Mhaskar, Rahul

Objective: To assess the efficacy of trichloroacetic acid (TCA) as treatment for high-grade cervical intraepithelial neoplasia (CIN 2 or 3). Methods: Retrospective study of patients with CIN 2 or greater treated with TCA from 2016 to 2022. Patients who desired future childbearing had a satisfactory colposcopy and had not received prior treatment for CIN. Patients were offered excision as initial treatment and for lesions that did not regress. TCA was discussed as an alternative, off-label treatment. Under colposcopic guidance, 85% TCA was applied to the transformation zone and distal endocervix. Patients were followed with colposcopy and cytology every 3–6 months and subsequently underwent excision or reapplication of TCA. Primary outcomes were regression and remission after a minimum of 6 months of treatment with TCA. Results: A total of 43 patients elected treatment with TCA. The mean age was 28.6 years with a median follow-up time of 12 months. The majority of patients were nonsmokers (95.3%) and White (73.9%). Pretreatment diagnosis was CIN3 and CIN2 in 32.6% and 67.4% of cases, respectively. After a median of three TCA treatments, 23.3% regression and 55.8% remission were noted for an overall cytological response rate of 79.1%. 16.3% required excision within 1 year. There were no cervical cancer diagnoses. The median time to regression and remission was 9 months and 6 months, respectively. Conclusion: In patients with high-grade CIN, treatment with TCA may have favorable short-term outcomes. TCA may represent an alternative to excision in reproductive-aged patients, though additional studies are needed with a larger cohort in a prospective manner.

Abstract RATIONALE: 4G4G/4G5G SERPINE1 genotypes produce high concentrations of plasminogen activator inhibitor-1 and are associated with worse asthma outcomes. A secondary analysis of the American Lung Association (ALA) SOYA trial showed that soy isoflavones significantly reduced asthma exacerbations versus placebo among patients with 4G4G/4G5G SERPINE1 genotypes. We hypothesized that baseline characteristics predict optimal responders to soy isoflavones among this subgroup. METHODS: ALA-SOYA was a randomized controlled trial that tested the efficacy of soy isoflavones vs. placebo for reducing asthma exacerbations among adolescents and adults with symptomatic asthma. In this responder analysis among participants with 4G4G/4G5G SERPINE1 genotypes, baseline demographic and clinical characteristics were tested for effect modification of the treatment assignment (soy/placebo) on the primary outcome of annualized number of asthma exacerbations using interaction terms in negative binomial regression models, with a significance threshold of p-interaction=0.15. RESULTS: Data were available for n=168 participants. Soy reduced the annualized number of asthma exacerbations relative to placebo among patients with 4G4G/4G5G SERPINE1 genotypes (incident rate ratio (IRR)=0.37, 95% confidence interval (CI): 0.15-0.90, p=0.028). Self-reported adherence to baseline controller therapy was the only significant effect modifier of this association (interaction p=0.115), with those using inhaled corticosteroid (ICS)/long-acting beta-agonist (LABA) controller therapy at least twice weekly experiencing reductions in asthma exacerbations with soy versus placebo (IRR = 0.25, 95% CI: 0.09-0.69; p= 0.007) but not among those using ICS/LABA controller therapy less frequently (IRR = 1.33, 95% CI: 0.22-8.02; p= 0.757). CONCLUSION: Soy isoflavones reduce asthma exacerbations among patients with the 4G4G/4G5G SERPINE1 genotypes and are most effective in those with greater adherence to asthma controller therapy regimens.

AbstractBackgroundSignificant numbers of patients in the USA and UK die while waiting for solid organ transplant. Only 1–2% of deaths are eligible as donors with a fraction of the deceased donating organs. The form of consent to donation may affect the organs available. Forms of consent include: opt‐in, mandated choice, opt‐out, and organ conscription. Opt‐in and opt‐out are commonly practiced. A systematic review was conducted to determine the effect of opt‐in versus opt‐out consent on the deceased donation rate (DDR) and deceased transplantation rate (DTR).MethodsLiterature searches of PubMed and EMBASE between 2006 and 2016 were performed. Research studies were selected based on certain inclusion criteria which include USA, UK, and Spain; compare opt‐in versus opt‐out; primary data analysis; and reported DDR or DTR. Modeled effect on US transplant activity was conducted using public data from Organ Procurement and Transplantation Network and Centers for Disease Control WONDER from 2006 to 2015.ResultsA total of 2400 studies were screened and six studies were included. Four studies reported opt‐out consent increases DDR by 21–76% over 5–14 years. These studies compared 13–25 opt‐out countries versus 9–23 opt‐in countries. Three studies reported opt‐out consent increases DTR by 38–83% over 11–13 years. These studies compared 22–25 opt‐out versus 22–28 opt‐in countries. Modeled opt‐out activity on the USA resulted in 4753–17,201 additional transplants annually.ConclusionOpt‐out consent increases DDR and DTR and may be useful in decreasing deaths on the waiting list in the USA and other countries.Registration numberPROSPERO CRD42019098759.