , Hoffmann Jacob C.
Published: February 2025

Study Design.

Retrospective cohort study.

Objective.

We tested the hypothesis of no significant association between early postoperative ketorolac administration and pseudoarthrosis compared to matched controls prescribed acetaminophen, as measured by risk ratio (RR), through four years’ follow-up.

Summary of Background Data.

The potential association between ketorolac use and pseudoarthrosis following anterior cervical discectomy and fusion (ACDF) remains largely unexplored, despite concerns about its potential to hinder bone healing.

Methods.

This retrospective cohort study used the TriNetX database to examine adults (≥18 y old) undergoing primary ACDF from 2004 to 2020. Patients were divided into cohorts based on whether they received ketorolac (ketorolac cohort) or acetaminophen (control cohort) ≤2 days after ACDF. Risk factors for pseudoarthrosis were propensity matched. The primary outcome was the RR for pseudoarthrosis with 95% confidence intervals (CI). Secondary outcomes explored risk of reoperation, postoperative bleeding, and risk/count of oral opioid prescriptions.

Results.

There were 3,475 patients per cohort (mean age=53 y) after matching. Through four years’ follow-up after ACDF, comparing the ketorolac versus control cohorts, there was no statistically significant increase in risk of pseudoarthrosis [95% CI] (14.8% vs. 16.4%; RR=0.90 [0.81,1.01]; P=0.069), reoperation (7.8% vs. 7.6%; RR=1.03 [0.88,1.21]; P=0.719), or severe postoperative bleeding (0.5% vs. 0.5%; RR=1.00 [0.52,1.92]; P=1.000). Regarding oral opioids, the ketorolac cohort had a small, statistically significant increase in risk of prescription (79.3% vs. 74.2%; RR=1.07 [1.04,1.10]; P<0.001), yet no significant difference in mean prescription count (6.1 vs. 5.5; P=0.064).

Conclusion.

Receiving ketorolac within two days after ACDF does not appear to be associated with an increased risk of pseudoarthrosis through four years follow-up in adults. Furthermore, there appears to be no meaningful difference in risk of reoperation, severe bleeding, and oral opioid prescriptions, although secondary outcomes should be interpreted with caution. Further corroboration is warranted.
Early PCSK9 Inhibitor Therapy Following Percutaneous Coronary Intervention (PERFECT): A Pilot Randomized Controlled Trial
Authors: Xia Jiachun , Xiao Zhengguang , Wu Luyao , Yu Haiyang , Pang Yanan , Hu Shan , Hou Lei
Published: February 2025

Objective:

This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5–10 d after the procedure.

Methods:

The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group (n = 16) or the control group (n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5–10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5–10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period.

Results:

Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI.

Conclusions:

Early treatment with alirocumab did not exhibit a significant increase in MSI at 5–10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.
Ibuprofen Oral Administration Protocols for Analgesia After Cesarean Delivery: A Prospective Randomized Controlled Study
Authors: Li Shuang , Bao Ju , Qu Yuan , Zhang Bo , Cao Xinni , Huang Yanping , Liu Zhe
Published: February 2025

Objective:

To compare the analgesic effects of ibuprofen administered orally via two modes combined with a conventional, patient-controlled intravenous analgesia pump on maternal pain after cesarean section (CS).

Methods:

This prospective, randomized, controlled study enrolled females who underwent CS from August 2022 to August 2023 at Peking University First Hospital, Beijing, China. The participants were randomly assigned to the as-needed group (ibuprofen administered orally if demanded) or the scheduled group (ibuprofen administered orally 6 hours postpartum at 12-hour intervals for 48 hours). The post-delivery pain scores, oxycodone consumption at different time points, time to exhaust, ambulation, and lactation initiation, analgesia satisfaction level, and depression scores were compared between the two groups using relevant statistical methods with IBM SPSS version 26. The level of significance was 0.05.

Results:

The scheduled group showed significantly better pain control at 12 hours (4.00 (2.00–5.50) vs. 4.00 (4.00–6.00), P < 0.001), 24 hours (4.00 (2.00–4.00) vs. 4.00 (2.00–6.00), P < 0.001), and 36 hours (2.00 (2.00–4.00) vs. 4.00 (2.00–4.00), P < 0.001), and 48 hours (2.00 (2.00–4.00) vs. 2.00 (2.00–4.00), P = 0.004) post-delivery and lower levels of oxycodone consumption at 36 hours (10.20 (8.20–13.35) vs. 11.00 (8.80–14.40), P = 0.042) and 48 hours (12.40 (10.40–15.95) vs. 13.80 (11.00–16.00), P = 0.020) postpartum compared with those in the as-needed group. Additionally, the time to the return of bowel movements was shorter in the scheduled group than in the as-needed group (23.50 (16.94, 31.47) vs. 27.00 (19.88, 35.97), P = 0.004). Differences in post-delivery ambulation, lactation initiation, satisfaction levels, and depression scores were not significantly different between the two groups.

