Autodeterminazione e trattamento medico: il rifiuto alle cure

IX n.s.Il presente studio, relativo all’autodeterminazione in campo medico ed al diritto di rifiutare i cd. trattamenti di fine vita, si apre con l’individuazione della copertura costituzionale dei concetti che regolano la materia. Si opera così un’analisi costituzionalmente orientata del principio di autodeterminazione e di quello di consensualità nella specifica sfera dei trattamenti sanitari. Da un approccio puramente scientifico, cioè estraneo da influenze non giuridiche, si evince che solo il consenso o il rifiuto sono gli elementi decisivi nella scelta delle cure. In questa prospettiva si percepisce nitidamente che il discrimen sia rappresentato dalla sussistenza o meno della capacità del soggetto interessato. Di conseguenza il primo capitolo è dedicato alla condizione del soggetto capace di autodeterminarsi ma impossibilitato ad agire. Ci si è occupati dei cd. diritti di terza generazione e del cd. diritto a lasciarsi morire sia da un punto di vista generale sia nei suoi riflessi pratici così come si sono manifestati, tra gli altri nel noto caso “Welby”. Sulla scorta di tale bipartizione tra capacità ed incapacità del malato lo spettro d’analisi si è rivolto, poi, allo studio di quest’ ultimo status. In particolare, restringendo la ricerca al consenso nel preciso ambito delle cure sanitarie, se ne individuano le caratteristiche ed i tipi lasciando intravedere le maggiori criticità del sistema giuridico nella misura in cui esso è diretto alla tutela degli individui. Anche in questo capitolo, senza perdere di vista i valori ed i principi generali ed il loro inquadramento sistematico, si opera un collegamento ad un’altra vicenda giuridica oltre che umana, nota a tutti come caso “Englaro”. Di ciò si sostanzia il secondo capitolo. Il terzo, in stretta connessione logica ed argomentativa, s’incentra sulle risposte che l’ordinamento ha inteso offrire per garantire la libera autodeterminazione qualora il soggetto interessato non sia capace nel momento in cui è chiamato ad esprimere la propria volontà. Si sottopone ad analisi pertanto il disegno di legge sulle dichiarazioni anticipate di trattamento. Di tale nuovo istituto se ne sottolineano, da un lato, i requisiti di validità ed efficacia e dall’altro, la particolare importanza della nomina del fiduciario e del rapporto di quest’ultimo con il medico da cui dovrebbe essere estrinsecata la “ voce” del paziente. Infine, dirigendo la lente di indagine oltre i confini nazionali, è stato possibile intravedere elementi tanto assonanti quanto dissonanti delle discipline straniere rispetto a quella in elaborazione in Italia. Pertanto, seguendo il classico schema di suddivisione, proprio del diritto comparato, tra aree di common law e di civil law, mentre le prime si caratterizzano per una certa compattezza ed omogeneità nelle soluzioni legislative approntate, turbate solo dalle diversità di impostazione tra living will e best interests, le seconde, ossia i paesi di civil law si presentano, invece, estremamente variegate negli assetti legislativi adottati. In via d’ultima analisi, seguendo il percorso appena descritto, si è voluto per un verso definire le più recenti risposte legislative al problema, partendo dai loro presupposti giuridici e per l’altro, collocarle in una prospettiva più ampia da cui trarne spunti di riflessione e possibilità di miglioramento. [a cura dell'autore]2009 - 201

Correction to: Metachromatic leukodystrophy with late adult-onset: diagnostic clues and differences from other genetic leukoencephalopathies with dementia

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Effectiveness of valproate for the treatment of manic-like behavior in X-linked adrenoleukodystrophy

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Patient-specific computational fluid dynamics of femoro-popliteal stent-graft thrombosis

Intra-stent thrombosis is one of the major failure modes of popliteal aneurysm endovascular repair, especially when the diseased arterial segment is long and requires overlapping stent-grafts having different nominal diameters in order to accommodate the native arterial tapering. However, the interplay between stent sizing, post-operative arterial tortuosity, luminal diameter, local hemodynamics, and thrombosis onset is not elucidated, yet. In the present study, a popliteal aneurysm was treated with endovascular deployment of two overlapped stent-grafts, showing intra-stent thrombosis at one-year follow-up examination. Patient-specific computational fluid-dynamics analyses including straight- and bent-leg position were performed. The computational fluid-dynamics analysis showed that the overlapping of the stent-grafts induces a severe discontinuity of lumen, dividing the stented artery in two regions: the proximal part, affected by thrombosis, is characterized by larger diameter, low tortuosity, low flow velocity, low helicity, and low wall shear stress; the distal part presents higher tortuosity and smaller lumen diameter promoting higher flow velocity, higher helicity, and higher wall shear stress. Moreover, leg bending induces an overall increase of arterial tortuosity and reduces flow velocity promoting furtherly the luminal area exposed to low wall shear stress

Impact of leg bending in the patient-specific computational fluid dynamics of popliteal stenting

Abstract Endovascular treatment of the femoro-popliteal artery has recently become a valuable therapeutic option for popliteal arterial aneurysms. However, its efficacy remains controversial due to the relatively high rate of complications, such as stent occlusion as result of intra-stent thrombosis. The elucidation of the interplay among vessel geometrical features, local hemodynamics, and leg bending seems crucial to understand onset and progression of popliteal intra-stent thrombosis. To this aim, patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm by stent-grafts and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. Results were presented in terms of tortuosity, luminal area exposed to low ( 1.5 Pa) time-averaged wall shear stress (TAWSS), area exposed to high (> 0.3) oscillatory shear index (OSI), and flow helicity. Study outcomes demonstrated that leg bending induced significant hemodynamic differences (> 50% increase) in both patients for all the considered variables, except for OSI in one of the two considered patients. In both leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low TAWSS, and high OSI; while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI. Sensitivity study on applied boundary conditions showed that the different inlet velocity profiles for a given inlet waveform affect slightly the numerical solution; conversely, the shape and magnitude of the prescribed inlet waveform is determinant. Focusing on the comparison between the Newtonian and non-Newtonian blood models, the area with low TAWSS is greater in the Newtonian model for both patients, while no significant difference occurs between the surfaces with high TAWSS. GraphicAbstract Patient-specific computational fluid dynamic simulations were performed in order to assess the intra-stent hemodynamics of two patients endovascularly treated for popliteal arterial aneurysm and experiencing intra-stent thrombosis. Both Newtonian and non-Newtonian blood rheological models were considered. In both straight and bent leg configurations, stent-graft overlapping induced a severe discontinuity of the lumen diameter where the proximal stented zone is characterized by low tortuosity, low velocity, low helicity, low time-averaged wall shear stress (TAWSS), and high oscillatory index (OSI); while the distal part has higher tortuosity, velocity, helicity, TAWSS, and lower OSI

Regional diastolic function by tissue Doppler echocardiography in systemic sclerosis: correlation with clinical variables

The incidence of left ventricular (LV) diastolic dysfunction is increased in systemic sclerosis (SSc), while systolic dysfunction is present in a small percentage of patients. The aim of this study was to asses the LV "regional" diastolic abnormalities in SSc patients by the mean of Doppler tissue imaging (DTI). Echocardiographic echo-Doppler (DE) and DTI parameters were analyzed for 67 SSc patients: abnormal E/A ratio at DE was detected in 24, while abnormal e/a at DTI was observed in 41. A significant prevalence of DTI diastolic abnormalities in the segments reflecting longitudinal versus those reflecting radial LV motion was found. The segments of the basal regions of LV myocardium were significantly more involved than those of the middle portion. Linear correlation was observed between the extent of the diastolic abnormalities and the duration of disease. Longitudinal myocardial systolic velocities were significantly reduced in patients with abnormal e/a DTI

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent.

OBJECTIVES: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. METHODS: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C(18) alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. RESULTS: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. CONCLUSION: The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy

Risk factors for infections due to carbapenem-resistant Klebsiella pneumoniae after open heart surgery

OBJECTIVES Patients undergoing major surgery are at increased risk of developing infections due to resistant organisms, including carbapenem-resistant Klebsiella pneumoniae (CR-Kp). In this study, we assessed risk factors for CR-Kp infections after open heart surgery in a teaching hospital in northern Italy. METHODS A retrospective study was conducted from January to December 2014. The primary outcome measure was postoperative CR-Kp infection, defined as a time-to-event end-point. The effect of potentially related variables was assessed by univariable and multivariable analyses. Secondary end-points were in-hospital mortality and 180-day postoperative mortality. RESULTS Among 553 patients undergoing open heart surgery, 32 developed CR-Kp infections (6%). In the final multivariable model, CR-Kp colonization [hazard ratio (HR) 227.45, 95% confidence intervals (CI) 67.13-1225.20, P < 0.001], cardiopulmonary bypass time in minutes (HR 1.01, 95% CI 1.01-1.02, P < 0.001), chronic obstructive pulmonary disease (HR 3.99, 95% CI 1.61-9.45, P = 0.004), SOFA score (HR 1.29, 95% CI 1.08-1.53, P = 0.007), preoperative mechanical ventilation (HR 8.10, 95% CI 1.31-48.57, P = 0.026), prolonged mechanical ventilation (HR 2.48, 95% CI 1.08-6.15, P = 0.032) and female sex (HR 2.08, 95% CI 1.00-4.36, P = 0.049) were associated with the development of CR-Kp infection. Increased in-hospital mortality and 180-day mortality were observed in patients who developed CR-Kp infections in comparison with those who did not. CONCLUSIONS In our cohort, CR-Kp colonization was an important predictor of CR-Kp infection after open heart surgery. CR-Kp infection after surgery significantly affected survival. Preventing colonization is conceivably the most effective current strategy to reduce the impact of CR-Kp

A cross‐sectional, prospective ocular motor study in 72 patients with Niemann‐Pick disease type C

Objective: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). Methods: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). Results: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. Conclusions: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis