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Not only since the Corona pandemic has bedside ultrasound examination of the lung become an indispensable part of acute medicine. In addition to a presentation of the technical basics, this article provides an overview of how lung sonography can also be used in surgical acute medicine., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein Erklärung zu nichtfinanziellen Interessen Bettina Siepe: Mitglied in der Deutschen Gesellschaft für Thoraxchirurgie Armin Seibel: Leiter des Arbeitskreises Notfallsonographie der Deutschen Gesellschaft für Ultraschall in der Medizin (DEGUM), Mitglied des Arbeitskreises Ultraschall der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI), (Thieme. All rights reserved.)

Hypoglossal nerve stimulation for obstructive sleep apnea - Updated position paper of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Since the first statement of the German Society of Oto-Rhino-Laryngology, hypoglossal nerve stimulation (HNS) is meanwhile an established treatment option for obstructive sleep apnea (OSA). There are three HNS systems available in Germany which differ in their technical details of the underlying comparable basic principle. For the unilateral HNS with respiratory sensing, several comparative studies, high-volume register analysis and long-term reports exist. The continuous HNS without respiratory sensing does not require a sleep endoscopy for indication. For the bilateral continuous HNS as the single partially implantable device, a feasibility study exists. For indication, the assessment of positive airway pressure failure by sleep medicine is crucial, and the decision for HNS should be made in discussion of other treatment options for at least moderate OSA. The implantation center holds primarily responsibility among the interdisciplinary sleep team and is primary contact for the patient in problems. This depicts why structural processes are required to secure outcome quality and minimize complications. The aftercare of HNS patients can be provided interdisciplinary and by different medical institutions whereat minimal reporting standards to document outcome and usage are recommended., Competing Interests: Armin Steffen ist Berater für Merz Pharmaceuticals und Respicardia, Inc., und erhielt Forschungsunterstützung von Inspire Medicals sowie Vortragshonorare von Intersect Inc, Proveca Inc, Onyx Health sowie Panakes.Clemens Heiser war Berater für Inspire Medical Systems. Clemens Heiser erhielt Forschungsunterstützung von Inspire Medical Systems, Nyxoah, Löwenstein Medizintechnik. Clemens Heiser erhielt Vortragshonorare von Jazz Pharma, Neuwirth Medical Products.Joachim T. Maurer ist Berater für Nyxoah und erhielt Forschungsförderung und/oder Vortragshonorare von Inspire Medicals, ImThera/LivaNova, MedEl, NeuwirthMedical Products, Gramann Veranstaltungsorganisation sowie XM Consults.Günther Eck gibt Interessenskonflikte bzgl. ALK-Abelló Arzneimittel GmbH, Bencard Allergie GmbH Deutschland, Bionorica SE, Inspire Medical Systems, Inc. und Sanofi-Aventis Deutschland GmbH an.Holger Woehrle erhielt Forschungsunterstützung von ResMed und Weinmann, war Mitarbeiter bei Resmed als Medical Director und erhielt Vortragshonorare bzw. ist Berater bei Allergopharma, AstraZeneca, Bayer, GSK, Boehringer Ingelheim, Inspire Medical, ResMed, Novartis und VitalAir.Jan Löhler gibt einen Interessenskonflikt bzgl. der finanziellen Unterstützung durch den Deutschen Berufsverband der HNO-Ärzte e.V. an.Winfried Randerath hat Honorare für die Mitarbeit in einem Advisory Board der Firmen Philipps Respironics, SoClean, Bioprojet, Bayer Sleep Research sowie Honorare und Reisekosten für Vortragstätigkeiten der Firmen Boehringer Ingelheim, Philipps Respironics, Heinen und Löwenstein, Vanda Pharma und Night Balance erhalten. Wolfgang Galetke, Simon-Dominik Herkenrath geben keine Interessenskonflikte an., (Thieme. All rights reserved.)

A one-page questionnaire assessing physicians' prior involvement in and attitudes about clinical trials was distributed to primary care physicians (PCPs) and specialists practicing in Texas. The survey form was completed and returned by 57 PCPs and 80 specialists. The two physician groups agreed strongly about the value of what can be learned in clinical trials, and agreed that the greatest barriers to participation were paperwork requirements, time constraints, and concern for patient welfare. Both PCPs and specialists were concerned about enrolling patients if they felt that the patients did not understand what was involved. Because PCPs report only a limited experience with clinical trials, a realistic strategy to increase patient accrual involves developing effective educational outreaches to this group of physicians. In general, PCPs are trusted by their patients and can play an important role in providing information and in encouraging participation in appropriate trials.

Objectives: Motivation is the most influential factor in the drive and performance of adolescents with cerebral palsy (CP). As identification and analysis of volition in Iranian adolescents with CP seem to be essential, designing appropriate tools for assessing their motivation is crucial. To achieve this goal, we developed an adolescent motivation inventory-CP (AMI-CP) and evaluated its psychometric properties. Methods: In the first phase, item generation was conducted. Next, in the second phase, face and content validities of the items were assessed. Moreover, construct validity was assessed by exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). A total of 304 adolescents with CP participated in the EFA, while 210 adolescents with CP participated in the CFA. Afterward, convergent and discriminant validities of the inventory were measured. Moreover, reliability was evaluated by calculating Cronbach α, McDonald’s omega, average inter-item correlation, composite, and test re-test reliability. Lastly, the standard error of measurement (SEM) and the minimum detectable change (MDC) were applied. Results: Five factors with 22 items were extracted by EFA, accounting for 50.42% of the variance. The results of model fit indexes confirmed the goodness-of-fit of the final model with 20 items. In addition, the AMI-CP had a Cronbach α value of 0.75 and an intra-class correlation coefficient of 0.94. Moreover, the SEM and MDC of the inventory were 2.63 and 7.31, respectively. Discussion: The AMI-CP is a helpful measure of motivation in adolescents with CP. This inventory can enhance the assessment of the CP adolescents’ motivation by evaluating values, interests, personal causation, and physical and social environments.