Conclusion:

The results of this study promote the use of ibuprofen (scheduled oral administration) combined with a conventional, patient-controlled intravenous analgesia pump for achieving better post-CS pain control than an as-needed dosage regimen.

Registration:

Chinese Clinical Trial Registry, ChiCTR2400082474.
Recurrence Following Operative vs. Non-Operative Management of Adhesive Small Bowel Obstruction in Children
Authors: Patwardhan Utsav M. , Ignacio Romeo C. , Pickett-Nairne Kaci , Russell Katie W. , Lee Justin , Padilla Ben , Melhado Caroline , Kelley-Quon Lorraine I. , Rothstein David H. , Thangarajah Hariharan , Ibarra-Meraz Ana , Barq Rabab M. , Larsen Kezlyn E. , Fowler Kathryn L , Hunteman Zebediah , Valencia-Bradd Maria , Lofberg Katrine , Jensen Aaron , Pandya Samir , Acker Shannon N. ,   on behalf of the Western Pediatric Surgery Research Consortium
Published: February 2025

Objective:

Data on the incidence of recurrent adhesive small bowel obstruction (ASBO) following index admission for ASBO in children are limited. We sought to determine if operative management was associated with a lower rate of recurrence compared to non-operative management (NOM).

Methods:

We conducted a prospective observational study of children with ASBO admitted to nine hospitals from 10/2020 to 12/2022 who underwent a trial of NOM. Children were followed for a year after admission. The primary outcome was readmission for recurrent ASBO. Adjusted comparisons were made between children successfully managed nonoperatively at the index admission and those who underwent surgery.

Results:

Among 136 children, 87 (63.9%) had successful NOM at the index admission. Within 1 year, twenty patients (14.7%; 17/87 NOM group; 3/49 operative group) had recurrent ASBO. On unadjusted analysis, there was a higher risk of recurrent ASBO in the NOM group (19.5 vs. 6.1%, P=0.04). However, after adjusting for age (HR 0.35, CI 0.10-1.23), there was no significant difference. Among patients with recurrent ASBO, 7/20 (35%) underwent an urgent or emergent operation at readmission; this rate was similar between initial management groups.

Conclusion:

Although the rate of recurrent ASBO in children is nearly 15% within one year, this rate does not differ based on the initial management strategy. Among children with recurrent ASBO, one-third underwent an urgent or emergent operation at readmission. NOM appears to be as effective in preventing recurrent ASBO as surgery.
Temporary Portal Vein Bypass for Resection of Pancreatic Neoplasms
Authors: Heckler Max , Abdallah Souhaylah , Kinny-Köster Benedict , Berchtold Christoph , Al-Saeedi Mohammed , Mehrabi Arianeb , Hackert Thilo , Hinz Ulf , Hank Thomas , Michalski Christoph W. , Büchler Markus W. , Loos Martin
Published: February 2025

Objective:

We analyzed perioperative outcomes of patients undergoing pancreatectomy with portal vein resection for pancreatic cancer using temporary intraoperative mesoportal or mesocaval bypass.

Summary Background Data:

Pancreatectomy for advanced pancreatic cancer with long-segment involvement or complete occlusion of the mesoportal venous axis and cavernous transformation represents a major technical challenge. To avoid major bleeding as well as to overcome severe bowel congestion or ischemia due to long portal venous clamping, a mesoportal or mesocaval venous bypass graft first approach has been proposed. If an additional hepatic arterial resection needs to be considered, the mesoportal bypass seems preferable to ensure portal venous flow avoiding complete temporary vascular exclusion of the liver. However, the mesocaval approach appears to be a technically easier alternative.

Methods:

All consecutive patients who underwent pancreatectomy with venous bypass were identified from a prospectively maintained database. Patient characteristics, perioperative data, and postoperative short-term outcomes were analyzed.

