New and emerging treatments for fungal infections

Although several new antifungal drugs have been licensed in the last 5 years, some patients remain difficult to treat. The main reasons for this include intrinsic or acquired antifungal resistance, organ dysfunction preventing the use of some agents and drug interactions. In addition, some drugs pene-trate poorly into sanctuary sites including eye and urine, and others are associated with considerable adverse events. Here, we review the preclinical and clinical development progress with four new anti-fungal agents: isavuconazole, ravuconazole, albaconazole and aminocandin. Isavuconazole and ravu-conazole are extremely similar, with a broad spectrum of activity, a very long half-life and large volume of distribution and good in vivo data supporting their efficacy in invasive aspergillosis and candidosis. Both compounds are in early Phase 3 development. Albaconazole has also shown very potent activity against species of Candida, Cryptococcus and Aspergillus. It was well tolerated and effective in women with vaginal candidosis. Aminocandin is an intravenous-only echinocandin with in vivo activity against Candida spp. and Aspergillus spp. Its extended half-life probably permits dosing less fre-quently than once a day. Overall these new antifungal agents in development offer extended half-lives, possibly reduced drug interaction profiles and good tolerance. Their antifungal spectrum is narrower than posaconazole and probably similar to voriconazole (isavuconazole and ravuconazole) and caspo-fungin (aminocandin). Licensure and determination of their place in clinical practice requires random-ized clinical studies, which are or will be underway

Subchondroplasty in the treatment of bone marrow lesions of the knee: Preliminary experience on first 15 patients

Purpose The aim of this prospective study was to assess the effectiveness in terms of pain relief and functional improvement of the Subchondroplasty procedure in the treatment of osteoarthritis-related bone marrow lesions (BMLs) of the knee. Methods The study included first 15 consecutive patients undergone to Subchon-droplasty procedure for the treatment of chronic degenerative BMLs in which previous conservative treatment have failed. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, Knee Injury and Osteoarthritis Outcome Scores (KOOS), and visual analog scale (VAS) pain scores were obtained preoperatively and at 1, 6, and 12 months of follow-up. Results WOMAC scores significantly improved from 39.7 \ub1 20.2 before surgery to 26.8 \ub1 16.1 at the 1-month follow-up (p = 0.045). A further significant improvement to 15.5 \ub1 12.7 (p = 0.02) and to 8.6 \ub1 3.1 (p <0.01) was obtained both at 6-month and at 1-year follow-up. KOOS scores improved significantly from 47.5 \ub1 16.6 before surgery to 65.4 \ub1 14.9 at 1 month (p = 0.013) and to 80.4 \ub1 15.1 at 6-month follow-up (p = 0.01). A further improvement to 85.6 \ub1 15.1 was recorded 1 year postoperatively, although nonsignificant. VAS score showed a significant improvement from 55.8 \ub1 20.5 preoperatively to 36.2 \ub1 16.9 at 1 month (p = 0.008) and to 18.2 \ub1 17.3 at 6-month follow-up (p = 0.005). This further improved to 12.8 \ub1 17.9 at 1-year follow-up, although not significantly. Conclusion Subchondroplasty procedure represents a safe and valid surgical option in the treatment of osteoarthritis-related BMLs of the knee, providing an improvement in terms of pain relief and functional recovery. Longer studies are required to evaluate how long these improvements may last. Level of Evidence Therapeutic case-series, Level IV study

Development and first operation of a Cavity Ring Down Spectroscopy diagnostic in the negative ion source SPIDER

The Neutral Beam Injectors of the ITER experiment will rely on negative ion sources to produce 16.7 MW beams of H/D particles accelerated at 1 MeV. The prototype of these sources was built and is currently operated in the SPIDER experiment (Source for the Production of Ions o Deuterium Extracted from an RF plasma), part of the Neutral Beam Test Facility of Consorzio RFX, Padua. In SPIDER, the H-/D- ion source is coupled to a three grids 100 kV acceleration system. One of the main targets of the experimentation in SPIDER is to uniformly maximize the extracted current density; to achieve this it is important to study the density of negative ions available in proximity of the ion acceleration system. In SPIDER, line-integrated measurements of negative ion density are performed by a Cavity Ring Down Spectroscopy (CRDS) diagnostic. Its principle of operation is based on the absorption of the photons of a laser beam pulse by H-/D- photo-detachment; the absorption detection is enhanced by trapping the laser pulse in an optical cavity, containing the absorbing medium (i.e. negative ions). The paper presents and discusses the CRDS diagnostic setup in SPIDER, including the first measurements of negative ion density, correlated to the main source parameters.Comment: 5 pages, 7 figures. Contributer paper for the HTPD 2020 conference. Accepted manuscrip

Polymorphisms in toll-like receptor genes and susceptibility to pulmonary aspergillosis

Toll-like receptors (TLRs) are important components of innate immunity. We investigated the association between polymorphisms in the TLR2, TLR4, and TLR9 genes and susceptibility to noninvasive forms of pulmonary aspergillosis. A significant association was observed between allele G on Asp299Gly (TLR4) and chronic cavitary pulmonary aspergillosis (odds ratio [OR], 3.46; P =.003). Susceptibility to allergic bronchopulmonary aspergillosis was associated with allele C on T-1237C (TLR9) (OR, 2.49; P =. 043). No particular polymorphism was associated with severe asthma with fungal sensitization. These findings reinforce the importance of innate immunity in the pathogenesis of different forms of aspergillosis.Fundação para a Ciência e Tecnologia, Portugal (POCI/SAU-ESP/61080/ 2004 and fellowship to A.C., contract SFRH/BD/11837/2003); CAPES (Brazilian government) (grant to A.P); and the Fungal Research Trust, United Kingdom

Seleção precoce de clones da variedade robustão capixaba irrigada por gotejamento no Norte de Minas Gerais.

