fentanyl citrate (OX20 / Rapinyl / EN 3267)

Association between fentanyl dose and willingness to undergo repeat bronchoscopy in a standardized EBUS-GS-TBB setting.

Monden Kazuya K, Akamatsu Ayumi A, Takada Yohei Y, Totani Risa R et al.

Discomfort experienced during bronchoscopy may limit patients' willingness to undergo repeat procedures. Although guidelines recommend benzodiazepine-opioid sedation, evidence regarding optimal opioid dosing remains limited. We evaluated whether the total fentanyl dose was associated with willingness to undergo repeat bronchoscopy in a standardized endobronchial ultrasonography with guide-sheath transbronchial biopsy (EBUS-GS-TBB) setting. We conducted a retrospective single-center study of consecutive patients who underwent radial endobronchial ultrasonography with guide-sheath transbronchial biopsy. Patients were categorized by fentanyl dose: none (0 μg), low (1-49 μg), and moderate (≥50 μg). The primary outcome was willingness to undergo repeat bronchoscopy, assessed on a 5-point Likert scale (lower scores indicate greater willingness). Ordinal logistic regression was conducted using complete case analysis. Sensitivity analyses were conducted using alternative dose thresholds and continuous dose modeling. Among 300 patients with evaluable primary outcome data, moderate-dose fentanyl was independently associated with greater willingness to undergo repeat bronchoscopy (adjusted odds ratio, 0.49; 95% confidence interval, 0.27-0.91), whereas low-dose fentanyl was not. The associations remained consistent in direction across different categorizations, and the continuous model demonstrated a dose-response relationship. Severe adverse events included two cases of pneumothorax requiring chest drainage in the moderate-dose group; no other severe events were noted. In this standardized EBUS-GS-TBB setting, moderate-dose fentanyl was associated with greater willingness to undergo repeat bronchoscopy. These findings suggest that willingness to undergo repeat bronchoscopy may depend not only on opioid use, but also on how opioids are titrated.

Voluntary oral fentanyl intake produces dose- and sex-dependent physical dependence in mice without overt affective disturbances.

Allichon Marie-Charlotte MC, Boehm Samuel F SF, Jordan Nilah D ND, Nelson Lars H LH et al.

The ongoing opioid epidemic underscores the need for scalable and translational preclinical models of voluntary opioid intake and dependence. We therefore sought to establish and validate a voluntary two-bottle choice drinking-in-the-dark (DID) model of oral opioid intake in mice and to determine relationships between experimental parameters and behaviors during and after withdrawal. Male and female C57BL/6J mice were given daily access to two bottles during the dark phase for 24 drinking sessions over 5 weeks. Control mice received two bottles containing water. Experimental mice received one water bottle and one bottle containing oxycodone (0.1-1 mg/mL) or fentanyl (10-100 µg/mL) under varying session durations and concentrations. On the final day, physical dependence was assessed using naloxone-precipitated withdrawal and then a behavioral battery to assess negative affect was performed in the following week. Mice voluntarily consumed both oxycodone and fentanyl without taste adulteration and maintained drug preference across most concentrations. Oxycodone intake produced minimal withdrawal symptoms. In contrast, fentanyl intake resulted in naloxone-precipitated withdrawal that was modulated by session duration and concentration. Four-hour sessions produced stronger withdrawal than two-hour sessions at equivalent concentrations. Escalating high-concentration fentanyl exposure revealed emerging sex differences, with females exhibiting greater intake and withdrawal at higher concentrations. Affective behavioral assays following withdrawal revealed minimal persistent alterations in any cohort. These findings establish key parameters for a scalable voluntary fentanyl model that produces dose- and session-dependent physical dependence in male and female mice. This paradigm provides a cost-effective and straightforward platform for future investigations of opioid use and dependence.

CORR Insights®: Is a Resorbable Citrate-based Bioceramic Device Associated With Osseous Integration? An Early Retrospective MRI Analysis.

DeCoster Thomas A TA

Structures of the human sodium-citrate cotransporter NaCT with and without substrates.

Sauer David B DB, Song Jinmei J, Marden Jennifer J JJ, Wang Bing B et al.

The human sodium-citrate cotransporter NaCT imports various tri- and dicarboxylates into the cell as TCA cycle intermediates. This substrate uptake process is driven by an inward sodium gradient. The protein is a member of the Divalent Anion-Sodium Symporter (DASS) family. Whereas extensive biochemical and structural studies have been carried out for NaCT, how the substrate binding and translocation is coupled to the sodium gradient remains unclear. Here using single particle cryo-electron microscopy, we determined the structures of the human NaCT protein in three states: sodium-free, in the presence of sodium, and sodium- and substrate-bound. These structures suggest a simultaneous binding mechanism for sodium-substrate coupling, distinct from the sequential binding, conformational selection mechanism previously observed for the bacterial DASS protein VcINDY.