Outcome measures for chronic rhinosinusitis with nasal polyps.

BACKGROUND: With the recent proliferation of novel therapeutics for chronic rhinosinusitis with nasal polyps (CRSwNP), there is an immediate need for comprehensive means to assess CRSwNP disease status as well as to determine treatment efficacy. Outcome measures exist in different forms. Patient-reported outcome measures (PROMs) allow patients to provide direct input about their condition that is not possible to obtain in any other way. Common constructs that are measured using PROMs include quality of life or the burden of disease manifestations (e.g., symptom severity). Outcomes may also include the results of objective diagnostic testing/measurement of clinical signs or measured using psychophysical tests. Biomarkers represent an emerging class of outcome measures for CRSwNP and are chosen to directly reflect the active pathophysiologic processes of CRSwNP in the peripheral blood, sinus/polyp tissues, and sinonasal mucus. METHODS: Narrative review of the literature, identifying and describing outcome measures that may be used in the evaluation of CRSwNP and for assessment of treatment responses. RESULTS: In this review, we identify many different outcome measures for CRSwNP that fall under the categories of PROM, objective test, psychophysical test or biomarker. We describe the history of each - including seminal studies - and demonstrate the formal validation, psychometric performance, and limitations of each. CONCLUSIONS: PROMs, objective tests, psychophysical tests and biomarkers represent different classes of outcome measures that are complementary means of assessing CRSwNP disease status and treatment efficacy. The choice or interpretation of a CRSwNP outcome measure should be undertaken with full knowledge of its formal validation, psychometric performance, and limitations.

Effect of Periodontitis and Periodontal Therapy on Oral and Gut Microbiota.

Mounting evidence indicates that periodontitis-related oral bacteria may contribute to gut microbial dysbiosis. This clinical study aimed to explore the oral-gut microbial signatures associated with periodontitis and to longitudinally evaluate the effect of periodontal treatment on the oral and gut microbial composition. Stool and saliva samples from generalized stage III/IV periodontitis patients (n = 47) were collected and analyzed by 16S ribosomal RNA gene amplicon sequencing, before and 3 mo after steps I to II of periodontal therapy. Periodontally healthy matched subjects (n = 47) were used as controls. Principal component analysis was carried out to identify oral-gut microbial profiles between periodontitis patients at baseline and healthy subjects; periodontitis samples were longitudinally compared before and after treatment. ß-Diversity of gut microbial profiles of periodontitis patients before treatment significantly differed from healthy controls (P < 0.001). Periodontal therapy was associated with a significant change in gut microbiota (P < 0.001), with post-treatment microbial profiles similar to healthy volunteers. A higher abundance of Bacteroides, Faecalibacterium, Fusobacterium, and Lachnospiraceae was noted in fecal samples of periodontitis patients at baseline compared to healthy controls. In contrast, Lactobacillus was the only genus more abundant in the latter. Additionally, periodontal therapy led to a parallel reduction in the salivary carriage of periodontal pathobionts, as well as gut Bacteroides, Lachnoclostridium, Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae, to levels similar to healthy controls. Collectively, discriminating oral-gut microbial signatures of periodontitis were found. Periodontal treatment both mitigated oral dysbiosis and altered gut microbial composition, signifying potential broader implications for gastrointestinal health and disease.

Sensitivity of a mini-TEPC to radiation quality variations in clinical proton beams.

PURPOSE: This work aims at studying the sensitivity of a miniaturized Tissue-Equivalent Proportional Counter to variations of beam quality in clinical radiation fields, to further investigate its performances as radiation quality monitor. METHODS: Measurements were taken at the CATANA facility (INFN-LNS, Catania, Italy), in a monoenergetic and an energy-modulated proton beam with the same initial energy of 62 MeV. PMMA layers were placed in front of the detector to measure at different depths along the depth-dose profile. The frequency- and dose-mean lineal energy were compared to the track- and dose-averaged LET calculated by Monte Carlo simulations. A microdosimetric evaluation of the Relative Biological Effectiveness (RBE) was performed and compared with cell survival experiments. RESULTS: Microdosimetric distributions measured at identical depths in the two beams show spectral differences reflecting their different radiation quality. Discrepancies are most evident at depths corresponding to the Spread-Out Bragg Peak, while spectra at the entrance and in the dose fall-off regions are similar. This can be explained by the different energy components that compose the pristine and spread-out peaks at each depth. The trend of microdosimetric mean values matches that of calculated LET averages along the entire penetration depth, and the microdosimetric estimation of RBE is consistent with radiobiological data not only at 2 Gy but also at lower dose levels, such as those absorbed by healthy tissues. CONCLUSIONS: The mini-TEPC is sensitive to differences in radiation quality resulting from different modulations of the proton beam, confirming its potential for beam quality monitoring in proton therapy.

Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Microleakage and mechanical behavior of conical vs. internal hexagon implant-abutment connection under a cyclic load fatigue test.

OBJECTIVE: The aim of the present investigation was to evaluate, by an in vitro simulation, the mechanical behavior of the conical vs. internal hexagon under cyclic load and the microleakage of the prosthetic connection of the fixture. MATERIALS AND METHODS: A standardized cyclic loading was performed considering the implant with conical connection (diameter 4 mm - length 10 mm) (CS) and internal hexagon connection (diameter 4 mm - length 10 mm) (IH). The toluidine blue infiltration has been evaluated with the paper cone test. RESULTS: After a total of 5x104 loads, the screw has been removed and the abutment appears solid and stable to the implant fixture for CS, while the IH was unstable. There was no infiltration of the toluidine marker in the connection interfaces of CS implants, while the IH was positive to the paper cone test. CONCLUSIONS: The study data showed that the conical connection showed higher stability compared to the internal hexagon connection under the loading and it is able to prevent bacterial microleakage. This effectiveness should be considered for the long-term maintenance of the peri-implant soft and hard tissues around the fixture.

Safety of nurse-directed triage intranasal fentanyl protocol for acute pain management in a European pediatric emergency department: A retrospective observational analysis.

Background: Nurse-directed pain protocols for intranasal fentanyl administration are not widely implemented in European (EU) pediatric emergency departments (PED). Barriers include perceived safety concerns for intranasal (IN) fentanyl. The aim of this study is to describe our experience with a nurse-directed triage IN fentanyl protocol with a focus on safety in a tertiary EU PED. Methods: We conducted a retrospective analysis of patient records of children aged 0-16 years who received nurse-directed IN fentanyl between January 2019 and December 2021 at the PED of the University Children's Hospital of Bern, Switzerland. Extracted data points included demographics, presenting complaint, pain score, IN fentanyl dosage, concomitant pain medication use, and adverse events. Results: A total of 314 patients were identified with ages ranging from 9 months to 15 years. The main indication for nurse-directed fentanyl administration was musculoskeletal pain due to trauma (n = 284, 90%). Mild adverse events (vertigo) were reported in two patients (0.6%), without a correlation to concomitant pain medication or protocol violation. The only reported severe adverse event of syncope and hypoxia in a 14-year-old adolescent occurred in a setting where the institutional nurse-directed protocol was violated. Conclusion: In accordance with previous studies outside of Europe, our data support the case that when appropriately used, nurse-directed IN fentanyl is a safe potent opioid analgesic for pediatric acute pain management. We strongly encourage the introduction of nurse-directed triage fentanyl protocols Europe-wide in order to provide effective and adequate acute pain management in children.

Quantifying virtual self-motion sensations induced by galvanic vestibular stimulation.

BACKGROUND: The vestibular system provides a comprehensive estimate of self-motion in 3D space. Widely used to artificially stimulate the vestibular system, binaural-bipolar square-wave Galvanic Vestibular Stimulation (GVS) elicits a virtual sensation of roll rotation. Postural responses to GVS have been clearly delineated, however quantifying the perceived virtual rotation vector has not been fully realised. OBJECTIVE: We aimed to quantify the perceived virtual roll rotation vector elicited by GVS using a psychophysical approach on a 3D turntable. METHODS: Participants were placed supine on the 3D turntable and rotated around the naso-occipital axis while supine and received square-wave binaural-bipolar GVS or sham stimulation. GVS amplitudes and intensities were systematically manipulated. The turntable motion profile consisted of a velocity step of 20°/s2 until the trial velocity between 0-20°/s was reached, followed by a 1°/s ramp until the end of the trial. In a psychophysical adaptive staircase procedure, we systematically varied the roll velocity to identify the exact velocity that cancelled the perceived roll sensation induced by GVS. RESULTS: Participants perceived a virtual roll rotation towards the cathode of approximately 2°/s velocity for 1 mA GVS and 6°/s velocity for 2.5 mA GVS. The observed values were stable across repetitions. CONCLUSIONS: Our results quantify for the first time the perceived virtual roll rotations induced by binaural-bipolar square-wave GVS. Importantly, estimates were based on perceptual judgements, in the absence of motor or postural responses and in a head orientation where the GVS-induced roll sensation did not interact with the perceived direction of gravity. This is an important step towards applications of GVS in different settings, including sensory substitution or Virtual Reality.

