Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of "polypharmacy" in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS

Kidney failure during HIV disease treated with tenofovir, multiple concurrent diseases and drug therapies

A significant case report of a HIV infected patient in his fifties who experienced an excellent virological and immunological response to antiretroviral therapy (which has been modified just to prevent or avoid some adverse events), but developed a severe, sudden acute kidney failure while under a polypharmacy due to some underlying and overwhelming disorders (i.e. arterial hypertension, non-insulin-dependent diabetes mellitus, a recent acute heart infarction with remarkable remnants, and finally an anecdotal muscle-joint pain with self-prescription of non-steroideal anti-inflammatory drugs), represents the key point for a debate around the increasing frequency of “polypharmacy” in the field of HIV infection, even when HIV resistance to antiretroviral is not a concern. The continuing increase of mean age of HIV-infected population, plus the existing, sometimes unmodifiable risk factors for cardiovascular, dysmetabolic, and renal disorders, plus the adjunct of anecdotal illnesses prompting the resort to different drugs and medications, either prescribed for HIV infection itself, or taken for concurrent or subsequent diseases, or self-prescribed occasionally due to an intercurrent, trivial disorders per se, may prompt a complicated scenario culminating with a life-threatening acute renal failure of tubular origin. Our report gives us the opportunity to revise and discuss the expected interactions between antiretroviral therapy and the even growing exposure to multiple different drug and drug classes, which may be responsible for relevant drug interactions and direct or adjunctive end-organ impairment, up to life-threatening conditions, which may be avoided or prevented by considering carefully all comorbidites and co-treatments potentially administered to HIV infected patients, thirty years after the discovery of AIDS

Cost-effectiveness analysis of initial HIV treatment under Italian guidelines

INTRODUCTION: Since the mid-1990s, highly active antiretroviral therapy (HAART) has modified the clinical course of human immunodeficiency virus (HIV) infection, reducing the rate of disease progression, the incidence of opportunistic infections, and mortality. The authors of this paper performed an economic analysis to estimate the cost-effectiveness of the HAART regimens in Italy for managing HIV-infected patients according to national guidelines. PATIENTS AND METHODS: The incremental cost-effectiveness analysis was carried out by means of a Markov model, which through a decision-analytic approach, made it possible to compare the studied antiretroviral regimens. The population considered in the model consisted of adult subjects with HIV who received antiretroviral HAART treatment for the first time. The population considered in the analysis reflects the patients' characteristics according to one of the regional surveillance systems HIV/AIDS infection report currently operating in Italy. The analysis was carried out from the point of view of the Italian health care system. The considered outcome measures were quality-adjusted life years (QALYs) and direct health costs calculated for the year 2010. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. RESULTS: The model shows, in terms of cost per gained QALY, single tablet regimen (STR) appeared to be the most cost-effective therapeutic choice (22,017), followed by tenofovir (TDF) + lamivudine + efavirenz (EFV) (24,526), and TDF/emtricitabine (FTC) + nevirapine (26,416), and TDF + FTC + EFV (26,558); the remaining strategies have an incremental cost-effectiveness ratio (ICER) value varying from 28,000 to 41,000 per QALY. The sensitivity analysis on the main variables confirmed the validity of the base case scenario. CONCLUSION: STR is the most cost-effective treatment strategy, compared with the other therapeutic regimens recommended by the Italian guidelines. All the ICER values of the various regimens considered by the Italian guidelines were lower than the threshold value of 50,000 commonly accepted at the international level. The model developed represents a tool for policy makers and health care professionals to make short- and long-term cost projections and thus evaluate their impact on the available budgets for HIV patients

Patients Specific Spine Simulators for Surgical Training and Rehearsal in Pedicle Screws Placement: A New Way for Surgical Education

In pedicle screws placement using a free-hand technique or a fluoroscopic guided technique the main difficulties are facing to the bone morphology (i.e in deformity cases) and it could be easily reproduced in a patient’s specific spine simulator (we can choose the case). The aim of this work is to evaluate the use of 3D printed patient- specific models (3D printing) not only as a surgical planning tool but also as a surgical training tool in spine surgery and in particular in pedicle screws placement. The manufacturing of patient-specific physical replica involves the elaboration of CT dataset and rapid prototyping techniques. . Five resident surgeons were involved in different training sessions on simulators. To evaluate the exact screws position we performed a CT evaluation of each instrumented simulators. Statistical analysis was conducted using SPSS software. A total of 120 pedicle screws were positioned, 90 screws were well-positioned and 30 screws were bad-positioned. There were a significant difference (p = 0.000008) between the bad-positioning screw rate of the “senior” resident (13/72) and those of “young” participants (17/48). Timeline analysis of pedicle instrumentation training showed the presence of a learning effect, with a lower error rate in the latest session (p=000001). We believe that the use of patient- specific surgical simulators, especially for those surgical tasks in which the complexity is mainly linked to the spine morphology (i.e. deformity), may represent a valid alternative to the use of cadavers that generally present a standard or otherwise poorly predictable anatomy

Hybrid Simulation and Planning Platform for Cryosurgery with Microsoft HoloLens

Cryosurgery is a technique of growing popularity involving tissue ablation under controlled freezing. Technological advancement of devices along with surgical technique improvements have turned cryosurgery from an experimental to an established option for treating several diseases. However, cryosurgery is still limited by inaccurate planning based primarily on 2D visualization of the patient's preoperative images. Several works have been aimed at modelling cryoablation through heat transfer simulations; however, most software applications do not meet some key requirements for clinical routine use, such as high computational speed and user-friendliness. This work aims to develop an intuitive platform for anatomical understanding and pre-operative planning by integrating the information content of radiological images and cryoprobe specifications either in a 3D virtual environment (desktop application) or in a hybrid simulator, which exploits the potential of the 3D printing and augmented reality functionalities of Microsoft HoloLens. The proposed platform was preliminarily validated for the retrospective planning/simulation of two surgical cases. Results suggest that the platform is easy and quick to learn and could be used in clinical practice to improve anatomical understanding, to make surgical planning easier than the traditional method, and to strengthen the memorization of surgical planning

Targeting the Serotonin (5-HT) system to control seizures

Compelling animal and human evidence suggests that serotonin plays an important role in the pathophysiology of epilepsy as it is involved in iperexcitability, epileptogenesis, seizure generation, depression and psychiatric disorders comorbid with epilepsy. Serotonin involvement in epilepsy is complex; the reasons are twofold i) epilepsy is in reality a spectrum disorder, and ii) serotonin effects vary from one form of epilepsy to another, due also to the different serotonin receptors involved. Here, we will focus on the role of serotonin and its 5-HT2 receptors in absence epilepsy. Our recent pharmacological experimental evidence in GAERS will be reviewed together with our preliminary optogenetic results. 5-HT2C receptor agonists may represent a new approach to interfere with seizure generation and seizure management. Our optogenetic experiments also indicate that by modulating rhythmic cortical activity, optogenetic stimulation of the serotonergic system may provide seizure control without the adverse effects induced by pharmacological activation of 5-HT2C receptors. Thus, targeting the serotonergic system could provide novel insights into the pathophysiological mechanisms of seizure generation and lead to potentially novel treatments.peer-reviewe

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods: Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm). Results: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy

Evidence for the formation of comet 67P/Churyumov-Gerasimenko through gravitational collapse of a bound clump of pebbles

The processes that led to the formation of the planetary bodies in the Solar System are still not fully understood. Using the results obtained with the comprehensive suite of instruments on-board ESA’s Rosetta mission, we present evidence that comet 67P/Churyumov-Gerasimenko likely formed through the gentle gravitational collapse of a bound clump of mm-sized dust aggregates (“pebbles”), intermixed with microscopic ice particles. This formation scenario leads to a cometary make-up that is simultaneously compatible with the global porosity, homogeneity, tensile strength, thermal inertia, vertical temperature profiles, sizes and porosities of emitted dust, and the steep increase in water-vapour production rate with decreasing heliocentric distance, measured by the instruments on-board the Rosetta spacecraft and the Philae lander. Our findings suggest that the pebbles observed to be abundant in protoplanetary discs around young stars provide the building material for comets and other minor bodies