Results:

Between 2011 and 2024, 63 patients were operated with temporary construction of an alloplastic venous bypass, including 34 patients with mesoportal and 29 patients with mesocaval bypass. Severe complications (Clavien-Dindo >3a) occurred in 16 of 63 patients (25.4%). No postoperative liver failure was observed. The median length of ICU and hospital stays were 2 and 21 days, respectively. The 90-day mortality rate was 6.3%. There were no differences in complication rates, median length of stays, and 90-day mortality rates between mesoportal and mesocaval shunts.

Conclusions:

Temporary intraoperative venous bypass graft first techniques are important surgical approaches for safe resection of advanced pancreatic tumors. Mesoportal and mesocaval shunts are both safe with comparable postoperative morbidity and mortality rates. The decision for mesoportal versus mesocaval bypass should be made according to the anatomy, particularly taking into account the extent of arterial involvement and the potential need for concomitant arterial resection.
Cost-analysis of Implementing robot-assisted Versus Open Pancreatoduodenectomy
Authors: Menso Julia E. , Francken Michiel F.G. , de Graaf Nine , Bonomi Alessandro M. , Guastella Riccardo , Balaban Dylan , Ali Mahsoem , Bonjer H. Jaap , van Dieren Susan , Dijkgraaf Marcel G.W. , van Hilst Jony , Pilz da Cunha Gabriela , Erdmann Joris , Kazemier Geert , Swijnenburg Rutger-Jan , Zonderhuis Barbara M. , Daams Freek , Festen Sebastiaan , Busch Olivier R. , Besselink Marc G. ,   for HPB-Amsterdam
Published: February 2025

Objective:

To perform a cost-analysis during the implementation of robot-assisted pancreatoduodenectomy (RPD) in a high-volume center.

Background:

Many high-volume centers are implementing RPD as alternative to open pancreatoduodenectomy (OPD) but the persevering concerns about increased costs of RPD versus OPD have not been addressed by large studies.

Methods:

Post-hoc cost-analysis of consecutive RPD versus OPD in a singly high-volume center (Jan 2015–May 2024). The eligibility criteria for RPD (i.e. no vascular contact, no chronic and necrotizing pancreatitis, and BMI<35 kg/m2) were used to select patients undergoing OPD, to minimize selection bias. Primary outcomes were total hospital costs and total hospital stay. Sensitivity analyses excluded the first half of the RPD experience.

Results:

Overall, 588 patients undergoing pancreatoduodenectomy were included (214 RPD, 374 OPD). Total hospital stay was shorter after RPD (10 [6–17] vs. 12 [8–21] days, P=0.001). Mean total hospital costs were €4,804 higher for RPD (€27,307 vs. €22,503, P=0.010). Outcomes improved in the second half of the RPD experience (n=107): total hospital stay (12 [7–23] to 9 [6–15] days, P<0.001), pancreatic fistula (48.6% to 31.8%, P=0.012), delayed gastric emptying (33.6% to 15.0%, P=0.001), and operative time (373 [341–411] to 310 [272–352] minutes, P<0.001). Consequently, costs per RPD procedure decreased with €11,058 (€32,836 to €21,778, P=0.001). Costs in the second half of the OPD experience remained stable (€24,025 to €21,013, P=0.210). Hence, total costs for RPD and OPD became comparable in the second half (€21,778 vs. €21,013, P=0.644).

Conclusion:

Implementing RPD is associated with considerable additional costs compared to OPD. With growing experience, both the outcomes and cost-efficiency of RPD improve, with costs decreasing by approximately a third, leading to similar costs as OPD. Large scale randomized trials will have to confirm these findings.
Rectus Sheath and Transversus Abdominis Plane Blocks for Preaponeurotic Endoscopic Repair: Is the Double Block the Solution for Postoperative Pain Management?
Authors: Toscano Antonio , Bonomo Luca Domenico , Capuano Paolo , Cremascoli Luca , Castelli Filippo , Puppo Mattia , Aprà Fabrizio , Jannaci Alberto , Cuccomarino Salvatore
Published: February 2025

Background:

Diastasis recti abdominis (DRA) is a prevalent postpartum condition characterized by the separation of the rectus abdominis muscles with an interrectal distance >2.5 cm, often leading to symptoms like back pain, constipation, and urinary incontinence. Preaponeurotic endoscopic repair (REPA) is a novel, minimally invasive surgical approach for DRA, offering an alternative to traditional abdominoplasty. Despite its minimally invasive nature, REPA surgery poses significant postoperative pain challenges, typically managed with opioids, which carry numerous side effects.

