Notes

Affect of ENaC downregulation within transgenic rats around the outcomes of intense lungs injury caused by bleomycin.
In vivo therapeutic gene transfer has emerged as a novel class of medicines. Its feasibility relies on the safe and efficacious delivery of genetic cargo to the appropriate targets. The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to enhance its targeting specificity, safety, and endurance. While each and every desirable trait can be individually remodeled, combining several attributes in one capsid amounts to a significant engineering challenge. Taking advantage of virion structure and phylogenetics, harnessing directed evolution, sequence analyses, and machine learning, researchers develop novel capsid variants to realize the goals of safe and enduring gene therapy.
CBT with ATG use is a well-known PTLD risk factor. However, little is known regarding the clinical features of PTLD after ATG-free CBT.

We analyzed the incidence, risk factors and prognosis of PTLD in 183 adults undergoing ATG-free CBT.

Fifteen patients (diffuse large B-cell lymphoma, n=9, mucosa-associated lymphoid tissue lymphoma, n=2 nondestructive PTLD, n=1, T-cell lymphoma, n=3) developed PTLD. The 2-year CuI of PTLD was 8.0% (95% CI 4.6-12.7). Pathologically, all 12 B-cell PTLD patients had Epstein-Barr virus (EBV), compared with 1 of 3 T-cell PTLD patients. All patients, excluding one with nondestructive PTLD, showed extranodal involvement. In the univariate analysis, the 2-year CuI of PTLD was significantly higher in patients who received mycophenolate mofetil to prevent graft-versus-host disease than in nonrecipients (11.2%/2.9%, P=.0457). However, multivariate analysis revealed no independent PTLD risk factors. All 11 PTLD patients who received specific therapy achieved complete remission. The 1-year overall survival of PTLD patients was 70.9%.

Although we found a higher CuI of PTLD than previously reported, the prognosis was generally good. In CBT recipients, many factors, including MMF use, may be associated with the clinical features of PTLD.
Although we found a higher CuI of PTLD than previously reported, the prognosis was generally good. In CBT recipients, many factors, including MMF use, may be associated with the clinical features of PTLD.
The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients.

Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed.

A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI 36.3-89.9) for those with escalation.

A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.
A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.
To evaluate whether the Coronavirus Disease 2019 (COVID-19) pandemic resulted in a prolonged duration of symptoms, a delayed presentation to the medical facility, and consequently more orchiectomy procedures among children with testicular torsion compared to the pre-COVID-19 period.

Systematic search of four scientific databases was performed. The search terms used were (coronavirus OR novel coronavirus OR SARS-CoV-2 OR COVID-19) AND (testicular torsion OR orchidectomy OR orchiectomy OR orchidopexy OR orchiopexy). The inclusion criteria were all boys presenting with testicular torsion during the COVID-19 and pre-COVID-19 periods. A comparison of the average duration of symptoms, the proportion of children with delayed presentation (>24h), and the proportion of children requiring orchiectomy was made among the two groups. The Downs and Black scale was used for methodological quality assessment.

The present meta-analysis included six comparative studies (five retrospective studies). A total of 711 patiidence of the available comparative studies is limited.
It is unclear whether survivors of stroke or transient ischemic attack (TIA) routinely receive, and understand, education about secondary prevention medications.

To investigate whether survivors of stroke/TIA understand explanations about their prescribed prevention medications and associations with medication adherence, control of risk factors, and unmet needs.

A survey was administered among survivors of stroke/TIA (random sample N=1500) from the Australian Stroke Clinical Registry (Victoria and Queensland, 2016). Participants reported whether they understood explanations about each prescribed medication, as well as their unmet needs, perceived control of risk factors, and 30-day medication adherence. Linked pharmacy claims data were also used to determine medication adherence in the previous two years (proportion of days covered ≥80%). Outcomes were analyzed using multivariable logistic regression or multivariable negative binomial regression for frequency of unmet needs.

Overall, 630/1455 eligibled to secondary prevention.

Expanded efforts are needed to improve the delivery of information about prevention medications to promote medication adherence, control of risk factors, and potentially prevent unmet needs following stroke/TIA.
Expanded efforts are needed to improve the delivery of information about prevention medications to promote medication adherence, control of risk factors, and potentially prevent unmet needs following stroke/TIA.
The authors aimed to investigate the rates, predictors, and prognostic impact of technical success in patients undergoing transcatheter aortic valve replacement (TAVR).

The Valve Academic Research Consortium-3 (VARC-3) has introduced a composite endpoint to assess the immediate technical success of TAVR.

In the prospective Bern TAVR registry, patients were stratified according to VARC-3 technical success. Technical failure differentiated between vascular and cardiac complications.

In a total of 1,624 patients undergoing TAVR between March 2012 and December 2019, 1,435 (88.4%) patients had technical success. Among 189 patients with technical failure, 140 (8.6%) had vascular and 49 (3.0%) had cardiac technical failure. Female, larger device landing zone calcium volume, and the early term of the study period were associated with an increased risk for cardiac technical failure, whereas higher body mass index and the use of the Prostar(Abbott Vascular Inc) MANTA (Teleflex) (compared with the ProGlide [Abbott Vascular Inc]) were predictors of vascular technical failure. In multivariable analysis, technical failure conferred an increased risk for cardiovascular death or stroke (HR 2.01; 95% CI 1.37-2.95). The adverse effect remained when stratified to cardiac (HR 2.62; 95%CI 1.38-4.97) or vascular technical failure (HR 1.95; 95%CI 1.28-2.95) and limited to the periprocedural period (0-30days HR 3.42 [95%CI 2.05-5.69]; 30-360days HR 1.36 [95%CI 0.79-2.35]; P for interaction=0.002).

Technical failure according to VARC-3 was observed in 1 of 10 patients undergoing TAVR and was associated with a 2-fold increased risk of the composite outcome at 1 year after TAVR. (Swiss TAVI Registry; NCT01368250).
Technical failure according to VARC-3 was observed in 1 of 10 patients undergoing TAVR and was associated with a 2-fold increased risk of the composite outcome at 1 year after TAVR. (Swiss TAVI Registry; NCT01368250).
The aim of this study was to assess the impact of age on outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for HeartFailure Patients with Functional Mitral Regurgitation) trial.

In the COAPT trial, TEER with the MitraClip device in patients with heart failure (HF) and moderate to severe or severe secondary mitral regurgitation (SMR) reduced the risk for HF hospitalization (HFH) and all-cause mortality compared with maximally tolerated guideline-directed medical therapy (GDMT) alone. There are limited data regarding the effectiveness of MitraClip therapy in elderly patients.

Patients (n=614) were grouped by median age at randomization (74 years) and by MitraClip treatment vs GDMT alone. The primary endpoint was the 2-year rate of death or HFH assessed by multivariable Cox regression.

Death or HFH within 2 years occurred less frequently after treatment with the MitraClip vs GDMT alone in patieHFH and improved survival and quality of life regardless of age. As such, young and elderly patients with HF and severe SMR benefit from TEER, although elderly patients may not have as great a benefit from the MitraClip device in reducing HFH.
Prognostic features in locally recurrent rectal cancer (LRRC), beyond R0 surgery, are unknown.

Aim of the present study was to evaluate the prognostic role of peripheral immune estimators, such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), on survival outcomes in LRRC patients.

184 LRRC patients treated at the National Cancer Institute of Milan (Italy) were included. Optimal cut-off values for NLR and PLR were determined. Kaplan-Meier curves and multivariate Cox analyses were used to assess the 5-yr overall survival (OS) according to NLR and PLR, also considering margins status.

NLR >3.9 (hazard ratio [HR] 3.96, P=0.049), PLR >275 (HR 5.39, P = 0.002) and size on imaging (HR 1.36, P = 0.044) were associated to worse OS. R+ patients with NLR >3.9 showed a significantly lower 5-yr OS compared to NLR ≤3.9 (13.5% vs. 36.7%, P<0.0001). Also PLR >275 was related with a lower 5-yr OS compared to PLR ≤275 in R+ patients (6.4% vs. 36.8%, P = 0.0003). Conversely, NLR and PLR were irrelevant in case of R0 surgery.

NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases.
NLR and PLR predict 5-yr OS in LRRC, also identifying a subset of R+ patients with a similar expected survival compared to R0 cases.
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