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Aim: Metformin is used for the management of type 2 diabetes mellitus (T2DM) and is being tested clinically as an anticancer agent. Metformin concentrations safely achievable in human solid tissues including tumours are unknown. This study was designed to determine metformin concentration in tissue compartments as a function of dose to inform rational dosing in preclinical models and interpretation of clinical results." Methods: Subjects with solid tumours to be treated by resection and either (A) willingness to take metformin for 7‐10 days before surgery or (B) taking metformin for T2DM were eligible. Whole blood, plasma, tumour, tumour‐adjacent uninvolved tissue and subcutaneous adipose tissue were obtained for liquid chromatography with tandem mass spectrometry to measure metformin concentrations. Results: All subjects had primary lung tumours. Metformin dose was significantly correlated with drug concentrations in all tissues analysed. Intersubject metformin concentrations varied by over two orders of magnitude. Metformin concentrations were significantly higher in tumour tissues and lower in adipose tissues compared to other tissues. Concentrations in blood and plasma were significantly correlated with concentrations in solid tissues. Conclusion: Metformin accumulates in cellular compartments. Concentrations observed in plasma, blood, lung and tumour tissues in subjects treated with US Food and Drug Administration‐approved doses for T2DM are lower than those typically used in tissue culture studies. However, such tissue concentrations are in line with those found within cultured cells treated with supra‐pharmacological doses of metformin. Given the large intersubject variability in metformin concentrations, it is imperative to determine whether there is an association between tissue metformin concentration and anticancer activity in humans. [ABSTRACT FROM AUTHOR]

Defining the electrical property contrast between benign and malignant lung tissue plays an important role when designing surgical tools and imaging systems to differentiatiate these tissue types. Intraoperative procedures often involve tissue manipulation with instruments in which pressure is applied and tissue deformed. Embedding bioimpedance sensors within these instruments represents a potential mechanism for real-time intraoperative tissue assessment to ensure adqueate resection margins. We recorded impedance spectra (100 Hz -- 10 MHz) under varied applied pressure from fresh ex vivo tissue specimens resected from 12 patients undergoing surgical treatment for lung nodules. Generally we see higher resistivities for normal lung tissue compared to lesions. With applied pressure, we see an increase in real part of resistivity while a decrease in the imaginary part. Finally, we observed significant differences (p>0.05) between normal and lesion tissue resisitivity at multiple frequencies. This electrical property contrast suggest electrical impedance spectroscopy could be implemented in intraoperative margin sensing devices in lung cancer surgeries. [ABSTRACT FROM AUTHOR]

Determine the utility of using scoring systems in a serial fashion to identify distinct phenotypes of sepsis. Sepsis is a heterogenous clinical syndrome with distinct phenotypes and no universally accepted gold standard for diagnosis. Current scoring systems are usually used once during a presentation. Single-center, retrospective study that screened all adults who activated the hospital's SIRS (systemic inflammatory response syndrome) based sepsis alert into culture positive (Cx+) & culture negative (Cx-) groups. Pre-defined location-based subgroups (emergency department–ED, Step down–SDU & floor) were also analyzed. SIRS scores were calculated at t=0 (time of activating > 2 SIRS criteria) as well as 3,6,12 & 24 hours before and after t=0. Primary outcome was a difference in SIRS scores amongst those that were Cx+ or Cx- at any time point. Secondary outcomes were comparing SIRS scores in subgroups over consecutive time points. 7,955 patients met inclusion criteria, including 4,701 Cx+ and 3254 Cx- patients. Differences in both length of stay (LOS) (Cx+ 16.9 days vs Cx- 9.7 days) and in-hospital mortality (IHM) (Cx+ 14.1% vs Cx- 10.5%) were statistically significant (p<.05). LOS and IHM for each subgroup are shown below [table1]. Statistically significant differences were seen in overall SIRS score between Cx + and Cx- groups at hours 6 (Cx+ 1.40+1.04 vs Cx- 1.35+1.01) & 12 (Cx+ 0.95+0.95 vs Cx- 0.90+0.90) after t=0. For patients who met SIRS criteria in the ED the difference between culture positive and negative sepsis was only significant at 24 hours after t=0 (Cx+ 1.10+0.98 vs Cx- 1.00+0.88). For patients on the floor the only significant difference was at t=0 (Cx+ 1.99+1.02 vs Cx- 1.88+0.95). Lastly, the only significant difference for patients in the SDU was at 3 hours after t=0 (Cx+ 1.10+0.98 vs Cx- 1.00+0.88). SIRS scores at all time points for all subgroups and all patients can be found below [table2]. Using readily available clinical scoring systems such as SIRS in a serial fashion over time shows a clear increase in SIRS score (window of bioreactivity) before t=0 and a subsequent decrease in scores after t=0. While not all locational subgroups showed these differences, these findings suggest potential utilities in early detection, intervention, and a real time provision for monitoring response to therapeutics. Further studies need to address whether the lack of differences in subgroups is an issue with power versus too much clinical heterogeneity. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to describe the incidence of and modifiable risk factors for post intubation hemodynamic collapse in prehospital and interfacility critical care transport., Methods: Single center retrospective chart review of adult patients (≥18 years) intubated by a critical care transport team between January 2017 and May 2023. The primary outcome was incidence of hemodynamic collapse (systolic blood pressure <90 mmHg for greater than 30 min, new vasopressor requirement, vasopressor dose increase, fluid bolus of >15 mL/kg, systolic blood pressure <65 mmHg at least once, or cardiac arrest). Secondary outcomes included post intubation hypoxia, as well as association of hemodynamic collapse with potentially modifiable risk factors including pre intubation shock index, pre intubation heart rate, pre intubation systolic blood pressure, and induction agent., Results: Three hundred and thirty-three patients were included. Ninety-seven (29.1%) patients experienced hemodynamic collapse and 36 (10.8%) of patients experienced life threatening hemodynamic collapse. Pre intubation shock index >1 (OR 3.18, 95% CI 1.15-8.74) was associated with post intubation hemodynamic collapse. Choice of induction agent, fluid bolus prior to intubation, location of intubation, presence of traumatic injury, and age were not correlated with risk of hemodynamic collapse. The number of intubation attempts and methods of intubation were similar between groups., Conclusions: Hemodynamic collapse and life-threatening hemodynamic collapse after intubation occurred frequently in this critical care transport cohort. Shock index greater than one was associated with significantly higher risk of hemodynamic collapse and life-threatening hemodynamic collapse.