Abstract Triticale is a man-made crop produced by crossing wheat (Triticum aestivum) and rye (Secal cereal) with the aim of increasing the adaptability and potential production of its parental line (wheat) under environmental stresses and harsh conditions. Accordingly, the objectives of this study are as follow, a: compare different stability measurement methods regarding their suitability, b: identify most stable genotypes for cultivar release, and c: provide a freely available package in R programming language (named ‘Stbidx’) capable of exploiting all stability methods for similar studies. Accordingly, 30 triticale genotypes were evaluated for their stability and adaptability to changing environments during four consecutive years from 2016 to 2020 in different locations in Iran (one year in Zarghan, two years in Ghorveh, one year in Sanandaj) and under two different irrigation regimes (normal irrigation and water deficit stress conditions). All 30 triticale genotypes were cultivated in a randomized complete block design (RCBD) with three replications in each environment (12 environments: 6 trials in 2 conditions). Grain yield of triticale genotypes was measured and it applied to calculate all known stability indices (univariate methods) along with the meta-analysis models were evaluated in this study. Additionally, two novel techniques (Stability ID: SID and AMMI PC Value: APCV) were introduced and successfully tested for screening stable genotypes. These methods were introduced to improve and resolve the limitation of the previous stability methods. Meanwhile, heatmap analysis, as a proper data-mining technique, has been successfully applied for the first time to find stable genotypes in different environments in this study. The results clearly indicated a higher suitability of our introduced methods over previous multi-trials screening methods. Based on our methods and considering all environments, triticale genotypes ELTTCL21 (SID = 8.00; APCV = 28.12), ELTTCL25‌ (SID = 8.14; APCV = 30.02), ELTTCL30 (SID = 8.43; APCV = 17.00), ET-90-8 (SID = 14.00; APCV = 42.05), and Sanabad (SID = 10.57; APCV = 12.44) were among stable genotypes and they can be nominated as new cultivars. Additionally, for stress condition genotypes ELTTCL30 (stress: 380.6 g/m2) and ELTTCL18 (stress: 360.79 g/m2) and for normal condition genotypes ET-90-4 (normal: 849.4 g/m2) and ELTTCL20 (normal:845 g/m2) were respectively the most proper genotypes with the highest production to be considered for each condition separately.

Abstract The statistical properties of the detection events constituting the interference fringes at the output of an interferometer are well-known. Nevertheless, there is still no unified view of what is happening to a quantum system inside an interferometer. Strong measurements of path operators destroy the interference effect. In weak measurements, an observable is weakly coupled to a pointer system and the resulting weak values quantify the observable by minimally disturbing the system. Previous which-way experiments with weak measurements could extract either the real or imaginary part of a single weak value with each ensemble. Here, we present the simultaneous full complex quantification of two path weak values with a single ensemble in a Mach–Zehnder neutron interferometer. Magnetic fields, oscillating with different frequencies, change the energy state in each interferometer path. The time-dependent phase between the energy states distinctly marks each path. The resulting beating intensity modulation at the interferometer output gives both path weak values. For the present experiment, the weak values’ absolute value and phase directly describe the observed amplitude and phase of the intensity modulation.

Abstract Shock is a life-threatening condition. This study evaluated if sublingual microcirculatory perfusion on admission is associated with 30-day mortality in older intensive care unit (ICU) shock patients. This trial prospectively recruited ICU patients (≥ 80 years old) with arterial lactate above 2 mmol/L, requiring vasopressors despite adequate fluid resuscitation, regardless of shock cause. All patients received sequential sublingual measurements on ICU admission (± 4 h) and 24 (± 4) hours later. The primary endpoint was 30-day mortality. From September 4th, 2022, to May 30th, 2023, 271 patients were screened, and 44 included. Patients were categorized based on the median percentage of perfused small vessels (sPPV) into those with impaired and sustained microcirculation. 71% of videos were of good or acceptable quality without safety issues. Patients with impaired microcirculation had significantly shorter ICU and hospital stays (p = 0.015 and p = 0.019) and higher 30-day mortality (90.0% vs. 62.5%, p = 0.036). Cox regression confirmed the independent association of impaired microcirculation with 30-day mortality (adjusted hazard ratio 3.245 (95% CI 1.178 to 8.943, p = 0.023). Measuring sublingual microcirculation in critically ill older patients with shock on ICU admission is safe, feasible, and provides independent prognostic information about outcomes. Trial registration NCT04169204.

Abstract Decision to explore new options with uncertain outcomes or exploit familiar options with known outcomes is a fundamental challenge that the brain faces in almost all real-life decisions. Previous studies have shown that humans use two main explorative strategies to negotiate this explore-exploit tradeoff. Exploring for the sake of information is called directed exploration, and exploration driven by behavioral variability is known as random exploration. While previous neuroimaging studies have shown different neural correlates for these explorative strategies, including right frontopolar cortex (FPC), right dorsolateral prefrontal cortex (DLPFC), and dorsal anterior cingulate cortex (dACC), there is still a lack of causal evidence for most of these brain regions. Here, we focused on the right DLPFC, which was previously supported to be involved in exploration. Using the continuous theta burst stimulation (cTBS) and Horizon task on twenty-five healthy right-handed adult participants, we showed that inhibiting rDLPFC did not change directed exploration but selectively reduced random exploration, by increasing reward sensitivity over the average reward of each option. This suggests a causal role for rDLPFC in random exploration, and further supports dissociable neural implementations for these two explorative strategies.

Abstract The (re-)construction of past and future personal experiences, termed mental time travel (MTT), is highly adaptive and contributes to self-related beliefs and attitudes. Mounting evidence suggests that self-efficacy (SE), the belief that one can overcome obstacles on their own account, is functionally related to MTT. In the present study, we used novel methods for the analysis of MTT narratives based on natural language processing (NLP) to investigate the relation between SE and MTT. We demonstrated that self-efficacious participants remembered and imagined experiences which were semantically less similar and contained a wider variety of contents. Additionally, increased SE was related to a positive reappraisal of personal episodes and reports of a more active role within mental scenarios. In conclusion, NLP appears to be a valuable method to quantify changes to the (re-)construction of personal experience that might support cognitive and emotional functioning.

Abstract Introduction Appendicitis is a common cause of acute abdomen. Rarely, it may form adhesions to nearby structures, complicating surgeries, especially when involving vascular structures such as the internal iliac artery, potentially causing severe intraoperative hemorrhage. Case presentation A 65-year-old Middle Eastern male presented with abdominal pain and anorexia for 5 days. Examination and imaging confirmed acute appendicitis with complications. Additionally, a large pelvic mass was noted. During surgery, severe bleeding was encountered due to an adhesion between the appendix and the right internal iliac artery, managed by ligating the artery. The patient recovered well and was discharged in stable condition. Histopathology confirmed the diagnosis. Conclusion This case highlights a rare vascular complication of appendectomy due to abnormal adhesions between the appendix and the internal iliac artery, associated with a large pelvic mass. This study emphasizes the need for thorough preoperative evaluation and careful surgical planning in patients with unusual anatomical variations or specific underlying conditions such as neurofibromatosis. Early recognition and strategic management of vascular adhesions are essential to optimize patient outcomes in appendectomies complicated by such rare scenarios.

Objective: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), have been associated with sleep disturbances as extra-intestinal manifestations. We aimed to evaluate sleep quality in a group of Middle Eastern IBD patients while assessing the links between disease characteristics, sleep disturbances, and related comorbidities. Materials and Methods: Outpatient IBD cases who attended our hospital clinic from 2019 to 2021 were recruited in this prospective study. The patients filled in verified translations of the insomnia severity index, Epworth sleepiness scale, Pittsburgh sleep quality index, Berlin questionnaire for obstructive sleep apnea (OSA), and restless legs syndrome (RLS) questionnaire by means of online or phone surveys. The chi-squared test and Student’s t-test were used for binary and continuous variables, respectively. The Mann-Whitney U test was used for non-normally distributed data. Results: The sleep quality of 82 IBD patients (13 CD and 69 UC) was assessed. Low sleep quality was observed in 52 cases (63.4%), and UC patients with pancolitis were significantly more likely to have sleep disturbances compared to patients with partial colitis (p=0.015). Moreover, patients with elevated C-reactive protein (CRP) displayed significantly higher frequencies of OSA and RLS (p=0.038 and p=0.040, respectively). Conclusion: Sleep impairment was identified in more than half of our IBD patient pool. Therefore, we suggest screening for sleep disturbances (particularly in UC patients with pancolitis) and related comorbidities, such as OSA and RLS (especially in patients with elevated CRP levels), in IBD patients to enhance their quality of sleep.

Abstract Although reduced experimental pain habituation is proposed as a proxy of diminished endogenous pain modulatory capacity in chronic pain, prior studies show contradictory findings. Even across healthy participants, pain habituation varies substantially, which may relate to another measure of endogenous pain modulation, i.e., conditioned pain modulation (CPM). Hence, this study investigated the relationship between pain habituation and CPM. Pain habituation was assessed in 45 healthy participants between two blocks of 15–20 contact-heat stimuli applied to the hand. Habituation of subjective pain ratings and objective neurophysiological readouts (contact-heat evoked potential (CHEP) and palmar sympathetic skin response (SSR)) was investigated. CPM was assessed by comparing heat pain thresholds before and after hand immersion in a noxious cold (9 °C) and lukewarm water bath (32 °C, to control for repeated measures effects). Pain habituation showed a large variability, with subjective but not objective pain habituation correlating with cold-induced CPM effects (r = 0.50; p = 0.025). This correlation was not observed for ‘true’ CPM effects (corrected for repeated measures effects) nor for CPM effects induced by a lukewarm water bath. These findings suggest that the observed variability in subjective pain habituation may be influenced by both descending endogenous pain modulation and peripheral adaptation processes associated with repeated measures. Objective pain habituation readouts, i.e., CHEPs and SSRs, capture different, complementary aspects of endogenous pain modulation.

Abstract This study was designed to investigate the effect of vitamin D and/or synbiotics on the response to treatment, cytokines profile and hormonal biomarkers in breast cancer patients undergoing neoadjuvant therapy. A total of 76 patients were recruited and completed the course of the intervention between 2019 and 2021 in Kerman, Iran. breast cancer patients were randomly enrolled in this study. Patients divided into four groups to receive one of the following regimens: placebo, vitamin D, synbiotics and a combination of vitamin D and synbiotics. clinicopathologic parameters, inflammatory and anti-inflammatory biomarkers and hormonal levels were measured at the baseline and four months after intervention. The study results found no clear link between the interventions and achieving pathological complete response (pCR), and a similar trend was observed in Ki-67 index examination. After neoadjuvant therapy, TNF-α concentrations decreased, with vitamin D supplementation moderating this decline. Vitamin D supplemented groups showed a significant increase in serum IL-6 levels. While IL-10 levels decreased in the placebo group, all intervention groups were protected from this decline. Moreover, there was a notable increase in the anti-inflammatory index, particularly in the group receiving both vitamin D and synbiotic supplementation, suggesting potential synergistic anti-inflammatory effects from their combined administration. The outcomes suggest a potential anti-inflammatory function of this combination. Consequently, more extensive studies with prolonged follow-up periods and substantial sample sizes are warranted to thoroughly evaluate their potential benefits for breast cancer patients.

Abstract Hodgkin lymphoma (HL) is a rare malignancy affecting the lymphatic system. Our study examined the incidence rates of adult HL based on sex, race/ethnicity, age, and histological subgroups in the United States (US) from 2000 to 2020. Data for this study were extracted from the Surveillance, Epidemiology, and End Results 22 database. HL patients were identified utilizing the International Classification of Diseases for Oncology version 3 and categorized as classical HL, lymphocyte-rich/mixed cell/lymphocyte depleted, nodular sclerosis, classical HL, not otherwise specified, and nodular lymphocyte-predominant HL. The study reported average annual percent change (AAPC). All estimates were presented as counts and age-standardized incidence rates (ASIRs) per 100,000 individuals. Between 2000 and 2019, a total of 70,924 cases of HL were reported in the US. Classical HL was the predominant subtype (94.27%), and most incident cases were among non-Hispanic Whites (66.92%) and those aged 20–29 years (24.86%). The ASIR per 100,000 population was 3.83 for men and 2.92 for women. Both sexes showed declines in the AAPCs between 2000 and 2019 (− 0.64% [− 0.99, − 0.28] and − 0.40% [− 0.77, − 0.03] for men and women, respectively). There was a significant decrease in ASIRs after COVID-19 among both sexes (percent change: − 7.49% [− 11.58, − 3.40]). Throughout all age groups, men had a higher incidence rate compared to women, except for those aged 20–29 years. Although the overall HL incidence rate was lowered in the study period from 2000 to 2019, a dramatic decrease in ASIRs of HL patients following COVID-19 pandemic was observed.

