Real-world study on the effectiveness and safety of basal insulin IDegLira in type 2 diabetic patients previously treated with multi-injective insulin therapy.

OBJECTIVE: Achieving glycemic target is paramount to control diabetes mellitus (DM) and reduce micro-vascular and macro-vascular complications. Despite the mostly recent-developed drugs, most patients still show an above desired glycated hemoglobin (HbA1c) level due to DM complex pathophysiology, therapeutic and dietary compliance and clinical inertia in introducing or intensifying insulin therapy. To support the promising results of clinical trials on the effectiveness and safety of the degludec/liraglutide combination (IDegLira) in type 2 DM patients with C-peptide values >1 ng/ml who were previously treated with basal-bolus multiple daily-dose insulin injections. PATIENTS AND METHODS: This observational, prospective and non-randomized trial enrolled type 2 DM patients referred to our outpatient clinic between January 2019 and December 2019, who were shifted from multiple daily-dose insulin injection therapy to degludec/liraglutide combination as per the physician's decision. The main assessment was HbA1c variation at 6 months from baseline. Secondary assessments included variation in fasting glycemia, routine anthropometric assessments, blood chemistry, blood pressure and patients' quality of life (measured by the Diabetes Treatment Satisfaction Questionnaire [DTSQ]), from baseline to 6 months. RESULTS: HbA1c (8.4 vs. 7.4%; p<0.0001) and body weight (94.1 vs. 93 kg; p<0.0001) were significantly lower after 6 months for patients on the degludec/liraglutide combination. A similar trend was observed in fasting glycemia levels (159 vs. 125 mg/dl; p<0.0001). An improved glycemic control was achieved with degludec/liraglutide despite a reduction in total daily insulin units (42 U at 6 months vs. 22 U at baseline; p<0.0001). In addition, higher scores in the DTSQ were registered after 6 months on degludec/liraglutide (mean score: 27 vs. 20; p<0.0001). The combination therapy also proved more convenient than basal-bolus therapy in terms of costs, with an average per-patient cost difference of €-0.41±0.59/die (p<0.0001). CONCLUSIONS: These real-world findings show that degludec/liraglutide seems to be more effective than basal-bolus insulin in achieving glycemic control, allowing cost sustainability and improving patient satisfaction.

Outbreak of Salmonella Chailey infections linked to precut coconut pieces - United States and Canada, 2017†.

Foodborne salmonellosis causes an estimated one million illnesses and 400 deaths annually in the United States (US). During March-May 2017, an outbreak of 19 cases of Salmonella Chailey associated with precut coconut pieces from a single grocery store chain occurred in the United States and Canada. The chain voluntarily recalled precut coconut pieces. This was the first time that coconut has been associated with a Salmonella outbreak in the United States or Canada. In recent years, salmonellosis outbreaks have been caused by foods not typically associated with Salmonella. Raw coconut should now be considered in investigations of Salmonella outbreaks among fresh food consumers.

Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial.

BACKGROUND: Platinum-based chemoradiation (CCRT) is the standard treatment for Locally Advanced Head and Neck Squamous-Cell Carcinoma (LAHNSCC). Cetuximab/RT (CET/RT) is an alternative treatment option to CCRT. The efficacy of induction chemotherapy (IC) followed by chemoradiation compared to chemoradiation alone has not been demonstrated in randomized clinical trials. The goals of this phase II-III trial were to assess: (i) the overall survival (OS) of IC versus no-induction (no-IC) and (ii) the Grade 3-4 in-field mucosal toxicity of CCRT versus CET/RT. The present paper focuses on the analysis of efficacy. MATERIALS AND METHODS: Patients with LAHNSCC were randomized to receive concomitant treatment alone [CCRT (Arm A1) or CET/RT (Arm A2)], or three cycles of induction docetaxel/cisplatin/5 fluorouracil (TPF) followed by CCRT (Arm B1) or followed by CET/RT (Arm B2). The superiority hypothesis of OS comparison of IC versus no-IC (Arms B1 + B2 versus A1 + A2) required 204 deaths to detect an absolute 3-year OS difference of 12% (HR 0.675, with 80% power at two-sided 5% significance level). RESULTS: 414 out of 421 patients were finally analyzed: 206 in the IC and 208 in the no-IC arm. Six patients were excluded because of major violation and one because of metastatic disease at diagnosis. With a median follow-up of 44.8 months, OS was significantly higher in the IC arm (HR 0.74; 95% CI 0.56-0.97; P = 0.031). Complete Responses (P = 0.0028), Progression Free Survival (P = 0.013) and the Loco-regional Control (P = 0.036) were also significantly higher in the IC arm. Compliance to concomitant treatments was not affected by induction TPF. CONCLUSIONS: IC followed by concomitant treatment improved the outcome of patients with LAHNSCC without compromising compliance to the concomitant treatments. The degree of the benefit of IC could be different according to the type of the subsequent concomitant strategy. CLINICAL TRIAL NUMBER: NCT01086826, www.clinicaltrials.gov.