Age, gender and degree of inclusion are predictors of timing for spontaneous repositioning of intruded primary teeth in pre-school children.

AIM: To investigate the timing for spontaneous repositioning of primary teeth with intrusive luxation in relation to degree of inclusion, gender and age of injured children. METHODS: This retrospective study analysed records of 1- to 6-year-old children referred to the Section of Paediatric Dentistry, C.I.R. Dental School, University of Turin (Italy) between January 2009 and December 2020 for traumatic intrusion of primary teeth. Time to the total re-eruption was calculated, and related factors were explored using Cox and Kaplan-Meier analyses. CONCLUSION: Timing for spontaneous re-eruption seems to be associated to age, particularly as far as total intrusion of primary teeth is concerned. This observation could be related to the degree of bone mineralisation, which is modified during growth.

Application of a portable primary standard level graphite calorimeter for absolute dosimetry in a clinical low-energy passively scattered proton beam.

Objective. A calibration service based on a primary standard calorimeter for the direct determination of absorbed dose for proton beams does not exist. A new Code of Practice (CoP) for reference dosimetry of proton beams is being developed by a working party of the UK Institute of Physics and Engineering in Medicine (IPEM), which will recommend that ionisation chambers are calibrated directly in their clinical beams against the proposed Primary Standard Proton Calorimeter (PSPC) developed at the National Physical Laboratory (NPL). The aim of this work is to report on the use of the NPL PSPC to directly calibrate ionisation chambers in a low-energy passively scattered proton beam following recommendations of the upcoming IPEM CoP.Approach. A comparison between the dose derived using the proposed IPEM CoP and the IAEA TRS-398 protocol was performed, andkQvalues were determined experimentally for three types of chambers. In total, 9 plane-parallel and 3 cylindrical chambers were calibrated using the two protocols for two separate visits.Main results. The ratio of absorbed dose to water obtained with the PSPC and with ionisation chambers applying TRS-398 varied between 0.98 and 1.00, depending on the chamber type. The new procedure based on the PSPC provides a significant improvement in uncertainty where absorbed dose to water measured with a user chamber is reported with an uncertainty of 0.9% (1σ), whereas the TRS-398 protocol reports an uncertainty of 2.0% and 2.3% (1σ) for cylindrical and plane-parallel chambers, respectively. ThekQvalues found agree within uncertainties with those from TRS-398 and Monte Carlo calculations.Significance. The establishment of a primary standard calorimeter for the determination of absorbed dose in proton beams combined with the introduction of the associated calibration service following the IPEM recommendations will reduce the uncertainty and improve consistency in the dose delivered to patients.

Impairment of salivary function in juvenile idiopathic oligoarticular arthritis is a sign of early onset disease.

AIM: Recent evidences of the presence of reduced stimulated salivary flow rate and altered saliva composition in oligoarticular juvenile idiopathic arthritis (o-JIA) suggest a specific damage to the salivary glands. The aim of this cross-sectional study was to investigate whether reduced salivary flow rate could be related to age and gender at disease onset in o-JIA. METHODS: A total of 57 Caucasian patients (41 females and 16 males) aged 5 to 16 years affected by o-JIA were consecutively enrolled in the study. Information on medication intake, dietary and oral hygiene habits were gathered through a standardised questionnaire. All patients underwent oral and sialometry examination. CONCLUSION: Early onset disease would seem to be associated with salivary glands impairment. Regular dental and salivary gland function assessments may be highly recommended in o-JIA patients considering that saliva collection is a non-invasive and inexpensive procedure.

Long-term effect of anticancer therapy on dentition of Italian children in remission from malignant disease: A cross-sectional study.

AIM: To investigate the effects of anticancer therapy on dental development and caries formation in Italian childhood cancer survivors compared to healthy controls. METHODS: A total of 52 children treated with chemotherapy and/or radiotherapy when younger than 10 years and in remission from at least 2 years, and 52 healthy age- and gender-matched children were consecutively enrolled in this cross-sectional study. All participants were examined for dental caries and enamel defects according to the decayed-missing-filled teeth (dmft/DMFT) index and the Aine rating scale. Panoramic radiographs were taken to estimate dental age and to assess dental abnormalities using the Höltta Defect Index. CONCLUSION: These children are at high risk for tooth developmental abnormalities and poor dental health and should be closely monitored by a specialist dentist.