Materials and Methods:

This retrospective study evaluates the efficacy of combining 2 ultrasound-guided abdominal wall blocks, rectus sheath block (RSB) and transversus abdominis plane block (TAPB), to manage postoperative pain in 55 DRA patients who underwent REPA surgery. We performed lateral TAPB in 28 cases, whereas 27 received an association of TAPB and RSB.

Results:

At 6 hours postsurgery, 61% of patients in the TAPB group reported significant pain (Numeric Rating Scale >3), compared with 19% in the TAPB-RSB group (P = 0.001). The TAPB-RSB group also required fewer analgesic rescue doses (P = 0.042) and showed earlier recovery, with faster initiation of oral intake and mobility.

Conclusion:

The combination of TAPB and RSB significantly reduces opioid consumption, postoperative pain, and the need for rescue analgesia compared with TAPB alone. The dual-block approach, providing a multi-dermatomal sensory block, suggests a promising strategy for improving postoperative pain management in REPA surgery.
Longer time to surgery for pelvic ring injuries is associated with increased systemic complications
Authors: Patel Mihir , McGwin Gerald , Spitler Clay
Published: February 2025

BACKGROUND

Increased time to surgery is a well-established risk factor for complication and mortality among patients undergoing hip fracture fixation. However, few studies have been completed evaluating the association between time to surgery and complication rates in patients undergoing operative fixation of pelvic ring injuries.

METHODS

A retrospective cohort study was performed at a Level I trauma center including all patients with operative pelvic ring injuries from 2015 to 2022. Time from hospital admission to surgery, basic demographics, and comorbidities were determined for all patients. Systemic complications including acute respiratory distress syndrome, pneumonia, sepsis, deep venous thrombosis, pulmonary embolus, ileus, acute kidney injury, myocardial infarction, and mortality were recorded. The association between time to surgery and overall complications and each complication individually was estimated using multivariable statistical models.

RESULTS

A total of 1,056 patients were included in the final cohort. Patients who underwent surgery within 48 hours (n = 724) had an overall lower complication rate (17.8%) compared with those patients (n = 332) who underwent surgery greater than 48 hours after admission (34.9%). Each additional hour delay to surgery from admission was associated with a 0.4% increased odds of any complication. With respect to specific complications, each additional hour also increased the odds of sepsis (0.7%), deep venous thrombosis (0.3%), acute kidney injury (0.3%), myocardial infarction (0.5%), and pneumonia (0.4%). The odds of overall complication was 2.10 when patients underwent surgery within 42 hours after admission and increased at every time point afterwards.

CONCLUSION

Among patients with pelvic ring injuries, increased time to surgery was associated with an increased odds of systemic complication. This underscores the importance of aggressive resuscitation and prompt surgical intervention to reduce morbidity and improve overall patient outcomes.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Single cell level analysis of ATP release kinetics and cell fate following ultrasound targeted microbubble cavitation using microscopy techniques
Authors: Amate Marie , Tan Ju Jing , Boudreault Francis , Grygorczyk Ryszard , Gervais Thomas , Yu François T. H.
Published: February 2025

It is known that ultrasound-targeted microbubble cavitation (UTMC) can induce vasodilation. This image guided spatially targeted approach is called provascular therapy when used as a radiotherapy sensitizer in radiation oncology. Extracellular adenosine-5’-triphosphate (eATP), which plays an important role in vascular tone regulation, is released by cells following UTMC, possibly through sonoporation (formation of temporary and non-deadly pores in the cell membrane) and/or cell death. Herein, we were interested in quantifying UTMC-mediated ATP releasedin vitrousing a microfluidics-based model and study its relationship with UTMC-mediated cell fate to better understand and improve UTMC mediated bioeffects.

Lipid microbubbles (MB, Definity®), luciferin-luciferase (LL – for eATP quantification), and propidium iodide (PI – poration tracer) were flown over HUVEC cells cultured in a microfluidic device. Ultrasounds at 1 MHz, varying in pressure (300, 400 kPa) and length (10, 100, 1000 cycles) were applied to the chip. The LL chemiluminescent signal after the ultrasound pulse was acquired with an EMCCD camera to characterize ATP release kinetics. Then, a viability assay was performed with calcein-AM. An in-house MATLAB program pairing eATP kinetics with PI/calcein data was used to classify cells into three categories (sonoporated, dead, and untreated).

