Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are ...considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections.
We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies.
Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%–85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%–51%, p 0.053). In Kaplan–Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days).
While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.
Breast cancer has a high incidence and increasing mortality in Southern Brazil. The present study evaluated clinical and sociodemographic characteristics, and their association with overall survival ...in a private cancer center.
1113 breast cancer patients were included in this study. The association between survival and clinicopathological and sociodemographic characteristics was analyzed using Cox regression and Kaplan-Meyer curves.
Median age at diagnosis was 52 years (SD 13.5). Most patients were diagnosed in stages 0 and I (62.7%), while only 1.3% had stage IV disease. Five- and 10-year overall survival were 93.5% and 83.8%, respectively. According to multivariate analysis, age at diagnosis (HR 1.05; CI95 1.03–1.06), staging (stage III: HR 4.04; CI95 1.34–12.19; stage IV: HR 9.61; CI95 2.17–42.50), high KI67 (HR 5.46; CI95 1.27–23.32) and distant recurrence (HR 7.28; CI95 4.79–11.06) were significantly associated with survival. Smoking status, years of education, BMI, and tumor biological status were not significantly associated with mortality.
This cohort of Brazilian patients, who received timely and appropriate treatment, achieved outcomes that are comparable to those from high income countries. Breast cancer mortality seems dependent on the quality of health care available to patients.
•High breast cancer mortality in Brazil might be associated with the type of health care that is available to women.•Staging, intermediate/high KI67, distant recurrence and increasing age at diagnosis were associated with higher risk of death.•Brazilian patients who receive adequate and timely treatment may achieve outcomes similar to those of high-income countries.•The high breast cancer mortality in Brazil seems dependent on the health care system available to cancer patients.
Abstract
The famous combinatorial problem of Euler concerns an arrangement of 36 officers from six different regiments in a 6×6 square array. Each regiment consists of six officers each belonging to ...one of six ranks. The problem, originating from Saint Petersburg, requires that each row and each column of the array contains only one officer of a given rank and given regiment. Euler observed that such a configuration does not exist. In recent work, we constructed a solution to a quantum version of this problem assuming that the officers correspond to superpositions of quantum states. In this paper, we explain the solution which is based on a partition of 36 officers into nine groups, each with four elements. The corresponding quantum states are locally equivalent to maximally entangled two-qubit states, hence each quantum officer is represented by a superposition of at most 4 classical states. The entire quantum combinatorial design involves 9 Bell bases in nine complementary 4–dimensional subspaces.
A total of 155 patients with acute myeloid leukemia (AML) received hematopoietic stem cell transplants from unrelated donors after standard conditioning. Clinical outcome after the use of two ...different antithymocyte globulins for the prevention of graft-versus-host disease (GvHD) was analyzed in a retrospective study as follows: rabbit ATG (Thymoglobulin Sangstat/Genzyme, n=49, median age 42 years, 53% in CR, further ATG-S); rabbit ATG (ATG-Fresenius, n=38, median age 42 years, 58% in CR, further ATG-F) or no ATG (n=68, median age 36 years, 55% in CR). The groups were comparable regarding disease status at transplant, age, CMV status and cytogenetics. Grade III-IV acute GvHD was found in 15% in the ATG and 27% in the no ATG group (P=0.44). The most important independent risk factors for chronic GvHD (cGvHD) were the use of ATG, disease status at transplant and conditioning. cGvHD developed significantly more frequently in no ATG group. With the median follow-up of 34 months, the 5-year survival is 42% for those transplanted in CR. To conclude, these data demonstrate that the transplants performed in CR, with ATG, are associated with a good outcome, low incidence of cGvHD and no increase of relapse.
Oral contraceptive use has been associated with a higher breast cancer risk; however, evidence for the associations between different oral contraceptive formulations and breast cancer risk, ...especially by disease subtype, is limited.
This study aimed to evaluate the associations between oral contraceptive use by formulation and breast cancer risk by disease subtype.
This prospective cohort study included 113,187 women from the Nurses’ Health Study II with recalled information on oral contraceptive usage from 13 years of age to baseline (1989) and updated data on usage until 2009 collected via biennial questionnaires. A total of 5799 breast cancer cases were identified until the end of 2017. Multivariable Cox proportional hazards models estimated hazard ratios and 95% confidence intervals for the associations between oral contraceptive use and breast cancer risk overall and by estrogen and progesterone receptor and human epidermal growth factor receptor 2 status. Oral contraceptive use was evaluated by status of use (current, former, and never), duration of and time since last use independently and cross-classified, and formulation (ie, estrogen and progestin type).
Current oral contraceptive use was associated with a higher risk for invasive breast cancer (hazard ratio, 1.31; 95% confidence interval, 1.09–1.58) when compared with never use, with stronger associations observed for longer durations of current use (>5 years: hazard ratio, 1.56; 95% confidence interval, 1.23–1.99; ≤5 years: hazard ratio, 1.19; 95% confidence interval, 0.95–1.49). Among former users with >5 years since cessation, the risk was similar to that of never users (eg, >5 to 10 years since cessation: hazard ratio, 0.99; 95% confidence interval, 0.88–1.11). Associations did not differ significantly by tumor subtype. In analyses by formulation, current use of formulations containing levonorgestrel in triphasic (hazard ratio, 2.83; 95% confidence interval, 1.98–4.03) and extended cycle regimens (hazard ratio, 3.49; 95% confidence interval, 1.28–9.53) and norgestrel in monophasic regimens (hazard ratio, 1.91; 95% confidence interval, 1.19–3.06), all combined with ethinyl estradiol, was associated with a higher breast cancer risk when compared with never oral contraceptive use. No association was observed for current use of the other progestin types evaluated (norethindrone, norethindrone acetate, ethynodiol diacetate, desogestrel, norgestimate, and drospirenone), however, sample sizes were relatively small for some of the subgroups, limiting these analyses.
Current oral contraceptive use was associated with a higher risk for invasive breast cancer regardless of disease subtype, however, the risk in former users was comparable with never users 5 years after cessation. In analyses by progestin type, associations were observed for select formulations containing levonorgestrel and norgestrel. Assessment of the associations for newer progestin types (desogestrel, norgestimate, drospirenone) was limited by sample size, and further research on more recently introduced progestins is warranted.
Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with ...longer-term risk. A total of 107,069 women from the Nurses’ Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals 95% CI for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 95% CI 0.65–0.91; >10 years of use, 0.43 0.32–0.58 vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 0.41–0.67) and second-generation progestins (0.43 0.30–0.61), both versus never use, were more strongly associated with lower risk than mestranol (0.66 0.50–0.88, p-het = 0.01) and first-generation progestins (0.62 0.49–0.78, p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.
The synthesis of racemic 2'-(trimethylammonium)ethyl-3-hexadecyloxy-2-fluoro-2-(methoxymethyl)prop-1-yl-phosphate (6), a fluorinated analogue of an anticancer active ether lipid 5 was realized with ...3% overall yield in a nine-step synthesis starting from 2-methylene-1,3-propanediol (7) using a bromofluorination as the key step. Both enantiomers of the precursor 8 of the ether lipid 6 were synthesized by lipase-catalyzed desymmetrization of the diacetate 17, either by hydrolysis (83% ee) or by lipase-catalyzed acetylation of the diol 22 (82% ee). The antitumor activity of 6 has been found in an in vivo model of the methylcholanthrene-induced fibrosarcoma of mice.
PDF
