Precision Automated Critical Care Management: Closed-loop critical care for the treatment of distributive shock in a swine model of ischemia-reperfusion.

BACKGROUND: Goal-directed blood pressure management in the intensive care unit can improve trauma outcomes but is labor-intensive. Automated critical care systems can deliver scaled interventions to avoid excessive fluid or vasopressor administration. We compared a first-generation automated drug and fluid delivery platform, Precision Automated Critical Care Management (PACC-MAN), to a more refined algorithm, incorporating additional physiologic inputs and therapeutics. We hypothesized that the enhanced algorithm would achieve equivalent resuscitation endpoints with less crystalloid utilization in the setting of distributive shock. METHODS: Twelve swine underwent 30% hemorrhage and 30 minutes of aortic occlusion to induce an ischemia-reperfusion injury and distributive shock state. Next, animals were transfused to euvolemia and randomized into a standardized critical care (SCC) of PACC-MAN or an enhanced version (SCC+) for 4.25 hours. SCC+ incorporated lactate and urine output to assess global response to resuscitation and added vasopressin as an adjunct to norepinephrine at certain thresholds. Primary and secondary outcomes were decreased crystalloid administration and time at goal blood pressure, respectively. RESULTS: Weight-based fluid bolus volume was lower in SCC+ compared with SCC (26.9 mL/kg vs. 67.5 mL/kg, p = 0.02). Cumulative norepinephrine dose required was not significantly different (SCC+: 26.9 µg/kg vs. SCC: 13.76 µg/kg, p = 0.24). Three of 6 animals (50%) in SCC+ triggered vasopressin as an adjunct. Percent time spent between 60 mm Hg and 70 mm Hg, terminal creatinine and lactate, and weight-adjusted cumulative urine output were equivalent. CONCLUSION: Refinement of the PACC-MAN algorithm decreased crystalloid administration without sacrificing time in normotension, reducing urine output, increasing vasopressor support, or elevating biomarkers of organ damage. Iterative improvements in automated critical care systems to achieve target hemodynamics in a distributive-shock model are feasible.

Boney abnormalities cause arterial, venous, and/or neurogenic thoracic outlet syndrome.

Background: Thoracic outlet syndrome (TOS) is a rare condition caused by compression of the neurovascular structures within the thoracic outlet. Different classifications of TOS exist depending on the neurovascular structure being compressed: neurogenic, venous, or arterial. Any of these forms can present independently or coexist with one other. TOS symptoms are sometimes precipitated by the presence of boney abnormalities that often require surgical intervention for ultimate resolution. This retrospective review will examine the presentations and outcomes of patients with TOS whose cause was a boney abnormality. Methods: A total of 73 patients who underwent thoracic outlet surgery between 2016 and 2021 were retrospectively reviewed via electronic medical records. Twelve (16%) patients demonstrated boney abnormalities on presentation causing their symptoms. The patients with boney abnormalities were analyzed based on venous, arterial, or neurogenic TOS diagnosis. Results: Of the 12 patients with boney abnormalities, 5 were classified as venous TOS, 6 patients as neurogenic TOS, and 1 as arterial TOS. The boney abnormalities were as follows: venous TOS: three clavicular fractures, one nonfused congenital clavicle, and one residual rib; neurogenic TOS: three fractured first ribs, one fractured clavicle, and two cervical ribs; and arterial TOS: fused first and second rib with bilateral cervical ribs and arterial compression. Postoperatively, there were no artery, vein, or nerve injuries. Five patients had a pneumothorax treated over night with a chest tube, and one patient had a superficial wound infection. The median hospital stay was 1 day. All patients completed physical therapy after surgery. All patients have symptom resolution at follow-up. Conclusions: Patients with boney abnormalities constitute about one-fifth of patients who can present with all three forms of TOS: neurogenic, arterial, and venous, and some will have more than one of these presentations. Results in patients undergoing surgery with boney abnormalities causing thoracic outlet syndrome are excellent with symptom resolution and without substantial complications.

Delay in Diagnosis for Two Patients With McCleery Syndrome.

McCleery syndrome is a rare form of venous thoracic outlet syndrome characterized by intermittent obstruction of the subclavian vein (SCV) without thrombosis. In 2022, two patients presented to our clinic with McCleery syndrome after living with venous symptoms for over one year. Duplex scans of both patients revealed compression of the SCV on abduction. A first rib resection and anterior scalenectomy were performed to decompress the SCV. At two weeks post-op, a follow-up venogram revealed widely patent, unobstructed SCVs in both patients.

Prolonged ethanol exposure modulates constitutive internalization and recycling of 5-HT1A receptors.

Alcohol exposure alters the signaling of the serotoninergic system, which is involved in alcohol consumption, reward, and dependence. In particular, dysregulation of serotonin receptor type 1A (5-HT1AR) is associated with alcohol intake and withdrawal-induced anxiety-like behavior in rodents. However, how ethanol regulates 5-HT1AR activity and cell surface availability remains elusive. Using neuroblastoma 2a cells stably expressing human 5-HT1ARs tagged with hemagglutinin at the N-terminus, we found that prolonged ethanol exposure (18 h) reduced the basal surface levels of 5-HT1ARs in a concentration-dependent manner. This reduction is attributed to both enhanced receptor internalization and attenuated receptor recycling. Moreover, constitutive 5-HT1AR internalization in ethanol naïve cells was blocked by concanavalin A (ConA) but not nystatin, suggesting clathrin-dependent 5-HT1AR internalization. In contrast, constitutive 5-HT1AR internalization in ethanol-treated cells was blocked by nystatin but not by ConA, indicating that constitutive 5-HT1AR internalization switched from a clathrin- to a caveolin-dependent pathway. Dynasore, an inhibitor of dynamin, blocked 5-HT1AR internalization in both vehicle- and ethanol-treated cells. Furthermore, ethanol exposure enhanced the activity of dynamin I via dephosphorylation and reduced myosin Va levels, which may contribute to increased internalization and reduced recycling of 5-HT1ARs, respectively. Our findings suggest that prolonged ethanol exposure not only alters the endocytic trafficking of 5-HT1ARs but also the mechanism by which constitutive 5-HT1AR internalization occurs.