Lung Transplantation in the United States for COVID-19 Related Lung Disease During the Pandemic (2597/2600).

PURPOSE: Lung transplantation (LTx) is a potential intervention for end-stage COVID-19 lung disease. Current literature is sparse regarding the outcomes of LTx for COVID-19 related acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). This study aims to characterize outcomes and patterns of LTx for COVID-19 related lung disease throughout the pandemic. METHODS: Patients who underwent LTx during the pandemic for COVID-19 related lung disease were retrospectively identified using the UNOS registry. Demographics, as well as outcomes measures and nationwide patterns of care were collected and analyzed. RESULTS: A total of 510 adult cases of LTx for COVID-19 (259 ARDS, 251 PF) were compared to 4,031 without COVID-19 (3,994 PF, 37 ARDS). Patients who received LTx for COVID-19 ARDS did not differ in 2-year survival when compared to those with COVID-19 PF (81.9% vs 77.2%, p = 0.4428). Compared to non-COVID-19 etiologies, COVID-19 ARDS patients had higher rates of stroke (2.3% vs 0%, p = 0.0005), lower rates of graft failure (12.8% vs 36.1%, p = 0.0003) and post-transplant ECMO (29.6% vs 41.7%, p = 0.0002), and improved 2-year survival following LTx (81.9% vs 61.7%, p = 0.0064). No difference in 2-year survival following LTx was observed between patients with COVID-19 and non-COVID-19 PF (77.2% vs 71.8%, p = 0.34). Rates of LTx spiked with variant emergence and declined with rounds of vaccination. CONCLUSION: Our results are consistent with early reports of survival outcomes following LTx for COVID-19 ARDS and PF while providing an increased layer of granularity. LTx may be considered as a safe and effective intervention for COVID-19 lung disease.

Challenges in closing the gap between evidence and practice: International survey of institutional surgical stabilization of rib fractures guidelines.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) has gained increasing interest over the past decade, yet few candidates who could benefit from SSRF undergo operative management. We conducted an international survey of institutional SSRF guidelines comparing congruence between practice and contemporary evidence. We hypothesized that few guidelines reflect comprehensive evidence to facilitate standardized patient selection, operation, and postoperative management. METHODS: A request for institutional rib fracture guidelines was distributed from the Chest Wall Injury Society. Surgical stabilization of rib fractures-specific guideline contents were extracted using a priori-designed extraction sheets and compared against 28 SSRF evidence-based recommendations outlined by a panel of 14 international experts. Fisher's exact test compared the proportion of strong and weak evidence-based recommendations specified within a majority of institutional guidelines to evaluate whether strength of evidence is associated with implementation. RESULTS: A total of 36 institutions from 3 countries submitted institutional rib fracture management guidelines, among which 30 had SSRF-specific guidance. Twenty-eight guidelines (93%) listed at least one injury pattern criteria as an indication for SSRF, while 22 (73%) listed pain and 21 (70%) listed impaired respiratory function as other indications. Quantitative pain and respiratory function impairment thresholds that warrant SSRF varied across institutions. Few guidelines specified nonacute indications for SSRF or perioperative considerations. Seven guidelines (23%) detailed postoperative management but recommended timing and interval for follow-up varied. Overall, only 3 of the 28 evidence-based SSRF recommendations were specified within a majority of institutional practice guidelines. There was no statistically significant association ( p = 0.99) between the strength of recommendation and implementation within institutional guidelines. CONCLUSION: Institutional SSRF guidelines do not reflect the totality of evidence available in contemporary literature. Guidelines are especially important for emerging interventions to ensure standardized care delivery and minimize low-value care. Consensus effort is needed to facilitate adoption and dissemination of evidence-based SSRF practices. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Factors resulting in postoperative dysphagia following esophagectomy: a narrative review.

Esophagectomy is a technically involved surgery and can have significant postoperative morbidity. Although the mortality rate following esophagectomy has decreased in recent years, this surgical procedure has a relatively high complication rate compared to other surgeries to resect cancer. One of the most common complaints after esophagectomy is dysphagia. Dysphagia after esophagectomy can significantly affect quality of life. Dysphagia is a complication following esophagectomy that can lead to respiratory deterioration and death. The most common sites of postoperative dysphagia are the gastroesophageal anastomosis, gastric conduit, pylorus and the hiatus. Without appropriate treatment of dysphagia, malnutrition and dehydration can develop. These factors can lead to significant impacts to the overall health of a patient and increase mortality. A detailed literature review provided data to support diagnostic modalities and management strategies to treat postoperative dysphagia at these common areas. A systematic, evidence-based approach to diagnosis and treatment of postoperative dysphagia allows for prompt intervention and a decrease in morbidity and mortality. Treatment options for dysphagia vary, depending on the etiology. Based on the location and mechanism of dysphagia, options include stenting, dilation and surgical revision. Early treatment of dysphagia after esophagectomy can lessen the morbidity from this complication and improve quality of life.

The effects of transforming growth factor-ß2 on the expression of follistatin and activin A in normal and glaucomatous human trabecular meshwork cells and tissues.

PURPOSE: To compare follistatin (FST) and activin (Act) expression in normal and glaucomatous trabecular meshwork (TM) cells and tissues and determine if exogenous TGF-ß2 regulates the expression of FST and Act in TM cells. METHODS: Total RNA was isolated from TM cell strains, and mRNA expression for FST 317/344 isoforms and Act was determined via RT-PCR and quantitative PCR (qPCR). Western immunoblotting and immunocytochemistry determined FST and Act A protein levels in normal TM (NTM) and glaucomatous TM (GTM) cells. Cells were treated with recombinant human TGF-ß2 protein at 0 to 10 ng/mL for 0 to 72 hours. qPCR, Western immunoblotting, immunocytochemistry, and ELISA immunoassay were utilized to determine changes in FST and Act A mRNA and protein levels. In addition, NTM and GTM tissue samples were examined by immunohistochemistry for expression of FST, FST 315, FST 288, and Act A. RESULTS: Both FST mRNA and protein levels were significantly elevated in GTM cells. FST mRNA transcripts FST 317/344 were also significantly elevated in GTM cells. Immunohistochemistry showed FST levels were significantly elevated in GTM tissues. Exogenous TGF-ß2 significantly induced FST mRNA and protein expression. Immunohistochemistry demonstrated that Act A protein levels were significantly higher in NTM tissues compared to GTM tissues. CONCLUSIONS: FST is elevated in GTM cells and tissues. FST is known to be an inhibitor of bone morphogenetic proteins (BMPs), which, coupled with the ability of TGF-ß2 to upregulate FST levels, may indicate a possible role of FST in the pathogenesis of glaucoma. These results suggest that additional endogenous molecules in human TM may regulate TGF-ß2 signaling via inhibition of BMP family members.