Femtosecond Plasmonic Laser Nanosurgery (fs-PLN) mediated by molecularly targeted gold nanospheres at ultra-low pulse fluences.

Plasmonic Laser Nanosurgery (PLN) is a novel photomodification technique that exploits the near-field enhancement of femtosecond (fs) laser pulses in the vicinity of gold nanoparticles. While prior studies have shown the advantages of fs-PLN to modify cells, further reduction in the pulse fluence needed to initiate photomodification is crucial to facilitate deep-tissue treatments. This work presents an in-depth study of fs-PLN at ultra-low pulse fluences using 47 nm gold nanoparticles, conjugated to antibodies that target the epithelial growth factor receptor and excited off-resonance using 760 nm, 270 fs laser pulses at 80 MHz repetition rate. We find that fs-PLN can optoporate cellular membranes with pulse fluences as low as 1.3 mJ/cm2, up to two orders of magnitude lower than those used at lower repetition rates. Our results, corroborated by simulations of free-electron generation by particle photoemission and photoionization of the surrounding water, shed light on the off-resonance fs-PLN mechanism. We suggest that photo-chemical pathways likely drive cellular optoporation and cell damage at these off-resonance, low fluence, and high repetition rate fs-laser pulses, with clusters acting as local concentrators of ROS generation. We believe that the low fluence and highly localized ROS-mediated fs-PLN approach will enable targeted therapeutics and cancer treatment.

Evaluation of respiratory volume monitoring (RVM) to detect respiratory compromise in advance of pulse oximetry and help minimize false desaturation alarms.

BACKGROUND: Monitoring respiratory function is important. By continuously monitoring respiratory volumes, respiratory depression could be identified before hypoxemia and drive earlier intervention. Here, we evaluate the temporal relationship of respiratory volume monitoring (providing real-time minute ventilation [MV], tidal volume, and respiratory rate in nonintubated patients) to hypoxemic episodes and its potential to help classify true vs false desaturations (related to patient movement/probe dislodgement). METHODS: Respiratory volume monitoring data, oxygen saturation (SpO2), oxygen supplementation, and opioid use were analyzed in 259 patients following orthopedic surgery. Detection of "low MV" (<40% of predicted MV) in advance of low SpO2 (<90%) was used to classify true and false desaturations. Patients were also stratified based on opioid use and development of low MV. Patient's length of stay (LOS) and number of SpO2 alarms were compared across groups (± opioids; ± low MV). RESULTS: The electronic health records reported 113 SpO2 alarms; 105 (93%) not preceded by low MV and considered false. Low MV preceded the eight true desaturations by 12.8 ± 2.8 minutes. One hundred ninety-eight patients (76%) of 259 experienced one or more low MV events. Patients with low MV had significantly longer postanesthesia care unit (PACU) LOS than those maintaining "adequate MV": 2.8 ± 0.1 hours vs. 2.4 ± 0.1 hours (p < 0.001). Patients receiving opioids had increased likelihood of low MV (69% vs. 80%; p < 0.05) and had significantly longer PACU LOS than those without opioids (2.9 ± 0.1 hours vs. 2.3 ± 0.1 hours; p < 0.001). In the opioid group, PACU LOS was 75% longer in patients developing low MV versus maintaining adequate MV (3.0 ± 0.1 hours vs. 1.7 ± 0.2 hours; p < 0.001). CONCLUSION: Respiratory volume monitoring can provide advanced warning of impending oxygen desaturation and potentially reduce the number of false SpO2 alarms. Opioid administration increased low MV events correlating with increased LOS. Respiratory volume monitoring can help clinicians individualize patient care, decrease false alarms, adjust opioid dosing, and increase PACU throughput. Similar benefits may translate to the general care floor and prehospital and posthospital environments. LEVEL OF EVIDENCE: Diagnostic study, level II.