Total parenteral nutrition is associated with worse hospital outcomes among elderly diabetic patients: a propensity score matched analysis on discharge records.

Background: Recent trials and reviews have raised question about the safety of total parenteral nutrition (TPN), due to the increased rate of TPN related complications. Diabetic patients are vulnerable to hyperglycaemia, and poor studies have investigated hospital out-comes of diabetic patients requiring TPN. The aim of this study was to evaluate the association of in-hospital mortality, prolonged length of stay and transfer to long-term care facilities among diabetic patients with TPN. Methods: The study considered all hospital admissions of diabetic patients over 65 years of age performed between 2006 and 2015 in Abruzzo Region, Italy. To compare the outcomes of TPN and non-TPN patients, a propensity score matching procedure was performed. Results: A total of 140,556 admissions were analyzed. After matching, 1947 patients were included into the analyses: 649 patients with TPN and 1298 controls. TPN was significantly associated to in-hospital mortality (OR=7.15; 95%CI 5.54-9.22), prolonged LOS (OR=2.78; 95%CI 2.28-3.38) and transfer to LTCF (OR=2.16; 95%CI 1.64-2.85). Discussion: TPN is associated with poor outcomes among elderly diabetic patients in the Italian setting. Being aware of the risk factors among diabetic patients with TPN can be used to anticipate the patients' needs during the admission and the immediate post-discharge period.

Cystic lung diseases: radiological aspects.

Cystic lung diseases (CLDs) are a heterogeneous group of pathophysiological entities comprising gas-filled lesions with imperceptible walls, which can occur throughout lung parenchyma. CLDs can arise from different mechanisms and may often have an unpredictable progression. As CLDs are infrequent and may be associated to many different processes, they pose a diagnostic challenge to the radiologist and referring physician. CLDs require a comprehensive diagnostic approach. An essential tool in the evaluation of CLDs is high-resolution computed tomography (HRCT). The first step is in distinction from true cysts, from other cysts mimicking entities, as emphysema, honeycombing, pneumatocoele, cavitate nodules, or bronchiectasis. Thereafter the identification of number, distribution, wall size, and other systemic manifestations provides an accurate characterisation of CLD, often avoiding further evaluation with lung biopsy. Features of pulmonary lucencies, classification of CLDs based on pathophysiological mechanisms, and radiological criteria, the less common aetiologies, and a multidisciplinary approach in pulmonary cysts are reported. Finally, a systematic diagnostic algorithm to guide radiologists in the evaluation of CLDs is discussed.

Determination of beam quality correction factors for the Roos plane-parallel ionisation chamber exposed to very high energy electron (VHEE) beams using Geant4.

Detailed characterisation of the Roos secondary standard plane-parallel ionisation chamber has been conducted in a novel 200 MeV Very High Energy Electron (VHEE) beam with reference to the standard 12 MeV electron calibration beam used in our experimental work. Stopping-power-ratios and perturbation factors have been determined for both beams and used to calculated the beam quality correction factor using the Geant4 general purpose MC code. These factors have been calculated for a variety of charged particle transport parameters available in Geant4 which were found to pass the Fano cavity test. Stopping-power-ratios for the 12 MeV electron calibration beam quality were found to agree within uncertainties to that quoted by current dosimetry protocols. Perturbation factors were found to vary by up-to 4% for the calibration beam depending on the parameter configuration, compared with only 0.8% for the VHEE beam. Beam quality correction factors were found to describe an approximately 10% lower dose than would be originally calculated if a beam quality correction were not accounted for. Moreover, results presented here largely resolve unphysical chamber measurements, such as collection efficiencies greater than 100%, and assist in the accurate determination of absorbed dose and ion recombination in secondary standard ionisation chambers.

The neutrophil/lymphocyte ratio as a prognostic factor in COVID-19 patients: a case-control study.

