Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.

Peripheral artery disease (PAD), a highly prevalent global disease, associates with significant morbidity and mortality in affected patients. Despite progress in endovascular and open revascularization techniques for advanced PAD, these interventions grapple with elevated rates of arterial restenosis and vein graft failure attributed to intimal hyperplasia (IH). Novel multiomics technologies, coupled with sophisticated analyses tools recently powered by advances in artificial intelligence, have enabled the study of atherosclerosis and IH with unprecedented single-cell and spatial precision. Numerous studies have pinpointed gene hubs regulating pivotal atherogenic and atheroprotective signaling pathways as potential therapeutic candidates. Leveraging advancements in viral and nonviral gene therapy (GT) platforms, gene editing technologies, and cutting-edge biomaterial reservoirs for delivery uniquely positions us to develop safe, efficient, and targeted GTs for PAD-related diseases. Gene therapies appear particularly fitting for ex vivo genetic engineering of IH-resistant vein grafts. This manuscript highlights currently available state-of-the-art multiomics approaches, explores promising GT-based candidates, and details GT delivery modalities employed by our laboratory and others to thwart mid-term vein graft failure caused by IH, as well as other PAD-related conditions. The potential clinical translation of these targeted GTs holds the promise to revolutionize PAD treatment, thereby enhancing patients' quality of life and life expectancy.

Utilization and Outcomes of Observation for Spontaneous Pneumothorax at an Integrated Health System.

INTRODUCTION: Though limited, recent evidence supports observation rather than intervention for spontaneous pneumothorax management. We sought to compare the utilization and outcomes between observation and intervention for patients with primary and secondary spontaneous pneumothoraces. METHODS: A retrospective cohort study of all adults presenting to Kaiser Permanente Northern California emergency rooms with spontaneous pneumothorax from 2016 to 2020 was performed. Those with prior pneumothoraces, tension physiology, bilateral pneumothoraces, effusions, and prior thoracic procedures or surgery on the affected side were excluded. Groups included observation versus intervention. Baseline clinicodemographic variables and outcomes were compared. Treatment was considered successful if further interventions were not required for pneumothorax resolution. Wilcoxon rank-sum tests, chi-square tests, Fischer exact tests, and multivariable logistic regression models were performed. RESULTS: Of the 386 patients with primary spontaneous pneumothorax, age, race/ethnicity, body mass index, smoking status, and the Charlson comorbidity index were not different between treatment groups. Of 86 patients with secondary spontaneous pneumothorax, age, gender, and smoking status were not different between treatment groups. Among patients with primary pneumothoraces, 83 underwent observation while 303 underwent intervention. The success rate was 92.8% for observation and 60.4% for intervention (P < 0.0001). Among patients with secondary pneumothoraces, 15 underwent observation while 71 underwent intervention, with a successful rate of 73.3% for observation and 32.4% for intervention (P = 0.003). CONCLUSIONS: Given the high success rates for observation of both small and moderate primary and secondary pneumothoraces, observation should be considered for clinically stable patients. Observation may be the superior choice for decreasing morbidity and healthcare costs.

Vertical rectus abdominis myocutaneous free flap repair of post-pneumonectomy bronchopleural fistula: a case report.

Background: Bronchopleural fistula (BPF) is a seldom encountered yet serious complication after thoracic surgery, and is often difficult to treat. Large BPFs usually require surgical intervention, and a variety of different surgical reconstruction options have been previously described. This case report presents the first description of a successful vertical rectus abdominis myocutaneous (VRAM) free flap repair of a BPF after pneumonectomy. Case Description: A 46-year-old male with a cough was found to have a right upper lobe lung mass with hilar involvement initially remarkable for epithelioid malignant mesothelioma on biopsy. After neoadjuvant chemotherapy, he underwent right extrapleural pneumonectomy and developed a late right mainstem BPF with associated empyema from adjuvant chemotherapy and COVID-19 pneumonia. He was treated with open Clagett window (OCW) to address the infection and then staged VRAM free flap coverage of the BPF. The patient recovered successfully and has since been able to pursue more demanding activities at home. Conclusions: This case presents the only successful VRAM free flap for a BPF involving the entire right mainstem bronchus at the carina. VRAM free flap repair offers a useful treatment option for BPFs, especially in patients with large pleural cavity defects.

Delineating the Role of Serum Immunoglobulin Titers in Burn Patients at High Risk for Herpes Simplex Virus Infection.

Herpes simplex virus (HSV) is common in the population and reactivation of latent infection often occurs in times of physiologic stress, including postburn injury. Active HSV infection complicates burn injury recovery and increases morbidity. A retrospective chart review of high-risk burn patients (≥20%TBSA and/or facial burns) who had screening HSV immunoglobulin titers drawn from 2015 to 2018 was conducted. Titer levels and morbidity-related outcomes were compared between patients who developed active infection and those who did not. Fifty-six patients had serum HSV titers measured. Twenty-nine patients (52%) developed clinical signs of HSV infection, almost all of which (97%) suffered facial burns. Titers were ordered on median hospital day 1.5 (0.00-4.0) and infection occurred on day 8.0 (2.0-16). Median HSV-1,2 IgM titers were significantly increased in patients who developed clinically active HSV infection (0.71 [0.44-1.1] vs 0.52 [0.34-0.74], P = .02). Median HSV-1 IgG (P = .65) and HSV-2 IgG titers (P = .97) were not different between groups. Patients who developed active infection had a comparable hospital length of stay (27 [9.5-40] days vs 20 [8.0-28] days, P = .17) and ICU length of stay (26 [13-49] days vs 19 [11-27] days, P = .09) to those who did not develop infection. There was no difference in mortality. Increased HSV-1 and 2 IgM screening levels were associated with an increased risk of developing active HSV infection, and offer a specific screening modality in high-risk patients. Elevated IgM titers warrant further consideration for administration of HSV prophylaxis, as earlier intervention may prevent infection onset and minimize morbidity.

Intravenous Ketamine as an Adjunct to Procedural Sedation During Burn Wound Care and Dressing Changes.

Little has been published regarding intravenous (IV) ketamine for burn wound care in adult patients. Ketamine may serve as a safe alternative to provide conscious sedation and limit opioid administration to patients. The purpose of this study was to characterize IV ketamine use during burn wound care and establish its potential role as a safe adjunct to opioid and benzodiazepine medications. This is a retrospective review of adult patients admitted to a regional burn center who received IV ketamine for burn wound care. Patient demographics, medications, and ketamine-related adverse effects including hypertension and dysphoric reactions were recorded. Cardiopulmonary complications were also tracked. Thirty-six patients met inclusion criteria; fifty total cases were performed. The median patient age was 37 (interquartile range [IQR]: 28-55] years with a median burn size of 9.5 (IQR: 4.0-52) %TBSA. The median ketamine dose administered was 1.2 (IQR: 0.8-2.1) mg/kg. IV midazolam was administered in almost all cases (98%) at a median dose of 3.0 (IQR: 2.0-5.0) mg. Opioids were administered in 13 of 50 cases (26%) at a median morphine equivalent dose of 10 (IQR: 5.0-18) mg. In 46 cases (92%), patients denied unpleasant recall of medication. Dysphoric reactions were observed in three cases (6%). Ketamine-induced hypertension occurred in three cases (6%) and all immediately responded to IV labetalol. There were no cardiopulmonary complications. These findings suggest that IV ketamine provides a safe analgesia and sedative option for burn wound care. Given these findings, IV ketamine for burn wound care warrants further study.