Opportunities for Drug Repurposing of Serotonin Reuptake Inhibitors: Potential Uses in Inflammation, Infection, Cancer, Neuroprotection, and Alzheimer's Disease Prevention.

Serotonin reuptake inhibitors (SRIs) are safe and widely used for a variety of indications including depressive disorders, anxiety, and chronic pain. Besides inhibiting the serotonin transporter, these medications have broad-spectrum properties in many systems. Their roles have been studied in cancer, Alzheimer's disease, and infectious processes. The COVID-19 pandemic highlighted the importance of drug repurposing of medications already in use. We conducted a narrative review of current evidence and ongoing research on drug repurposing of SRIs, with a focus on immunomodulatory, antiproliferative, and neuroprotective activity. SRIs may have clinical use as repurposed agents for a wide variety of conditions including but not limited to COVID-19, Alzheimer's disease, and neoplastic processes. Further research, particularly randomized controlled trials, will be necessary to confirm the utility of SRIs for new indications.

Use of Physician-Modified Endografts to Repair Unilateral or Bilateral Aortoiliac Aneurysms.

BACKGROUND: This article presents an endovascular approach to repair a unilateral or bilateral aortoiliac aneurysm with a bifurcated iliac limb that can maintain perfusion to the internal iliac artery (IIA) bilaterally through a brachial access. METHODS: A standard infrarenal aortic aneurysm repair is performed followed by iliac aneurysm exclusion. To obtain exclusion in the common iliac artery aneurysm, a bifurcated Endurant iliac limb is modified to compartmentalize iliac flow 2-3 cm above the internal iliac ostia. Then, a balloon-expandable covered stent graft is used to achieve sealing in the IIA and external iliac artery (EIA). The IIA is stented from the arm and the EIA is stented from the groin. RESULTS: There was no in-hospital or 30-day mortality. The procedural design was followed in each of the patients who received treatment. Technical success was 100%, short-term clinical success was 92%, and midterm clinical success was 83%. Average dosage of contrast medium was 116 mL (range, 55-193 mL), and average fluoroscopy time was 42.1 min (range, 20.8-91.6 min). Average length of hospital stay was 2.6 days (range, 1-9 days). There was 1 recorded endoleak. No reports of gluteal claudication, sexual dysfunction, or bowel or spinal claudication have been found. CONCLUSIONS: The technique described here does not require an up-and-over approach, allowing simplified bilateral repair. Although this is a promising technique, long-term durability needs to be evaluated in a controlled prospective study.

Complete endovascular debranching of the aortic arch: A report of two cases.

Patients suffering from aortic arch aneurysms continue to encounter few treatment options. Because of co-morbidities, most are deemed to not be open surgical candidates. The two cases presented here demonstrate a novel endovascular approach in the care of an arch aneurysm complicated by dissection. Even though final graft configurations differed slightly between the two cases, all three great vessels were successfully de-branched through the combination of standard endovascular aneurysm repair techniques and modifications to off-the-shelf devices. Aortic flow was compartmentalized in the ascending aorta at or near the level of the sinotubular junction. This was done with a physician-assembled endografts. One of these lumens was dedicated to the descending aorta, while the other was further divided into three channels used to stent the great vessels. Completion angiography demonstrated patency in the arch, great vessels, and descending aorta. No endoleaks have been reported. Although data is limited, this approach appears promising.

A novel endovascular debranching technique using physician-assembled endografts for repair of thoracoabdominal aneurysms.

OBJECTIVE: The objective of this study was to demonstrate a technique that uses physician-assembled endografts to make use of the benefits of parallel grafts while also providing for circumferential seal and fixation in repair of thoracoabdominal aneurysms in inoperable patients. METHODS: A single-center all-comers retrospective analysis of 14 patients was performed that looked at the early outcomes of patients treated for thoracoabdominal aneurysms. Three Crawford type II, four type III, four type IV, and three type V thoracoabdominal aneurysms were treated. Contrast material, fluoroscopy time, length of stay, clinical success, and technical success were measured. RESULTS: There was no in-hospital, 30-day, or 6-month mortality. We found two type III endoleaks in the early design. One required coil embolization. Average volume of contrast material and average fluoroscopy time were 76.9 mL and 119.1 minutes, respectively. Average length of stay was 10.5 days, and average procedure time was 251.2 minutes. Clinical success was observed in 78.6% of patients to date, and technical success was observed in 85.7% of patients. CONCLUSIONS: Short-term results show that this approach is safe. The device can be safely implanted, is off-the-shelf, and can treat each of the Crawford thoracoabdominal aneurysm types. Finally, the assembly of off-the-shelf components may shorten the regulatory path for this physician-assembled endograft.

