Efficacy of omalizumab in an atopic young adult with asthma and eosinophilic chronic rhinosinusitis with nasal polyps.

OBJECTIVE: Chronic rhinosinusitis (CRS) presents a multifactorial etiology due to interactions between the immune host system and external agents. It can be classified into two phenotypes based on the presence or absence of polypoid neoformation (respectively CRSwNP and CRSsNP). According to EPOS2020, CRS is now classified into two endotypes, eosinophilic (ECRS) and non-eosinophilic (non-ECRS), based on eosinophil tissue count (more than 10 eosinophils per High Power Field, HPF). CASE PRESENTATION: We present the case of a 31-year-old man affected by recalcitrant ECRSwNP and asthma. RESULTS: He was treated with a combination of omalizumab and endoscopic sinus surgery. This combination led to a reduction in blood eosinophils, modified Lund-Kennedy endoscopic score, Lund-Mackay score, and Sino-Nasal Outcome Test (SNOT-22), almost 6 months after surgery. CONCLUSIONS: In this clinical case, omalizumab regulated nasal symptoms for more than a year and with good control of the recalcitrant pattern when combined with ESS.

Effects of a behavioural approach on lifestyle habits in a healthy Italian population: a before-after interventional study.

Background: The study aimed to assess the effectiveness of an educational intervention promoting adherence to healthy diet and physical activity. Study design: Before-after interventional study. Methods: Participants were healthy volunteers, 18-70 y old, from Bologna. They followed a training course consisting of seven meetings and signed a contract to comply with the promoted habits, verified through questionnaires at the engagement phase (T0), three months later (T1) and one year later (T2). Results: One hundred, fifty-three subjects were involved, 75.8% were evaluated at T1 and 41.2% at T2. More than 80% of the subjects involved at T1 achieved an improvement of planned goals. Moreover, 77% of T1 compliants retained healthy eating and physical activity at T2. Conclusions: The proposed pathway of empowerment positively affected nutrition and promotion of physical activity at 3 months after the intervention (T1) and were maintained even after a year. The results appear to be promising for primary prevention across the spectrum of a healthy lifestyle educational approach.

Controlling the structure of sequence-defined poly(phosphodiester)s for optimal MS/MS reading of digital information.

Digital polymers are monodisperse chains with a controlled sequence of co-monomers, defined as letters of an alphabet, and are used to store information at the molecular level. Reading such messages is hence a sequencing task that can be efficiently achieved by tandem mass spectrometry. To improve their readability, structure of sequence-controlled synthetic polymers can be optimized, based on considerations regarding their fragmentation behavior. This strategy is described here for poly(phosphodiester)s, which were synthesized as monodisperse chains with more than 100 units but exhibited extremely complex dissociation spectra. In these polymers, two repeating units that differ by a simple H/CH3 variation were defined as the 0 and 1 bit of the ASCII code and spaced by a phosphate moiety. They were readily ionized in negative ion mode electrospray but dissociated via cleavage at all phosphate bonds upon collisional activation. Although allowing a complete sequence coverage of digital poly(phosphodiester)s, this fragmentation behavior was not efficient for macromolecules with more than 50 co-monomers, and data interpretation was very tedious. The structure of these polymers was then modified by introducing alkoxyamine linkages at appropriate location throughout the chain. A first design consisted of placing these low dissociation energy bonds between each monomeric bit: while cleavage of this sole bond greatly simplified MS/MS spectra, efficient sequencing was limited to chains with up to about 50 units. In contrast, introduction of alkoxyamine bonds between each byte (i.e. a set of eight co-monomers) was a more successful strategy. Long messages (so far, up to 8 bytes) could be read in MS3 experiments, where single-byte containing fragments released during the first activation stage were further dissociated for sequencing. The whole sequence of such byte-truncated poly(phosphodiester)s could be easily re-constructed based on a mass tagging system which permits to determine the original location of each byte in the chain. Copyright © 2017 John Wiley & Sons, Ltd.

¿Conoce cuál es su riesgo de tener diabetes? / Do you know your risk of having diabetes?

