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BACKGROUND: Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. METHODS: This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. RESULTS: A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. CONCLUSION: This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.

Background: Increasing age increases the incidence of chronic constipation and fecal impaction. The contribution of the natural aging process to this phenotype is unclear. This study explored the effects of age on key motility patterns in the murine colon and determined the contribution that altered neurokinin 2 (NK2) ‐mediated signaling made to the aging phenotype. Methods: Mucosal reflexes, colonic migrating motor complexes (CMMCs) and colonic motility assays were explored in isolated ex vivo colons from 3, 12–14, 18‐ and 24‐months old mice and the NK2‐mediated response determined. Electrical field stimulation (EFS) or exogenous drug application were used to explore the role of the mucosa in colonic segments. Key Results: Aging reduced the force of contraction of the distal colon mucosal reflex, the frequency and force of contraction of CMMCs and the NK2‐mediated component of both motility patterns. Ondansetron, a 5‐HT3 receptor antagonist, blocked a component of both motility patterns in full thickness but not in mucosa‐free segments of the distal colon. 5, hydroxytryptamine (5‐HT) and EFS‐evoked NK2‐dependent contractions were reduced with increasing age. Smooth muscle sensitivity to 5‐HT or neurokinin A (NKA) was not altered with age. In isolated colon motility assays application of NKA decreased transit time in 24‐months colon and the NK2 antagonist GR159897 increased transit times in both 3‐ and 24‐months old colons. Conclusions and Inferences: Aging impairs key motility patterns in the murine colon. These changes involve a decrease in mucosally‐evoked NK2‐mediated signaling. Targeting NK2‐mediated signaling may provide a novel approach to treating age‐related motility disorders in the lower bowel. [ABSTRACT FROM AUTHOR]

Serotonin, a monoamine neurotransmitter, is important in both the central nervous system (CNS) and the peripheral nervous system. Malfunction of serotonin signaling leads to various disorders. We studied serotonin signaling from serotonergic neurons inside the ventral nerve cord of Drosophila melanogaster. Serotonergic neurons and stimulated release were visualized and achieved with mCherry and channelrhodopsin‐2 (an optogenetically transfected ion channel), respectively, and two electrochemical techniques quantified serotonin release and vesicular content. Mean vesicular serotonin content released during exocytosis from these neurons was 84 %, considerably higher than reported in previous studies regarding octopamine (4.5 %) and glutamate release (31 %). Serotonin content within all vesicles is uniformly changed when serotonin concentration is inhibited or enhanced. However, serotonin release exhibits two Gaussian distributions: higher frequency of small release events, and similar or slightly higher frequency of large events, resulting in differential release fractions ranging from partial (13–18 %) to full (100 %) release after treatment with agents to either enhance or diminish release. This is the first example of consistent full exocytotic release events we have observed in any system. We suggest one pool of vesicles can release significantly diverse fractions of transmitter load during exocytosis, a potentially novel pathway to regulate exocytosis and neuronal signaling. [ABSTRACT FROM AUTHOR]

Background: Differential kidney function assessment is an important part of preoperative evaluation of various urological interventions. It is obtained through dedicated nuclear medical imaging and is not yet implemented through conventional Imaging. Objective: We assess if differential kidney function can be obtained through evaluation of contrast-enhanced computed tomography(CT) using a combination of deep learning and (2D and 3D) radiomic features. Methods: All patients who underwent kidney nuclear scanning at Mayo Clinic sites between 2018–2022 were collected. CT scans of the kidneys were obtained within a 3-month interval before or after the nuclear scans were extracted. Patients who underwent a urological or radiological intervention within this time frame were excluded. A segmentation model was used to segment both kidneys. 2D and 3D radiomics features were extracted and compared between the two kidneys to compute delta radiomics and assess its ability to predict differential kidney function. Performance was reported using receiver operating characteristics, sensitivity, and specificity. Results: Studies from Arizona & Rochester formed our internal dataset (n = 1,159). Studies from Florida were separately processed as an external test set to validate generalizability. We obtained 323 studies from our internal sites and 39 studies from external sites. The best results were obtained by a random forest model trained on 3D delta radiomics features. This model achieved an area under curve (AUC) of 0.85 and 0.81 on internal and external test sets, while specificity and sensitivity were 0.84,0.68 on the internal set, 0.70, and 0.65 on the external set. Conclusion: This proposed automated pipeline can derive important differential kidney function information from contrast-enhanced CT and reduce the need for dedicated nuclear scans for early-stage differential kidney functional assessment. Clinical Impact: We establish a machine learning methodology for assessing differential kidney function from routine CT without the need for expensive and radioactive nuclear medicine scans. [ABSTRACT FROM AUTHOR]

Background: Distinguishing benign from malignant pancreaticobiliary disease is challenging because of the absence of reliable biomarkers. Circulating extracellular vesicles (EVs) have emerged as functional mediators between cells. Their cargos, including microRNAs (miRNAs), are increasingly acknowledged as an important source of potential biomarkers. This multicentric, prospective study aimed to establish a diagnostic plasma EV-derived miRNA signature to discriminate pancreatic ductal adenocarcinoma (PDAC) from benign pancreaticobiliary disease. Methods: Plasma EVs were isolated using size exclusion chromatography (SEC) and characterised using nanoparticle tracking analysis, electron microscopy and Western blotting. EV-RNAs underwent small RNA sequencing to discover differentially expressed markers for PDAC (n = 10 benign vs. 10 PDAC). Candidate EV-miRNAs were then validated in a cohort of 61 patients (n = 31 benign vs. 30 PDAC) by RT-qPCR. Logistic regression and optimal thresholds (Youden Index) were used to develop an EV-miR-200 family model to detect cancer. This model was tested in an independent cohort of 95 patients (n = 30 benign, 33 PDAC, and 32 cholangiocarcinoma). Results: Small RNA sequencing and RT-qPCR showed that EV-miR-200 family members were significantly overexpressed in PDAC vs. benign disease. Combined expression of the EV-miR-200 family showed an AUC of 0.823. In an independent validation cohort, application of this model showed a sensitivity, specificity and AUC of 100%, 88%, and 0.97, respectively, for diagnosing PDAC. Conclusions: This is the first study to validate plasma EV-miR-200 members as a clinically-useful diagnostic biomarker for PDAC. Further validation in larger cohorts and clinical trials is essential. These findings also suggest the potential utility in monitoring response and/or recurrence. [ABSTRACT FROM AUTHOR]