Within the testing conditions, a single UTMC pulse caused between 4% and 55% PI-positive (PI+) cells in the ultrasound-treated area. Amongst PI+ cells, we generally found more dead cells than sonoporated cells, except for milder pulses (300 kPa; 10 and 100 cycles). The analysis of individual responses of ATP release demonstrated that dead cells released more ATP (up to 22.4 ± 12.2 fmol/cell) than sonoporated cells (6.8 ± 3.4 fmol/cell) and at a faster release rate which peaked at 4s.

This study showed that sonoporation plays a significant role in UTMC-mediated ATP release, advancing our understanding of UTMC’s potential use as a radiosensitizer in solid tumors.
Dynamic fMRI networks of emotion
Authors: Janssen Niels , Elvira Uriel K.A. , Janssen Joost , van Erp Theo G.M.
Published: February 2025

The experience of emotions is that of dynamic, time changing processes. Yet, many fMRI studies of emotion average across time to focus on maps of static activations, overlooking the temporal dimension of emotional responses. In this study, we used time-resolved fMRI, group spatial independent component analysis (ICA), dual regression, and Gaussian curve fitting to examine both the spatial and temporal properties of whole-brain networks during a behavioral task. This task included trials that spanned over 25 seconds of watching short, emotionally evocative movie clips, making emotion-related decisions, and an intertrial rest period. We identified four whole-brain networks with unique spatial and temporal features that mapped onto different stages of the task. A network activated early in the course of the task included perceptual and affective evaluation regions, while two later networks supported semantic interpretation and decision-making, and a final network aligned with default mode activity. Both spatial and temporal properties of all four networks were modulated by the emotional content of the movie clips. Our findings extend current models of emotion by integrating temporal dynamics with large-scale network activity, offering a richer framework for understanding how emotions unfold across distributed circuits. Such temporal-spatial markers of emotional processing may prove valuable for identifying and tracking alterations in clinical populations.
Immune responses to human pathogens exposed to simulated Mars conditions
Authors: Zaccaria Tommaso , Bulut Özlem , Ferreira Anaisa V. , Dona Margo , Langereis Jeroen D. , Mesman Rob J. , Wesseling Joppe , van Niftrik Laura , Netea Mihai G. , Rettberg Petra , Beblo-Vranesevic Kristina , de Jonge Marien I. , Domínguez-Andrés Jorge
Published: February 2025

The identification of health risks associated with long-term crewed missions to Mars is critical for mission planning and crew safety. Human-associated pathogens can be part of the microbiome and are likely to be transported during these missions. This study examines the immunological responses of human immune cells stimulated with non-fastidious bacterial species that cause opportunistic infections, i.e.Klebsiella pneumoniaeandSerratia marcescens, after exposure to simulated Martian conditions, including UV radiation, desiccation and atmospheric pressure. We observed that exposure of the bacteria to these conditions altered cytokine secretion, reactive oxygen species (ROS) production, and phagocytic activity in human peripheral blood mononuclear cells (PBMCs). Specifically, exposure to desiccation reduced cytokines and ROS production, indicating impaired innate immune recognition and stimulation. Notably, the altered immune response was partially restored when desiccated bacteria were regrown in standard media. Flow cytometry revealed decreased bacterial size and complexity of both species post-exposure. These findings indicate that Martian conditions induce bacterial morphological and physiological changes, which could impair immune recognition and response. Expanding these studies toin vivomodels and a broader range of potentially pathogenic microorganisms is essential to estimate infection risks during Mars missions, which is vital for developing strategies to mitigate infection risks and maintain astronaut health during long-term space travel.

Importance

Since Yuri Gagarin’s 1961 flight, human space exploration has expanded, unintentionally transporting microorganisms, including pathogens, into space environments. Our previous studies demonstrated that opportunistic pathogens likeKlebsiella pneumoniaeandSerratia marcescenscan survive simulated Mars conditions. With upcoming Mars missions, it is crucial to understand how such conditions influence these pathogens and their interaction with the human immune system. This research evaluates immune responses to bacteria pathogens exposed to Martian stressors such as UV radiation and desiccation, revealing significant changes of the immune responses to the exposed bacteria. These findings provide essential insights into the health risks that astronauts may face if infected with Mars-adapted pathogens. Understanding these interactions will help to develop preventive strategies and therapeutic measures, ensuring the safety and health of crew members during long-term missions. Ultimately, this work contributes to the broader objective of safe human exploration and colonization of Mars.
Phosphorylated CheV interacts with a subset of chemoreceptors
Authors: Matilla Miguel A. , Cano-Muñoz Mario , Monteagudo-Cascales Elizabet , Krell Tino
Published: February 2025