Modeling of SAM Impedance Onto Gold and Silver Thin-Film Mass-Produced Electrodes and Their Use for Optimization of Lactic Acid Detection.

In this work, we demonstrate how an innovative, out-of-cleanroom customized CD/DVD fabrication process can be successfully used for mass production of biosensors with thin-film electrodes. We show that silver and gold electrodes can be used for impedimetric and voltammetric biosensing applications, both in presence and absence of a redox mediator. We modeled the redox/non-redox electrodes impedance through equivalent electrical circuits, and we evaluated their transfer function sensitivity with a one-factor-at-a-time approach. Using this approach, we introduced a new prediction method to find which equivalent electrical circuit elements contribute more to the transfer function variations, then we experimentally validated the predictions measuring the electrodes electrochemical impedance spectroscopy responses with relevant self-assembled monolayer molecules immobilized on them, i.e., MCH and DTSP. We also assess the silver electrodes long-term stability with impedance spectroscopy measurements over a period of 1200 hours, proving their possible use in point-of-care applications. Finally, we also prove that the sensors correctly perform in a practical case, i.e., as a lactic acid biosensor, by studying the optimization of the biosensor efficiency through different enzyme immobilization methods. By comparing lactate oxidase enzyme direct adsorption and covalent binding to DTSP self-assembling monolayers, we found that covalent binding to DTSP can boost the catalytic current of about 40% with respect to that obtained from the direct adsorption of the same enzyme concentration.

Enhancement and control of surface plasmon resonance sensitivity using grating in conical mounting configuration.

In this work we propose a method to enhance and control the angular sensitivity of a grating coupled surface plasmon resonance (GCSPR) sensor. We lighted a silver grating, mounted in conical configuration, with a laser source and we measured the transmittance of the grating as a function of the azimuthal angle. To evaluate the sensitivity, grating surface was functionalized with four different alkanethiol self assembled monolayers (SAM) and the correspondent azimuthal transmittance peak shifts were measured. The sensitivity control was performed by simply change the light incident angle. This method offers the possibility to design dynamic GCSPR sensor benches that can be used to amplify the SPR angle shift at any step of a biological detection process.

Development of a complete plasmonic grating-based sensor and its application for self-assembled monolayer detection.

This work presents an integrated plasmonic biosensing device consisting of a one-dimensional metallic lamellar grating designed to exploit extraordinary transmission of light toward an underlying silicon photodetector. By means of finite element simulations, the grating parameters have been optimized to maximize the light transmission variation induced by the functionalization of the gold nanostructures. An optimized grating was fabricated using an electron beam process and an optoelectronic test bench suitable for sample tests was developed. A clear difference in the grating transmitted light due to surface functionalization was observed in presence of TM polarized illumination.

Analysis and improvement of organizational models for the management of patients with type 2 diabetes mellitus: a case study in north-east Italy.

PURPOSE: The study aimed to establish whether the organization for the management of type 2 diabetes mellitus at 9 diabetic units (DUs), in 5 neighboring local health authorities (LHAs), was able to (a) comply with the organizational model prescribed by specific regional standards; (b) ensure adequate clinical management of diabetic patients; (c) assess whether the relationship between primary care physicians (PCPs) and diabetologists (SDs) was instrumental to the needs of patients; (d) optimize specialist treatment at the DUs; (e) optimize drug management; and (f) check whether organizational changes led to variations in clinical results. METHODS: This 6-stage study analyzed procedures, precoded actions, and recordable processes. Stage (1) Defining clinical and organizational endpoints; (2) Drafting flowcharts to describe the actions and work procedures implemented within each LHA; (3) Comparing the flowcharts with the data obtained from related literature; (4) Establishing a protocol shared with PCPs for the management and treatment of patients with type 2 diabetes; (5) Changing the procedures at the DUs; and (6) Evaluating the results. The data were assessed before and after establishing a shared protocol for SDs and PCPs (year 2009 vs 2011). RESULTS: The study shows inconsistencies in the organization of work in the 5 LHAs; however, collaboration with PCPs has guaranteed: (a) unchanged hemoglobin A1C values before and after applying the protocol; (b) a percentage increase in the number of patients with type 2 diabetes who were identified thanks to these protocols; (c) an increase in the use of biguanides compared to the preprotocol period; and (d) no change in the number of patients hospitalized because of acute complications from type 2 diabetes mellitus. CONCLUSIONS: This study confirms how adequate collaboration between SDs and PCPs keeps the risk of complications stable. Nevertheless, shared protocols and clearly defined roles are required.