O cultivo do café Conilon tem sido considerado uma alternativa para a agricultura da Região Norte de Minas Gerais, que possui disponibilidade de área e altitude favoráveis à sua exploração . Este trabalho objetivou selecionar clones superiores Coffea canephora sob cultivo irrigado, mediante o emprego do método de modelos mistos. O experimento foi instalado sob sistema de cultivo irrigado por gotejamento, sendo implantados dez clones da variedade Robustão Capixaba. Aos sete meses após o plan tio, foram avaliadas sete características de crescimento vegetativo. Foram realizadas três contagens de sobrevivênci a das mudas, aos dois, sete e doze meses. Os clones RC9, RC7, RC2 e RC1 foram os mais promissores e poderão compor populações base para o prog rama de seleção recorrente que potencialmente poderá originar vari edades clonais especificas para a regi ão. As estimativas de coeficiente de herdabilidade média entre clones, de acur ácia, e o coeficiente de variação relativ a no número de nós do primeiro ramo plagiotrópico e número de ramos plagiotrópicos sugerem a maximização dos ganhos genéticos com a seleção e a obtenção de clones superiores na região estudada

Produtividade de clones da variedade vitoria sob sistema de cultivo sequeiro no vale de Jequitinhonha-MG.

A variedade vitória que se caracteriza pela tolerância à seca, alta adaptabilidade e estabilidade de produção, surge como uma alternativa ao cultivo sequeiro na região do Vale do Jequitinhonha-MG. Entretanto, como os clones possuem heterogeneidade genética pode haver variação na sua capacidade de aclimatação. Assim, esse trabalho objetivou avaliar a produtividade inicial de clones da variedade vitória sob cultivo sequeiro no vale do Jequitinhonha. Para tanto, foram implantados 13 clones da variedade Vitória no delineamento foi blocos casualizados, com quatro repetições e parcelas constituídas por seis plantas e espaçamento de 3,0 x 1,0 m. A média de produtividade de todos os clones que compõem a variedade no biênio 2011/2012 foi de 51,53 sc.benef./há, sendo que a segunda colheita apresentou produtividade média 85% maior em relação a primeira. Os clones que mais se destacaram foram os 7V, 9V e 10V, com produtividades médias do primeiro biênio oscilando entre 69,53 a 82,11 sc. benef./ha. Houve variabilidade genética e ambiental entre os clones quanto às características relação coco/beneficiado, percentagem de frutos chochos, percentagem de grãos com peneira média superior a 13 e percentagem de grãos tipo moca, porém a maioria dos clones apresentaram esses parâmetros dentro de limites aceitáveis para a variedade Vitória. De maneira geral, a variedade Vitória possui elevada capacidade produtiva inicial nas condições no Vale do Jequitinhonha

Should the patella be everted during primary total knee arthroplasty? : A systematic review of overlapping meta-analyses

Patellar eversion during total knee arthroplasty (TKA) is a debated issue. The aim of this study is to perform a review of overlapping meta-analyses analyzing clinical outcomes of patellar eversion compared to noneversion. A search was performed in PubMedMEDLINE, Scopus, and Cochrane Library. Inclusion criteria were meta-analysis of randomized controlled trials (RCTs) or quasi-RCTs;l comparison between TKAs with or without patellar eversion; and at least one outcome, such as reoperation rate, pain, and functional scores. Meta-analyses were evaluated with the A Measurement Tool to Assess Systematic Review (AMSTAR) score, addressing the most relevant one with the Jadad algorithm. Three meta-analyses were identified and included in this review. No significant differences were found regarding complications, quadriceps strength, functional, and radiological outcomes. The meta-analysis by Zan et al. was selected as the best available one. Patellar eversion group showed a shorter tourniquet time but a longer skin incision. In conclusion, eversion and noneversion techniques did not demonstrate any significant or clinically relevant difference

Fast determination of voriconazole in oral fluid using microextractionby packed sorbent and HPLC with fluorescence detection

A fast and reliable method for the determination of voriconazole in oral fluid using microextraction by packed sorbent and liquid chromatography with fluorescence detection was developed and validated. MEPS was performed at basic pH with only 50 μL of oral fluid and the extract was injected without an evaporation step. The overall procedure, including extraction and chromatographic analysis, took only 15 min. Voriconazole and internal standard were separated on a Lichrospher RP 8ec column (250 x 4 mm, particle diameter 5 μm) eluted with a mobile phase composed of phosphate pH 2.3 (containing 0.1 % triethylamine) and acetonitrile (64:36, v/v) at a flow rate of 1.4 mL min-1 . Total run time was 11 min, with detection being performed with excitation at 254 and emission at 372 nm. The method was successfully applied to oral fluid samples, with voriconazole concentrations presenting an average of 57.6 % of those measured in paired plasma samples.Colegio de Farmacéuticos de la Provincia de Buenos Aire

PTX3-based genetic testing for risk of aspergillosis after lung transplant

[Excerpt] We read with interest the article by Wójtowicz et al [1], and would like to comment on it and to share findings from our complementary study. We have recently established genetic variation in the long pentraxin 3 (PTX3) as a major determinant of susceptibility to invasive aspergillosis (IA) after hematopoietic stem cell transplant [2]. Wójtowicz et al are the first to uncover similar findings in solid organ transplant (SOT) recipients, highlighting a potential applicability of these markers in predicting infection across patients with intrinsically different predisposing conditions (...).ESCMID -European Society of Clinical Microbiology and Infectious Diseases(undefined