Unraveling the blue shift in porphyrin fluorescence in glioma: The 620 nm peak and its potential significance in tumor biology.

In glioma surgery, the low-density infiltration zone of tumors is difficult to detect by any means. While, for instance, 5-aminolevulinic acid (5-ALA)-induced fluorescence is a well-established surgical procedure for maximizing resection of malignant gliomas, a cell density in tumor tissue of 20-30% is needed to observe visual fluorescence. Hyperspectral imaging is a powerful technique for the optical characterization of brain tissue, which accommodates the complex spectral properties of gliomas. Thereby, knowledge about the signal source is essential to generate specific separation (unmixing) procedures for the different spectral characteristics of analytes and estimate compound abundances. It was stated that protoporphyrin IX (PpIX) fluorescence consists mainly of emission peaks at 634 nm (PpIX634) and 620 nm (PpIX620). However, other members of the substance group of porphyrins fluoresce similarly to PpIX due to their common tetrapyrrole core structure. While the PpIX634 signal has reliably been assigned to PpIX, it has not yet been analyzed if PpIX620 might result from a different porphyrin rather than being a second photo state of PpIX. We thus reviewed more than 200,000 spectra from various tumors measured in almost 600 biopsies of 130 patients. Insufficient consideration of autofluorescence led to artificial inflation of the PpIX620 peak in the past. Recently, five basis spectra (PpIX634, PpIX620, flavin, lipofuscin, and NADH) were described and incorporated into the analysis algorithm, which allowed more accurate unmixing of spectral abundances. We used the improved algorithm to investigate the PpIX620 signal more precisely and investigated coproporphyrin III (CpIII) fluorescence phantoms for spectral unmixing. Our findings show that the PpIX634 peak was the primary source of the 5-ALA-induced fluorescence. CpIII had a similar spectral characteristic to PpIX620. The supplementation of 5-ALA may trigger the increased production of porphyrins other than PpIX within the heme biosynthesis pathway, including that of CpIII. It is essential to correctly separate autofluorescence from the main PpIX634 peak to analyze the fluorescence signal. This article highlights the need for a comprehensive understanding of the spectral complexity in gliomas and suggests less significance of the 620 nm fluorescence peak for PpIX analysis and visualization.

A new microfluidic platform for the highly reproducible preparation of non-viral gene delivery complexes.

Transfection describes the delivery of exogenous nucleic acids (NAs) to cells utilizing non-viral means. In the last few decades, scientists have been doing their utmost to design ever more effective transfection reagents. These are eventually mixed with NAs to give rise to gene delivery complexes, which must undergo characterization, testing, and further refinement through the sequential reiteration of these steps. Unfortunately, although microfluidics offers distinct advantages over the canonical approaches to preparing particles, the systems available do not address the most frequent and practical quest for the simultaneous generation of multiple polymer-to-NA ratios (N/Ps). Herein, we developed a user-friendly microfluidic cartridge to repeatably prepare non-viral gene delivery particles and screen across a range of seven N/Ps at once or significant volumes of polyplexes at a given N/P. The microchip is equipped with a chaotic serial dilution generator for the automatic linear dilution of the polymer to the downstream area, which encompasses the NA divider to dispense equal amounts of DNA to the mixing area, enabling the formation of particles at seven N/Ps eventually collected in individual built-in tanks. This is the first example of a stand-alone microfluidic cartridge for the fast and repeatable preparation of non-viral gene delivery complexes at different N/Ps and their storage.

Remodeling an existing rare disease registry to be used in regulatory context: Lessons learned and recommendations.

Disease registries have been used as an interesting source of real-world data for supporting regulatory decision-making. In fact, drug studies based on registries cover pre-approval investigation, registry randomized clinical trials, and post-authorization studies. This opportunity has been investigated particularly for rare diseases-conditions affecting a small number of individuals worldwide-that represent a peculiar scenario. Several guidelines, concepts, suggestions, and laws are already available to support the design or improvement of a rare disease registry, opening the way for implementation of a registry capable of managing regulatory purposes. The present study aims to highlight the key stages performed for remodeling the existing Registry of Multiple Osteochondromas-REM into a tool consistent with EMA observations and recommendations, as well as to lead the readers through the entire adapting, remodeling, and optimizing process. The process included a variety of procedures that can be summarized into three closely related categories: semantic interoperability, data quality, and governance. At first, we strengthened interoperability within the REM registry by integrating ontologies and standards for proper data collection, in accordance with FAIR principles. Second, to increase data quality, we added additional parameters and domains and double-checked to limit human error to a bare minimum. Finally, we established two-level governance that has increased the visibility for the scientific community and for patients and carers. In conclusion, our remodeled REM registry fits with most of the scientific community's needs and indications, as well as the best techniques for providing real-world evidence for regulatory aspects.

