Local Ethics Committee Research Articles

BN O05 - Physiological Transit Assessment of the Oesophagus In Patients With Anti-Reflux Surgery

Abstract Background High-resolution manometry (HRM) is the gold-standard investigation for oesophageal motility in patients with dysphagia. The HRM findings may influence surgical decision for myotomy or anti-reflux surgery (ARS). However, HRM pitfall is the inability to measure oesophageal transit in parallel to the motility during physiology testing. Both transit and motility are complementary that offer insights in the pathophysiology and aetiology of the dysphagia symptoms. This research evaluates the multichannel intraoesophageal impedance transit (MIIT) concept [1] to assess the oesophageal transit in symptomatic patients who undertook the postoperative oesophageal physiology testing between January 2020 and June 2024. Method This cross-sectional retrospective study selected patients with intact Nissen fundoplication (NF) wrap on gastroscopy or with known LINX implant in-situ. HRM with Chicago Classification (version 4.0)[2] compared the ARS cases with augmented antireflux barrier [AARB] from the surgery to healthy treatment naïve controls. The multichannel impedance-pH studies assessed both reflux and the MIIT [1]. MIIT >0.76 minutes were considered positive and comparable to GOJ outflow obstruction [1]. This project was approved by the NHS institution and the local research ethics committee (REC 18/NW/0120)(IRAS 333800). Results 60 patients were found (NF 54, LINX implant 6)(females 30, mean age 51.3 years). 11 patients(18.3%) had pathological reflux despite ARS(DeMeester scores >14.72); 2 patients (18.2%) demonstrated hypotensive AARB. Conversely, 6 patients(10%) showed poor relaxation from the AARB and were compatible to outflow obstruction (5 patients [83.3%] showed conformation with MIIT >0.76 minutes). Patients with ineffective oesophagus (20%) and absent contractility(11.7%) showed MIIT >0.76 minutes in respectively two-thirds with ineffective oesophagus and in all patients with absent contractility. Normal HRM study was observed in 35 patients (58.3%) with 27 patients (77.1%) demonstrating MIIT >0.76 minutes. Conclusion MIIT was able to explain the post-surgical dysphagia in majority of patients from the equivalent transit to outflow obstruction (n=52 patients, 86.7%). Half of these cases had a normal HRM study and would have been perceived as having functional dysphagia. We would recommend performing MIIT adjunctive testing as part of postoperative oesophageal physiology assessment in symptomatic patients. Incidentally, we observed 16 patients (26.7%) having hypotensive AARB post ARS comparing to healthy treatment naïve controls with 2 patients (12.5%) having persistent pathological reflux who may still benefit from surgical revision.

BN SO18 - Considering Physiology Surveillance in Patients with Oesophageal Atresia

Abstract Background Oesophageal atresia (OA) is a congenital malformation found between one in every 2,400 to 4,500 new-borns per year world-wide [1] who require immediate oesophageal surgery and lifelong endoscopic surveillance for complications of gastroesophageal reflux, oesophagitis, Barrett's oesophagus, anastomotic strictures, oesophageal dysmotility and dysphagia [2, 3]. This study investigates whether ad-hoc oesophageal physiology surveillance would be clinically beneficial for patients with post OA surgical history. Method Retrospective study was conducted on patients with surgical history for OA and undergone oesophageal physiology studies between 2010 and 2023. 11 patients were found (6 females) who had oesophageal physiology at mean age of 29 years (95% CI 26.7 to 35.3 years) or correspondingly post-surgery for OA. Standard high-resolution manometry assessment was re-interpreted with reference Chicago Classification(version 4.0)[4]. This followed by stimulation with multiple water swallowing and solid bolus swallows as adjunctive testing [5, 6, 7]. This project was approved by the NHS institution and the local research ethics committee (REC 18/NW/0120)(IRAS 333800). Results Major dysmotility was observed in 7 patients (63.6%)(achalasia 3, absent contractility(AC) 4) and minor dysmotility was apparent in 4 patients (ineffective oesophageal motility [IOM]). Development of major dysmotility was at a later onset post-surgery to minor dysmotility (30.4 years vs 26.5 years, p=0.214). As was achalasia to AC (32.3 years vs 29.0 years, p=0.379). Adjunctive testing augmented oesophageal smooth muscle contractility in all patients with IOM and invoked remaining neuromuscular functioning in 2 patients with AC. The achalasia diagnosis in the 3 patients remained unchanged during the adjunctive testing. Conclusion Oesophageal physiology surveillance in patients with post OA surgery would enable identifying the staging of the motility disorder and which may direct further surgical management. This study revealed patients were still suitable for partial fundoplication post OA surgery (54.5%) and surgical myotomy for achalasia (27.3%). The prevalence of achalasia (27.3%) and absent contractility (36.4%) in post OA surgery observed this study are significantly higher compared to the non-OA treatment-naïve patients found in the general population living with achalasia and absent contractility disorders.

Abstract 4135835: Prevalence of Diabetes Mellitus in Calcutta Schoolteachers and its Relationship with Cardiovascular Risk as Assessed by the ASCVD Model