Nutritional intervention for amyotrophic lateral sclerosis.

AIM: The aim of the study was to assess the consequences of early and systematic nutritional intervention on the clinical conditions of amyotrophic lateral sclerosis (ALS) patients and on the opportunity to maintain a good nutritional status for as long as possible. METHODS: Thirty-three subjects with ALS. Protocol Group: 12 subjects (9 M and 3 F) monitored according to a precise nutritional intervention protocol. CONTROL GROUP: 21 subjects (10 M and 11 F) monitored before applying the protocol. RESULTS: Data recorded at the time of initial assessment were compared and expressed as the mean ± standard deviation for the Protocol Group vs. the CONTROL GROUP: BMI (kg/m2) 23.6 ± 4.1 vs. 21.6 ± 3.5; weight loss as a percentage of usual weight 6.6 ± 7.9 vs. 16.3 ± 8.8 (P=0.003). At six months: weight loss as a percentage of usual weight 4.9 ± 6.2 vs. 16.9 ± 10.2 (P=0.002). At 12 months: weight loss as a percentage of usual weight 7.3 ± 7.1 vs. 17.5 ± 11.1 (P=0.03). At the first follow-up visit, fewer patients in the Protocol Group were receiving enteral nutrition (25%) than patients in the CONTROL GROUP (60%). At six-month follow-up visit: 30% vs. 68%. Standard enteral nutrition formulas were used. One year after initial assessment, the mortality rate was 17% for the Protocol Group, whereas it was 24% at six months and 33% after one year for the CONTROL GROUP. CONCLUSION: If patients are treated before any significant weight loss occurs, early and specific nutritional intervention allows good nutritional status to be maintained for a longer period; if artificial nutrition is required, standard diets are able to ensure adequate clinical results.

A multicentre Phase II study of non-pegylated liposomal doxorubicin in combination with trastuzumab and docetaxel as first-line therapy in metastatic breast cancer.

To evaluate the cardiotoxicity, general toxicity, and activity of non-pegylated liposomal doxorubicin, in combination with docetaxel and trastuzumab, as first-line therapy in metastatic breast cancer. Thirty-one patients with metastatic human epidermal growth factor receptor 2-overexpressing breast cancer, who had not previously received chemotherapy for metastatic disease, received non-pegylated liposomal doxorubicin (50 mg/m(2)), docetaxel (75 mg/m(2)) and trastuzumab (2 mg/kg/week) for up to eight cycles, followed by trastuzumab alone for up to 52 weeks. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) to below 45%, or a decrease in LVEF of at least 20% from baseline. Mean LVEF was maintained at baseline level also in the subset of patients who had received anthracycline previously. Cardiotoxicity developed in three patients during the treatment cycles, and in two further patients after the end of the study. The most common adverse events were haematological toxicity, alopecia, asthenia and fever. The best overall response rate was 65.5%. Median time to progression was 13.0 months. The combination of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab combines acceptable cardiac and general toxicity and promising activity as first-line therapy in metastatic breast cancer.

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

ESPEN Guidelines on Parenteral Nutrition: on cardiology and pneumology.

Nutritional support is becoming a mainstay of the comprehensive therapeutic approach to patients with chronic diseases. Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are frequently associated with the progressive development of malnutrition, due to reduced energy intake, increased energy expenditure and impaired anabolism. Malnutrition and eventually cachexia have been shown to have a negative influence on the clinical course of CHF and COPD, and to impinge on patients' quality of life. Nutritional support in these patients should be therefore considered, particularly to prevent progressive weight loss, since restoration of lean and fat body mass may not be achievable. In CHF and COPD patients, the gastrointestinal tract is normally accessible and functioning. Although recent reports suggest that heart failure is associated with modifications of intestinal morphology, permeability and absorption, the clinical relevance of these are still not clear. Oral supplementation and enteral nutrition should represent the first choices when cardiopulmonary patients need nutritional support, particularly given the potential complications and economic burden of parenteral nutrition. This appropriately preferential enteral approach partly explains the lack of robust clinical trials of the role of parenteral nutrition in CHF and COPD patients. Based on the available evidence collected via PubMed, Medline, and SCOPUS searches, it is recommended that parenteral nutrition is reserved for those patients in whom malabsorption has been documented and in those in whom enteral nutrition has failed.

