Voriconazole plus terbinafine combination antifungal therapy for invasive Lomentospora prolificans infections: analysis of 41 patients from the FungiScope® registry 2008-2019.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The effect of cicerfuran, an arylbenzofuran from Cicer bijugum, and related benzofurans and stilbenes on Leishmania aethiopica, L. tropica and L. major.

The effect of 3 arylbenzofurans and 7 stilbenes on the growth of Leishmania parasites and human monocytes was evaluated. Promastigotes from cultures of L. aethiopica, L. major and L. tropica were tested in the exponential phase of growth. All compounds were active at concentrations of 100 microg/mL within 6 hours. The 2-hydroxylstibene showed activity at a concentration < 1 microg/mL, with an LD (50) of 3 - 5 microg/mL after 48 hours of incubation. The most active compounds: cicerfuran, 2-hydroxy-2'-methyl-4',5'-methylenedioxystilbene, 2-hydroxy-2'-methoxy-4',5'-methylenedioxystilbene and 2-hydroxystilbene had even stronger activity against the temperature-induced amastigotes of L. aethiopica, with the latter having the highest relative potency against all three species. Leishmanicidal activity seemed to be associated with the level of oxygen substitution in each compound. The ratio between leishmanicidal activity on promastigotes and toxicity to human cells suggested that the compounds could be considered as leishmanicidal drug leads.

Effect of hyaluronidase on ocular motility and eyelid function in sub-Tenon's anaesthesia: randomised controlled trial.

PURPOSE: To assess the effect of hyaluronidase on eye and eyelid movements when used as an adjunct in sub-Tenon's anaesthesia. METHODS: A total of 60 patients who had sub-Tenon's anaesthesia prior to phacoemulsification surgery were divided into two equal groups in a double-masked randomised controlled fashion. Of these, Group A had 4 ml lignocaine 2%, while Group B had 4 ml lignocaine 2% with the addition of sodium hyaluronidase 75 IU/ml. Ocular motility, levator, and orbicularis oculi function were measured in all patients at 5 and 8 min. Levator function was scored from 0 (no function) to 3 (complete function) while orbicularis function was scored from 0 to 2. The score for ocular motility was the sum in four positions of gaze, each position scoring from 0 to 2. Results were compared using a nonparametric test. RESULTS: Group B achieved significantly better ocular and lid akinesia than Group A both at 5 and 8 min with P<0.01. The median scores for levator function at 5 and 8 min were 2 for Group A and 0 for Group B. For orbicularis function, the median scores at both time intervals were 2 for Group A and 1 for Group B. For ocular motility, the median score for Group A at 5 min was 3 and at 8 min was 2.5; for Group B at 5 min was 0.5 and at 8 min was 0. CONCLUSIONS: The addition of hyaluronidase in sub-Tenon's anaesthesia has a significant effect in improving ocular and lid (levator and orbicularis) akinesia.

Vitamin D deficiency alters the immune responses of broiler chicks.

Three experiments were conducted to test the hypothesis that a vitamin D deficiency alters the immune responses of female broiler chicks. The control diet contained 800 IU of cholecalciferol (vitamin D3)/kg and the deficient diet was the same except without supplemental vitamin D3. The vitamin D deficiency status was established on the basis of a significantly lower blood ionized calcium or total serum calcium (75 to 85% of the control). Vitamin D-deficient chicks also had lower growth rate and bone ash. In Experiment 1 at 8 d of age, and Experiment 2 at 23 d of age, the cutaneous basophil hypersensitivity response as determined by the increase in interdigital skin thickness 20 h after a single injection of 100 microg phytohemagglutinin-P was significantly depressed in vitamin D-deficient chicks (62 to 64% of the control). Thymus weight, adjusted for body weight, was significantly lower in the vitamin D-deficient chicks at 24 d of age (61% of the control). Primary and secondary antibody responses against SRBC in vitamin D-deficient chicks were not different from the control. In Experiment 3, in 17-d-old chicks, vitamin D deficiency decreased the number of abdominal macrophages phagocytizing SRBC in vitro within 45 min from 14.7 to 10.1%. These results indicate that vitamin D deficiency depresses the cellular immune responses in young broiler chicks.