Introduction: Cardiovascular disease (CVD) is rising in prevalence in India with economic development and the adoption of a Western lifestyle. Hypothesis: The increase in incidence and prevalence of CVD is possibly due to a rise in the incidence of risk factors like diabetes mellitus (DM), hypertension, hyperlipidemia, lack of physical activity and obesity, among various other causes. Aims: 1. To estimate the prevalence of DM in the community of Calcutta schoolteachers 2. To examine the relationship between the prevalence of DM and CVD risk as assessed by the different traditional CVD risk factors (age, sex, hypertension, current smoking, DM, and hyperlipidemia). Methods: We recruited 4,150 schoolteachers from 400 schools in Calcutta, India between June, and August 2019 with approval of the Tufts IRB and the local Ethics Committee. Participants were asked questions about their different risk factors to ascertain their cardiovascular risk by the ASCVD risk calculator. Baseline values (total cholesterol 170 mg/dL, HDL-C 50 mg/dL, no DM) were used when a participant’s glycemic status or lipid profile was not available. Based on the risk score, participants were stratified as mild (<5%), moderate (5-10%), or high (>10%) risk for developing ASCVD. A total of 240 participants were randomly selected from a stratified sample of the participants for evaluation for diabetes using HbA1c. DM was diagnosed when the Hb A1 C was 6.5% or more. Results: The mean age of the participants was 44 years, and 41% were male. Out of a total of 4,150 participants, 85.7% (3,558) were in the low-risk for CVD category, 9.0% (374) were moderate-risk, and 5.3% (218) were high-risk. Among the 240 screened for DM, 17.1% (41) were found to have the condition, and 41.3% (99) were pre-diabetic. There was no significant difference in prevalence of DM between men and women in the overall study population and in the mild risk group. However, more women in the medium risk group and more men in the high-risk group were found to be diabetic (p value <0.001 in both). Some participants were reclassified based on their new diagnosis of DM. Conclusions: The prevalence of DM was high among Calcutta schoolteachers, which contributes to being at increased risk for ASCVD. Most participants were unaware of their DM or cardiovascular risk, highlighting the need for increased testing and awareness. The estimates from this study may be used to understand the community burden of DM and cardiovascular risk.

Season-dependent characteristics of shock-related injuries in the Arctic zone of the Arkhangelsk region

Relevance. Studying the dynamics of injury rates, injury types and severity, as well as the treatment quality across various country regions, in particular the Arctic, is a prerequisite for managerial, healthcare, and strategic efficiency prior to and during hospital stay, taking into account the climate, geography, social and economic characteristics of every Russian Federation constituent.The objective is to analyse shock-related injuries in the Arctic zone of the Arkhangelsk region to understand season-related injury dynamics.Methods. Retrospective case series description parameters were used to study 140 patients with traumatic shock admitted to the Arkhangelsk Regional Clinical Hospital (ARCH) - a tier 1 trauma center. The analysed medical registration records included patient ambulance record and token (form 114/u), inpatient medical record (form 003/u), surgery logbook (form 008/u), patient radiographs, CT and nuclear MRI reports, as well as laboratory results. The study was conducted in accordance with ethical standards of the Declaration of Helsinki and European Community Directives (8/906 EC) and was approved by the local ethics committee of the Northern State Medical University of the Russian Ministry of Healthcare, Arkhangelsk (protocol no. 02/4-15 dated 04/08/2015). Statistical application package STATA ver.12 was used for statistical data processing.Results and discussion. The research demonstrated that the incidence of shock trauma is 4 times higher in men than in women. The vast majority of the injured are of working age. Seasonal distribution analysis per type of injuries and shock severity, including due to alcohol abuse, was carried out. The number of shock injuries is highest in winter, mainly due to road accidents which constitute 75.6 % of all injuries in winter. Throughout the year, over 50 % of shock injuries are combined injuries, that outperform isolated and multiple injuries in number. In particular, numerous combined injuries occur in winter with a responsible for almost 60 % among all other injuries. The majority the injured with shock-related trauma presented with stage 2 shock (49.3 %), whereas stage 1 and stage 3 shock was diagnosed in 27.9 % and in 21.4 % respectively. In winter, one in four patients with a shock-related injury presented with stage 3 shock. Alcohol-associated shock injuries are more numerous in summer (35.3 %), showing almost the same incidence as road traffic, domestic, and street injuries.Conclusion. The analysis of various types of injuries and season-related incidence of shock injuries in the Arctic territory of the Arkhangelsk region provides evidence to justify preventive measures to reduce the injury rates. Intensified efforts are required to minimise road traffic accidents in winter and combat alcohol abuse responsible for most injuries in summer. Since the vast majority of shock injuries occur in winter, in cold months ambulances must be equipped with local heating facilities, such as evacuation thermal bags with autonomous electric heating, thermal blankets, infusion warmers for blood transfusion and infusion sets.

Comparison of the effectiveness of drug therapy and non-drug technology of post-COVID rehabilitation of workers with intensive computer load

Currently, there is sufficient evidence of the importance and clinical effectiveness of non-drug therapy. The scientific discussion on the priority of the clinical application of pharmacological and non-pharmacological methods of rehabilitation of patients with mononeuropathies has acquired particular importance against the background of neurological post-COVID complications in patients with COVID-19. The study aims to compare the effectiveness of drug therapy and non–drug technology of post-covid rehabilitation of workers with intensive computer workload based on the study of clinical and laboratory parameters. Scientists have conducted a survey of two groups of workers with intensive computer workload who underwent rehabilitation after COVID-19 with the use of drug therapy and non-drug technologies, including balneotherapy, drinking narcotherapy, aerosol inhalations, low-frequency magnetic therapy. The authors have evaluated the effectiveness of therapy based on the results of studies of asthenization, degree of fatigue, latent coronary insufficiency, the state of the blood microcirculation system, immune status, the state of the POL-AOSIS system and endogenous intoxication of patients. Asthenization, the degree of fatigue, and latent coronary insufficiency decreased in the majority of the examined patients after post-COVID non-drug measures. Whereas in patients of the drug group, a decrease in these indicators was noted in a small number of examined patients. The indicators of the immune status of patients after non-drug therapy returned to normal, after drug therapy they only approached the limits of the norm, but did not reach it. After the treatment, the indicators of lipid peroxidation in the group of patients undergoing post-COVID rehabilitation using non-drug technologies decreased more significantly than in the group receiving drug treatment. The content of the antioxidant enzymes catalase and ceruloplasmin and the fat-soluble antioxidant α-tocopherol after treatment increases in both groups, but in the group of drug treatment they do not reach the lower limit of the reference intervals. The decrease in the content of medium-molecular peptides is more pronounced when using non-drug technologies. The application of the proposed non-drug technology for the rehabilitation of patients with post-COVID syndrome who are subjected to intense computer loads during work showed a significantly more pronounced normalization of asthenization, fatigue, latent coronary insufficiency and the state of the blood microcirculation system, immune status, the state of the POL-AOSIS system and endogenous intoxication of patients. The data obtained indicate a high therapeutic effect of the use of non-drug technology. Limitations. The surveyed groups included only persons permanently registered in Kislovodsk. Ethics. The research was conducted in accordance with the principles of biomedical ethics and approved by the local Ethics Committee of the Izmerov Research Institute of Occupation Health, Moscow (Protocol No. 4 dated 04/14/2021). Each participant of the study submitted a voluntary written informed consent signed by him after explaining to him the potential risks and benefits.

Pathological changes on the skin due to the combined effects of polycyclic aromatic hydrocarbons and ultraviolet radiation

Introduction. In the National Healthcare Project, one of the key areas is the federal project "Fight against oncological diseases for 2019-2024". The influence of the nature of work activities of workers in contact with industrial carcinogens — polycyclic aromatic hydrocarbons (PAHs) significantly increases the risk of skin neoplasms, as evidenced by differences in the frequency of their occurrence among representatives of different labor categories. The leading factor in the development of skin neoplasms is ultraviolet radiation (UV) of the A and B spectrum. There is literature evidence of a possible mutual enhancement of the combined effects of PAHs and UV in the occurrence of skin neoplasms and their malignancy. The study aims to evaluate the role of the combined effects of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet radiation (UV) in the occurrence of pigmented skin tumors in workers engaged in the construction of highways and highways and in housing and communal services. Materials and methods. During periodic medical examinations (PMEs) in 2022–2024, specialists have examined 140 people who formed 4 study groups. The researchers have conducted a physical examination of skin tumors; examination in the rays of a Wood lamp; dermatoscopy of skin tumors using a Heine Delta 20 dermatoscope. Hyperpigmentation was assessed according to the hyperpigmentation area and severity index (NASI). Results. During the clinical examination, the authors assessed the presence of pigmentation and skin neoplasms (lentigo, ephelides, seborrheic keratomas). The most frequent localizations of pigmentation and skin neoplasms were open areas of the body: face, hands, upper third of the back. At the same time, in asphalt concrete workers — group I, working under the influence of PAHs and solar insolation (spectrum A and B, in the range of 320–400 nm and 280–320 nm), specialists revealed pigmented neoplasms in a larger number of individuals compared with the population control for all skin localizations. The HASI index (in the surveyed groups) showed that the highest rates (24–48) of HASI were observed in a larger number of individuals — 57.1% — from group I (UV+PAHs), compared with groups of individuals (II, III, IV) who do not work under conditions of exposure to solar insolation (spectra A and B, in the range of 320–400 nm and 280–320 nm). The authors noted that the intensity of pigmentation is higher and the lesion area is larger when assessing the foci of hyperpigmentation in the rays of the Wood lamp compared with the clinical examination in all the examined groups. Limitations. The study is limited by the number of subjects examined, corresponding to the design of the study and the time interval of the study. Conclusion. To obtain objective results of the study of the role of the combined effects of polycyclic aromatic hydrocarbons (PAHs) and ultraviolet irradiation (UV) in the occurrence of pigmented skin tumors, scientists used a method for determining the hyperpigmentation area index and severity index (HASI) in the rays of a Wood's lamp. When comparing the results obtained, experts revealed an increase in the area of hyperpigmentation and its intensity with localization in open areas of the body in workers engaged in the construction of highways and housing and communal services, in contact with the combined effects of carcinogens (PAHs) and ultraviolet irradiation (UV A and B). Further in-depth studies are needed to study the etiopathogenesis of photogenotoxicity depending on the dose-effect ratio. Ethics. The work was performed in accordance with the ethical standard set out in the Helsinki Declaration of the World Medical Association of 1964 (as amended and supplemented in 2013). The authors conducted all the studies after receiving informed consent and a decision of the Local Ethics Committee (extract from Protocol No. 7 dated 10/21/2020).

A machine learning approach for the design optimization of a multiple magnetic and inertial sensors wearable system for the spine mobility assessment

BackgroundRecently, magnetic and inertial measurement units (MIMU) based systems have been applied in the spine mobility assessment; this evaluation is essential in the clinical practice for diagnosis and treatment evaluation. The available systems are limited in the number of sensors, and neither develops a methodology for the correct placement of the sensors, seeking the relevant mobility information of the spine.MethodsThis work presents a methodology for analyzing a system consisting of sixteen MIMUs to reduce the amount of information and obtain an optimal configuration that allows distinguishing between different body postures in a movement. Four machine learning algorithms were trained and assessed using data from the range of motion in three movements (Mov.1—Anterior hip flexion; Mov.2—Lateral trunk flexion; Mov.3—Axial trunk rotation) obtained from 12 patients with Ankylosing Spondylitis.ResultsThe methodology identified the optimal minimal configuration for different movements. The configuration showed good accuracy in discriminating between different body postures. Specifically, it had an accuracy of 0.963 ± 0.021 for detecting when the subject is upright or bending in Mov.1, 0.944 ± 0.038 for identifying when the subject is flexed to the left or right in Mov.2, and 0.852 ± 0.097 for recognizing when the subject is rotated to the right or left in Mov.3.ConclusionsOur results indicate that the methodology developed results in a feasible configuration for practical clinical studies and paves the way for designing specific IMU-based assessment instruments.Trial registration: Study approved by the Local Ethics Committee of the General Hospital of Mexico “Dr. Eduardo Liceaga” (protocol code DI/03/17/471).

Localized FDG loss in lung cancer lesions

BackgroundAnalysis of [18F]-Fluorodeoxyglucose (FDG) kinetics in cancer has been most often limited to the evaluation of the average uptake over relatively large volumes. Nevertheless, tumor lesions also contain inflammatory infiltrates whose cells are characterized by a significant radioactivity washout due to the hydrolysis of FDG-6P catalyzed by glucose-6P phosphatase. The present study aimed to verify whether voxel-wise compartmental analysis of dynamic imaging can identify tumor regions characterized by tracer washout. The study included 11 patients with lung cancer submitted to PET/CT imaging for staging purposes. Tumour was defined by drawing a volume of interest loosely surrounding the lesion and considering all inside voxels with a standardized uptake value (SUV) > 40% of the maximum. Eight whole-body scans were repeated after 20 min of dynamic imaging centered on the heart. Six parametric maps were generated progressively by computing a Patlak regression line for each voxel. Each analysis considered a different set of frames: starting with all eight frames, then the last seven frames, and so on, down to the last three frames.ResultsDelaying the starting point of the compartmental analysis revealed a progressive increase in the prevalence of voxels with a negative slope. In the most delayed parametric map, these voxels represented 0.5–4.5% (median 2%) of the tumor volume. This effect was independent of tumor size and was predominantly located at the lesion borders.ConclusionsThe voxel-wise parametric maps provided by compartmental analysis identify a measurable volume characterized by radioactivity washout. The spatial localization of this pattern is compatible with the recognized preferential site of inflammatory infiltrates populating the tumor stroma and might improve the power of FDG imaging in monitoring the effectiveness of treatments aimed at empowering the host immune response against cancer.Trial registration: ClinicalTrials. The study was approved by the local ethical committee and it represented a single Institution ancillary trial within the expanded-access program for Nivolumab. NCT02475382. Registered 2015-06-16. URL: https://clinicaltrials.gov/study/NCT02475382?id=NCT02475382.&rank=1

External Validation of the Predictive Accuracy of Clinical and Immunological Scores in COVID-19 Outcomes in a Retrospective Cohort Study

Background and Objectives: The COVID-19 pandemic has necessitated the development of reliable prognostic tools to predict patient outcomes and guide clinical decisions. This study evaluates the predictive utility of several clinical scores—PAINT, ISARIC4C, CHIS, COVID-GRAM, SOFA, and CURB-65—for in-hospital mortality among COVID-19 patients, comparing their effectiveness at admission and seven days post-symptom onset. Methods: In this retrospective cohort study conducted at the Clinical Emergency Hospital Pius Brînzeu in Timișoara, adult patients hospitalized with confirmed SARS-CoV-2 infection were included. The study was approved by the Local Ethics Committee, adhering to GDPR and other regulatory standards. Prognostic scores were calculated using patient data at admission and Day 7. Statistical analyses included ROC curves, Kaplan–Meier survival analysis, and multivariate Cox regression. Results: The study comprised 269 patients, with a notable distinction in outcomes between survivors and non-survivors. Non-survivors were older (mean age 62.12 years) and exhibited higher comorbidity rates, such as diabetes (55.56% vs. 31.06%) and cardiovascular diseases (48.15% vs. 29.81%). Prognostic scores were significantly higher among non-survivors at both time points, with PAINT and ISARIC4C showing particularly strong predictive performances. The AUROC for PAINT increased from 0.759 at admission to 0.811 by Day 7, while ISARIC4C demonstrated an AUROC of 0.776 at admission and 0.798 by Day 7. Multivariate Cox regression indicated that a PAINT score above 8.10 by Day 7 was associated with a hazard ratio (HR) of 4.9 (95% CI: 3.12–7.72) for mortality. Conclusions: The study confirms the strong predictive value of the PAINT, ISARIC4C, CHIS, COVID-GRAM, SOFA, and CURB-65 scores in determining mortality risk among hospitalized COVID-19 patients. These scores can significantly aid clinicians in early-risk stratification and resource prioritization, potentially enhancing patient management and outcomes in acute care settings.

Arterial blood gases in SCUBA divers at depth

BackgroundCurrent diving physiology postulates that SCUBA divers’ arterial blood gas (ABG) levels vary proportionally to environmental pressure, but, to date, ABGs have only been obtained during simulated dives. Also, recent evidence supports the use of the arterial/alveolar (a:A) partial pressures of oxygen (PO2) ratio to predict the arterial PO2 (PaO2) under hyperbaric conditions from measurements obtained at 1 atmosphere absolute (ATA). This work summarizes ABGs obtained in SCUBA divers in real underwater conditions and aims to validate the a:A ratio in predicting PaO2 in this subset of individuals at depth.MethodsThe study was approved by the local ethics committee. After cannulating the radial artery of the non-dominant limb, ABGs were sampled at the surface before the dive (A), at depth (15 meters of freshwater (mfw) or 42 mfw) before (B) and after (C) pedaling on a submersed bicycle for 10 minutes, and back at surface (D). After calculating the surface alveolar PO2 for each subject, the a:A ratio was obtained and used to predict PaO2 at depth. A linear regression between measured and predicted PaO2 was reported, along with the goodness-of-fit F test.ResultsSix subjects performed the dive at 15 mfw, and four others at 42 mfw. The PaO2 proportionally increased at both depths, remaining stable before and after pedaling. The a:A calculated from the baseline ABG obtained at rest, out of the water, adequately predicted the PaO2 at depth (R2 = 0.97, p<0.001), better at 15 mfw but losing accuracy at 42 mfw.ConclusionsThe ABGs confirmed the proportional rise of PaO2 in SCUBA divers underwater. The a:A ratio could be used to predict the magnitude of PaO2 rise at depth to limit exposure to hyperoxia, especially in repetitive recreational dives and professional divers.

Biomarkers for monitoring patients with cardiac amyloidosis during transthyretin-stabilizer therapy

Abstract Introduction Cardiac amyloidosis is characterized by deposition of amyloid fibrils in the heart, leading to structural abnormalities and functional impairments resulting in heart failure. Amyloid transthyretin amyloidosis cardiomyopathy (ATTR-CM) is the most common form with increasing incidence due to growing awareness and improved diagnosis. The ATTR stabilizer tafamidis serves as the first specific therapy approved for ATTR-CM, and many promising substances are in late-stage clinical trials. With growing numbers of patients receiving stabilizer therapy, valid tools for monitoring treatment response and detecting disease progression are currently lacking. Here, we aim to assess systemic and cardiac biomarkers in patients receiving stabilizer therapy. Method All individuals diagnosed with ATTR-CM at our university hospital, were systematically assessed for eligibility in this study. We enrolled patients who were undergoing therapy with tafamidis. Biomarkers including Hemoglobin (Hb), Creatinine, estimated glomerular filtration rate (eGFR), International Normalized Ratio (INR), C-reactive protein (CRP), Troponin and NT-proBNP were examined at baseline and during 6 and 12 months follow-up. Wilcoxon signed rank test was used for statistical analysis. The study was approved by the local ethics committee (23-11500-BO). Results 194 patients were included in the analysis with median age of 80 (76-83) years (86,6% male). Results showed an impaired renal function at baseline (all mean ± SD) with creatinine 1.24 ± 0.46 mg/dl and eGFR 58.64 ± 18.24 ml/min/kg with statistically significant increase after 6 months in creatinine (1.31 ± 0.51 mg/dl, p<0.001) and eGFR (55.06 ± 17.65 ml/min/kg, p<0.001) and after 12 months (creatinine 1.35 ± 0.54 mg/dl, p<0.001, eGFR 53.27 ± 17.68 ml/min/kg, p<0.001). Hb showed a significant increase after 6 (13.61 ± 1.78 g/dl, p<0.001) and 12 months (13.6 ± 1.79 g/dl, p<0.001), compared to baseline (13.41 ± 1.71 g/dl, p<0.001). Comparison of baseline values for CRP (0.08 ± 1.18 mg/dl), Troponin (86.33 ± 190.6 ng/l), NT-pro BNP (4703 ± 4385 pg/ml) and INR (1.25 ± 0.46) after 6 (CRP p=0.28, Troponin p=0.7, NT-pro BNP p=0.97, INR p=0.91) and 12 months (CRP p=0.12, Troponin p=0.59, NT-pro BNP p=0.78, INR p=0.28) showed no significant changes. Conclusion Although troponin and BNP are routinely used and recommended as biomarker for monitoring patients with ATTR-CM, the diagnostic value may be insufficient to assess therapy response. Results emphasize the need to identify new biomarkers to adequately reflect the specific aspects of ATTR-CM disease progression. This study reveals significant alterations in creatinine and eGFR due to a worsening of kidney function, but an increase of Hb, suggesting a potential indicator for treatment response. Future research should explore innovative approaches like proteomic analysis as promising approach for both diagnostic and prognostic biomarkers.

Antibiotic use and resistance: knowledge, attitudes and practices in Italian healthcare workers

Abstract Background Antimicrobial resistance (AMR) is one of the most significant public health challenges globally. The misuse or incorrect use of antibiotics has led to the emergence of resistant bacteria, making it increasingly difficult to treat infections. This study aims to identify knowledge, attitudes, and practices among Italian healthcare workers (HWs) - medical doctors (MDs) and nurses - regarding antibiotics, antibiotic use, and antibiotic resistance. Methods Cross-sectional study; a validated questionnaire from the European Centre for Disease Prevention and Control was distributed via web survey starting from April 2024 to a voluntary sample of healthcare workers employed in Italy. Descriptive analysis and multivariable logistic regression were performed to investigate predictors of knowledge regarding antibiotic use and AMR. Ethical approval was obtained from the local ethics committee. Results So far, 154 HWs were enrolled, of which 132 were nurses (85.7%). The average level of knowledge regarding AMR and antibiotic use was 6.8/7 (± 0.2) for MDs and 6.1/7 (± 0.2) for nurses, with an overall score, among HWs of 6.19 (± 0.99), compared to a European average of 6.35. The multivariable analysis highlighted that the medical profession reported higher knowledge regarding prudent antibiotic use and AMR (aOR 6.90; 95% CI 1.83-26.01, p-value = 0.004), while concerning professional practice, the unavailability and difficulty of access to guidelines seemed to increase the risk of reporting inadequate knowledge (aOR 2.04; 95% CI 1.01-4.13, p-value = 0.046). Conclusions Our preliminary results provide an insight into the importance of structuring and actively disseminating procedures/protocols and guidelines to deepen the issues of AMR and prudent antibiotic use. Also, there appears to be a need to enhance the delivery of refresher courses targeting HWs, with particular attention to settings at high infection transmission risk. EU funding: Project no. PE00000007, INF-ACT. Key messages • Although a higher knowledge about prudent antibiotic use and AMR, more efforts are needed to increase access to guidelines. • Constant updating of knowledge and practices is necessary to face the challenges of antibiotic resistance in public health.

Delays in diagnosis and treatment initiation of ATTR cardiac amyloidosis: a real-world data analysis

Abstract Introduction Cardiac amyloidosis (CA) is a serious condition characterized by the accumulation of abnormal protein deposits in the heart muscle, leading to functional impairments and, ultimately, heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form encountered in CA diagnosis with previously underestimated prevalence. ATTR-CM poses a diagnostic challenge, with a substantial number of cases diagnosed late and at advanced stages. The availability of specific pharmacological treatment using the transthyretin-stabilizer tafamidis further emphasizes the need for timely diagnosis. Here, we aim to assess delays in diagnosis and initiation of therapy in a real-world collective of patients with ATTR-CM. Methods All individuals diagnosed from 01/2018 to 05/2023 with ATTR-CM at our university hospital, Germany, were systematically assessed for eligibility in this study. Specifically, we enrolled patients who were undergoing transthyretin stabilizer therapy. The investigation aimed to determine the duration, in days, from the initial suspicion of heart disease to the definitive diagnosis of ATTR-CM. It was also investigated whether the diagnosis of ATTR-CM was made more quickly over time as awareness increased. Additionally, the study assessed the time elapsed until patients received pharmacological therapy following the confirmed diagnosis. The study was approved by the local ethics committee (23-11500-BO). Results After screening of 194 consecutive patients, 154 were included in the analysis, while 40 patients were excluded due to insufficient records. The results of this study reveal that a median of 300 (113-962) days elapsed from the initial suspicion of amyloidosis to the final confirmation. Initial indications of CA often presented as nonspecific symptoms such as unclear dyspnea (16.2% n=25), abnormal echocardiography (75.3% n=116), or, in rare cases, incidental findings (8.4% n=13). Following the diagnosis, an additional median of 84 (46-163.5) days passed before the first prescription of a transthyretin stabilizer. To assess an improvement of ATTR-CM diagnosis over time, we stratified the data into tertiles by date of first diagnosis. The results showed a gradually decrease in medium time to diagnosis of 466 (181-1035) days in the earliest tertile (2018-2019) to 389 (141-1508) days in the most recent tertile (2022-2023) (p<0.001). Conclusion This study shows a major healthcare deficit and underscores the medical need for improved screening procedures and diagnostic modalities to expedite the timely diagnosis of CA, as early identification of the condition is crucial for enhancing the quality of life for patients and preventing life-threatening complications.

Potential impact of cold water immersion on arrhythmogenesis: a pilot exploratory study surrounding the Geneva christmas cup

Abstract Background Cold-water immersion (CWI) is gaining popularity and is regulated by sports federations with guidelines for various cold temperature ranges. Small studies suggest cardiovascular and stress reduction benefits from regular CWI, yet acute effects and cardiac risks remain underexplored. Purpose This study aimed to assess the impact of CWI on arrhythmogenesis among participants of the 2023 Geneva Christmas Cup, the world's largest cold-water swimming event. Methods Volunteers aged 45 and older were recruited through the organizing committee. Each underwent baseline cardiovascular risk assessment 10 days prior to the event, including medical interviews, physical exams, blood tests, and 12-lead ECGs. A waterproof ECG recorder (BodyGuardian Mini®) was attached to participants, monitoring them for 10 days up to the end of the race. An activity diary recorded training sessions, CWI exposure, and any symptoms. Data from BodyGuardian Mini® were analyzed for CWI-induced arrhythmias and conduction disturbances. The local ethics committee approved the study. Results Twenty volunteers (11 women, mean age 56 ± 6.4 years) participated. Their mean SCORE2/SCORE2-OP was 4 ± 1.8%, with 60% at low to moderate and 40% at high cardiovascular risk. Average weekly training was 5.5 ± 2.9 hours. Lake temperature was 7.0 degrees. One participant could not race but all completed CWI training and wore ECG recorders for an average of 226 ± 32 hours. Sixteen participants (80%) exhibited non-sustained atrial tachycardia (average 12.4 ± 8.8 events), and four (20%) had non-sustained ventricular tachycardia events (average 1.2 ± 0.5), with no significant pauses or >1st degree AV block observed. No arrhythmic events were directly linked to CWI. Conclusion This exploratory study of active, middle-aged participants with moderate cardiovascular risk found no association between CWI and arrhythmias. Further, larger-scale studies are necessary to conclusively determine CWI's safety.

Minimalist Approach for HoLEP with A Low-Power Holmium Source: A Retrospective Study.

To assess the efficacy and safety of very low-power Holmium Laser Enucleation of the Prostate (HoLEP) on a 30-W holmium laser source. With the approval of the local ethics committee, we retrospectively analysed 60 patients treated with HoLEP. There were 30 patients in the low-power (LP) group and 30 patients in the very low-power (VLP) group. For the LP group, we used a 60-W holmium laser machine. Throughout the en bloc process, we used laser settings of 2 J and 20 Hz. We used a 30-W low-power holmium source in the VLP group. We used laser settings of 2 J and 10 Hz. All patients were operated on by an experienced surgeon. We evaluated the surgical parameters and practicality of the low-power laser vs. the very low-power laser. All patients underwent successful HoLEP in the very low-power group; it was not necessary to increase the output of the laser in any case. Mean preoperatively estimated prostate volume was 88.1 mL (range, 30-300 mL). Mean enucleation time and enucleation efficiency were 67.9 min (range, 25-150 min) and 0.99 gm/min (range, 0.8-1.8 gm/min), respectively. No patient required blood transfusion postoperatively. No stress urinary incontinence (SUI) was observed in the 3rd month postoperative follow-up. The use of a low-power laser source is encouraging for the learning curve of new surgeons who will begin HoLEP surgery; it can facilitate the adoption of HoLEP in developing countries, where the initial capital investment may be a major obstacle.

The difference in clinical characteristics between patients with rhegmatogenous retinal detachment during partial and complete lock-down periods related to COVID-19 pandemics 2-year long follow-up results

BackgroundWe aimed to compare results of clinical presentation of rhegmatogenous retinal detachment (RRD), and the surgical approach during partial or complete lock-down periods (LP), and non-COVID periods in a tertiary ophthalmology clinic.MethodsThe medical data of the patients who were diagnosed with RRD in a tertiary hospital. The demographic data of patients, the duration from the beginning of the visual symptoms to hospital admission, the status of lens, the anatomical quadrant of retinal break, best-corrected visual acuity (BCVA) at presentation, the type of intraocular tamponade, and final BCVA were recorded. The exclusion criteria were RD other than rhegmatogenous (tractional or exudative), and incomplete follow-up until 2nd-year.ResultsThe study included 20 eyes of 20 RRD cases in partial LP, 20 eyes of 20 RRD cases in complete LP, and 23 eyes of 23 RRD cases in non-COVID period. The ratio of perfluoropropane (C3F8) gas to silicone oil which was applied as intraocular tamponade at the end of the surgery for RRD was 15/8 in non-COVID period, 11/9 in partial LP, and 11/9 in complete LP (p = 0.730). In final visit at postoperative 2nd-year, the BCVA was logMAR 0.613 ± 0.425 in non-COVID period, logMAR 0.668 ± 0.348 in partial LP, and logMAR 0.730 ± 0.368 in complete LP (p = 0.612). In both inferior and superior quadrant RD, there was significant difference between baseline and final BCVA after surgery. (Baseline and final BCVA in inferior RD: logMAR 1.71 ± 0.40, and logMAR 0.950 ± 0.30 (p = 0.011) and, in superior RD: logMAR 1.35 ± 0.59, and logMAR 0.505 ± 0.321 (p = 0.0001), respectively.)ConclusionsAs a result, it seems that both partial and complete LP did not modify the typology of RRD surgeries.Trial registrationRetrospectively registered. The study followed the tenets of the Declaration of Helsinki, and it was approved by the local ethical committee (2023-088).

Assessment of the quality of life of GPs in situations of high epidemic risk

The purpose is to assess the characteristics of the decrease in the quality of life of GPs working in a specialized COVID-19 hospital, a multidisciplinary hospital, and a poly clinic during the pandemic of the novel coronavirus infection COVID-19, as well as early diagnosis, prediction, and prevention of a decrease in the quality of life in this category of medical workers. Material and research methods. The study was carried out on the basis of the Department of Occupational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation professor V. V. Kosarev, FSBEI HE Samara State Medical University of the Ministry of Health of the Russian Federation, and the Department of Occupational Pathology, Regional Center for Occupational Pathology of the Samara City Hospital No. 5. The study was carried out within the framework of a complex theme «Systematic ap proach to early diagnosis, prevention, and prediction of the impact of low-intensity pro duction factors on workers’ health» of the Department of Occupational Diseases and Clinical Pharmacology named after honored scientist of the Russian Federation profes sor V. V. Kosarev, FSBEI HE Samara State Medical University (state registration number AAAA-A18‑118122190069‑6, registration date — December 21, 2018). The study was approved by the local ethics committee of the FSBEI HE Samara State Medical University of the Ministry of Health of the Russian Federation on November 23, 2021. The study included the following groups of examined medical workers: group 1 consisted of physicians of internal medicine working in a COVID hospital (in the «red zone») (n = 111); group 2 included GPs working in a multidisciplinary hospital (n = 106); group 3 consisted of GPs working in a polyclinic (n = 102); group 4 was the control group (n = 190) comprising employees of engineering, technical, and economic specialties not relat ed to work in medical organizations (healthy). To assess the psychophysiological state and quality of life of medical workers during the pandemic of the novel coronavirus infection COVID-19, the SF-36 questionnaire [J. E. Ware, 1993], designed to study all components of the quality of life, was used. The obtained data were processed using the Statistica package from StatSoft (USA). Results. The professional activities of GPs providing medical care in the «red zone», mul  tidisciplinary hospitals, and clinics are associated with the exposure of physicians to a number of risk factors in the working environment and the labor process, related to the provision of regular or occasional care to infected COVID-19 patients, which, under con ditions of exposure to an increased level of occupational stress, leads to a decrease in the quality of life in these categories of health workers. The decrease in the quality of life among medical workers in medical institutions of various profiles during the pandemic of the novel coronavirus infection COVID-19 is due to the fact that health workers faced many additional difficulties during this period: sleep deprivation, stress, strain, and chronic fa tigue. Chronic fatigue can affect behavior, communication, learning, and decision-making, which overall leads to a decrease in the qualit y of life of medical workers. Conclusion. Thus, the obtained data indicate that when identifying risk factors for a de crease in the quality of life in medical workers working in situations of high epidemic risk, there is the need to use specialized rehabilitation measures with relaxation techniques, art therapy, as well as professional adaptation programs, physiotherapeutic techniques, such as electrosleep and reflexology, and, if possible, resort treatment in health care centers, local sanatoriums, etc. with visits to psychotherapy offices, as well as psychopharmaco logical medications.

Hand dynamometer and clinical tests to evaluate the recovery of neuromuscular conductance in atracurium versus rocuronium in patients undergoing laparoscopic surgery

Background. Postoperative muscle weakness is not unusual and may be related to postoperative complications in patients after general anesthesia. However, the clinical practice of neuromuscular conductance monitoring is uncommon among anesthesiologists.The objective was to evaluate the rate of neuromuscular recovery after atracurium and rocuronium and to determine the numerical value of grip strength using a hand dynamometer, indicating the safety of transferring a patient from the postoperative ward.study design. A prospective, observational, clinical comparison study.Materials and Methods. Upon proper authorization and approval from the local ethics committee, patients referred for laparoscopic surgery, 120 patients of the American Society of Anesthesiology (ASA) physical status I &II between ages 20–49 years were randomly assigned into 2 groups of 60 each. Group I received a single atracurium dose of 0.5mg/kg of ideal body weight and Group II patients received a single rocuronium dose of 0.6mg/kg of ideal body weight. Parameters such as modified Alderete score (MAS), grip strength, and sustained head and leg lift for five seconds were compared in both groups 50 minutes after giving the reversal agent at 10-minute intervals.Results. Postoperative muscle recovery (grip strength) was faster in the atracurium group than the rocuronium group, with a p-value of 0.042 at 20 minutes, and 0.0000 for 30, 40, and 50 minutes after giving the reversal agent. The time to obtain a modified Alderete score (MAS) > 8 scores was statistically insignificant with a p-value of 0.335. Positive clinical test for sustained head lift for 5 seconds was statistically insignificant within a majority of the time, except in the 20 minutes, most of the cases in the atracurium group were able to sustain head elevation for 5 seconds with a p-value of 0.021. In the 10 &20 minutes, most cases in the atracurium group could sustain leg elevation for 5 seconds with a p-value of 0.015 and 0.014 respectively. However, most cases in both groups could sustain head and leg elevation for 5 seconds in the 30 minutes after giving a reversal agent.Conclusion. Compared to rocuronium, atracurium has been associated with faster muscle recovery after a single tracheal intubation dose for a short surgery. This was determined by utilizing an electronic hand dynamometer to measure grip strength. 42% grip strength from baseline might be applicable for safe discharge from the recovery room. A hand dynamometer assessment revealed more post-operative muscle weakening than a clinical evaluation.

Does selective root canal retreatment preserve the tooth’s fracture resistance? An ex-vivo study

ObjectivesTo assess the tooth’s fracture resistance when submitted to a selective root canal retreatment compared to the conventional approach.Methods33 intact permanent mandibular first molars were selected according to specific criteria. After teeth mounting, the primary root canal treatment was conducted and followed by thermo-mechanical aging procedures to mimic a few clinical conditions. The specimens were randomly divided into three groups (n = 11); a control group in which intact teeth were used and two experimental groups according to the retreatment approach: conventional non-surgical retreatment (Conventional-NSR), and selective non-surgical retreatment (Selective-NSR). Later, the teeth were submitted to a final thermo-mechanical aging procedure and tested regarding their fracture resistance (static fracture test). The maximum load to fracture was recorded as were the types of failure modes (repairable or non-repairable fracture). A proper statistical analysis was conducted, considering a significance level of 5%.ResultsThe Conventional-NSR group showed a mean failure load of 867.7 ± 108.9 N while the Selective-NSR group had 1106.8 ± 159.8 N (P = 0.012). Both retreatment groups showed significantly lower results when compared to the control group. Additionally, the Conventional-NSR group showed higher proportions of non-repairable fractures (54.5%) when compared to both the Selective-NSR (36.4%) and control (18.2%) groups.ConclusionsSelective root canal retreatment preserved the tooth’s fracture resistance compared to the conventional retreatment approach.Clinical trial numberNon-applicable. Conducting the current experiment was limited to obtaining approval from the local Research Ethics Committee at the Faculty of Dentistry, Minia University (Committee No. 105, Registration No. 902, Date: 26/3/2024).

UROPOT: study protocol for a randomized, double-blind phase I/II trial for metabolism-based potentiation of antimicrobial prophylaxis in the urological tract

BackgroundUrinary tract catheters, including Double-J or ureteral stents, are prone to bacterial colonization forming biofilms and leading to asymptomatic bacteriuria. In the context of asymptomatic bacteriuria, endourological procedures causing mucosa-inducing lesions can lead to severe infections. Antibiotic prophylaxis is warranted, yet its efficacy is limited by biofilm formation on stents. Biofilms promote antibiotic tolerance, the capacity of genetically susceptible bacteria to survive a normally lethal dose of antimicrobial therapy. The UROPOT study evaluates the effectiveness of a first-in-type metabolism-based aminoglycoside potentiation for (i) preventing infectious complications of asymptomatic bacteriuria during mucosa lesion-inducing endourological procedures and (ii) assessing its anti-tolerance efficacy.MethodsThe UROPOT trial is a phase I/II single-center (Lausanne University Hospital (CHUV), Switzerland) randomized double-blinded trial. Over 2 years, patients with asymptomatic Escherichia coli and/or Klebsiella pneumoniae bacteriuria, undergoing endourological procedures, will be randomly allocated to one of three treatment arms (1:1:1 randomization ratio, 30 patients per group) to evaluate the efficacy of mannitol-potentiated low-dose amikacin compared to established standard treatments (ceftriaxone or amikacin standard dose). Patients will be recruited at the CHUV Urology Outpatient Clinic. The primary outcome is the comparative incidence of postoperative urinary tract infections (assessed at 48 h) between the investigational amikacin/mannitol therapy and standard (ceftriaxone or amikacin) antibiotic prophylaxis, defined by specific systemic symptoms and/or positive blood and/or urine culture. Secondary outcomes include assessing microbiological eradication through anti-biofilm activity, sustained microbiological eradication, and mannitol and antibiotics pharmacokinetics in blood and urine. Safety outcomes will evaluate the incidence of adverse events following amikacin/mannitol therapy and postoperative surgical complications at postoperative day 14.DiscussionUROPOT tests a novel antimicrobial strategy based on “metabolic potentiation” for prophylaxis enabling aminoglycoside dose reduction and targeting biofilm activity. The anti-biofilm effect may prove beneficial, particularly in patients who have a permanent stent in situ needing recurrent endourological manipulations strategies in preventing infections and achieving sustained microbiological eradication in pre-stented patients.Trial registrationThe protocol is approved by the local ethics committee (CER-VD, 2023–01369, protocole 2.0) and the Swiss Agency for Therapeutic Products (Swissmedic, 701,676) and is registered on the NIH’s ClinicalTrials.gov (trial registration number: NCT05761405). Registered on March 07, 2023.