Treatment of a massive left femoral arteriovenous malformation using an innovative modular hybrid bifurcated stent graft system.

BACKGROUND: Arteriovenous malformations (AVMs) are difficult to treat and manage because of their high recurrence and complication rates. In particular, peripheral AVMs pose multiple clinical challenges because of their high flow rates and the frequent presence of multifocal nidi. METHODS: A 37-year-old man with a massive AVM involving the left common, deep, and superficial femoral arteries and veins is discussed herein. After initially being treated at another facility with coil embolization in 2005, he went untreated until he presented to us in April 2012 with swelling, tissue breakdown, leg ulcers, pain, and difficulty walking. When our extensive packed coil embolization proved ineffective, we knew that other standard treatments would be impractical, given the size of the AVM. Because the patient was in significant danger of bleeding, we treated him endovascularly with a system of modified stent grafts to exclude the arterial branches feeding multiple nidi. RESULTS: Postoperative computed tomography angiography scans revealed exclusion of the AVM and excellent flow to the deep and superficial femoral arteries. At 6 months postoperatively, the patient had no complications, and the leg continued to decompress. At 8 months postoperatively, we started additional treatment using percutaneous sclerotherapy to treat residual areas. CONCLUSION: A modular hybrid bifurcated stent graft system is a viable option to treat or manage complex peripheral arteriovenous malformations.

Retrospective Evaluation of the Perioperative Management of Patients Undergoing Total Pancreatectomy With Islet Autotransplantation: Single Institution Review.

OBJECTIVE: The aim of this retrospective descriptive study was to examine associations with the perioperative management of patients undergoing total pancreatectomy with islet autotransplantation, which may impact complication rate and hospital length of stay. METHODS: We retrospectively collected data on 165 patients, and 161 patients were included in the final analysis. Data collected included preoperative, intraoperative, and postoperative patient and procedural characteristics. RESULTS: Approximately 46.6% of patients experienced 1 or more complications. The occurrence of complications was associated with postoperative day 1 hemoglobin levels, use of intraoperative goal-directed therapy, estimated intraoperative blood loss, and total amount of intraoperative insulin given. Hospital length of stay was significantly associated with number of complications, use of goal-directed therapy, procedure duration, and postoperative day 1 hemoglobin levels. CONCLUSIONS: Overall, our retrospective descriptive study adds to the emerging body of literature determining optimal perioperative management of patients undergoing total pancreatectomy with islet autotransplantation.

Safety and efficacy of ultrasound-accelerated catheter-directed lytic therapy in acute pulmonary embolism with and without hemodynamic instability.

OBJECTIVE: The objective of this study was to evaluate the safety and effectiveness of ultrasound-accelerated thrombolysis in acute pulmonary embolism. METHODS: A retrospective study of 45 patients was performed to evaluate treatment of acute pulmonary embolism at a single center from January 2011 to December 2013. All patients were diagnosed with computed tomography or ventilation-perfusion scan and had hemodynamic instability (systolic blood pressure <100 mm Hg) or right-sided heart strain evidenced by right ventricular dilation, septal deviation, or hypokinesis by echocardiography or computed tomography. EkoSonic catheters (EKOS Corporation, Bothell, Wash) were placed into the affected pulmonary arteries, and recombinant tissue plasminogen activator was infused through the catheters at 0.5 to 1.0 mg/h per catheter. RESULTS: Hypotension (systolic blood pressure <100 mm Hg) was present in 12 patients, with 100% resolution by treatment completion. Tachycardia (heart rate >100 beats/minute) was present in 26 patients and resolved in 92% by treatment completion; the average heart rate for all patients decreased from 109 to 77 beats/minute during the treatment period. Direct pulmonary artery pressure measurement showed average decrease of 21.5 mm Hg, representing a 40.2% reduction. Postprocedure echocardiography demonstrated complete resolution of cardiac dysfunction in 64%. Patients received a total dose of 30.5 mg (range, 14-66 mg) recombinant tissue plasminogen activator during an infusion time of 14.2 hours (range, 8-21 hours). There were no deaths through 90 days of follow-up and no major periprocedural bleeding events. CONCLUSIONS: This retrospective study demonstrates the safety and efficacy of current ultrasound-accelerated thrombolysis methods to treat acute pulmonary embolism.