Emerging issue of fluconazole-resistant candidemia in a tertiary care hospital of southern italy: time for antifungal stewardship program

An increased number of patients is at risk of Candida spp. bloodstream infection (CBSI) in modern medicine. Moreover, the rising of antifungal resistance (AR) was recently reported. All consecutive CBSI occurred in our Hospital (consisting of 1,370 beds) between 2015 and 2018, were reviewed. For each case, Candida species, AR pattern, ward involved and demographic data of patients were recorded. Overall, 304 episodes of CBSI occurred, with a median (q1:first-,q3:third quartile) of 77 (71-82) CBSI/year. Over the years, a significant increase of CBSI due to C. albicans compared to non-albicans strains was recorded in medical wards (from 65% to 71%, p=0.030), while this ratio remained stable in others. An increase of resistant strains to multiple antifungals such as C. guillermondii was noticed in recent years (from 0% to 9.8%, p=0.008). Additionally, from 2015 to 2018 an increase in fluconazole-resistance was recorded in our Hospital (from 7.4% to 17.4%, p=0.025) and a slight increase in voriconazole-resistance (from 0% to 7% in 2018, p=0.161) was observed, while resistance to echinocandin and amphotericin B remained firmly below 2%.This study suggests a rapid spread of antifungal resistance in our Hospital; therefore, an appropriate antifungal stewardship programs is urgently warranted.     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

Marine omega-3 fatty acid supplementation in non-alcoholic fatty liver disease: Plasma proteomics in the randomized WELCOME* trial

1. Download : Download high-res image (274KB)
2. Download : Download full-size image

     

Comprehensive geriatric assessment is an independent prognostic factor in older patients with metastatic renal cell cancer treated with first-line Sunitinib or Pazopanib: a single center experience

BackgroundThere is poor data on the prognostic role of Comprehensive Geriatric Assessment (CGA) in older patients with metastatic renal cell carcinoma (mRCC) treated with first line Tyrosine Kinase Inhibitors (TKIs).Materials and MethodsWe retrospectively reviewed the clinical charts of mRCC patients older than 70 years treated at our Institute with first-line Sunitinib or Pazopanib for at least 6 months. Every patient received a CGA at baseline and was identified as fit, vulnerable or frail according to Balducci's Criteria. We then assessed the impact of CGA category on survival, disease control and tolerability of TKIs.ResultsWe identified 86 eligible patients. Median age: 74.5 years, 56% males; 45.4% were fit, 37.2% vulnerable and 17.4% frail at CGA. There were no significant differences in the rate of Grade (G)1–2 and G3-4 toxicities, dose reduction rates, PFS and OS between Sunitinib and Pazopanib. Fit, vulnerable and frail patients achieved significantly different median PFS (18.9 vs 11.2 vs 5.1 months; p < 0.001) and OS (35.5 vs 14.6 vs 10.9 months; p < 0.001). Patients categorized as fit had higher chance of receiving a second-line treatment (66.6% vs 28.9% in vulnerable/frail; p = 0.002). The incidence of G3/4 events was significantly lower in the fit subgroup (19% vs 45% in vulnerable/frail; p = 0.0025).ConclusionsIn our retrospective single-center experience, CGA could accurately discriminate patients with higher risk of experiencing G3/4 toxicities, shorter PFS, and lower chance of receiving a second line treatment. CGA strongly impacted on OS, independently from International mRCC Database Consortium (IMDC) classification.     

Cell-based assays for the detection of MOG antibodies: a comparative study

Journal of Neurology - The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the...