Artificial intelligence in healthcare: why not apply the medico-legal method starting with the Collingridge dilemma?

Technology has greatly influenced and radically changed human life, from communication to creativity and from productivity to entertainment. The authors, starting from considerations concerning the implementation of new technologies with a strong impact on people's everyday lives, take up Collingridge's dilemma and relate it to the application of AI in healthcare. Collingridge's dilemma is an ethical and epistemological problem concerning the relationship between technology and society which involves two approaches. The proactive approach and socio-technological experimentation taken into account in the dilemma are discussed, the former taking health technology assessment (HTA) processes as a reference and the latter the AI studies conducted so far. As a possible prevention of the critical issues raised, the use of the medico-legal method is proposed, which classically lies between the prevention of possible adverse events and the reconstruction of how these occurred.The authors believe that this methodology, adopted as a European guideline in the medico-legal field for the assessment of medical liability, can be adapted to AI applied to the healthcare scenario and used for the assessment of liability issues. The topic deserves further investigation and will certainly be taken into consideration as a possible key to future scenarios.

Electro-osmotic flow enhancement in carbon nanotube membranes.

In this work, experimental evidence of the presence of electro-osmotic flow (EOF) in carbon nanotube membranes with diameters close to or in the region of electrical double layer overlap is presented for two different electrolytes for the first time. No EOF in this region should be present according to the simplified theoretical framework commonly used for EOF in micrometre-sized channels. The simplifying assumptions concern primarily the electrolyte charge density structure, based on the Poisson-Boltzmann (P-B) equation. Here, a numerical analysis of the solutions for the simplified case and for the nonlinear and the linearized P-B equations is compared with experimental data. Results show that the simplified solution produces a significant deviation from experimental data, whereas the linearized solution of the P-B equation can be adopted with little error compared with the full P-B case. This work opens the way to using electro-osmotic pumping in a wide range of applications, from membrane-based ultrafiltration and nanofiltration (as a more efficient alternative to mechanical pumping at the nanoscale) to further miniaturization of lab-on-a-chip devices at the nanoscale for in vivo implantation.

Team-building through sailing: effects on health status, job satisfaction and work performance of health care professionals involved in organ and tissue donation.

The aim of this study was to evaluate the effects of a team-building learning project on job satisfaction, psychological wellbeing, and performance of health care workers involved in the process of organ and tissue donation. The project was conducted between June and September 2011 and consisted of two one-day meetings and a one week sailing, involving 20 staff members. GHQ-12, MBI-HSS, and 25 items taken from the Multidimensional Organizational Health Questionnaire (MOHQ) were used to assess health status, burnout, and job satisfaction. Results of the descriptive analyses were expressed as mean ± SD and as counts and percentages; Chi-square test was used to evaluate statistical significance of differences before and after the initiative. 6 (30,0%) participants showed the likelihood to suffering from anxiety and depression (i.e. recognized as 'cases' by the GHQ-12), 3 (15.0%) of them at baseline and 3 (15.0%), different from the previous ones, in the post-intervention. The presence of stress was revealed in 9 (45.0%) and 12 subjects (60.0%) before and after the experience, respectively (6 subjects showed the presence of stress in both circumstances). We documented 4 burnout cases, 3 (15.0%) at baseline and 1 (5.0%) after the experience. Nevertheless, about 80% of the participants showed a high degree ofjob satisfaction, in terms of positive influence of job in the professional satisfaction and of clear satisfaction for the organization, during both evaluation. In respect to 2010, the number of organ donors and that of ocular tissue donors improved of about 16% and 10%, respectively, during the year of the project and in the following year (mean value). We recognize that our team-building project for personnel involved in the stressful and demanding setting of organ and tissue donation, worthwhile and recompensing at the same time, possibly influenced the personal commitment and the quality of job provided. The high level of stress showed by participants should be appropriately targeted in order to prevent burnout.

Flow enhancement in nanotubes of different materials and lengths.

The high water flow rates observed in carbon nanotubes (CNTs) have previously been attributed to the unfavorable energetic interaction between the liquid and the graphitic walls of the CNTs. This paper reports molecular dynamics simulations of water flow in carbon, boron nitride, and silicon carbide nanotubes that show the effect of the solid-liquid interactions on the fluid flow. Alongside an analytical model, these results show that the flow enhancement depends on the tube's geometric characteristics and the solid-liquid interactions.

Global cognitive function correlates with P-wave dispersion in frail hypertensive older adults.