Space and time-resolved gene expression experiments on cultured mammalian cells by a single-cell electroporation microarray.

Single-cell experiments represent the next frontier for biochemical and gene expression research. Although bulk-scale methods averaging populations of cells have been traditionally used to investigate cellular behavior, they mask individual cell features and can lead to misleading or insufficient biological results. We report on a single-cell electroporation microarray enabling the transfection of pre-selected individual cells at different sites within the same culture (space-resolved), at arbitrarily chosen time points and even sequentially to the same cells (time-resolved). Delivery of impermeant molecules by single-cell electroporation was first proven to be finely tunable by acting on the electroporation protocol and then optimized for transfection of nucleic acids into Chinese Hamster Ovary (CHO-K1) cells. We focused on DNA oligonucleotides (ODNs), short interfering RNAs (siRNAs), and DNA plasmid vectors, thus providing a versatile and easy-to-use platform for time-resolved gene expression experiments in single mammalian cells.

[Organisational aspects of a donated breast milk bank: experience of the Treviso hospital]. / Aspetti organizzativi di una banca di latte umano donato: l'esperienza dell'Ospedale di Treviso.

AIM: This study analyses the organisational aspects and the volume of milk managed by the donated breast milk bank (banca del latte umano donato, BLUD) in Treviso. METHODS: The data gathered refer to the years 2003, 2004 and 2005. In particular the hygiene methodology is described in order to obtain a high-quality product from a clinical point of view which is in line with the recent norms regarding the management of food products. RESULTS: During the three-year study 5,647 L of milk were collected (on average: 155 L/month; 5 L/day). Seventy-two percent of breast milk collected was from mothers for their own children; the remaining 28% of milk was from ''donors for the pool''. In the same period 5,053 L of milk was pasteurised and distributed (pool=31%; frozen breast milk=61%; chilled unpasteurized breast milk =8%). Microbiological data show total effectiveness of the methods of pasteurisation used (Holder method). The tracking of the product is possible through the BLUD organisation. CONCLUSION: We propose: 1) that scientific organisations and legislators try to optimise the control of this important product by providing guidelines, indications, microbiological parameters and legal obligations for the correct continuation of the work carried out by BLUDs; 2) that BLUDs create a network for rapid communication, integration and possible collaboration; 3) that a study be carried out regarding BLUDs and population density in order to balance costs and benefits.

Biopsychosocial approach to home enteral nutrition: measure of subjective satisfaction and quality of life.

AIM: Home enteral nutrition (HEN) has become a therapeutic option used to prolong considerably the life of those patients who were previously doomed to malnutrition. The recent biopsychosocial suggests to consider the person in a global vision that takes into account not only the physiological but also the psychological and social implications of any treatment we use. In such a vision the wellness of the patients treated in HEN has to be considered in a more general view that considers the effect of the therapy related to quality of life of the person itself. In this study the effects of HEN on the quality of life of the patients and of their primary caregivers was assessed. METHODS: Twenty patients, 12 males and 8 females, were included in the study. Twelve patients were excluded from the study due to their inability to give informed consent due to a decrease in consciousness and/or cognitive functioning. The 20 patients' mean age was 59.5+14 years with average of 7 years of school education. Twenty-nine caregivers, 25 females and 4 males (mean age = 55.3+/-9 years), were also considered. RESULTS: The patients' condition was good since none showed symptoms related to the therapy. Of the 20 patients, 14 were hospitalized in the past 12 months and since their clinical conditions were stable they were sent back home, while 4 were hospitalized because of HEN issues. None of the patients showed gastro-enteric complications related to their disease state during the previous 12 months, although 5 patients had constipation, and 2 had temporary diarrhea (spontaneously receded) which reduced the infused caloric intake for 2-3 days from the symptom onset. CONCLUSIONS: The biopsychosocial approach we used in this study shows that aspects traditionally treated as ''positive'' and desirable by health-care professionals (i.e. the possibility to provide home care) do not have a straightforward correspondence in the emotional sphere of the patient undergoing HEN. On the contrary, in some cases, the subjective perception of the health related quality of life tends to be lower than expected, since the patient endures a treatment which appears to be essentially ineffective in modifying the prognosis of the basal disease.