OBJECTIVE: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been identified in China as responsible for viral pneumonia, now called COVID-19 (Coronavirus Disease 2019). Patients infected can develop common symptoms like cough and sore throat, and, in severe cases, acute respiratory syndrome and even death. To optimize the available resources, it is necessary to identify in advance the subjects that will develop a more serious illness, therefore requiring intensive care.The neutrophil / lymphocyte ratio (NLR) parameter, resulting from the blood count, could be a significant marker for the diagnosis and management of risk stratification. PATIENTS AND METHODS: A retrospective, single-center case-control observational study was conducted. The differential cell count of leukocytes, the NLR and the clinical course of patients hospitalized in intensive care with COVID-19 were analyzed, comparing them with other patients (COVID-19 and non-COVID-19) and healthy individuals selected among workers of the Teaching Hospital Policlinico Umberto I in Rome. RESULTS: 370 patients (145 cases and 225 controls) were included in the case-control study, 211 males (57%) and 159 females (43%). The average age of the population was 63 years (SD 16.35). In the group of cases, out of 145 patients, 57 deaths and 88 survivors were recorded, with a lethality rate of 39.3%. The group of cases has an NLR of 7.83 (SD = 8.07), a much higher value than the control group where an NLR of 2.58 was recorded (SD = 1.93) (p <0.001). The Neutrophils / Lymphocytes ratio may prove to be a diagnostic factor for COVID-19, an NLR> 3.68 revealed an OR 10.84 (95% CI = 6.47 - 18.13) (p <0.005). CONCLUSIONS: The value of NLR considered together with the age variable allows a risk stratification and allows the development of diagnostic and treatment protocols for patients affected by COVID-19. A high neutrophil to lymphocyte ratio suggests worse survival. Risk stratification and management help alleviate the shortage of medical resources and reduce the mortality of critically ill patients.

Predictors of Prolonged Hospitalization and In-Hospital Mortality After Hip Fracture: A Retrospective Study on Discharge Registry.

Background: Hip fracture injury is one of the principal health problems affecting the elderly. Patients reporting hip fractures often show relevant comorbidities leading to prolonged hospital stay, significant complications and higher mortality rates. This study aims to assess the risk factors associated with prolonged hospitalization after hip fracture, in-hospital mortality and transfers to other facilities. Study design: Retrospective cross-sectional study. Methods: The study considered all admissions performed between 2006 and 2015 in Abruzzo region, Italy. Logistic regression analyses were performed to evaluate odds ratios for each risk factor as predictor of in-hospital mortality, length of stay, and transfer to other facilities. Results: Age over 85 (OR=5.38) and cancer (OR=3.62) were identified as the strongest risk predictors for in hospital mortality; diabetes (OR=2.24) and heart failure (OR=1.57) were identified as predictors of prolonged length of stay and age over 85 (OR=1.38) and atrial fibrillation (OR=1.69) were identified as predictors of transfer to other facilities. Conclusions: With the rising incidence of hip fractures, identification of modifiable factors may help to reduce morbidity and mortality.

Fatal acute lung injury after balloon valvuloplasty in a dog with pulmonary stenosis.

A one-year-old French Bulldog was referred for the management of a severe form of pulmonary valve stenosis (PS) complicated by right-sided congestive heart failure. Echocardiography showed severe valvular PS with right ventricular concentric hypertrophy, dilatation and severe right atrial enlargement. A pulmonary balloon valvuloplasty (PBV) was performed with a balloon-to-pulmonary annulus ratio of 1.36. Echocardiography immediately after PBV showed a significant reduction in right atrial and ventricular size, improved opening and mobility of the pulmonary valve leaflets, and a 75% reduction in the pulmonary pressure gradient from 158 mmHg pre-operative to 40 mmHg post-operative. The dog recovered well from anesthesia, but 2 h later, it suddenly showed severe respiratory distress. Focus cardiac ultrasound showed increased left cardiac size with echocardiographic signs of high left ventricular filling pressure. Bedside lung ultrasound showed diffuse numerous-to-confluent B lines, compatible with a severe alveolar-interstitial syndrome. The dog was treated with furosemide, helmet continuous positive airway pressure, and then mechanical ventilation but without success. At post-mortem evaluation, histological examination of the lung showed diffuse, severe broncho-alveolar edema with mixed leukocyte, fibrin, and red blood cell infiltrate. Moreover, severe congestion and multifocal alveolar hemorrhages were evident. All findings were compatible with fatal acute lung injury after PBV secondary to pulmonary reperfusion-ischemia injury and increased pulmonary capillary hydrostatic pressure. Based on the present case, acute lung injury should be considered as a rare but serious complication of PBV.