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.     

Trends in Cervical Cancer Mortality in Brazilian Women who are Screened and Not Screened

Objective: This study aimed to analyze the trend in cervical cancer (ICD C53) mortality in Brazilian regions in women who are who are screened and not screened from 1996 to 2015. Methods: An epidemiological study, of time series of mortality from cervical cancer performed in 90,856 women under 24 years old (343 women), between 25 and 64 years old (32,703 women), and over 65 years old (10,909 women). The data from this research were collected from the DATASUS, from the SIM Health Surveillance Secretariat files, captured through TABNET selecting the resident population by gender and age group and ICD 10 C53 from 1996 to 2015. Results: Among women, 43.8% were white, and 76% had less than eight years of formal education. Polynomial regression showed an increasing trend in cervical cancer mortality in Brazil for women aged 15 - 24 years (p=0.01). Between 25 - 64 and 65 years or older it remained constant, but high (p=0.07; 0.99). The Northeast region pointed a growing trend in women aged 15 to 24 (p=0.01), 25 to 64 years (p=0.01) and 65 or older (p=0.001). The Northeast presented the highest average growth per year. In the Southeast, South and Midwest regions, decreasing trends were observed despite the high rates. The Joinpoint regression showed a 95% confidence interval, and that mortality from cervical cancer in the North region increased throughout the period analyzed. an increasing trend was observed from 1996 to 1998, whereas in the Midwest region, the trend remained stable throughout the period analyzed. The Federal District presented an upward trend from 1996 to 2015. In Brazil, an upward trend was observed throughout the whole period analyzed. Conclusions: Cervical cancer mortality in younger women is becoming more predominant, in addition to the high rate observed for women aged 65 or older.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

Dietary Fatty Acids and Other Nutrients in Relation to Inflammation and Particularly to Oral Mucosa Inflammation. A Literature Review

Oral mucosa is site of inflammatory process development. When they are chronic, they provide a microenvironment based on cytokines and inflammatory mediators that contribute to cancer initiation, progression, invasion, and metastasis. Certain dietary fatty acids (FAs) have immunomodulatory, inflammatory, and antiinflammatory effects. This review examined the literature on inflammation, mainly referred to the oral mucosa, and its association with dietary FAs and other nutrients. A Pubmed search of studies published in English until June 2018 was carried out. N-3 FAs have shown immunomodulatory and antiinflammatory activity in certain human diseases. These FAs and their mediators may inhibit inflammation, angiogenesis, and cancer via multiple mechanisms. Studies on cellular models of murine and human intestinal mucosa indicate association between dietary n-3?FA intake and the inflammatory state of mucosa membranes. Nevertheless scarce information on the association between dietary FAs and oral inflammation could be found. Based on the evidence, we hypothesize that n-3 FAs reduce the oral mucosa inflammation thus decreasing the risk of developing precancerous lesions and cancer. Molecular and clinical studies referred to this topic should be carried out as a contribution to the oral cancer prevention.     

Dupilumab therapy for patients with refractory eosinophilic otitis media associated with bronchial asthma

ObjectivesEosinophilic otitis media (EOM) is an intractable otitis media mostly associated with bronchial asthma. Dupilumab, an anti-interleukin (IL)-4 receptor (R)α, is effective and has been approved for use in patients with moderate to severe bronchial asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyposis, whose diseases are not controlled by previous treatments including other molecular targeted drugs. We aimed to assess efficacy of dupilumab in three EOM patients with associated bronchial asthma, who were poor responders to previous topical and systemic corticosteroid therapy and molecular targeted therapies.Patients and methodsThree patients with severe, refractory EOM (two with a granulation type) associated with bronchial asthma received dupilumab as add-on therapy for at least 6 months. The efficacy of dupilumab therapy was evaluated using severity scores, symptom scores, hearing acuities, temporal bone computed tomography (CT) scores, and surrogate markers before and after therapy.ResultsSeverity scores in all patients were dramatically reduced to 2 points or less (full score: 16 points) after initiation of therapy. Air conduction hearing levels were improved in all patients. Temporal bone CT scores in two patients were reduced, and serum IgE levels in all three patients also decreased following therapy.ConclusionWe provide the first report that add-on dupilumab therapy was effective in patients with severe, refractory EOM who did not respond to the treatments including other molecular targeted therapy. Patients with severe middle ear mucosal change may benefit particularly from dupilumab therapy.