Single-ion dosemeter based on floating gate memories.

Floating Gate (FG) nonvolatile memories are based on a tiny polysilicon layer (the FG) which can be permanently charged with electrons or holes, thus changing the threshold voltage of a MOSFET. Every time a FG is hit by a high energy ion, it experiences a charge loss, depending on the ion linear energy transfer (LET) and on the transistor geometrical and electrical characteristics. This paper discusses the opportunities to use this devices as single an ion dosemeter with sub-micrometer spatial resolution and capable of distinguish the impinging ion LET.

5-year prospective results of trimodality treatment for malignant pleural mesothelioma.

AIM: Even though followed by a prolonged survival in highly selected patients, the promising results of Sugarbaker's trimodality treatment for malignant pleural mesothelioma (MPM) are debated and not yet uniformly replicated. The purpose of this study is to evaluate prospectively the reproducibility of the trimodality treatment results in a patient population with mesothelioma staged by the IMIG classification. METHODS: Fifty-four patients with MPM have been judged candidable to extended pleuropneumonectomy (EPP), to be followed by chemotherapy (paclitaxel+carboplatin) and radiotherapy (50 Gy). RESULTS: At thoracotomy, 44 of the 54 surgical candidates (81%) underwent EPP; 73% of the operated patients completed the entire adjuvant chemo-radiotherapy with no major toxicity. The 30-day or in-hospital operative mortality rate was 4.5% (2 deaths), the major morbidity 36%, and the overall complication rate 50%. At 5 years the projected survival of the 42 surgical survivors submitted to EPP is 19%; median survival is 20 months. The restricted group of patients with epithelial, N0-1, completely resected MPM (microscopic negative margins) exhibits a projected 50% 5-year survival. Clinical understaging has shown up to be noticeable both at the thoracotomy exploration and pathology examination. Most of the disease recurrences are loco-regional and the current insufficiency of intraoperative or postsurgical radicality needs improvement, along with earlier diagnosis, more accurate staging, and preoperative induction for the multimodality treatment of pleural mesothelioma to become an established curative option. CONCLUSIONS: This series confirms the reproducibility of the trimodality treatment for MPM,which is associated with prolonged survival for early-stage tumors at the cost of a not prohibitive treatment-related mortality rate.

Sensitivity and dynamic range of FGMOS dosemeters.

UVPROM memory devices employing FGMOS transistors as memory cells make excellent dosemeters for applications involving ionising radiation. With proper preparation and programming, these devices can be used in remote-sensing applications in high-radiation environments with no power required during exposure.

A novel Shigella dysenteriae serovar isolated in Canada.

The etiological agent most commonly associated with bacillary dysentery is Shigella. As part of its mandate, the Bacteriology and Enteric Disease Program of Health Canada identifies and serotypes unusual isolates of Shigella received from provincial laboratories of public health. In this report, six unusual isolates from three provinces were analyzed biochemically and serologically using slide and tube agglutinations and molecularly using standard pulsed-filed gel electrophoresis (PFGE), PCR, and PCR-restriction fragment length polymorphism (RFLP) techniques. All six isolates were identical. PFGE analysis grouped these strains; biochemically, they were mannitol negative and consistent with the profile of Shigella. Serologically, these strains produced weak reactions in Shigella dysenteriae serovars 4 and 16 and Escherichia coli O159 and O173 antisera. Molecular serotyping by PCR-RFLP of the rfb gene produced an S. dysenteriae serovar 2/E. coli O112ac pattern. They were positive by PCR for ipaH and ial enteroinvasive genes but negative for all other genes tested. Antiserum was prepared from one of the isolates and tested against Shigella and E. coli reference strains as well as the other isolates. The antiserum reacted with the five remaining isolates and showed cross-reactivity with S. dysenteriae serovars 1, 4, and 16; Shigella flexneri type 3; and E. coli O118, O159, O168, O172, and O173 antigens. Absorbing the sera with E. coli O159 and S. dysenteriae serovar 4 antigen removed all cross-reactions and only slightly reduced the homologous titer. Based on biochemical, molecular, and complete serological analysis, we propose that these six isolates represent a new provisional serovar of S. dysenteriae, type strain BEDP 02-5104.