P-Wave Dispersion (PWD) is an ECG parameter defined as the difference between the longest and the shortest P-Wave duration. PWD has been associated with hypertension, a leading cause of age-related cognitive decline. Moreover, hypertension is associated with vascular dementia and Alzheimer's Disease. Based on these considerations, we evaluated PWD and global cognitive function in frail hypertensive older adults with a previous diagnosis of cognitive decline. We evaluated consecutive frail hypertensive patients ≥65-year-old with a Mini-Mental State Examination (MMSE) score <26. Patients with evidence of secondary hypertension, history of stroke, myocardial infarction, or therapy with beta-blockers or acetylcholinesterase inhibitors were excluded. Beta-blocker therapy causes a significant decrease in PWD; patients treated with acetylcholinesterase inhibitors were not included to avoid confounding effects on cognitive function. By examining 180 patients, we found that PWD significantly correlated with MMSE score. Strikingly, these effects were confirmed in a linear multivariate analysis with a regression model. To our knowledge, this is the first study showing that PWD correlates with global cognitive function in frail hypertensive older adults.

Effect of a Fixed Combination of Curcumin, Artemisia, Bromelain, and Black Pepper Oral Administration on Optical Coherence Tomography Angiography Indices in Patients with Diabetic Macular Edema.

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 µm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

Precision medicine and machine learning towards the prediction of the outcome of potential celiac disease.

Potential Celiac Patients (PCD) bear the Celiac Disease (CD) genetic predisposition, a significant production of antihuman transglutaminase antibodies, but no morphological changes in the small bowel mucosa. A minority of patients (17%) showed clinical symptoms and need a gluten free diet at time of diagnosis, while the majority progress over several years (up to a decade) without any clinical problem neither a progression of the small intestine mucosal damage even when they continued to assume gluten in their diet. Recently we developed a traditional multivariate approach to predict the natural history, on the base of the information at enrolment (time 0) by a discriminant analysis model. Still, the traditional multivariate model requires stringent assumptions that may not be answered in the clinical setting. Starting from a follow-up dataset available for PCD, we propose the application of Machine Learning (ML) methodologies to extend the analysis on available clinical data and to detect most influent features predicting the outcome. These features, collected at time of diagnosis, should be capable to classify patients who will develop duodenal atrophy from those who will remain potential. Four ML methods were adopted to select features predictive of the outcome; the feature selection procedure was indeed capable to reduce the number of overall features from 85 to 19. ML methodologies (Random Forests, Extremely Randomized Trees, and Boosted Trees, Logistic Regression) were adopted, obtaining high values of accuracy: all report an accuracy above 75%. The specificity score was always more than 75% also, with two of the considered methods over 98%, while the best performance of sensitivity was 60%. The best model, optimized Boosted Trees, was able to classify PCD starting from the selected 19 features with an accuracy of 0.80, sensitivity of 0.58 and specificity of 0.84. Finally, with this work, we are able to categorize PCD patients that can more likely develop overt CD using ML. ML techniques appear to be an innovative approach to predict the outcome of PCD, since they provide a step forward in the direction of precision medicine aimed to customize healthcare, medical therapies, decisions, and practices tailoring the clinical management of PCD children.

One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy.

BACKGROUND: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. METHODS: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >-10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. RESULTS: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: -0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. CONCLUSIONS: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

Correction: One week of levofloxacin plus dexamethasone eye drops for cataract surgery: an innovative and rational therapeutic strategy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Large cell neuroendocrine carcinoma of the lung: a retrospective analysis of 144 surgical cases.

OBJECTIVE: Large cell neuroendocrine carcinoma of the lung are considered aggressive. However, reported prognoses are heterogeneous and the optimum treatment remains undefined. We retrospectively evaluated outcomes in a series of patients with a pathological diagnosis of large cell neuroendocrine lung carcinoma, who underwent lung resection. We also assessed the utility of chemotherapy in a small subgroup. PATIENTS AND METHODS: The clinical records of 144 consecutive patients were reviewed in a multicenter study. Survival times, assessed from the day of surgery until death or most recent follow-up, were estimated by the Kaplan-Meier method, and compared by the log rank test. RESULTS: There were 117 men and 27 women of median age 63 years. Twelve wedge resections, 3 segmentectomies, 95 lobectomies, 7 bilobectomies and 24 pneumonectomies were performed. Induction chemotherapy was given in 21 and postoperative chemotherapy in 24. Pathologically, 73 (50%) were stage I, 29 (20%) stage II, 40 (28%) stage III and 2 stage IV. Postoperative mortality was 2.8% and morbidity 26%. Overall 5-year survival was 42.5%: 52% for stage I, 59% for stage II and 20% for stage III (p=0.001 log-rank test on Kaplan-Meier curves). A trend to better outcome was associated with preoperative or postoperative chemotherapy in stage I disease (p=0.077) compared to no chemotherapy. The response rate to induction chemotherapy was 80% in the 15 patients with data available. CONCLUSION: large cell neuroendocrine carcinoma of the lung are confirmed as aggressive but are also chemosensitive. Our experience suggests that chemotherapy may improve prognosis in stage I disease.

Is sampling really effective in staging non-small cell lung cancer? A prospective study.

Is sampling really effective in staging non-small cell lung cancer? The aim of the study was to assess if systematic nodal dissection is necessary in order to stage non-small cell lung cancer correctly or whether mediastinal lymph node sampling can be used and whether in selected cases it could replace systematic nodal dissection for the treatment of lung cancer. A prospective study was conducted in 94 patients affected by clinically resectable non-small cell lung cancer (stages I-IIIB) who were surgically treated by the same team of surgeons. During surgery mediastinal lymph node sampling was done first and then another surgeon completed the systematic nodal dissection and performed the lung resection. One hundred and ninety-three mediastinal nodal stations were investigated using the American Thoracic Society lymph node map to identify them. On analysing the 193 mediastinal nodal stations investigated, it emerged that in 181 cases (94%) mediastinal lymph node sampling and systematic nodal dissection yielded the same histopathological findings, whereas in 12 cases (6%) there was no agreement between the two techniques. The negative predictive value of mediastinal lymph node sampling was 92.8% (103/111). The results of the study show no statistical difference between mediastinal lymph node sampling and systematic nodal dissection in staging non-small cell lung cancer. However, it is possible that in a limited percentage of cases a nodal station could be understaged and thus the surgical resection could prove incomplete if mediastinal lymph node sampling alone is performed. Moreover, in those cases where mediastinal lymph node sampling detects N2 disease and systematic nodal dissection has not been completed, the intervention cannot be considered radical.

[Non-small cell lung cancer (NSCLC): the evolution of neo-adjuvant chemotherapy in the last 15 years]. / Tumore polmonare non a piccole cellule: evoluzione della chemioterapia neo-adiuvante negli ultimi 15 anni.

Retrospective analysis of surgical data-base of NSCLC have showed that, except stage IA, the prognosis of locally advanced disease is very poor if treated with surgery and/or radiotherapy and it is probably due to distant micrometastasis present at the diagnosis. The aim of neo-adjuvant chemotherapy is to address early the distant micrometastasis and to allow, through a downstaging, surgical resection of tumor not suitable to surgery or partially respectable at diagnosis.

[Mediastinoscopy for diagnosis of diseases of the chest and staging of lung cancer: our experience in 253 cases]. / La mediastinoscopia nella diagnostica delle malattie del torace e nella stadiazione del cancro del polmone: nostra esperienza di 253 casi.

The main indications for cervical mediastinoscopy are preoperative staging of lung cancer and diagnostic biopsy of mediastinal mass (lymphoma, sarcoidosis, tuberculosis etc.). We undertook a retrospective review of our experience of mediastinal exploration by cervical media-stinoscopy: 253 mediastinoscopies were performed on 252 patients (195 male and 57 female; mean age 53 years, range 14-88 years) between 1995 and June 2003. Four extended mediastinoscopies were performed and 1 patient had a re-mediastinoscopy following a non-diagnostic procedure. 319 lymph nodal stations were investigated in 253 procedures. We observed no mortality, while 2 patients had major bleeding (0.7%), with the need for open surgical treatment in order to achieve haemostasis. The median length of hospital-stay was one day, with discharge in the first postoperative day. 69 out of 170 patients, who eventually resulted to be affected by a histologically proven lung cancer, had a negative mediastinoscopy. Fifteen of them resulted N2 at the time of surgery: 8 patients with a false negativity in a biopsied station (4 in station 4R and 4 in station 7), while 7 cases showed infiltration in stations which were not sampled (5 in station 5, 1 in station 8 and 1 in station 7, the latter being the only one in which a standard cervical mediastincoscopy could have been able to stage it correctly). So, having observed 61 true negatives and 8 false-negatives in the sampled stations, in our experience the negative predictive value of cervical mediastinoscopy was 88.4%, with 78.2% of patients correctly staged without using other diagnostic tools. In conclusion, mediastinoscopy is an important procedure for the diagnostic biopsy of mediastinal mass and a useful tool in preoperative staging of lung cancer, especially if associated with chest CT-scan and Positron Emission Tomography (PET). In our experience, the spreading of PET does not lead to a reduction of cervical mediastinoscopies, both for the contemporary introduction of new chemotherapeutic preoperative protocols and, above all, for the not negligible incidence of false-positive results using PET, suggesting that media-stinoscopy should always be performed in patients affected by a PET-positive mediastinal growth.

Bronchoplastic procedures for central carcinoid tumors: clinical experience.

OBJECTIVE: To evaluate the short-term and the long-term results of bronchoplastic resections (BR) performed for central carcinoid tumors (CCT). METHODS: Retrospective study of patients who underwent BR for a CCT between 1966 and 2003. RESULTS: BRs were performed in 25 patients out of 92 (27%) who were resected for CCT. Median age was 37 years. All patients were symptomatic. Preoperative bronchoscopy was diagnostic in 15 patients. The bronchoplasties performed were: 11 sleeve lobectomies, 1 sleeve segmentectomy, 8 wedge lobectomies, 4 flap lobectomies and 1 wedge segmentectomy. There were 22 typical and 3 atypical carcinoids without nodal metastasis. No major complications or mortality occurred. One patient with a typical carcinoid developed pretracheal metastatic adenopathy 19 years after resection. No recurrence or stenosis has occurred at the sites of bronchoplasty so far. Three patients died of unrelated disease. Overall the 10-, 15- and 20-year survival rates were 100, 100 and 71%. CONCLUSIONS: Bronchoplastic resections are the treatment of choice for CCT. Short- and long-term results are excellent. Life-long follow-up is necessary, however, due to the possibility of late recurrence.

Invasive pulmonary aspergillosis after renal transplantation treated by surgery.

Invasive pulmonary aspergillosis is a serious complication in immunocompromised patients. In those unresponsive to pharmacological treatment, or when drug toxicity is excessive, surgery may resolve the condition. A 48-year-old woman with invasive pulmonary aspergillosis after renal transplantation underwent resection of the right upper lobe and the apical segment of the inferior lobe, followed by complete recovery.

True 3q chromosomal amplification in squamous cell lung carcinoma by FISH and aCGH molecular analysis: impact on targeted drugs.

Squamous lung carcinoma lacks specific "ad hoc" therapies. Amplification of chromosome 3q is the most common genomic aberration and this region harbours genes having role as novel targets for therapeutics. There is no standard definition on how to score and report 3q amplification. False versus true 3q chromosomal amplification in squamous cell lung carcinoma may have tremendous impact on trials involving drugs which target DNA zones mapping on 3q. Forty squamous lung carcinomas were analyzed by FISH to assess chromosome 3q amplification. aCGH was performed as gold-standard to avoid false positive amplifications. Three clustered patterns of fluorescent signals were observed. Eight cases out of 40 (20%) showed ≥8 3q signals. Twenty out of 40 (50%) showed from 3 to 7 signals. The remaining showed two fluorescent signals (30%). When corrected by whole chromosome 3 signals, only cases with ≥8 signals maintained a LSI 3q/CEP3 ratio >2. Only the cases showing 3q amplification by aCGH (+3q25.3-3q27.3) showed ≥8 fluorescent signals at FISH evidencing a 3q/3 ratio >2. The remaining cases showed flat genomic portrait at aCGH on chromosome 3. We concluded that: 1) absolute copy number of 3q chromosomal region may harbour false positive interpretation of 3q amplification in squamous cell carcinoma; 2) a case results truly "amplified for chromosome 3q" when showing ≥8 fluorescent 3q signals; 3) trials involving drugs targeting loci on chromosome 3q in squamous lung carcinoma therapy have to consider false versus true 3q chromosomal amplification.

Acute respiratory distress caused by a giant mediastinal lipoblastoma in a 16-month-old boy.

Lipoblastoma is a rare benign tumor arising from embryonic fat; it occurs mainly in the extremities and almost exclusively in infants and children younger than 3 years. We present a case of giant mediastinal lipoblastoma in a 16-month-old boy who presented with acute respiratory distress. The mass was completely excised through a left posterolateral thoracotomy. The postoperative course was uneventful, and the pathologic final diagnosis was lipoblastoma. Although extremely rare, mediastinal lipoblastoma can be life threatening; therefore, it should be included in the differential diagnosis of mediastinal mass in younger subjects.

The split latissimus dorsi muscle flap to protect a bronchial stump at risk of bronchial insufficiency.

Consistent branching of the thoracodorsal vessels to the latissimus dorsi makes it possible to split the muscle into independent branched units. The use of the lateral split latissimus dorsi muscle flap to protect the bronchial stump in case of bronchus at risk of insufficiency is described.