La diabetes mellitus tipo 2 (DM2) es una enfermedad silenciosa que afecta hasta el 20% de nuestra población y de ella, hasta el 50% desconoce que la padece. Esta enfermedad se asocia a una alta prevalencia sobre factores de riesgo como el sobrepeso, la obesidad y la inactividad física. Con frecuencia, la DM2 se diagnostica en forma tardía y a veces genera diversas complicaciones asociadas que podrían evitarse

Etiología y perfil de resistencia antimicrobiana en infecciones del pie diabético / Etiology and antimicrobial resistance profile in diabetic foot infections

El pie diabético infectado (PDI) es aquel que presenta infección de piel y partes blandas u óseas por debajo del maléolo; constituye la complicación más frecuente de diabetes que causa hospitalización y amputación. En nuestro hospital los pacientes con pie diabético son asistidos en un consultorio multidisciplinario; el 40% presenta infección leve moderada o grave

Inter-hemispheric coupling changes associate with motor improvements after robotic stroke rehabilitation.

PURPOSE: In the chronic phase of stroke brain plasticity plays a crucial role for further motor control improvements. This study aims to assess the brain plastic reorganizations and their association with clinical progresses induced by a robot-aided rehabilitation program in chronic stroke patients. METHODS: 7 stroke patients with an upper limb motor impairment in chronic phase underwent a multi-modal evaluation before starting and at the end of a 12-week upper-limb neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and performance indices of hand movement performance (isometric pinch monitored through a visual feedback) were collected. Cerebral reorganizations were characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional and contralesional resting state properties investigating both bipolar derivations overlying the middle cerebral artery territory and the primary somatosensory sources (S1) obtained through the Functional Source Separation (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh) at rest were measured and correlated with clinical and hand control robot-induced improvements. RESULTS: After the robotic rehabilitation we found an improvement of FMAS scores and hand motor control performance and changes of brain connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement of motor performance correlated with the modulation of the interhemispheric S1 coherence in the high beta band (24-33 Hz). CONCLUSIONS: Recently it has been shown that an upper limb robot-based rehabilitation improves motor performance in stroke patients. We confirm this potential and demonstrate that a robot-aided rehabilitation program induces brain reorganizations. Specifically, interhemispheric connectivity between primary somatosensory areas got closer to a 'physiological level' in parallel with the acquisition of more accurate hand control.

Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences on a human amputee.

The performance of motor neuroprostheses or robotic arm prostheses can be significantly improved by delivering sensory feed-back related to the ongoing motor task (e.g. the slippage of an object during grasping). Microfabricated neural electrodes implantable in peripheral nervous system seem a promising approach to this aim. New generation of thin-film intrafascicular electrodes longitudinally implantable in peripheral nerves (tf-LIFE4) has been developed and tested for afferent stimulation in human amputee case study.

Prevalence of polyomaviruses BK, JC, SV40, KI, and WU in non-malignant tonsil specimens.

AIM: The recently described polyomaviruses KI and WU have been detected in respiratory samples, stools, tonsils, and blood, particularly in immunocompromised conditions, although little is known about tissue tropism. Herein we investigated the occurrence of KIV and WUV in non-malignant tonsillar specimens by Real-time quantitative PCR; the presence of polyomaviruses BK, JC and SV40-DNA was also evaluated. METHODS: Twenty-nine non-malignant tonsil specimens obtained from children and adults admitted for tonsillectomy were prospectively studied. Real-time quantitative TaqMan PCR for polyomaviruses KI, WU, BK, JC, and SV40 were performed. RESULTS: KI-DNA was positive in 2/29 tonsillar specimens (6.9%), while BK- DNA, JC-DNA, SV-40 DNA, and WU-DNA sequences were not identified. CONCLUSION: Few studies have investigated the prevalence of polyomaviruses in tonsil specimens, with varying results, and data are particularly scant as regards the newly discovered KIV and WUV. Two major questions remain to be definitely answered at this regard: the possibility that human tonsils represent the initial site of infection and/or a latency site and the biological and clinical meaning of KIV and WUV in different contexts and groups of patients, in that it is not clear whether they are simple bystanders or play a role in tonsil disease.

Self-esteem and personality in subjects with and without body dysmorphic disorder traits undergoing cosmetic rhinoplasty: preliminary data.

BACKGROUND: Many individuals with body dysmorphic disorder (BDD) seek non-psychiatric treatment. BDD occurs in about 5% of patients who seek cosmetic surgery, and rhinoplasty is the most frequently sought treatment. A correlation exists between individuals' self-esteem and demand for cosmetic surgery. OBJECTIVE: To investigate whether those subjects with BDD traits requesting cosmetic rhinoplasty differ from those without BDD traits in self-esteem, personality and quality of life. METHODS: This study included 54 patients applying to the 1st ENT Division of Turin University. Assessment of the patients before cosmetic rhinoplasty includes: nasal obstruction symptom evaluation, health-related quality of life, Rosenberg self-esteem scale, body dysmorphic disorder questionnaire (BDDQ) and temperament and character inventory (TCI). Based on their responses to BDDQ questions 1, 3 and 4, patients were subdivided into subgroups and then compared. RESULTS: No difference emerged in the objective data. Lower self-esteem, higher harm avoidance (HA) and lower self-directedness (SD) are found in subjects who are worried about how they look, in those with interference in their social life due to this worry and in those who spend more than 3h per day thinking about the way they look. Novelty seeking (NS) is significantly higher in subjects who think about their looks for up to 3h than in those who spend less than 1h. CONCLUSION: Different subgroups of patients are identified. The first group includes pessimistic, shy, insecure subjects; people with fragile and immature personality and poor self-esteem; individuals concerned about the way they look and those who spend more time thinking about it. The second group includes more confident subjects with stronger personality and greater self-esteem. A third, less differentiated group, includes more impulsive (high NS) subjects who spend an intermediate amount of time thinking about the way they look. Patients should be carefully screened and assessed before cosmetic surgery interventions to avoid frustration to both, clinicians and patients.

On the control of a robot hand by extracting neural signals from the PNS: preliminary results from a human implantation.

The development of hybrid neuroprosthetic systems (HBSs) linking the human nervous system with artificial devices is an important area of research that is currently addressed by several groups to restore sensorimotor function in people affected by different disabilities. It is particularly important to establish a fast, intuitive, bidirectional flow of information between the nervous system of the user and the smart robotic device. Among the possible solutions to achieve this goal, interfaces with the peripheral nervous system and in particular intraneural electrodes can represent an interesting choice. In the present study, thin-film longitudinal intra-fascicular electrodes were implanted in the median and ulnar nerves of an amputee. The possibility of restoring the bidirectional link between the subject and the external world was investigated during a 4 week trial. The result showed that both the extraction of motor information and the restoration of sensory function are possible.

Gefitinib in patients with progressive high-grade gliomas: a multicentre phase II study by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

To investigate the role of gefitinib in patients with high-grade gliomas (HGGs), a phase II trial (1839IL/0116) was conducted in patients with disease recurrence following surgery plus radiotherapy and first-line chemotherapy. Adult patients with histologically confirmed recurrent HGGs following surgery, radiotherapy and first-line chemotherapy, were considered eligible. Patients were treated with gefitinib (250 mg day(-1)) continuously until disease progression. The primary end point was progression-free survival at 6 months progression-free survival at 6 months (PFS-6). Tissue biomarkers (epidermal growth factor receptor (EGFR) gene status and expression, phosphorylated Akt (p-Akt) expression) were assessed. Twenty-eight patients (median age, 55 years; median ECOG performance status, 1) were enrolled; all were evaluable for drug activity and safety. Sixteen patients had glioblastoma, three patients had anaplastic oligodendrogliomas and nine patients had anaplastic astrocytoma. Five patients (17.9%, 95% CI 6.1-36.9%) showed disease stabilisation. The overall median time to progression was 8.4 (range 2-104+) weeks and PFS-6 was 14.3% (95% CI 4.0-32.7%). The median overall survival was 24.6 weeks (range 4-104+). No grade 3-4 gefitinib-related toxicity was found. Gefitinib showed limited activity in patients affected by HGGs. Epidermal growth factor receptor expression or gene status, and p-Akt expression do not seem to predict activity of this drug.

Improvement of clinical response in allergic rhinitis patients treated with an oral immunostimulating bacterial lysate: in vivo immunological effects.

Allergic rhinitis is known to be one of the most common chronic diseases in the industrialized world. According to the concept that allergic rhinitis patients generally suffer from an immune deficit, in order to stimulate specifically or aspecifically their immune system, immunomodulating agents from various sources, such as synthetic compounds, tissue extracts or a mixture of bacterial extracts, have been used. The aim of the present trial is to evaluate the efficacy of the treatment with an immunostimulating vaccine consisting of a polyvalent mechanical bacterial lysate (PMBL) in the prophylaxis of allergic rhinitis and subsequently to analyze its in vivo effects on immune responses. 41 allergic rhinitis patients were enrolled: 26 patients were randomly assigned to the group for PMBL sublingual treatment and 15 others to the group for placebo treatment. For all 26 patients blood samples were drawn just before (T0) and after 3 months of PMBL treatment (T3) to evaluate plasma IgE levels (total and allergen-specific) and the cytokine production involved in the allergic response (IL-4, IFN-gamma). The results of our study indicate that PMBL is effective in vivo in the reduction or in the elimination of the symptoms in rhinitis subjects during the treatment period in comparison to a non-immunostimulating treatment. A significant and clinically relevant improvement was found in 61.5%, a stationary clinical response was registered in 38.4% and no negative side effects associated with the medication or worsening were recorded. At the end of a 3-month follow up period the clinical picture remained the same as that observed at T3. PMBL treatment did not affect the serum IgE levels (either total or allergen-specific) and did not induce significant changes in IFN-gamma concentration. In contrast, PMBL therapy may be accompanied, in some patients, by a potential immunomodulating activity by decreasing IL-4 cytokine expression.

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO).

The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.

Is protracted low-dose temozolomide feasible in glioma patients?

The authors investigated the safety of 75 mg/m2 temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, cumulative lymphopenia, which leads to a high incidence of infections.

Design and development of a miniaturized 2-axis force sensor for tremor analysis during locomotion in small-sized animal models.

This work represents a first step towards the development of a sensorised environment for behavioral phenotyping of animal models. In particular, this paper focuses on tremor analysis in reeler mice, an emerging potential animal model for anatomical and behavioral traits observed in autism. Ground Reaction Force (GRF) sensing is indeed the most direct means of measuring tremor. Although force platforms have extensively been used for large size animals, only few attempts have been made to measure GRF at a single paw for animals as small as mice or rats. Under the hypothesis that in-plane GRF components are directly connected to tremor, a small size, low-cost, 2-axis force sensor for measuring the in-plane components of GRF was designed and developed. Special care was paid to allow self-aligned assembly for repeatability and modularity for combining multiple platforms for a sensorised floor. Preliminarily testing was performed with both reeler and wildtype mice. Fourier analysis was deployed to extract information due to tremor, validating the hypothesis of a direct connection between tremor and in-plane GRFs.

Phase II trial of carboplatin and etoposide for patients with recurrent high-grade glioma.

We present the results of a phase II trial of carboplatin and etoposide (CE) combination as first-line chemotherapy in patients with recurrent glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) after surgery and radiotherapy. We assess the activity and the tolerability of this combination. 30 patients with GBM (25) and AA (5) were treated with VP-16 (etoposide) 120 mg m(-2) and CBCDA (carboplatin) 100 mg m(-2) for 3 days every 4 weeks. Moreover, we performed a retrospective analysis of topoisomerase IIalpha gene status using chromogenic in situ hybridisation. The median age was 54 years (21-73 years); Eastern Cooperative Oncology Group performance score was 0-1 in 25 patients and 2 in five patients. All patients had been previously treated with surgical resection (21 radical resections) followed by radiation therapy (40-60 Gy). We observed six (20%) complete responses, three (10%) partial responses and 12 (40%) stable diseases, with a response rate of 30%. The median time to progression was 4 months, while progression-free survival at 6 months was 33.3%. The median survival time was 10 months. Neutropenia occurred in 9 patients: four patients had grade 4, two patients grade 3 and three patients grade 2. In the conclusion of this clinical trial, the CE combination has shown activity in recurrent GBM and AA, with a good toxicity profile. Alterations in the copy number of topoisomerase IIalpha gene seem to be a rare event and in our series do not influence response to the CE combination.

Stop-flow technique for loco-regional delivery of high dose chemotherapy in the treatment of advanced pelvic cancers.

AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of high-doses of mitomycin C and anthacyclines in patients with inoperable, recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using percutaneous double-balloon arterial-venous catheters that selectively isolate the pelvic vascular section and a perfusion provided by an extracorporeal pump for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon-rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm) plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts) infused into the isolated pelvic compartment. Blood samples were collected from the extracorporeal vascular flow and from peripheral plasma, and analysed for drug quantitation. RESULTS: During the procedure, there were no technical or hemodynamic complications, and no deaths occurred during surgery or in the postoperative period. MMC and DOXO peak levels measured in the extracorporeal system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3, MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the peripheral blood. Similarly; the area under concentration (AUC) versus time curves measured in the pelvic compartment during stop-flow perfusion were 19.9 (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the corresponding value in peripheral circulation. The drug percentage eliminated in the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0-24) were similar to those observed with iv bolus of equivalent drug doses. Minimal systemic and local toxicities were observed. One complete pathological and 2 partial responses were observed; pain remission in 8/10 patients. median survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into the local vasculature produces high pelvic-systemic concentration gradients during the stop-flow perfusion with limited local and systemic toxicity. The encouraging clinical results suggest further evaluation.

Epstein Barr viral load monitoring by quantitative PCR in renal transplant patients.

Post-transplant lymphoproliferative disorders (PTLD), ranging from lymphoid hyperplasia to clonal malignancy, are a severe complication arising in solid organ transplant patients. Their reported incidence ranges from 1 to 20%, according to factors such as type of transplanted organ and the age of recipients. A strong correlation between Epstein Barr virus (EBV) infection, the grade and type of immunosuppression and the development of PTLD has been recognized. The detection and quantification of EBV-DNA load in peripheral blood have been utilized as prognostic markers for the development of PTLD, showing a correlation between high levels of EBV-DNA in the blood and the development of PTLD. In this study, we monitored EBV viral load monthly in 15 renal transplant recipients for six months. The number of EBV-DNA copies was measured in peripheral blood mononuclear cells (PBMC) and serum samples by a quantitative PCR protocol developed in our laboratory that employes a previous screening of samples containing a significant number of viral DNA copies (> or =1000 copies/10(5) PBMC or 100 microl serum) by semi-quantitative PCR followed by a precise quantification of the only significant samples by quantitative-competitive (QC)-PCR. Our 15 renal transplant patients neither developed PTLD nor had recurrent acute illnesses or acute graft rejections during the study. The results obtained in the monthly follow up of EB viral load in PBMC samples confirmed its fluctuation in asymptomatic patients reported in literature. In particular, 5/14 (35.7%) of EBV seropositive patients had an EBV-DNA load equal to 1000 EBV copies /10(5) PBMC (roughly corresponding to 10.000 copies/microg PBMC DNA), and 1/14 (7.1%) reached 5000 EBV copies /10(5) PBMC (roughly corresponding to 50.000 copies/microg PBMC DNA), at least once in our study. In the EBV seronegative patient, EBV-DNA in PBMC samples was always undetectable (less than 100 DNA copies/10(5) PBMC). EBV-DNA load in all serum samples was less than threshold value of our quantification protocol (<100 DNA copies/100 microl serum), supporting the literature data. With regard to immunosuppressive treatment, 66.7% of the six patients in whom EBV load reached values equal to or higher than 1000 DNA copies/10(5) PBMC, were on FK506 whereas only 33.3% of them were on CyA. In conclusion, further investigations are needed to better understand the role of EBV infection in the pathogenesis of PTLD in immunosuppressed patients. Given the high positive predictive value of EB viral load in peripheral blood for diagnosis of PTLD reported by several authors, and the described absence of correlation between the serological evidence of EBV reactivation and EB viral load, EBV viral load measurement in PBMC and serum samples using quantitative PCR techniques is a powerful diagnostic tool to monitor transplanted patients at risk to develop PTLD.

Safety and efficacy of iron sucrose in patients sensitive to iron dextran: North American clinical trial.

Sensitivity to iron dextran is a potent obstacle to maintaining optimum iron status in patients with dialysis-associated anemia. As part of the North American clinical trials for iron sucrose injection, we examined the effect of intravenous (IV) iron sucrose in 23 hemodialysis patients with documented sensitivity to iron dextran, ongoing epoetin alfa therapy, and below-target-range hemoglobin (Hgb) levels (<11.0 g/dL). We assigned patients to treatment groups according to whether reactions they had experienced to iron dextran were judged to be mild (n = 16; group A) or severe (n = 7; group B). We prospectively examined adverse events and vital signs after administering 100 mg of IV iron sucrose in each of 10 consecutive dialysis treatment sessions and compared results with those recorded in each of three consecutive dialysis sessions without iron treatment. We administered iron sucrose by IV push over 5 minutes to group A patients and by IV push over 5 minutes or IV infusion over 15 to 30 minutes to group B patients. We did not administer a test dose. Results showed no serious adverse drug reactions after a total of 223 doses of iron sucrose (184 doses by IV push, 39 doses by IV infusion). Intradialytic blood pressure changes after IV iron sucrose injection did not differ from those recorded during dialysis sessions without treatment. An increase in values for Hgb, hematocrit, transferrin saturation, and ferritin, coupled with no significant change in epoetin dose and a decrease in total iron-binding capacity, confirmed the efficacy of iron sucrose injection in managing anemia. We conclude that iron sucrose injection is safe and effective in the management of anemia in patients sensitive to iron dextran and can be administered without a test dose by IV push or infusion.