Development and validation of a novel nomogram model for identifying risk of prolonged length of stay among patients receiving free vascularized flap reconstruction of head and neck cancer

BackgroundThe aim of the present study was to build and internally validate a nomogram model for predicting prolonged length of stay (PLOS) among patients receiving free vascularized flap reconstruction of head and neck cancer (HNC).MethodsA retrospective clinical study was performed at a single center, examining patients receiving free vascularized flap reconstruction of HNC from January 2011 to January 2019. The variables were obtained from the electronic information system. The primary outcome measure was PLOS. Univariate and multivariate analyses were used to find risk factors for predicting PLOS. A model was then built according to multivariate results. Internal validation was implemented via 1000 bootstrap samples.ResultsThe study included 1047 patients, and the median length of stay (LOS) was 13.00 (11.00, 16.00) days. Multivariate analysis showed that flap types ((radial forearm free flap (odds ratio [OR] = 2.238; 95% CI, 1.403-3.569; P = 0.001), free fibula flap (OR = 3.319; 95% CI, 2.019-4.882; P < 0.001)), duration of surgery (OR = 1.002; 95% CI, 1.001-1.003; P = 0.004), postoperative complications (OR = 0.205; 95% CI, 0.129-0.325; P = P < 0.001) and unplanned reoperation (OR = 0.303; 95% CI, 0.140-0.653; P = 0.002) were associated with PLOS. In addition to these variables, blood transfusion was comprised in the model. The AUC of the model was 0.78 (95% CI, 0.711–0.849) and 0.725 (95% CI, 0.605–0.845) in the primary and internal validation cohorts, respectively. The DCA revealed the clinical utility of the current model when making intervention decisions within the PLOS possibility threshold range of 0.2-0.8.ConclusionsOur study developed a nomogram that exhibits a commendable level of accuracy, thereby aiding clinicians in assessing the risk of PLOS among patients receiving free vascularized flap reconstruction for HNC

Efficacy and safety of ciprofol for sedation/anesthesia in patients undergoing hysteroscopy: a prospective, randomized, non-inferiority trial

Introduction Propofol is the preferred sedative for painless hysteroscopy and other procedures due to its fast onset and short duration. However, its limitations, including injection pain, respiratory depression, blood pressure decline, and bradycardia, cannot be disregarded. Ciprofol, a new short-acting gamma-aminobutyric acid receptor agonist, has shown effectiveness and safety in painless gastrointestinal endoscopy. This study aims to demonstrate that ciprofol is not inferior to propofol in terms of sedation efficacy for painless hysteroscopy.Patients and methods A randomized study was conducted with 124 women to evaluate the anesthetic effect of ciprofol during outpatient painless hysteroscopy. The primary outcome assessed was the success rate of hysteroscopy, while secondary indicators included induction and recovery time, injection pain, tidal volume and respiratory rate. Safety indicators comprised hypotension, hypoxemia, and sinus bradycardia.Results A total of 124 patients were enrolled in the study, with 62 in each group. The success rate of hysteroscopy was 100% in both groups. Patients in the ciprofol group had higher diastolic pressure, pulse oxygen saturation levels and minute breathing during surgery than patients in the propofol group, but their induction time and recovery time were longer. The proportion of patients in the propofol group who reported pain during intravenous anesthesia was 41.935%, which was significantly higher than that of patients in the ciprofol group (1.613%).Conclusion During painless hysteroscopy, ciprofol demonstrates non-inferiority to propofol in terms of anesthetic efficacy. Despite slightly longer induction and recovery times, ciprofol results in lower instances of injection pain and less impact on respiration and circulation compared to propofol.Trial number Clinical trial Registration Identifier: NCT06172140

FTO (Fat-Mass and Obesity-Associated Protein) Participates in Hemorrhage-Induced Thalamic Pain by Stabilizing Toll-Like Receptor 4 Expression in Thalamic Neurons

Background and Purpose: Hemorrhage-caused gene changes in the thalamus likely contribute to thalamic pain genesis. RNA N 6 -methyladenosine modification is an additional layer of gene regulation. Whether FTO (fat-mass and obesity-associated protein), an N 6 -methyladenosine demethylase, participates in hemorrhage-induced thalamic pain is unknown. Methods: Expression of Fto mRNA and protein was assessed in mouse thalamus after hemorrhage caused by microinjection of Coll IV (type IV collagenase) into unilateral thalamus. Effect of intraperitoneal administration of meclofenamic acid (a FTO inhibitor) or microinjection of adeno-associated virus 5 (AAV5) expressing Cre into the thalamus of Fto fl/fl mice on the Coll IV microinjection–induced TLR4 (Toll-like receptor 4) upregulation and nociceptive hypersensitivity was examined. Effect of thalamic microinjection of AAV5 expressing Fto (AAV5- Fto ) on basal thalamic TLR4 expression and nociceptive thresholds was also analyzed. Additionally, level of N 6 -methyladenosine in Tlr4 mRNA and its binding to FTO or YTHDF2 (YTH N 6 -methyladenosine RNA binding protein 2) were observed. Results: FTO was detected in neuronal nuclei of thalamus. Level of FTO protein, but not mRNA, was time-dependently increased in the ipsilateral thalamus on days 1 to 14 after Coll IV microinjection. Intraperitoneal injection of meclofenamic acid or adeno-associated virus-5 expressing Cre microinjection into Fto fl/fl mouse thalamus attenuated the Coll IV microinjection–induced TLR4 upregulation and tissue damage in the ipsilateral thalamus and development and maintenance of nociceptive hypersensitivities on the contralateral side. Thalamic microinjection of AAV5- Fto increased TLR4 expression and elicited hypersensitivities to mechanical, heat and cold stimuli. Mechanistically, Coll IV microinjection produced an increase in FTO binding to Tlr4 mRNA, an FTO-dependent loss of N 6 -methyladenosine sites in Tlr4 mRNA and a reduction in the binding of YTHDF2 to Tlr4 mRNA in the ipsilateral thalamus. Conclusions: Our findings suggest that FTO participates in hemorrhage-induced thalamic pain by stabilizing TLR4 upregulation in thalamic neurons. FTO may be a potential target for the treatment of this disorder. </jats:sec

Fgr contributes to hemorrhage-induced thalamic pain by activating NF-κB/ERK1/2 pathways

Thalamic pain, a type of central poststroke pain, frequently occurs following ischemia/hemorrhage in the thalamus. Current treatment of this disorder is often ineffective, at least in part due to largely unknown mechanisms that underlie thalamic pain genesis. Here, we report that hemorrhage caused by microinjection of type IV collagenase or autologous whole blood into unilateral ventral posterior lateral nucleus and ventral posterior medial nucleus of the thalamus increased the expression of Fgr, a member of the Src family nonreceptor tyrosine kinases, at both mRNA and protein levels in thalamic microglia. Pharmacological inhibition or genetic knockdown of thalamic Fgr attenuated the hemorrhage-induced thalamic injury on the ipsilateral side and the development and maintenance of mechanical, heat, and cold pain hypersensitivities on the contralateral side. Mechanistically, the increased Fgr participated in hemorrhage-induced microglial activation and subsequent production of TNF-α likely through activation of both NF-κB and ERK1/2 pathways in thalamic microglia. Our findings suggest that Fgr is a key player in thalamic pain and a potential target for the therapeutic management of this disorder