Factors associated with pressure ulcer onset after knee replacement.

OBJECTIVE: The aim of this study was to find the rate of pressure ulcers (PUs) in patients with knee replacements and identify predictive factors. The ability of the Braden scale to predict the onset of PUs was also investigated. METHOD: A retrospective prognostic cohort study was carried out involving all consecutive patients undergoing knee replacement surgery. The data were collected from patient records. The variables collected were grouped into two categories: those connected to the patient's own characteristics; and those linked to the care methods used. RESULTS: The total number of patients included in the study was 565. Of these, 2.3% had developed a PU: 0.5% at the heel and 1.8% at the sacrum. Multivariate analysis showed that the variables actually correlated to the outcome were age (p=0.074; odds ratio (OR)=1.08), body mass index (BMI, p=0.037; OR=1.13) and Braden scale (p=0.029; OR=0.72). A combination of these three parameters showed better predictivity of PUs (area under the curve (AUC) 84%). CONCLUSION: Age, BMI and preoperative Braden score were shown to be independent predictive factors of the onset of PUs in patients with knee replacements. The combined use of all three variables increased the ability to identify the patients at most risk of developing a PU. DECLARATION OF INTEREST: The study was financed by the Professional Nurse Register of Bologna as winner of a competition for research projects in the province of Bologna. The authors declare no conflicts of interest.

One-year mortality after hip fracture surgery and prognostic factors: a prospective cohort study.

Older adult patients with hip fractures are 3-4 times more likely to die within one-year after surgery than general population. The study aimed to identify independent predictive factors associated with one-year mortality after hip fracture surgery. A prospective prognostic cohort study was performed. All patients aged ≥65 years, consecutively admitted in three Italian hospitals with a diagnosis of fragility hip fracture were included. Patients with periprosthetic or pathological fractures were excluded. Multivariate analysis was used to determine variables that significantly increased the risk of one-year mortality and Receiver operating characteristic (ROC) curve analysis to assess their predictive capacity on the outcome.1083 patients fulfilled the inclusion criteria and the one-year follow-up was reached in 728 patients. The 16.6% of patients died within one-year after surgery. At the multivariate analysis, advancing age (OR = 1.094, 95% CI = 1.057-1.132), higher baseline Charlson Index (OR = 1.257, 95% CI = 1.114-1.418) and Activities of Daily Living scores (OR = 1.259, 95% CI = 1.143-1.388), presence of hospital-acquired pressure ulcers (PUs) (OR = 1.579, 95% CI = 1.002-2.489) and lack recovery of ambulation (OR = 1.736, 95% CI = 1.115-2.703), were found to be independent predictive factors of one-year mortality after surgery. The area under the ROC curve of the model was 0.780 (CI95% 0.737-0.824) for one-year mortality in elderly hip fractures patients. Early ambulation and careful long-term follow-up, with attention to frailty in elderly people, should be promoted.

Predictive factors for category II pressure ulcers in older patients with hip fractures: a prospective study.

OBJECTIVE: To identify the incidence of category II or higher hospital-acquired pressure ulcers (HAPU) and significantly associated factors in older patients with hip fractures. PUs are a frequent complication in hip fracture patients, negatively impacting patients' quality of life, the health-care system and society. METHOD: A prospective cohort study was conducted. A consecutive sample of patients with pertrochanteric, femoral neck or subtrochanteric fractures requiring surgical treatment, were included. A stepwise, multiple regression was performed to identify factors associated with PU development. RESULTS: A total of 761 patients aged ≥65 years were sampled. The incidence of category II or higher PUs was 12%. The study identified five factors that were significantly, independently associated with category II or higher PU development, including a higher preoperative Braden score (Hazard Ratio [HR]: 0.884; 95% confidence interval [CI]: 0.806-0.969), surgical procedure with osteosynthesis (HR 1.876; 95%CI: 1.183-2.975), a higher percentage of days with the presence of foam valve before surgery (HR: 1.010; 95%CI: 1.010-1.023) and a urinary catheter (HR: 1.013; 95%CI: 1.006-1.019) and diaper (HR: 1.007; 95% CI 1.001-1.013) in the postoperative period. CONCLUSION: Attention should be given by clinical staff to avoiding the use of foam valves, to limiting the use of diapers and to early removal of urinary catheters.