Chemotaxis pathways are among the most complex signaling systems in bacteria. A central feature of these pathways is the ternary complex formed by chemoreceptors, the autokinase CheA, and the coupling proteins CheW and CheV. Whereas CheW is present in all chemotaxis pathways, CheV is primarily found in bacteria that contain many chemoreceptors. CheV is a fusion of a CheW-like domain to a phosphorylatable receiver domain. The roles of CheV and its phosphorylation are currently uncertain.Pseudomonas aeruginosacontains many chemoreceptors for which the cognate signals have been identified. Quantitative capillary chemotaxis assays of acheVmutant revealed that responses to certain chemoeffectors, such as nitrate and α-ketoglutarate, were drastically reduced, while responses to others, such as amino acids and inorganic phosphate, were comparable to the wild type, indicating that CheV selectively acts on specific chemoreceptors. To study the mechanism of CheV action, we conducted protein-protein interaction experiments using isothermal titration calorimetry. These studies showed that unphosphorylated CheV fails to bind to cytosolic fragments of the McpN and PctA chemoreceptors, which mediate responses to nitrate and amino acids, respectively. In contrast, the phosphorylation-mimic CheV D238E bound with very high affinity (KD= 8 nM) to McpN but failed to interact with PctA. Thus, CheV inP. aeruginosabinds to some chemoreceptors but not to others in a phosphorylation-dependent manner. These results suggest that CheV is a regulatory protein that modulates signaling through specific chemoreceptors. CheV may thus facilitate the coordination of chemotaxis responses in complex, multi-chemoreceptor systems.

Importance

Of all chemosensory signaling proteins, CheV is perhaps the least understood. Our demonstration that CheV interacts only with certain chemoreceptors offers fundamental new insights. These findings, combined with the observation that CheV is present in bacteria with numerous chemoreceptors, suggest that CheV plays a role in coordinating chemotactic outputs in complex chemosensory systems. Understanding the mechanisms by which chemotactic responses are defined in bacteria with a high number of chemoreceptors is a major research priority in the field of chemotaxis. While previous studies, including this one, show that the ability to be phosphorylated is crucial for CheV function, the molecular consequences of CheV phosphorylation have remained unclear. Our discovery that phosphorylation is essential for CheV binding to certain chemoreceptors fills in this critical gap in understanding the molecular mechanism of CheV. This study is likely to inspire further research into CheV function in other bacteria using similar approaches.
Person-to-Person Microbiota Transmission Can Influence Depression and Anxiety in Newly Married Couples: Six-Month Interim Results
Authors: Rastmanesh Reza , Vellingiri Balachandar , Isacco Ciro Gargiulo , Sadeghinejad Abolfazl , Daghnall Neil
Published: February 2025

Background

Oral microbiota dysbiosis and salivary cortisol are associated with depression and anxiety. Bacterial transmission can occur between spouses.

Aims

We explored whether oral microbiota, salivary cortisol and a combined depression-anxiety (DA) phenotype affiliated in newly married couples.

Methods

The researchers administered validated Persian versions of the Pittsburgh Sleep Quality Inventory (PSQI), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory to 1740 couples, who had been married during the past six months. The investigators compared 296 healthy control spouses with 296 cases. Data analysis used appropriate statistical methods.

Results

After six months, at the phyla level, we identified a significant decrease in Firmicutes and Actinomycetota abundance and an increase in Bacteroidetes, Proteobacteria, Fusobacteria and Patescibacteria abundance in healthy spouses married to an insomniac with DA-phenotype, showing that oral microbiota were significantly changed and became similar to that of participant’s spouse, (i.e., if the spouse had DA-phenotype, then composition of oral microbiota became similar to their spouse DA-phenotype,p<0.001). These changes parallelled alterations in salivary cortisol, depression and anxiety scores. Linear discriminant analysis (LDA) showed that relative abundances of Clostridia, Veillonella, Bacillus and Lachnospiraceae were significantly higher in insomniacs with DA-phenotype than healthy controls (p<0.001). Results remained significant after controlling for confounders. The formal mediation analysis confirmed these outcomes. We observed distinct analogous gender differences for oral microbiota pattern, salivary cortisol level, and depression and anxiety scores.

Conclusions

Microbiota transamination between two people in close contact with one another partially mediated depression and anxiety.