Abstract When studying the working memory (WM), the ‘slot model’ and the ‘resource model’ are two main theories used to describe how information retention occurs. The slot model shows that WM capacity consists of a certain number of predefined slots available for information storage. This theory explains that there is a binary condition during information recall in which information is either wholly maintained within a slot or forgotten. The resource model has a resolution-based approach, suggesting a continuous resource able to be distributed among a number of items in WM capacity. Recently hybrid models have been introduced, suggesting that WM may not strictly conform to only one model. Accordingly, to understand the relationship between two of the most widely used paradigms in WM evaluation, we implemented a correlational assessment in two different psychophysics tasks, an analog recall paradigm with sequential bar presentation and a delayed match-to-sample (DMS) task with checkerboard stimuli. Our study revealed significant correlations between WM performance in the DMS task and recall error, precision, and sources of errors in the sequential paradigm. Overall, the findings emphasize the importance of considering both tasks in understanding WM processes, as they shed light on the debate between the slot and resource models by revealing overlapping elements in both theories and the tasks used to evaluate WM capacity.

Abstract Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48–1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17–1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18–0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Abstract Background The effects of mesenchymal stem cells (MSCs) on heart failure (HF) have been controversial. This study was conducted to investigate whether the transplantation of MSCs after HF could help improve clinical outcomes and myocardial performance indices. Methods Using a systematic approach, electronic databases were searched for randomized controlled trials (RCTs), which evaluated the transplantation of MSCs after HF. The outcomes owf interest included clinical outcomes and myocardial function indices. We also assessed the role of age, cause of heart failure, cell origin, cell number, type of donor (autologous/allogeneic), and route of cell delivery on these outcomes. Using the random-effects method, a relative risk (RR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) were pooled. Results Seventeen RCTs including 1684 patients (927 and 757 patients in the intervention and control arms, respectively) were enrolled. The RR (95% CI) of mortality was 0.78 (0.62; 0.99, p = 0.04) in the MSC group compared to the controls. HF rehospitalization decreased in the MSC group (RR = 0.85 (0.71–1.01), p = 0.06), but this was only significant in those who received autologous MSCs (RR = 0.67 (0.49; 0.90), p = 0.008). LVEF was significantly increased among those who received MSC (MD = 3.38 (1.89; 4.87), p

Abstract Performing mathematical calculations is a cognitive activity that can affect biological signals. This study aims to examine the changes in electroencephalogram (EEG) and electrocardiogram (ECG) signals of 36 healthy subjects during the performance of arithmetic tasks. To process EEG signals in different frequency bands, the energy and entropy of entropy (EoE) were extracted from the power spectrum and phase spectrum, respectively. Statistical analysis was conducted to determine meaningful features. These features were sent into support vector machine (SVM) and multi-layer perception (MLP) classifiers to assess their capability in separating math and rest classes. Results indicated the highest classification accuracy of 98.4% for classifying good counters in math and rest state using the MLP method. Based on the majority of features selected for each EEG channel, discriminative brain areas were identified. Analyzing EEG signals proved that math calculation may have multiple influences on various parts of the brain. By comparing good counters’ brain activities to those in a resting state, prominent changes were observed in the F4, C4, T4, T5, P3, and O2 areas. However, O1 and O2 channels showed significant changes in the brain of bad counters compared to the resting state. Considering ECG signals also demonstrated that during math calculation the number of heart rates per minute surpasses the rest state. These alterations can occur due to cognitive abilities or emotional processes which were observed to be prominent in subjects who performed more accurate calculations.

Abstract The COVID-19 pandemic has significantly impacted the working conditions of nurses, leading to a detrimental effect on their sleep quality. This cross-sectional study aimed to investigate the prevalence of poor sleep quality and its associated factors among nurses working in COVID-19 wards in Kermanshah, Iran. A total of 97 nurses were selected through simple random sampling from COVID-19 wards. Data was collected using a demographic information sheet and the Pittsburgh Sleep Quality Index. Descriptive and inferential statistical methods, including chi-square and multiple logistic regression, were used for data analysis. The results showed that 74.2% (n = 72) of the nurses experienced poor sleep quality. Significant associations were found between poor sleep quality and work experience (p = 0.045) as well as the type of work shift (p = 0.001). However, no significant relationships were observed between poor sleep quality and factors such as age, sex, body mass index, overtime hours per month, physical activity, or underlying diseases. The high prevalence of poor sleep quality among nurses working in COVID-19 wards underscores the necessity of implementing targeted interventions to address this issue. In this regard, in addition to periodic shift schedule changes and reductions in working hours, it is necessary to adopt purposeful measures to improve working conditions and enhance the physical and mental health of nurses. These measures may include providing sufficient human resources to reduce the workload and fatigue of nurses, appropriate scheduling of working hours, and the implementation of stress management programs.

Abstract Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p

Abstract Background Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year. Methods A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed. Results All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy. Conclusions Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO. Trial registration No registration, retrospective analysis. Graphical Abstract

Abstract Nurses may experience burnout more than other professions. Occupational burnout is a serious concern considering the importance of nurses' jobs in patient care. This study was carried out with the aim of designing and validating the questionnaire of burnout factors in the operating room nurses. Mixed method study was done in two qualitative and quantitative phases in 2022 on Iranian operating room nurses. In the first stage, the concept of operating room nurses' burnout was explained using interviews and literature review, and items were generated. In the second stage, the face validity, content and construct validity of the questionnaire was examined with 342 operating room nurses, and also the reliability of the questionnaire was tested using internal consistency (Cronbach's alpha) and stability (test–retest). After conducting the interview and literature review, 65 questions were extracted. Based on face validity, 4 items were modified. After content validity, 40 items remained. In construct validity, after exploratory factor analysis, 34 items with 5 dimensions were extracted. These dimensions included Organizational, Individual, Interpersonal, Occupational Nature and Managerial factors. Cronbach's alpha and intra-class correlation coefficient were equal to 0.937 and 0.946, respectively. The designed tool based on understanding the concept of burnout in operating room nurses has appropriate and acceptable validity and reliability. Therefore, it can be used to measure burnout in operating room nurses.