Predictive factors for thirty day mortality in geriatric patients with hip fractures: a prospective study.

PURPOSE: The study aims to analyze the incidence of 30-day mortality in elderly patients who underwent surgery for hip fractures and its associated factors. METHODS: A prospective multicentric study was performed. All patients aged ≥ 65 years, with fragility hip fractures, consecutively admitted in two Italian hospitals were included. Patients with periprosthetic or pathological fractures were excluded. Logistic regression was used to identify patient and patient care variables that independently influenced the 30-day mortality and receiver operating characteristic (ROC) curve analysis to assess their predictive capacity on the outcome. RESULTS: Of the patients, 728 met the inclusion criteria, of whom approximately 5% died within 30 days after admission. The 45.7% of the deceased patients died while hospitalized. Multivariate analysis showed that advancing age was the only independent predictor of 30-day mortality (OR = 1.084, 95% CI = 1.024-1.147), while a higher presence of informal caregivers was a protective factor (OR = 0.988, 95% CI = 0.979-0.997). The area under the ROC curve of the model was 0.723 (CI95% 0.676-0.770) for 30-day mortality in elderly hip fractures patients. CONCLUSIONS: Patients with an advanced age need careful follow-up, especially within 30 days following operation for hip fracture; at the same time, the presence of informal caregivers at the patient's bedside should be promoted.

Prospective Prognostic Cohort Study of Pressure Injuries in Older Adult Patients with Hip Fractures.

OBJECTIVE: The aim of this study was to assess the rate of pressure injury and real predictors thereof in the older adult population with hip fractures in an orthopedic hospital. METHODS: In this prospective prognostic cohort study, all patients admitted with fragility hip fractures were monitored over a 12-month period. On a daily basis, ward nurses and physiotherapists assessed the condition of the patients' skin and collected data about all the predictors connected to their healthcare and hospital organization until the patients were discharged from hospital or until the onset of pressure injury. RESULTS: From October 1, 2013, to September 30, 2014, 467 older adult patients with fragility fractures were enrolled in the study. Of these, 27% (n = 127) developed a pressure injury. Multivariate analysis identified the following predictive factors: age older than 81 years, type of surgery, and placing the limb in a foam rubber splint. No other factor connected to the patient or medical, nursing, or rehabilitation treatment was significantly correlated to the onset of pressure injury, even when the univariate analysis showed some of them were possible predictors. CONCLUSIONS: Pressure injury in older adults with hip fractures is a relatively common complication, especially in high-risk patients or following certain treatments. These potential indicators could help provide safe and targeted care by preemptively identifying patients at highest risk of pressure injury.

Effectiveness of using a new polyurethane foam multi-layer dressing in the sacral area to prevent the onset of pressure ulcer in the elderly with hip fractures: A pragmatic randomised controlled trial.

Hip fractures in the elderly are a serious problem for the health service due to the high rate of complications. One of these complications is pressure ulcers that, according to the literature, occur in 8.8% to 55% of patients and mainly arise in the sacral area. The present randomised controlled trial tests whether applying a new innovative multi-layer polyurethane foam dressing (ALLEVYN LIFE™), reduces the onset of pressure ulcers in the sacral area. From March to December 2016, 359 fragility hip fracture patients were randomly divided into 2 groups: 182 in the control group and 177 in the experimental group. Pressure ulcers occurred overall in 36 patients (10%): 8 patients (4.5%) in the experimental group compared to 28 (15.4%) in the control group: P = 0.001, relative risk 0.29 (95% CI 0.14-0.61) with NNT of 9 (95% CI 6-21). In the experimental group the onset of pressure ulcers occurred on average on the 6th day compared to the 4th day in the control group (HR 4.4). Using polyurethane foam is effective at reducing the rate of pressure ulcers in the sacrum in elderly patients with hip fracture. The adhesiveness of this device also enables costs to be kept down.

Predictive Factors for Pressure Ulcers in an Older Adult Population Hospitalized for Hip Fractures: A Prognostic Cohort Study.

BACKGROUND: Older adult patients with fragility hip fractures constitute a population at high risk for complications, in particular pressure ulcers. The aim was to evaluate the incidence of pressure ulcers and potential predictive factors. METHODS AND FINDINGS: A prospective multicentric prognostic cohort study in orthopedic wards in three Italian public hospitals. Participants were all consecutive patients 65 years of age or older diagnosed with a fragility hip fracture. Outcomes were incidence of pressure ulcers. The exposure variables were grouped into three macro areas in order to facilitate reading: "intrinsic" variables, "extrinsic" variables and variables linked to the organization of patient care. One thousand eighty-three older adult patients with fragility hip fractures were enrolled from October 1st, 2013 to January 31st, 2015, and pressure ulcers developed in 22.7%. At multivariate analysis, the following were found to be risk factors: age> 80 years (odds ratio (OR) 1.03; p = 0.015), the length of time a urinary catheter was used (OR 1.013; p<0.001), the length of time pain was present (OR 1.008; p = 0.008), the absence of side rails on the bed (OR 1.668; p = 0.026) and the use of a foam position valve (OR 1.025; p<0.001). Instead, the protective factors were the presence of a caregiver for at least half a day daily (OR 0.994; p = 0.012) and the number of positionings during the postoperative period (OR 0.897; p = 0.008). CONCLUSIONS: The study allowed the identification of the patients most at risk for developing pressure ulcers, and the construction of a pragmatic predictive model using significant risk or protective factors in order to reduce the number of pressure ulcers.

Use of sodium hypochlorite for skin antisepsis before inserting a peripheral venous catheter: a pilot study.

Although it can be prevented, catheter-related bacteremia is common and dangerous. The antiseptics most widely used during insertion of peripheral venous catheters (PVCs) include povidone iodine, alcohol, and chlorhexidine. Another widely used antiseptic is a solution of 0.057 g sodium hypochlorite. This pilot study explored the contamination rate of the PVC tip inserted after skin decontamination with sodium hypochlorite. Culture analysis of the tips of the PVCs inserted into the 42 participants showed 7 (16.7%) colonized catheters. The results of this pilot study suggest taking into serious consideration the assessment of this antiseptic in randomized experimental studies.

[The assessment of the impact of education and support to nursing research on nurses' scientific production in an Emilia Romagna Hospital]. / Valutazione dell'impatto della formazione e del supporto alla ricerca infermieristica sulla produttività scientifica in un ospedale dell'Emilia Romagna.

INTRODUCTION: In Italy research conducted by non medical professions is scarce also for the lack of knowledge on methods. At Rizzoli hospital in Bologna in 2006 a Centre for research to educate and support health professionals was implemented. AIM: To assess the impact of the research centre on number of research articles and protocols produced by nurses. METHODS: Interrupted time series. In the five years before and after the implementation of the centre data on the number of protocols approved by Ethical Committee with a nurse as principal investigator and on the number of articles published on impacted journals with a nurse as first author were collected. The number of nurses authors of the publications was also collected. RESULTS: For all the variables an increasing trend, starting from 2006 was observed, with statistically significant differences from 2008 for the number of research protocols presented (p=0.037), the number of nurses authors of scientific articles (p=0.027). Although the number of publications on impacted journals increased from 2006, differences were not statistically significant after 2008. CONCLUSIONS: An hospital based Centre for education and support to research for health professionals may facilitate the scientific and research production.

[Skin antisepsis with 0.05% sodium hypochlorite before the insertion of a peripheral venous catheter in adults, children and newborns]. / Utilizzo dell'ipoclorito di sodio 0.05% soluzione cutanea nella antisepsi della cute prima dell'inserimento del catetere venoso periferico in adulti, bambini e neonati.

INTRODUCTION: Antisepsis of the skin of adults, children and newborns before the insertion of a peripheral venous catheter (PVC) reduces the risk of catheter related infections (CRI). Data on the effectiveness of electrolytic sodium hypochlorite are missing. METHODS: An explorative study was conducted on children, adults and newborns admitted to hospital and with skin antisepsis with sodium hypoclorite 0.057g with active chlorine 0.055g in 100ml (Amukine Med®) to assess the level of contamination of PVC tips, as surrogate sign of infection. Quantitative methods were used and the catheter tip was considered colonized if >1000 CFU (colony forming Units)/catheter segment. RESULTS: In the sample of 42 adults, 51 children and 52 newborns, 16.7%, 7.8% and 3.8% of catheter tips were contaminated respectively. No catheter related phlebites were observed. CONCLUSIONS: Skin antisepsis with Amukine Med® seems effective in preventing CRIs but further comparative studies are needed with the antiseptics recommended by guidelines.

[Effectiveness of the transparent sterile dressing vs standard to fix the peripheral venous catheter (PVC) on the incidence of phlebitis. A randomized controlled trial]. / Efficacia della medicazione sterile trasparente rispetto a quella standard per il fissaggio del catetere venoso periferico (CVP) sull'incidenza delle flebiti.Trial randomizzato e controllato.

UNLABELLED: Effectiveness of the transparent sterile dressing vs standard to fix the peripheral venous catheter (PVC), on the incidence of phlebitis. A randomized controlled trial. INTRODUCTION: The type of dressing could contribute to the incidence of phlebitis, infiltration and accidental removals but the results of the studies are contrasting and samples are limited. AIM: To compare the effectiveness of a transparent polyurethane sterile dressing on the rate of phlebitis associated to peripheral venous catheter (PVC) vs a non sterile sticking plaster in use in current practice (standard dressing). DESIGN: Randomized controlled trial. Participants. 1061 PVCs (703 patients, adults and children) at a research orthopedic hospital in the north of Italy; 540 PVCs allocated to receive the sterile and 521 the standard dressing. RESULTS: 96 PVCs were excluded for phlebitis, 48 (9.6%) in the sterile and 48 (10.1%) in the standard dressing group, RR 0.96 (95%CI 0.697 - 1.335). Accidental removal of the PVCs was more frequent with the sterile dressing (9.6% vs 6.3%) but the number of catheters removed without complications was larger in the standard dressing group (48.9% vs 54.9% P=0.0503). Eighty-five PVCs were replaced for detachment of the dressing (50, 9.2% sterile and 35, 6.7% standard dressing). The cheapest transparent sterile dressing costs 32 cents while the standard 9 cents. CONCLUSIONS: A sticking non sterile plasters is not influential on the rate of phlebitis and ensures an good fix of the PVC compared the transparent sterile dressing to of polyurethane film.

[Cohort study of peripheral catheter related complications and identification of predictive factors in a population of orthopedic patients]. / Studio di coorte sulla popolazione ortopedica delle complicanze correlate all'utilizzo del catetere venoso periferico e identificazione dei fattori predittivi.

INTRODUCTION: Peripheral venous catheters (PVC) may cause complications, specifically local. Their management varies across health care workers and wards, and guidelines recommendations are often weak and based on experts' opinion. AIM: To measure the incidence of PVCs phlebitis, occlusions, accidental removal and infiltrations and their predictive factors in an orthopedic population. METHODS: From may 4 2009 to 30, in an orthopedic hospital, data on patients to whom a PVC was inserted were collected: patient's and PVC characteristics, management and securing strategies, until one of the following outcomes: phlebitis, occlusion, accidental removal, infiltration or end of treatment. RESULTS: Overall, 873 patients were recruited and 139 PVCs. The following complications occurred: phlebitis 10.9%; occlusions 16.8%; accidental removals 5.8%, local infiltrations 14.4%; 648 PVCs (46.5%) were removed without complications. The risk for all complications (multivariate analysis) increased with age and for the other complications also with the administration of blood transfusions thorough PVC, irritant drugs and use >3 times/day for phlebitis; small gauge, not using PVC and surgical site infections for occlusions; positioning the PVC in the hand and fixing the PVC with the Chevron method for accidental removals; and female sex, transfusions and thromboembolic therapy for infiltrations. CONCLUSIONS: The incidence of phlebitis is high compared to the gold standard of 5%. Knowing the incidence of main complications is a requirement for any improvement strategy and may favor the abandonment of useless or dangerous practices.