Impact of direct acting antivirals (DAAs) on cardiovascular events in HCV cohort with pre-diabetes

Background and aimsBeyond type 2 diabetes, even a condition of prediabetes is associated with an increased cardiovascular (CV) risk, and HCV infection coexistence represents an exacerbating factor. CV prognosis improvement in prediabetes represents a challenge, due to the increasing prevalence of this metabolic condition worldwide. Hence, we aimed to prospectively assess how direct acting antivirals (DAAs) could affect major cardiovascular events (MACE) in a prediabetic HCV positive cohort.Methods and resultsIn this prospective multicenter study, we enrolled HCV patients with overt prediabetes. We compared a subgroup of patients treated with DAAs with untreated prediabetic controls. We recorded all CV events occurred during an overall median follow-up of 24 months (IQR 19–34). 770 HCV positive prediabetic patients were enrolled, 398 untreated controls and 372 DAAs treated patients. Overall, the CV events annual incidence was much higher among prediabetic treated patients (1.77 vs. 0.62, p < 0.001), and HCV clearance demonstrated to significantly reduce CV events (RR: 0.411, 95%CI 0.148–1.143; p < 0.001), with an estimated NNT for one additional patient to benefit of 52.1. Moreover, an independent association between a lower rate of CV events and HCV clearance after DAAs was observed (OR 4.67; 95%CI 0.44–53.95; p = 0.016).ConclusionsHCV eradication by DAAs allows a significant reduction of MACEs in the prediabetic population, and therefore represents a primary objective, regardless of the severity of liver disease and CV risk factors.     

Octreotide long-acting release (LAR) in combination with other therapies for treatment of neuroendocrine neoplasia: a systematic review

BackgroundIn the last decades, the incidence of neuroendocrine neoplasia (NEN) increased from 1 to 5 new diagnoses/100,000 persons/year. The synthetic somatostatin analogues (SSAs) represent the first-choice treatment for both functionally active and inactive gastro-enteric-pancreatic NEN. This systematic review examines the role of octreotide long-acting release (LAR) in combination with other therapies for NEN management.MethodsPrimary outcomes were the disease control rate and the progression free survival (PFS), defined as the time between treatment initiation and progression of disease. Secondary outcomes were overall survival (OS) and safety.ResultsThis systematic review identified 13 studies, concerning the use of octreotide LAR in association with other therapies in advanced NENs and included 1,206 patients. Patients were treated with octreotide LAR in combination with other drugs, mainly with everolimus (404 patients, 35%), but even with Peptide Receptor Radionuclide Therapy, bevacizumab, interferon or fluoride-derivatives. Disease control was observed in 85% cases with SSAs in combination with other therapies; PFS ranged from 15 to 16.4 months and OS from 25 to 61.9 months. SSAs are very well tolerated drugs, with few side effects which are usually mild, not requiring drug withdrawn.ConclusionsThe review summarizes the effectiveness and available safety data on octreotide LAR in combination with other therapies in patients with NEN and may provide suggestions to address the therapeutic strategy. Further comparative head-to-head studies are needed to understand which is the best combination treatment for patients with progressive NEN after failure of first-line therapy.     

Biparametric prostate MRI: impact of a deep learning-based software and of quantitative ADC values on the inter-reader agreement of experienced and inexperienced readers

Objective

To investigate the impact of an artificial intelligence (AI) software and quantitative ADC (qADC) on the inter-reader agreement, diagnostic performance, and reporting times of prostate biparametric MRI (bpMRI) for experienced and inexperienced readers.

Materials and methods

A total of 170 multiparametric MRI (mpMRI) of patients with suspicion of prostate cancer (PCa) were retrospectively reviewed by one experienced and one inexperienced reader three times, following a wash-out period. First, only the bpMRI sequences, including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) sequences, and apparent diffusion coefficient (ADC) maps, were used. Then, bpMRI and quantitative ADC values were used. Lastly, bpMRI and the AI software were used. Inter-reader agreement between the two readers and between each reader and the mpMRI original reports was calculated. Detection rates and reporting times were calculated for each group.

Results

Inter-reader agreement with respect to mpMRI was moderate for bpMRI, Quantib, and qADC for both the inexperienced (weighted k of 0.42, 0.45, and 0.41, respectively) and the experienced radiologists (weighted k of 0.44, 0.46, and 0.42, respectively). Detection rate of PCa was similar between the inexperienced (0.24, 0.26, and 0.23) and the experienced reader (0.26, 0.27 and 0.27), for bpMRI, Quantib, and qADC, respectively. Reporting times were lower for Quantib (8.23, 7.11, and 9.87 min for the inexperienced reader and 5.62, 5.07, and 6.21 min for the experienced reader, for bpMRI, Quantib, and qADC, respectively).

Conclusions

AI and qADC did not have a significant impact on the diagnostic performance of both readers. The use of Quantib was associated with lower reporting times.

     

Chronic Diarrhea in Common Variable Immunodeficiency: a Case Series and Review of the Literature

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea.     

Bone conductive implantation in asymmetric hearing loss (AHL)

Abstract

Background: Bone conductive implants (BCI) represent one possible solution for rehabilitation of single-sided deafness (SSD).

Aims: The aim of the present study was to verify the efficacy of bone conduction implantation in subjects with unilateral severe-to-profound hearing loss and contralaterally impaired hearing, that is, asymmetric hearing loss (AHL), and to compare it with known BCI indications for SSD.

Material and methods: Twenty-one subjects received BCI for either SSD or AHL. All of the subjects underwent a battery of audiological and subjective tests, Data were collected and statistically evaluated within and between the SSD group and the AHL group.

Results: A PTA threshold gain was observed in AHL patients along with improved values in speech audiometry in quiet and noise. The two visual analogue scale evaluations (QoL and QoS) and the GBI showed significantly better scores in AHL patients compared to SSD patients.

Conclusions: BCI provided improvement for auditory or speech recognition in AHL subjects, as compare to SSD. From these findings, it is possible to predict a positive role of BCI for some audiological aspects of AHL subjects that are generally not present or not detectable in SSD cases.     

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016–March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT.