Translaryngeal tracheostomy in acute respiratory distress syndrome patients

Objective: To prevent gas exchange deterioration during translaryngeal tracheostomy (TLT) in patients with acute respiratory distress syndrome (ARDS) ventilation is maintained through a small diameter endotracheal tube (ETT; 4.0 mm i.d.) advanced beyond the tracheostoma. We report on the feasibility of uninterrupted ventilation delivered through a high-resistance ETT in ARDS patients, and relevant ventilatory adjustments and monitoring. Design and setting: Prospective, observational clinical study in an eight-bed intensive care unit of a university hospital. Patients: Eight consecutive ARDS patients scheduled for tracheostomy. Interventions: During TLT volume control ventilation was maintained through the 4.0-mm i.d. ETT. Tidal volume, respiratory rate, and inspiratory to expiratory ratio were kept constant. Fractional inspiratory oxygen was 1. Positive end expiratory pressure (PEEP) set on the ventilator (PEEPvent) was reduced to maintain total PEEP (PEEPtot) at baseline level according to the measured intrinsic PEEP (auto-PEEP). Measurements and main results: Data were collected before tracheostomy and while on mechanical ventilation with the 4.0-mm i.d. ETT. Neither PaCO2nor PaO2changed significantly (54.5\uc2\ub110.0 vs. 56.4\uc2\ub17.0 and 137\uc2\ub169 vs. 140\uc2\ub159 mmHg, respectively). Auto-PEEP increased from 0.6\uc2\ub11.1 to 9.8\uc2\ub16.5 cmH2O during ventilation with the 4.0-mm i.d. ETT. By decreasing PEEPventwe obtained a stable PEEPtot(11.4\uc2\ub14.3 vs. 11.8\uc2\ub14.3 cmH2O), and end-inspiratory occlusion pressure (26.7\uc2\ub17.4 vs. 28.0\uc2\ub16.6 cmH2O). Peak inspiratory pressure rose from 33.8\uc2\ub18.1 to 77.8\uc2\ub112.7 cmH2O. Conclusions: The high-resistance ETT allows ventilatory assistance during the whole TLT procedure. Assessment of stability in plateau pressure and PEEPtotby end-inspiratory and end-expiratory occlusions prevent hyperinflation and possibly barotrauma

Limits of endoscopic endonasal approach for cranio-vertebral junction tumors

The endoscopic endonasal approach has been recently proposed for cranio-vertebral junction lesions. The more common indication for this sagittal extension of the endonasal route is represented by odontoidectomy for irreducible ventral brainstem compression due to congenital or degenerative conditions. However, in an increasing number of studies its adoption for tumors involving the cranio-cervical junction has been reported. The aim of this study is to consider retrospectively our surgical series, focusing on the advantages and limits of this approach

Population pharmacokinetics of dalbavancin and dosing consideration for optimal treatment of adult patients with staphylococcal osteoarticular infections

Background: Dalbavancin is gaining interest in the treatment of complex osteoarticular (OA) infections. Objective: To conduct a population pharmacokinetic analysis of dalbavancin in a prospective cohort of adult patients with Gram-positive OA infections and to identify optimal dosing regimens for long term-treatment. Methods: Non-linear mixed-effects modelling was performed with Monolix. Monte Carlo simulations were performed with six dalbavancin regimens (1500mg at day 1; 1000mg at day 1 plus 500mg at day 8; 1500mg at day1 and 8; 1500mg at day1 and 8 plus 500, 1000 or 1500mg at day 36) to assess the PTA of three pharmacodynamic target of fAUC24h/MIC against S. aureus (>27.1, 53.3 and 111.1). Cumulative fraction of response (CFR) was calculated against MIC distribution of both MRSA and MSSA as well. Desirable PTAs and CFRs were 6590%. Results: Fifteen patients provided 120 plasma concentrations. Most (73.3%) had prosthetic joint infections. Clinical cure rate was 87%. A two-compartment model with linear elimination well described the data. No covariate was retained in the final model. Pharmacokinetic dalbavancin estimates were 0.106L/h for CL and 36.4L for Vss. The tested dosing regimens granted desirable CFRs against S. aureus at the most effective PK/PD target for a period ranging 3-to-9 weeks. Conclusion: Giving a two 1500mg dosing regimen of dalbavancin one week apart may ensure efficacy against both MSSA and MRSA up to 5 weeks in patients with OA infections. Clinical assessment at that time may allow for considering whether or not an additional dose should be administered for prolonging effective treatment

Changing Lifestyle of Persons With Multiple Sclerosis: Development, Feasibility and Preliminary Results of a Novel High-Impact Collaborative Intervention in Leisure Environments

Objective: Only a limited percentage of persons with MS (pwMS) participate to multidisciplinary rehabilitation (MDR) because of poor support, knowledge and motivation. We reasoned that pwMS should be more effectively prepared to increase their adherence. We implemented an innovative collaborative approach, called \u201cbrief highimpact preparatory experience\u201d (b-HIPE), inspired by an overarching model based on the interplay between competence, motivation and opportunity to increase in a short time awareness and motivation of pwMS. Methods: B-HIPE integrates physiotherapy, mindfulness, sailing, healthy diet, and cultural activities to be experienced in a convivial form at a beautiful seaside location in Sardinia. Sixteen pwMS participated to 3 successive one-week editions of the b-HIPE, co-sponsored by the Rotary Club of Milan and supported by researchers of our Institute and of partner associations. The feasibility was assessed with structured questionnaires and free reports concerning accommodation, logistics, coordination, social climate and the specific activities proposed. For this pilot study we used a single-group design with repeated measurements at baseline and post-intervention. The SF-36 QoL scale was the main outcome measure, the Fatigue Severity Scale (FSS), the Berg Balance scale (BBS) and the 9 hole peg test (9HPT) were the secondary outcomes. Results: The approach was feasible. Scores on several FS-36 scales and secondary outcomes were significantly improved. Participants\u2019 satisfaction with all aspects of the experience was above expectations. PwMS became more motivated and aware of physical and mental resources, all learned to sail adapted monohulls, strategies to master stress and to modify their diet according to specific recommendations. Conclusion: B-HIPE is safe and feasible. The interplay of multiple factors produced in a very short time the expected changes in participants\u2019 attitude toward a healthier lifestyle. A monitoring program is ongoing to assess long-term effects including adherence to hospital-based MDR

Genetic, epigenetic and immunologic profiling of MMR-deficient relapsed glioblastoma

PURPOSE: In-depth characterization of recurrent glioblastoma (rGBM) might contribute to a better understanding of the mechanisms behind tumor progression and enable rGBM treatment with targeted drugs. EXPERIMENTAL DESIGN: In this study, GBM samples were collected at diagnosis and recurrence from adult patients treated with Stupp protocol. Expression of mismatch repair (MMR) proteins was evaluated by IHC, followed by whole exome sequencing (WES) of tumor samples showing loss of MSH6 reactivity. Established genetic, epigenetic and immunologic markers were assessed by standard methods and correlated with loss of MMR proteins and patient survival. RESULTS: Expression of MMR proteins was partially or completely lost in 25.9% rGBM samples. Specifically, 12 samples showed partial or total MSH6 expression reduction. Conversely, 96.4% of GBM samples at diagnosis expressed MMR markers. WES disclosed lack of variants in MMR genes in primary samples, whereas two MSH6 negative rGBM samples shared a c.3438+1G>A* splicing MSH6 variant with a potential loss of function effect. MSH6 negative rGBM specimens had high tumor mutational burden (TMB), but no microsatellite instability. In contrast, GBM samples with partial loss of MMR proteins disclosed low TMB. MMR-deficient rGBM showed significant telomere shortening and MGMT methylation and are characterized by highly heterogeneous MHC class I expression. CONCLUSIONS: Multi-level profiling of MMR-deficient rGBM uncovered hypermutated genotype uncoupled from enriched expression of immune-related markers. Assessment of MHC class I expression and TMB should be included in protocols aiming to identify rGBM patients potentially eligible for treatment with drugs targeting immune checkpoint inhibitors

Multicentric Italian survey on daily practice for autoimmune pancreatitis: Clinical data, diagnosis, treatment, and evolution toward pancreatic insufficiency

BackgroundAutoimmune pancreatitis (AIP) is a rare, and relatively new, form of chronic pancreatitis. The management of AIP can vary considerably among different centres in daily clinical practice.ObjectivesThe aim of this study is to present a picture of epidemiological, clinical characteristics, outcomes, and the real-life practice in terms of management in several academic and non-academic centres in Italy.MethodsData on the clinical presentation, diagnostic work-up, treatments, frequency of relapses, and long-term outcomes were retrospectively collected in a cohort of AIP patients diagnosed at 14 centres in Italy.ResultsOne hundred and six patients were classified as type 1 AIP, 48 as type 2 AIP, and 19 as not otherwise specified. Epidemiological, clinical, radiological, and serological characteristics, and relapses were similar to those previously reported for different types of AIP. Endoscopic cytohistology was available in 46.2% of cases, and diagnostic for AIP in only 35.2%. Steroid trial to aid diagnosis was administered in 43.3% cases, and effective in 93.3%. Steroid therapy was used in 70.5% of cases, and effective in 92.6% of patients. Maintenance therapy with low dose of steroid (MST) was prescribed in 25.4% of cases at a mean dose of 5 (+/- 1.4) mg/die, and median time of MST was 60 days. Immunosuppressive drugs were rarely used (10.9%), and rituximab in 1.7%. Faecal elastase-1 was evaluated in only 31.2% of patients, and was pathological in 59.2%.ConclusionsIn this cohort of AIP patients, diagnosis and classification for subtype was frequently possible, confirming the different characteristics of AIP1 and AIP2 previously reported. Nevertheless, we observed a low use of histology and steroid trial for a diagnosis of AIP. Steroid treatment was the most used therapy in our cohort. Immunosuppressants and rituximab were rarely used. The evaluation of exocrine pancreatic insufficiency is underemployed considering its high prevalence

The InCosmiCon Research Center and its activities in the field of SETI, Big History and interculturality

As announced at the IAC 2019 held in Washington, at the beginning of 2020 the University of Insubria (Italy), in collaboration with the UCSS of Lima (Peru), has created a new research center called InCosmiCon (Intelligence in the Cosmic Context), based at the Department of Human Sciences, Innovation and Territory (DISUIT). Its goal is to investigate the nature of intelligence in an interdisciplinary way and with a realistic approach, in the context of the history of humankind, of our planet and the whole universe, avoiding the specular errors of reductionism and dualism. InCosmiCon has already been joined by various illustrious scientists in the field of space sciences, as the former IAU Secretary General Piero Benvenuti, now Honorary President of InCosmiCon, and also by some members of the IAA SETI Committee, as Paolo Musso, Director of InCosmiCon, and the present Chairman of the IAA SETI Committee Claudio Maccone, who has been nominated Coordinator of the InCosmiCon SETI Section, whose aim is to support the implementation of SETI programs everywhere it is possible, especially in Italy and Latin America, and to participate in the interdisciplinary work about extraterrestrial intelligence promoted by the IAA SETI Committee. Other Sections of InCosmiCon are devoted to Big History and Intercultural Communication, especially focusing on the extraordinary experience of the UCSS Amazonian seat, the UCSS-Nopoki of Atalaya, which could be also a model for a positive interaction with a hypothetical extraterrestrial civilization. In the present paper some of the InCosmiCon members are going to present its structure, its first results, and its projects for the next future, while a separate paper will be specifically devoted to a Peruvian project about Astrobiology and Optical SETI

SICE national survey: current status on the adoption of laparoscopic approach to the treatment of colorectal disease in italy

The real di usion of laparoscopy for the treatment of colorectal diseases in Italy is largely unknown. The main purpose of the present study is to investigate among surgeons dedicated to minimally invasive surgery, the volume of laparoscopic colorectal procedures, the type of operation performed in comparison to traditional approach, the indication for surgery (benign and malignant) and to evaluate the di erent types of technologies used. A structured questionnaire was developed in collaboration with an international market research institute and the survey was published online; invitation to participate to the survey was issued among the members of the Italian Society of Endoscopic Surgery (SICE). 211 surgeons working in 57 surgical departments in Italy ful lled and answered the online survey. A total of 6357 colorectal procedures were recorded during the year 2015 of which 4104 (64.1%) were performed using a minimally invasive approach. Colon and rectal cancer were the most common indications for laparoscopic approach (83.1%). Left colectomy was the operation most commonly performed (41.8%), while rectal resection accounted for 23.5% of the cases. Overall conversion rate was 5.9% (242/4104). Full HD standard technology was available and routinely used in all the responders’ centers. The proportion of colorectal resec- tions that are carried out laparoscopically in dedicated centers has now reached valuable levels with a low conversion ra

Clinical characteristics, management and in-hospital mortality of patients with COVID-19 In Genoa, Italy

To describe clinical characteristics, management and outcome of COVID-19 patients; and to evaluate risk factors for all-cause in-hospital mortality