Electroconvulsive therapy is an effective and well-tolerated antidepressant treatment for the elderly population. The place of electroconvulsive therapy in the treatment sequence for depression in the elderly is currently not well established. This review aims to identify the factors that contribute to a positive response and remission in elderly patients with depression undergoing electroconvulsive therapy treatment. We searched five bibliographic databases (Medline ALL Ovid, Embase.com, APA PsycInfo Ovid, Cochrane Library Wiley and Web of Science Core Collection) for articles published between 1995 and June 2023. Of the 2149 articles screened, 19 were included in the review. No significant associations were found between remission and/or response and salivary cortisol, baseline hippocampal and white matter hyperintensities, total amyloid load or global cortical atrophy. The reviewed articles did not show a significant difference in remission between unilateral and bilateral electroconvulsive therapy treatment. Other interesting findings are that moderately elevated levels of CRP and S100B levels, lower retardation scores, poorer performance on the word reading task at baseline and longer post-ictal reorientation time may be associated with higher remission and/or response rates. Medial temporal atrophy can be associated with lower Montgomery-Åsberg Depression Rating Scale (MADRS) decrease after electroconvulsive therapy. Finally, elderly patients had higher rates of electroconvulsive therapy response; retardation and psychotic features may mediate this association. Incorporation of this data into clinical practice may facilitate a personalised approach to electroconvulsive therapy. However, research on this topic is scarce and there are few studies that focus specifically on older people.

Summary: Background: Endotype classification becomes the cornerstone of understanding sepsis pathogenesis. Macrophage activation-like syndrome (MALS) and immunoparalysis are the best recognized major endotypes, so far. Interferon-gamma (IFNγ) action on tissue macrophages stimulates the release of the cytotoxic chemokine CXCL9. It was investigated if this mechanism may be an independent sepsis endotype. Methods: In this cohort study, 14 patient cohorts from Greece, Germany and Italy were studied. The cohorts were 2:1 randomly split into discovery and validation sets. Sepsis was defined by the Sepsis-3 definitions and blood was sampled the first 24 h from meeting the Sepsis-3 definitions. Concentrations of IFNγ, CXCL9, IP-10 (IFNγ induced protein-10), soluble CD163 and ferritin were measured. The endotype of IFNγ-driven sepsis (IDS) was defined in the discovery set as the combination of a) blood IFNγ above a specified cut-off associated with the minimal risk for immunoparalysis (defined as ≥8000 HLA-DR receptors on CD45/CD14-monoytes); and b) increase of CXCL9. Results were compared to the validation set. Findings: 5503 patients were studied; 3670 in the discovery set and 1833 in the validation set. IDS was defined as IFNγ more than 3 pg/ml and CXCL9 more than 2200 pg/ml. The frequency of IDS in the discovery set was 19.9% (732 patients; 95% confidence intervals-CIs 18.7–21.3%) and in the validation set 20.0% (366 patients; 95% CIs 18.2–21.9%). Soluble CD163, a marker of macrophage activation, was greater in IDS and IDS had features distinct from MALS. The mortality in IDS patients was 43.0% (315 patients; 95% CIs 39.5–46.6%) in the discovery set and 40.4% in the validation set (148 patients; 95% CIs 35.5–45.5%) (p = 0.44 compared to patients of the discovery set). IDS was an independent risk factor for death in the presence of other endotypes, severity scores and organ dysfunctions of the multivariate model [hazard ratio 1.71 (95% CIs 1.45–2.01) in the discovery set and 1.70 (95% CIs 1.34–2.16) in the validation set]. Decreases of IFNγ and CXCL9 blood levels within the first 72 h were associated with better outcome. Interpretation: IDS is a new sepsis endotype independently associated with unfavorable outcome. Funding: Hellenic Institute for the Study of Sepsis; Horizon 2020 project ImmunoSep; Swedish Orphan BioVitrum AB (publ) and German Federal Ministry of Education and Research.

AIMS OF THE STUDY: Health equity is a key component of quality of care and an objective for a growing number of quality improvement projects for deontological, ethical, public health and economic reasons. To monitor equity in the delivery of health services in Switzerland, there is a need to implement valid, measurable and actionable equity indicators, along with vulnerability stratifiers such as migrant status, which could lead to differences in quality of care. The aim of this study was to develop a set of healthcare equity indicators and stratifiers targeting inpatient and outpatient populations and to test their feasibility. METHODS: A scoping literature review and inputs from a national interprofessional expert taskforce provided a set of indicators and vulnerability stratifiers. The most valid and measurable indicators and stratifiers were retained using a Delphi process. They were then operationalised, and their implementation tested in three Swiss hospitals from the three language regions. RESULTS: A taskforce of 18 experts, including a patient representative, selected 11 indicators that evaluate structures, processes and outcomes, and five vulnerability stratifiers. Although most indicators and stratifiers could be implemented in all three hospitals, data availability was limited for some variables, including patient satisfaction and access to interpreters for foreign-language patients. CONCLUSIONS: The equity indicators and stratifiers identified by this two-stage process have content validity, wide patient coverage and are focused on inequities in the healthcare system that are actionable through improvement projects. Both the indicators and the project methodology could be replicated in institutions aiming for more equitable care.

Introduction: Hundreds of children suffer burn injuries each day, yet care guidelines regarding the need for acute inpatient treatment vs outpatient follow-up vs no required follow-up remain nebulous. This gap in the literature is particularly salient for the emergency clinician, who must be able to rapidly determine appropriate disposition. Methods: This was a retrospective review of patients presenting to a Level II pediatric trauma center, January 1, 2017–December 31, 2019, and discharged with an International Classification of Diseases, Rev 10, burn diagnosis. We obtained and analyzed demographics, burn characteristics, and follow-up data using univariate and bivariate analysis as well as logistic regression modeling. Patients were stratified into three outcome groups: group 1—patients who underwent emergent evaluation at a burn center or were admitted at their first follow-up appointment; group 2—patients who followed up at a burn center (as an outpatient) or at the emergency department (and were discharged home); and group 3—patients with no known follow-up. Results: A total of 572 patients were included in this study; 58.9% of patients were 1–5 years of age. Sixty-five patients met group 1 criteria, 189 patients met group 2 criteria, and 318 patients met group 3 criteria. Sixty-five percent of patients met at least one American Burn Association criteria, and 79% of all burns were second-degree burns. Flame and scald burns were associated with increased odds (odds ratio [OR] 1.21, OR 1.12) of group 1 vs group 2 + group 3 (P = 0.02, P

Abstract Excessive Cu2+ intake can cause neurological disorders (e.g. Wilson’s disease) and adversely affect the gastrointestinal, liver, and kidney organs. The presence of Cu2+ is strongly linked to the emergence and progression of Wilson's disease (WD), and accurately measuring the amount of copper is a crucial step in diagnosing WD at an early stage in a clinical setting. In this work, CQDs were fabricated through a facile technique as a novel fluorescence-based sensing platform for detecting Cu(II) in aqueous solutions, and in the serum samples of healthy and affected individuals by WD. The CQDs interact with Cu(II) ions to produce Turn-on and Turn-off states at nano-molar and micro-molar levels, respectively, with LODs of 0.001 µM and 1 µM. In fact, the Cu2+ ions can act like a bridge between two CQDs by which the charge and electron transfer between the CQDs may increase, possibly can have significant effects on the spectroscopic features of the CQDs. To the best of our knowledge, this is the first reported research that can detect Cu(II) at low levels using two different complexation states, with promising results in testing serum. The potential of the sensor to detect Cu(II) was tested on serum samples from healthy and affected individuals by WD, and compared to results obtained by ICP-OES. Astonishingly, the results showed an excellent correlation between the measured Cu(II) levels using the proposed technique and ICP-OES, indicating the high potential of the fluorimetric CQD-based probe for Cu(II) detection. The accuracy, sensitivity, selectivity, high precision, accuracy, and applicability of the probe toward Cu(II) ions make it a potential diagnostic tool for Wilson's disease in a clinical setting.

Abstract Laser-driven dynamic compression experiments of plastic materials have found surprisingly fast formation of nanodiamonds (ND) via X-ray probing. This mechanism is relevant for planetary models, but could also open efficient synthesis routes for tailored NDs. We investigate the release mechanics of compressed NDs by molecular dynamics simulation of the isotropic expansion of finite size diamond from different P-T states. Analysing the structural integrity along different release paths via molecular dynamic simulations, we found substantial disintegration rates upon shock release, increasing with the on-Hugnoiot shock temperature. We also find that recrystallization can occur after the expansion and hence during the release, depending on subsequent cooling mechanisms. Our study suggests higher ND recovery rates from off-Hugoniot states, e.g., via double-shocks, due to faster cooling. Laser-driven shock compression experiments of polyethylene terephthalate (PET) samples with in situ X-ray probing at the simulated conditions found diamond signal that persists up to 11 ns after breakout. In the diffraction pattern, we observed peak shifts, which we attribute to thermal expansion of the NDs and thus a total release of pressure, which indicates the stability of the released NDs.

Abstract Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes. Using data from trastuzumab deruxtecan-treated patients with HER2-positive and HER2-negative breast cancer from a phase 1 study (NCT02564900; DS8201-A-J101; N = 151), QCS-based patient stratification showed longer progression-free survival (14.8 vs 8.6 months) with higher prevalence of patient selection (76.4 vs 56.9%) and a better cross-validated log-rank p value (0.026 vs 0.26) than manual scoring based on the American Society of Clinical Oncology / College of American Pathologists guidelines. QCS-based features enriched the HER2-negative subgroup by correctly predicting 20 of 26 responders.

Abstract Cancers of the kidney and renal pelvis are among the most prevalent types of urinary cancers. We aimed to outline the incidence trends of kidney and renal pelvis cancers by age, sex, race/ethnicity, and histology in the United States (US) from 2000 to 2020. The data was obtained from the Surveillance, Epidemiology, and End Results (SEER) 22 database. The identification of patients with kidney and renal pelvis cancers with morphologies of renal cell carcinoma, nephroblastoma, sarcoma, and neuroendocrine tumor was conducted utilizing the International Classification of Diseases for Oncology version 3. The average annual percent change (AAPC) were presented. All estimates were given in the form of counts and delayed age-standardized incidence rates (ASIRs) per 100,000 people. From 2000 to 2019, a total of 490,481 cases of kidney and renal pelvic cancer were recorded across all age groups in the US. The majority of them were among Non-Hispanic Whites (NHWs) (69.75%) and those aged 55–69 years (39.96%). The ASIRs per 100,000 for kidney and pelvis cancers were 22.03 for men and 11.14 for women. Non-Hispanic Black men had the highest ASIR (24.53 [24.24, 24.81]), and increase in ASIR over the 2000–2019 period (AAPC: 2.19% [1.84, 2.84]). There was a noticeable increase in incidence of kidney and renal pelvis cancers. Individuals aged 70–84 years had the highest ASIR for kidney and renal pelvis cancers. The COVID-19 era has resulted in a significant reduction in incidence rates across all demographics.

Abstract Background Eptinezumab is a monoclonal antibody that targets calcitonin gene-related peptide (CGRP mAb) and is used for migraine prophylaxis. Efficacy data are mainly from clinical trials, real-world data are hardly available yet. Reimbursement policy in Germany leads to eptinezumab mainly being used in patients having failed pre-treatment with other CGRP mAb. To date, it is unclear whether eptinezumab is efficacious and well tolerated in this population and how the treatment response differs from patients who are naive to CGRP mAbs. Methods We analysed clinical routine data of 79 patients (episodic migraine (EM): n = 19; chronic migraine (CM): n = 60) from four different centres in Germany. All patients were treated with eptinezumab (100mg). Differences in monthly headache (MHD), migraine (MMD) and acute medication days (AMD) after three months were analysed. The correlation of response with the number of CGRP mAb failures was evaluated. Significance level has been corrected (alpha = 0.017). Results After three months MHD, MMD and AMD were significantly reduced. In EM, the median reduction for MHD was 4.0 days (IQR: -6.5 to -1.0; p = 0.001), for MMD 3.0 days (IQR: -5.5 to -1.5; p

Abstract Background PRiVENT (PRevention of invasive VENTilation) is an evaluation of a bundle of interventions aimed at the prevention of long-term invasive mechanical ventilation. One of these elements is an e-learning course for healthcare professionals to improve weaning expertise. The aim of our analysis is to examine the implementation of the course in cooperating intensive care units. Methods The course has been developed through a peer review process by pulmonary and critical care physicians in collaboration with respiratory therapists, supported by health services researchers and a professional e-learning agency. The e-learning platform “weLearn” was made available online to participating healthcare professionals. Feedback on the e-learning programme was obtained and discussed in quality circles (QCs). We measured the acceptance and use of the programme through access statistics. Results The e-learning course “Joint Prevention of Long-Term Ventilation” consists of 7 separate modules with practice-oriented training units as well as a cross-module area and corresponding interactive case studies. Users can receive 23 CME (continuing medical education) credits. The platform was released on July 1, 2021. By June 28, 2023, 214 users from 33 clinics had registered. Most users (77–98%) completed the modules, thus performing well in the test, where 90–100% passed. In the QCs, the users commended the structure and practical relevance of the programme, as well as the opportunity to earn CME credits. Conclusion Especially for medical staff in intensive care units, where continuous training is often a challenge during shift work, e-learning is a useful supplement to existing medical training. Trial registration The PRiVENT study is registered at ClinicalTrials.gov (NCT05260853) on 02/03/2022.

Abstract Hereby, we aimed to comprehensively compare different scoring systems for pediatric trauma and their ability to predict in-hospital mortality and intensive care unit (ICU) admission. The current registry-based multicenter study encompassed a comprehensive dataset of 6709 pediatric trauma patients aged ≤ 18 years from July 2016 to September 2023. To ascertain the predictive efficacy of the scoring systems, the area under the receiver operating characteristic curve (AUC) was calculated. A total of 720 individuals (10.7%) required admission to the ICU. The mortality rate was 1.1% (n = 72). The most predictive scoring system for in-hospital mortality was the adjusted trauma and injury severity score (aTRISS) (AUC = 0.982), followed by trauma and injury severity score (TRISS) (AUC = 0.980), new trauma and injury severity score (NTRISS) (AUC = 0.972), Glasgow coma scale (GCS) (AUC = 0.9546), revised trauma score (RTS) (AUC = 0.944), pre-hospital index (PHI) (AUC = 0.936), injury severity score (ISS) (AUC = 0.901), new injury severity score (NISS) (AUC = 0.900), and abbreviated injury scale (AIS) (AUC = 0.734). Given the predictive performance of the scoring systems for ICU admission, NTRISS had the highest predictive performance (AUC = 0.837), followed by aTRISS (AUC = 0.836), TRISS (AUC = 0.823), ISS (AUC = 0.807), NISS (AUC = 0.805), GCS (AUC = 0.735), RTS (AUC = 0.698), PHI (AUC = 0.662), and AIS (AUC = 0.651). In the present study, we concluded the superiority of the TRISS and its two derived counterparts, aTRISS and NTRISS, compared to other scoring systems, to efficiently discerning individuals who possess a heightened susceptibility to unfavorable consequences. The significance of these findings underscores the necessity of incorporating these metrics into the realm of clinical practice.

Aim To investigate out-of-hospital cardiac arrest (OHCA) trend, provided advanced life support (ALS) measures, automated external defibrillator (AEDs) utilization and by-standers involvement in cardiopulmonary resuscitation (CPR) during OHCA incidents.Methods This cross-sectional study encompassed data pertaining to all OHCA incidents attended to by the Emergency Medical Service of Canton Sarajevo, Bosnia and Herzegovina, covering the period from January 2018 to December 2022.Results Among a total of 1131 OHCA events, 236 (20.8 %) patients achieved return of spontaneous circulation (ROSC); there were 175 (74.1%) males and 61 (25.9%) females. The OHCA incidence was 54/100.000 inhabitants per year. After a 30-day period post-ROSC, 146 (61.9%) patients fully recovered, while 90 (38.1%) did not survive during this timeframe. Younger age (p

Aim Despite advancements in the diagnosis, treatment and monitoring of patients with acute coronary syndrome (ACS), morbidity and mortality following ACS remain high. The aim of this study was to actively seek possible predictors of adverse outcomes after ACS aiming to identify high-risk patients promptly.Methods This retrospective cohort study investigated patients with ACS hospitalized at Clinical Centre of the University of Sarajevo from 2019 to 2021. Patients were followed up for a period of 12 months post-discharge to assess major cardiovascular events (MACE) and MACE associated independent predictors. Results. The study included 121 patients, mostly male 102 (84.3%), with a mean age of 60.83±12.61 years; prevalent risk factors were hypertension 94 (77.7%), dyslipidaemia 84 (69.4%), diabetes mellitus 91 (75.2%), active smoking 67 (55.4%) and positive family history of cardiovascular diseases 81 (66.9%). MACE occurred in 33 (27.3%) patients since the initial ACS, and those patients were older (p=0.012), had higher level of creatinine (p

BackgroundDegenerative cervical myelopathy (DCM) is a progressive chronic spinal cord injury estimated to affect 1 in 50 adults. Without standardised guidance, clinical research studies have selected outcomes at their discretion, often underrepresenting the disease and limiting comparability between studies. Utilising a standard minimum data set formed via multi-stakeholder consensus can address these issues. This combines processes to define a core outcome set (COS)-a list of key outcomes-and core data elements (CDEs), a list of key sampling characteristics required to interpret the outcomes. Further "how" these outcomes should be measured and/or reported is then defined in a core measurement set (CMS). This can include a recommendation of a standardised time point at which outcome data should be reported. This study defines a COS, CDE, and CMS for DCM research.Methods and findingsA minimum data set was developed using a series of modified Delphi processes. Phase 1 involved the setup of an international DCM stakeholder group. Phase 2 involved the development of a longlist of outcomes, data elements, and formation into domains. Phase 3 prioritised the outcomes and CDEs using a two-stage Delphi process. Phase 4 determined the final DCM minimal data set using a consensus meeting. Using the COS, Phase 5 finalised definitions of the measurement construct for each outcome. In Phase 6, a systematic review of the literature was performed, to scope and define the psychometric properties of measurement tools. Phase 7 used a modified Delphi process to inform the short-listing of candidate measurement tools. The final measurement set was then formed through a consensus meeting (Phase 8). To support implementation, the data set was then integrated into template clinical research forms (CRFs) for use in future clinical trials (Phase 9). In total, 28 outcomes and 6 domains (Pain, Neurological Function, Life Impact, Radiology, Economic Impact, and Adverse Events) were entered into the final COS. Thirty two outcomes and 4 domains (Individual, Disease, Investigation, and Intervention) were entered into the final CDE. Finally, 4 outcome instruments (mJOA, NDI, SF-36v2, and SAVES2) were identified for the CMS, with a recommendation for trials evaluating outcomes after surgery, to include baseline measurement and at 6 months from surgery.ConclusionsThe AO Spine RECODE-DCM has produced a minimum data set for use in DCM clinical trials today. These are available at https://myelopathy.org/minimum-dataset/. While it is anticipated the CDE and COS have strong and durable relevance, it is acknowledged that new measurement tools, alongside an increasing transition to study patients not undergoing surgery, may necessitate updates and adaptation, particularly with respect to the CMS.

