Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes.

Introduction: The problem of organs' shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques' combination to develop hybrid scaffolds with increased performing properties was also evaluated. Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features. Results: Hybrid scaffolds showed the best properties in terms of viability (>100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1-10 MPa). Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted.

Prospective urinary albumin/creatinine ratio for diagnosis, staging, and organ response assessment in renal AL amyloidosis: results from a large cohort of patients.

OBJECTIVES: Quantification of 24 h-proteinuria is the gold standard for diagnosing, staging, and monitoring of patients with renal AL amyloidosis. However, 24 h-urine collection is cumbersome and may result in preanalytical error. In this prospective study, we investigated the role of urinary albumin/creatinine ratio (UACR) (cut-off: 300 mg/g) identifying renal involvement, evaluated a UACR-based staging system (UACR cut-off: 3,600 mg/g) and assessed whether UACR response (UACR decrease >30% without worsening in eGFR >25%) predicts renal outcome in 531 patients with newly-diagnosed AL amyloidosis. METHODS: From October 2013 paired 24 h-proteinuria and UACR (on first morning void) were measured in all newly-diagnosed patients with AL amyloidosis. Correlation between 24 h-proteinuria and UACR at baseline was assessed by Pearson's r test. Impact of UACR response on renal outcome was assessed in randomly created testing (n=354) and validation (n=177) cohorts. RESULTS: A strong linear correlation was found between 24 h-proteinuria and UACR at baseline (r=0.90; p<0.001). After a median follow-up of 31 months, 57 (11%) patients required dialysis. A UACR-based renal staging system identified three stages with significantly higher dialysis rate at 36 months comparing stage I with stage II and stage II with stage III. Achieving a renal response, according to a UACR-based criterion, resulted in lower dialysis rate in both testing and validation cohorts. CONCLUSIONS: UACR is a reliable marker for diagnosis, prognosis, and organ response assessment in renal AL amyloidosis and can reliably replace 24 h-proteinuria in clinical trials and individual patients' management.

Machine Learning-based Voice Assessment for the Detection of Positive and Recovered COVID-19 Patients.

Many virological tests have been implemented during the Coronavirus Disease 2019 (COVID-19) pandemic for diagnostic purposes, but they appear unsuitable for screening purposes. Furthermore, current screening strategies are not accurate enough to effectively curb the spread of the disease. Therefore, the present study was conducted within a controlled clinical environment to determine eventual detectable variations in the voice of COVID-19 patients, recovered and healthy subjects, and also to determine whether machine learning-based voice assessment (MLVA) can accurately discriminate between them, thus potentially serving as a more effective mass-screening tool. Three different subpopulations were consecutively recruited: positive COVID-19 patients, recovered COVID-19 patients and healthy individuals as controls. Positive patients were recruited within 10 days from nasal swab positivity. Recovery from COVID-19 was established clinically, virologically and radiologically. Healthy individuals reported no COVID-19 symptoms and yielded negative results at serological testing. All study participants provided three trials for multiple vocal tasks (sustained vowel phonation, speech, cough). All recordings were initially divided into three different binary classifications with a feature selection, ranking and cross-validated RBF-SVM pipeline. This brough a mean accuracy of 90.24%, a mean sensitivity of 91.15%, a mean specificity of 89.13% and a mean AUC of 0.94 across all tasks and all comparisons, and outlined the sustained vowel as the most effective vocal task for COVID discrimination. Moreover, a three-way classification was carried out on an external test set comprised of 30 subjects, 10 per class, with a mean accuracy of 80% and an accuracy of 100% for the detection of positive subjects. Within this assessment, recovered individuals proved to be the most difficult class to identify, and all the misclassified subjects were declared positive; this might be related to mid and short-term vocal traces of COVID-19, even after the clinical resolution of the infection. In conclusion, MLVA may accurately discriminate between positive COVID-19 patients, recovered COVID-19 patients and healthy individuals. Further studies should test MLVA among larger populations and asymptomatic positive COVID-19 patients to validate this novel screening technology and test its potential application as a potentially more effective surveillance strategy for COVID-19.

Long term evaluation of the impact of autologous peripheral blood stem cell transplantation in multiple myeloma: a cost-effectiveness analysis.

BACKGROUND: High-dose therapy with autologous peripheral stem cell transplantation represents today the standard approach for younger multiple myeloma patients. This study aimed to evaluate the long term economic impact of autologous transplantation with respect to conventional therapy. METHODS: We retrospectively reviewed the charts of multiple myeloma patients diagnosed at our department between 1986 and 2003 and treated according to the therapy considered standard at the time of diagnosis. Analysis of costs was done by assessing resource utilization and direct costs were measured and monetized before proceeding with the analysis, based on public health service tariffs. RESULTS: Group A including 78 patients treated with Melphalan and Prednisone was compared with Group B including 74 patients who received an autologous transplant. The median overall survival was 3.2 and 5.4 years respectively (p = 0.0002). Mean cost per patient was significantly higher in group B with respect to group A (102373€ vs 23825€; p<0.001). The final quality-adjusted-life-year gain in group B patients as compared to group A was 1.73 QALY, with an incremental cost-effectiveness ratio of 45460€. With a threshold of 75000€ per QALY gained, the cost effectiveness acceptability curve indicated that the probability that autologous transplantation in multiple myeloma is a cost-effective intervention is 90%. CONCLUSIONS: The cost of autologous transplantation remains high. The calculated incremental cost-effectiveness ratio, however, given the significant prolongation of overall survival obtained with autologous transplantation, is within an acceptable threshold. Notwithstanding, its high cost should be taken into account when considering the whole cost of multiple myeloma.