Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection.

Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.

Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.

Background: The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. Methods: We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Results: Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1ß relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1ß were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1ß expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1ß expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1ß in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1ß within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1ß levels when compared to other patients. Conclusions: Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

A new minimal invasive technique with in-situ stent-graft fenestration for type A aortic dissection.

Background: Aortic surgery successfully improves the prognosis of patients with type A aortic dissection. However, total arch replacement and reconstruction remain challenging. This study presents a new surgical modality, the in-situ stent-graft fenestration (ISSF) technique, for simplifying aortic arch reconstruction and assesses its short-term efficacy and safety in patients with type A aortic dissection. Methods: Data from 177 patients with type A aortic dissection who underwent aortic arch reconstruction were retrospectively analyzed. Sun's procedure was performed in 90 patients and ISSF was performed in the other 87. Results: The in-hospital mortality rate was 7.8% in the Sun's procedure group and 3.4% in the ISSF group (p = 0.357). Compared to the Sun's procedure group, the ISSF group had significantly shorter surgical duration, cardiopulmonary bypass time, circulatory arrest time, mechanical ventilation time, and aortic cross-clamp time (p < 0.05). Additionally, intraoperative blood loss was lower in the ISSF group than in the Sun's procedure group (p < 0.05). Patients who underwent ISSF also had a lower incidence of postoperative complications, including lung injury, renal failure, peripheral nerve injury, and chylothorax, than those who underwent Sun's procedure (p < 0.05). During the 6-month follow-up period after surgery, both groups showed significant improvements in the true lumen diameter of the descending thoracic aorta post-operation compared with the pre-operation measurements; meanwhile, the false lumen diameter decreased (p < 0.05). Conclusions: The ISSF technique appears to be an effective and safe alternative to conventional surgical procedures for patients with type A aortic dissection, with the potential to simplify the procedure, shorten the operation time, and yield satisfactory operative results. However, further investigation is needed to determine its long-term benefits.

Systematic review of the effect of cerebrospinal fluid drainage on outcomes after endovascular type B aortic dissection repair.

OBJECTIVE: The aim of the present systematic review was to determine whether prophylactic use of cerebrospinal fluid drainage (CSFD) contributes to a lower rate of spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were systematically searched to identify all relevant studies reported before May 7, 2023. A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42023441392). The primary outcome was permanent SCI. Secondary outcomes were temporary SCI and 30-day/in-hospital mortality. The data were presented as the pooled event rates (ERs) and 95% confidence intervals (CIs). RESULTS: A total of 1008 studies were screened, of which 34 studies with 2749 patients were included in the present analysis. The mean Downs and Black quality assessment score was 8.71 (range, 5-12). The pooled rate of permanent SCI with prophylactic CSFD was identical to that without prophylactic CSFD (2.0%; 95% CI, 1.0-3.0; P = 0.445). No statistically significant difference was found between the rates of permanent SCI with routine vs. selective prophylactic CSFD (P = 0.596). The pooled rate of temporary SCI was 1.0% (95% CI, 0.00-1.0%). The pooled rate for 30-day or in-hospital mortality was not significantly different (P = 0.525) in patients with prophylactic CSFD (4.0, 95% CI 2.0-6.0) or without prophylactic CSFD (5.0, 95% CI 2.0-7.0). CONCLUSIONS: The systematic review has shown that prophylactic CSFD was not associated with a lower rate of permanent SCI and 30-day or in-hospital mortality after TEVAR for TBAD.

Clinical impact of baseline mitral regurgitation on outcomes after transcatheter aortic valve replacement for severe aortic stenosis.

Objective: The clinical impact of baseline mitral regurgitation (MR) on the outcomes after transcatheter aortic valve replacement (TAVR) is not clear. This study sought to assess the clinical impact of baseline MR on outcomes after TAVR. Methods: The study was a retrospective analysis. Data was from 120 consecutive patients with severe aortic stenosis (AS) undergoing TAVR at our center from June 2018 and July 2020. Clinical outcomes were assessed at 30-day, 1- and 2-year follow-up. Results: The median follow-up was 736.0 (interquartile range, 666.0-965.0) days. Overall survival in patients with nonsignificant and significant baseline MR was not significantly different, while patients from the improved MR group after TAVR demonstrated a significantly higher survival than unchanged or worsened MR group during 2-year follow-up. NYHA functional class had generally improved at 1 year, with only 8.3 % of patients with nonsignificant MR and 17.5 % of patients with significant MR in class III or IV. Patients with improved MR at 1 year after TAVR had a significantly higher LVEF, smaller LVEDD and LVESD than those with unchanged or worsened MR. Among the significant baseline MR group, 70.4 % and 80.0 % of patients had improved to nonsignificant MR at 30-day and 1-year follow-up after TAVR, respectively. Conclusions: Significant baseline MR was not associated with the increased risk of all-cause mortality 2 years after TAVR. Significant baseline MR was improved in most patients at 1 year after TAVR. Patients with unchanged or worsened MR had an increased all-cause mortality.

Effect of transcatheter aortic valve replacement on ascending aorta dilatation rate in patients with tricuspid and bicuspid aortic stenosis.

Objectives: The aim of the present study was to assess the differences between BAV and TAV patients with chronic moderate to severe or severe AS regarding presentation, incidence of TAVR, survival, ascending aorta diameter and dilatation rate before and after TAVR. Methods: The study included 667 consecutive patients with chronic moderate to severe or severe AS from January 2012 and December 2022. Outcomes included all-cause mortality, incidence of TAVR, and ascending aorta diameter and dilatation rate. Results: There were 185 BAV-AS and 482 TAV-AS patients, and BAV-AS patients were younger (67 vs 78 years, P = 0.027). Total follow-up was 4.5 years (IQR: 2.7-8.9 years), 290 patients underwent TAVR, and 165 patients died. The 8-year TAVR incidence was higher in BAV-AS (55% ± 4%) vs TAV-AS (41% ± 5%; P = 0.02). The 8-year survival was higher in BAV-AS (85% ± 6%) vs TAV-AS (71% ± 6%; P < 0.0001) and became insignificant after age adjustment (P = 0.33). The dilatation rate of ascending aorta was significantly faster in BAV-AS patients compared with TAV-AS patients before TAVR. However, the ascending aorta dilatation rate for BAV-AS and TAV-AS patients was not significantly different after TAVR. Conclusions: Compared with TAV-AS, BAV-AS patients were younger and underwent TAVR more frequently, resulting in a considerable survival advantage. After TAVR, ascending aorta dilatation rates were similar in BAV-AS and TAV-AS patients, suggesting an important role of hemodynamics on ascending aorta dilatation in BAV-AS.

Early outcome of simplified total arch reconstruction under mild hypothermia (30-32 °C) with distal aortic perfusion.

OBJECTIVE: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30-32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). METHODS: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25-28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30-32 °C) with distal aortic perfusion (s-TAR group). RESULTS: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. CONCLUSIONS: s-TAR under mild hypothermia (30-32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

A modified prosthesis eversion technique for proximal anastomosis in ascending aorta replacement.

Background: One of the crucial aspects of ascending aorta replacement is to achieve hemostasis of the proximal anastomosis. This study aimed to describe a modified prosthesis eversion technique for proximal anastomosis in ascending aorta replacement and compare its operative outcomes with the conventional prosthesis eversion technique. Methods: We conducted a retrospective analysis of all consecutive patients who had ascending aortic aneurysm and underwent ascending aorta replacement with the modified or conventional prosthesis eversion technique between January 2019 and December 2022 in our center. Results: A total of 108 patients were included: 55 in the modified group and 53 in the conventional group. The durations of cardiopulmonary bypass, aortic cross-clamping and total operation in the conventional group were longer than those in the modified group. Furthermore, perioperative blood loss and the incidence of re-exploration for bleeding were significantly lower in the modified group. Accordingly, patients in the conventional group accepted more blood transfusion. The modified group had a shorter duration in intensive care unit (ICU) and hospital, and lower total hospitalization costs than those in the conventional group. Conclusions: The modified prosthesis eversion technique is an effective alternative for proximal anastomosis in ascending aorta replacement, with less blood loss, shorter operation time, and lower rate of postoperative complications compared with the conventional technique.

Supramolecular nanofiber of indomethacin derivative confers highly cyclooxygenase-2 (COX-2) selectivity and boosts anti-inflammatory efficacy.

Herein, we report a facile method for converting carboxylate-containing indomethacin (Idm) into a cyclooxygenase-2 (COX-2) selective inhibitor via the amidation of an unnatural peptide sequence (Nal-Nal-Asp). The resulting indomethacin amides (i.e., Idm-Nal-Nal-Asp) have high selectivity for COX-2, and can self-assemble into a one-component supramolecular hydrogel that acts as a 'self-delivery' system for boosting anti-inflammatory efficacy. Self-assembled Idm-Nal-Nal-Asp hydrogel robustly inhibits COX-2 expression in lipopolysaccharide (LPS)-activated Raw 264.7 macrophages while also exhibits superior anti-inflammatory and antioxidant activities via reactive oxygen species (ROS)-related NF-κB and Nrf2/HO-1 pathways. Moreover, a rabbit model of endotoxin-induced uveitis (EIU) reveals that the Idm-Nal-Nal-Asp hydrogel outperforms clinically used 0.1 wt% diclofenac sodium eye drops in terms of in vivo anti-inflammatory efficacy via topical instillation route. As a rational approach to designing and applying COX-2 selective inhibitors, this work presents a simple method for converting non-selective nonsteriodal anti-inflammatory drugs (NSAIDs) into highly selective COX-2 inhibitors that can self-assemble into supramolecular hydrogel for anti-inflammation applications.

Prognostic impact of new permanent pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: Conduction disturbances requiring permanent pacemaker implantation (PPI) are common following transcatheter aortic valve replacement (TAVR). There were conflicting data regarding the impact of new PPI on clinical outcomes after TAVR. OBJECTIVES: The study sought to evaluate the impact of new PPI on clinical outcomes in patients undergoing TAVR. METHODS: This study was a retrospective analysis of prospectively collected data. Data were from 210 consecutive patients without prior PPI who underwent TAVR due to severe symptomatic aortic stenosis at our center between June 2018 and July 2020. Clinical, echocardiographic, and pacing data were assessed at 30-day, 1- and 2-year follow-up. RESULTS: New PPI was required in 35 (16.7%) patients within 30 days after TAVR. The median time from TAVR to PPI was 3 days. The most common indication for PPI was high-degree or complete atrioventricular block. The median follow-up was 798.0 (interquartile range, 669.0-1115.0) days. There were no differences in all-cause mortality (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.85-2.36; p = 0.415) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.57-1.89; p = 0.609) between groups. However, PPI group had a higher risk of heart failure (HF) rehospitalization (adjusted HR: 1.53; 95% CI: 1.26-2.28; p = 0.027). Echocardiography showed no significant improvement of LVEF over time in patients with PPI. At the latest follow-up, 31.3% of patients exhibited low (≤10%) pacing burdens, whereas 28.1% of patients had near constant (>90%) right ventricular pacing. CONCLUSIONS: New PPI within 30 days following TAVR was not associated with an increased risk of all-cause or cardiovascular mortality. However, patients with PPI had a higher risk of HF rehospitalization and lack of LVEF improvement.