Bilateral luxatio erecta humeri and bilateral knee dislocations in the same patient.

Bilateral knee dislocations seldom occur, and fewer than a dozen cases of bilateral luxatio erecta humeri (erect dislocation of the shoulder) have been reported. Here we present the case of a patient who sustained bilateral knee dislocations and bilateral luxatio erecta humeri in a motorcycle accident. Transient neurologic compromise resolved with closed reduction of the bilateral shoulder and left knee dislocations. To our knowledge, this is the first case report of a patient with this combination of injuries.     

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients

PurposeTo assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes.MethodsRetrospective cohort study of 118 breast cancer patients undergoing fertility preservation treatment between 2008 and 2018. Patients who received letrozole (n = 36) or tamoxifen (n = 30) were compared to controls (n = 52) who underwent standard ovarian stimulation protocols. The primary outcome measures included the number of retrieved oocytes, mature oocytes (MII), fertilization, and top-quality embryo rates. The secondary outcome measures included duration of stimulation, gonadotropin dose and peak estradiol level.ResultsThe number of oocytes retrieved, MII oocytes, fertilization rate, duration of stimulation, or gonadotropin dose were similar in the letrozole and tamoxifen groups, compared to controls. Top-quality embryo rate was lower in the tamoxifen group compared to controls (25% vs 39.4%, respectively, P = 0.034). The abnormal fertilization rate was higher in the letrozole group compared to controls (7.8% vs 3.60%, respectively, P = 0.015). A stepwise logistic regression analysis revealed that letrozole and peak estradiol were significantly associated with abnormal fertilization (OR 11.94; 95% CI 2.35–60.4, P = 0.003 for letrozole and OR 1.075; 95% CI 1.024–1.12, P = 0.004 per 100 unit change in estradiol).ConclusionsThere may be a negative effect of letrozole or tamoxifen on fertilization and embryo quality, in fertility preservation cycles. Further studies are needed to confirm these findings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10815-020-02030-y.     

Inhibition of transferrin iron release increases in vitro drug carrier efficacy.

Transferrin (Tf) conjugates of CRM107 are currently being tested in clinical trials for treatment of malignant gliomas. However, the rapid cellular recycling of Tf limits its efficiency as a drug carrier. We have developed a mathematical model of the Tf/TfR trafficking cycle and have identified the Tf iron release rate as a previously unreported factor governing the degree of Tf cellular association. The release of iron from Tf is inhibited by replacing the synergistic carbonate anion with oxalate. Trafficking patterns for oxalate Tf and native Tf are compared by measuring their cellular association with HeLa cells. The amount of Tf associated with the cells is an average of 51% greater for oxalate Tf than for native Tf over a two hour period at Tf concentrations of 0.1 nM and 1 nM. Importantly, diphtheria toxin (DT) conjugates of oxalate Tf are more cytotoxic against HeLa cells than conjugates of native Tf. Conjugate IC(50) values were determined to be 0.06 nM for the oxalate Tf conjugate vs. 0.22 nM for the native Tf conjugate. Thus, we show that inhibition of Tf iron release improves the efficacy of Tf as a drug carrier through increased association with cells expressing TfR.