Integrated HTA and FMECA methodology for the evaluation of robotic surgery

Robotic surgery has been strongly improved since the beginning of the twenty-first century and chased important level of technical and clinical performances. Within the robotic area, the most worldwide used surgical robot is the da Vinci® system made by Intuitive Surgical Inc. The aim of this study was to evaluate at the hospital scale the robotic surgery (Hospital –Based Health Technology Assessment) in comparison to the open and laparoscopic procedures yet combining a FMECA analysis to accurately assess all those aspects involving patient and staff safety. The total number of robotic procedures directly observed by the surgical department and reported in the following study was 44, including 28 urology interventions and 16 general surgeries. The study confirmed clinical benefits carried out with the robot but bigger complexity in managing the whole surgical system in terms of structural needs, staff and technology. For the future, further steps regard the necessity to dispose of a wider number of robotic procedures in order to strength the analysis reliability and complete the socio-economic assessment with medium and long terms observation. Finally a new FMECA application will be essential to monitor the real effects of the suggested actions on the evaluated risks according to the already known and new failure modes

Delivery of thyronamines (TAMs) to the brain: A preliminary study

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy

OBJECTIVES: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). METHODS: In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. RESULTS: Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC],0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. CONCLUSIONS: Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.National Institutes of Health (U.S) (R0I-CA097966)National Institutes of Health (U.S) (P4I-RR02594- 21

IMPIEGO DI METODI MOLECOLARI (16SrRNA) PER L'IDENTIFICAZIONE DI AGENTI INFETTIVI RESPONSABILI DI INFEZIONI CATETERECORRELATE IN PAZIENTI EMODIALIZZATI

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Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): A cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts

Background: Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-Trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar. Methods: PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-To-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. Discussion: Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP. Trial registration: Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018

Clustering of leprosy beyond the household level in a highly endemic setting on the Comoros, an observational study

Background: The island of Anjouan (Comoros) is highly endemic for leprosy with an annual incidence of 5–10/10, 000. In May/June, 2015 single-dose Rifampicin post-exposure prophylaxis (SDR-PEP) was administered to 269 close contacts of 70 leprosy-patients in four villages as a pilot programmatic intervention. Two years later we revisited the villages for follow-up investigations. The main aim of our study was to quantify spatial associations between reported leprosy cases before and after PEP implementation. A secondary aim was to assess the effect of this single round of SDR-PEP at the individual level. Methods: We conducted door-to-door leprosy screening in all four villages in August/September, 2017. We screened all consenting individuals for leprosy and recorded geographic coordinates of their household. We also recorded whether they had received SDR-PEP and whether they had been diagnosed with leprosy, before or after the 2015 intervention. We fitted a Poisson model with leprosy as outcome and distance to the nearest preintervention case and SDR-PEP as predictors. Results: During the survey we found 114 new cases among 5760 contacts screened (2.0% prevalence), in addition to the 39 cases detected in the two preceding years. We found statistically significant associations of incident leprosy with physical distance to index cases ranging from 2.4 (95% confidence interval (95% CI) 1.5–3.6) for household contacts to 1.8 (95% CI 1.3–2.5) for those living at 1–25 m, compared to individuals living at ≥75 m. The effect of SDR-PEP appeared protective but did not reach statistical significance due to the low numbers, with an incidence rate ratio (IRR) of 0.6 (95% CI 0.3–1.2) overall, and 0.5 (95% CI 0.2–1.3) when considering only household contacts. Conclusions: This pilot demonstrated an increased risk of leprosy in contacts beyond the household, therefore a wider circle should be considered for chemoprophylaxis. Baseline surveys and extended contact definitions are essential for improving SDR-PEP effectiveness

Impact of Previous Nephrectomy on Clinical Outcome of Metastatic Renal Carcinoma Treated With Immune-Oncology: A Real-World Study on Behalf of Meet-URO Group (MeetUro-7b)

Background: Immune-Oncology (IO) improves Overall Survival (OS) in metastatic Renal Cell Carcinoma (mRCC). The prognostic impact of previous Cytoreductive Nephrectomy (CN) and radical nephrectomy (RN), with curative intent, in patients treated with IO is not well defined. The aim of our paper is to evaluate the impact of previous nephrectomy on outcome of mRCC patients treated with IO. Methods: 287 eligible patients were retrospectively collected from 16 Italian referral centers adhering to the MeetUro association. Patients treated with IO as second and third line were included, whereas patients treated with IO as first line were excluded. Kaplan–Meier method and log-rank test were performed to compare Progression Free Survival (PFS) and OS between groups. In our analysis, both CN and RN were included. The association between nephrectomy and other variables was analyzed in univariate and multivariate setting using the Cox proportional hazard model. Results: 246/287 (85.7%) patients had nephrectomy before IO treatment. Median PFS in patients who underwent nephrectomy (246/287) was 4.8 months (95%CI 3.9–5.7) vs 3.7 months (95%CI 1.9–5.5) in patients who did not it (HR log rank 0.78; 95%CI 0.53 to 1.15; p = 0.186). Median OS in patients who had previous nephrectomy (246/287) was 20.9 months (95%CI 17.6–24.1) vs 13 months (95%CI 7.7–18.2) in patients who did not it (HR log rank 0.504; 95%CI 0.337 to 0.755; p = 0.001). In the multivariate model, nephrectomy showed a significant association with OS (HR log rank 0.638; 95%CI 0.416 to 0.980), whereas gland metastases were still associated with better outcome in terms of both OS (HR log rank 0.487; 95%CI 0.279 to 0.852) and PFS (HR log rank 0.646; 95%CI 0.435 to 0.958). Conclusions: IO treatment, in patients who had previously undergone nephrectomy, was associated with a better outcome in terms of OS. Further prospective trials would assess this issue in order to guide clinicians in real word practice

Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian "Real-World" SAX Study.

Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib–axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93–7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6–17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39–13.40 months) vs. 5.46 months (95% CI 4.04–6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95–10.51 months, p = 0.01) and 8.67 (95% CI 4.0–13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65–5.27 months, p = 0.01) and 2.97 months (95% CI 0.66–5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib–Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4–51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice