Long-Term Survival Outcomes and Comparison of Different Treatment Modalities for Stage I-III Cervical Esophageal Carcinoma

Purpose: To investigate the survival outcomes, prognostic factors and treatment modalities of stage I-III cervical esophageal carcinoma (CEC) patients using data from the Surveillance, Epidemiology, and End Results (SEER) database from the period 2004–2016.Methods: Patients with a histopathologic diagnosis of CEC were included. The primary endpoint was overall survival (OS). Univariate and multivariate analyses of OS were performed using Cox proportional hazards models, and OS was compared using the Kaplan-Meier method and log-rank test.Results: A total of 347 patients in the SEER database were enrolled. The median OS was 14.0 months, with a 5-year OS rate of 20.9%. The parameters that were found to significantly correlate with OS in the multivariate analysis were age at diagnosis [P < 0.001, hazard ratio (HR) = 1.832], sex [P < 0.001, HR= 1.867], histology [P = 0.001, HR = 0.366], surgery at the primary site [P = 0.021, HR = 0.553], radiotherapy (RT, P = 0.017, HR = 0.637) and chemotherapy (CT, P < 0.001, HR = 0.444). Comparison among the three treatment modalities demonstrated that a triple therapy regimen consisting of surgery, RT and CT was associated with a longer survival time than the other two treatment modalities before and after propensity score matching (PSM). However, triple therapy showed no significant survival benefit over double therapy (P = 0.496 before PSM and P = 0.184 after PSM).Conclusions: The survival of patients with CEC remains poor. Surgery, RT and CT were all strongly correlated with OS. We recommend a triple therapy regimen for select CEC patients based on the findings of the current study, although this recommendation should be further confirmed by prospective studies with large sample sizes.

In Vitro Synergy of Colistin in Combination with Meropenem or Tigecycline against Carbapenem-Resistant Acinetobacter baumannii

Acinetobacter baumannii is currently classified as one of six pathogens that contribute to increased patient mortality. Thus, exploratory studies navigating alternative treatment strategies are of supreme interest. Herein, we completed minimum inhibitory concentration (MIC) testing, and time-kill analyses (TKA) on 50 carbapenem-resistant Acinetobacterbaumannii isolates including 28 colistin-resistant isolates. Upon testing of MEM or TGC in the presence of sub-inhibitory COL against the 50 isolates, there was a median 2-fold reduction in MEM and TGC MICs. In the TKAs, the COL+MEM combination was synergistic in 45 (90%) isolates and bactericidal in 43 (86%) isolates at 24 hours, whereas the COL+TGC combination TKAs demonstrated synergy in 32 (64%) isolates and bactericidal activity was shown in 28 (56%) isolates. Additionally, sulbactam (SUL) and TGC were added to the COL+MEM dual therapy regimen to assess the possible utility of a triple therapy regimen against five non-responsive isolates. The COL+MEM+SUL and COL+MEM+TGC regimens effectively restored synergy in (5/5) 100% of the isolates. The results of this study demonstrate the potential utility of COL combinations in the treatment of carbapenem-resistant isolates.

Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China

Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1–infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA <50 copies/ml (difference: 0.1%; 95% CI, –4.6–4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas.Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].