Key Clinical Message Homozygous variants of Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation were previously identified as causes of periodic paralysis and congenital early‐onset myopathy, while it could be manifested as a late‐onset congenital core myopathy. Abstract Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core‐like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late‐onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C > A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core‐like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S‐related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.

Abstract Introduction Death due to covid‐19 is one of the biggest health challenges in the world. There are many models that can predict death due to COVID‐19. This study aimed to fit and compare Decision Tree (DT), Support Vector Machine (SVM), and AdaBoost models to predict death due to COVID‐19. Methods To describe the variables, mean (SD) and frequency (%) were reported. To determine the relationship between the variables and the death caused by COVID‐19, chi‐square test was performed with a significance level of 0.05. To compare DT, SVM and AdaBoost models for predicting death due to COVID‐19 from sensitivity, specificity, accuracy and the area under the rock curve under R software using psych, caTools, random over‐sampling examples, rpart, rpartplot packages was done. Results Out of the total of 23,054 patients studied, 10,935 cases (46.5%) were women, and 12,569 cases (53.5%) were men. Additionally, the mean age of the patients was 54.9 ± 21.0 years. There is a statistically significant relationship between gender, fever, cough, muscle pain, smell and taste, abdominal pain, nausea and vomiting, diarrhea, anorexia, dizziness, chest pain, intubation, cancer, diabetes, chronic blood disease, Violation of immunity, pregnancy, Dialysis, chronic lung disease with the death of covid‐19 patients showed (p

Abstract Background and Aims Cardiovascular diseases (CVDs) are one of the major diseases in developing and developed countries and have high prevalence and mortality rates. Pharmacological interventions, especially the use of combination medications, can have preventive effects in patients with CVDs. Recently, in the PolyIran trial, a combination of atorvastatin, hydrochlorothiazide, aspirin, and valsartan or enalapril (Polypill) was shown to be effective in providing survival benefits as a primary prevention strategy. In the present study, we examine the cost‐effectiveness of the use of polypill compared to its individual components (named as medication monotherapy) in the prevention of CVDs in Iran. Methods This was an economic evaluation study conducted to compare the cost‐utility of polypill with that of medication monotherapy for 10,000 hypothetical cohorts of people over 35 years of age using the Markov model and with a lifetime horizon. The study perspective was patient perspective and direct medical costs, quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratio were estimated. To deal with uncertaintysensitivity analyses were used. Results The results showed that polypill, with the lowest costs (871 USD) and highest QALYs (14.55), had the most cost‐utility than medication monotherapy. Also, the results showed that the highest sensitivities were related to the utilities of angina and stroke states. At the 21,768 USD threshold, polypill had a 92% probability of being cost‐effective versus other medications. Conclusion Considering that polypill had the most cost‐utility, it is suggested that health system policymakers pay special attention to polypill in designing clinical guidelines. Also, through covering this medication by health insurance organizations, it is possible to complete the country's medicine pharmacopeia in preventing CVDs.

OBJECTIVES: Due to the increasing complexity of the healthcare system, effective communication and data exchange between hospitalists (in-hospital physicians) and primary care physicians (PCPs) is both central and challenging. In Switzerland, little is known about hospitalists’ perception of their communication with PCPs. The primary objective was to assess hospitalists’ satisfaction with their communication with PCPs. Secondary objectives addressed all information about the referral process and communication with PCPs during and after the hospital encounter. Lastly, the results of a previous survey among PCPs were juxtaposed to compare their responses to similar questions. METHODS: This study surveyed hospitalists in six hospitals in the Central Switzerland region. The survey was sent via email to hospitalists from November 2021 to February 2022. The questionnaire contained 17 questions with single- and multiple-choice answers and the option of free-text entry. Exploratory multivariable logistic regression was used to analyse independent associations. RESULTS: In total, 276 of 1134 hospitalists responded (response rate 24.3%): (1) the majority of hospitalists are satisfied with the general communication (n = 162, 58.7%) as well as with referral letters (n = 145, 52.5%), (2) preferred information channels for referral letters are email (n = 212, 76.8%) and electronic portals (n = 181, 65.5%), (3) the three most important items of information in referrals are: medication list, diagnoses and reason for referral. In multivariable regression, compared to other clinicians, internists independently favoured informing PCPs of emergency admissions of their patients in a timely manner (OR 2.04; 95%CI 1.21–3.49). Comparing responses from PCPs (n = 109), the most prominent discrepancy was that 67% (n = 184) of hospitalists claimed to “always” inform after an encounter, whereas only 7% (n = 8) of PCPs agreed. CONCLUSION: Most hospitalists are satisfied with the communication with PCPs and prefer electronic communication channels. Room for improvement was found around timely transmission of patient information before and after hospital encounters.

Background and aim: Tissue engineering has provided many hopes for reconstructing bone lesions. For bone engineering, stem cells are cultured on suitable scaffolds under controlled stimulation conditions with growth factors. A scaffold is a temporary matrix for bone growth that provides a specific environment for tissue development and facilitates cell adhesion, growth, and differentiation. The present study aimed to evaluate the effect of stem cell base scaffolds on bone regeneration and formation in maxillofacial bone disorders. Material and methods: Searching international databases PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase databases, and Google Scholar search engine based on PRISMA 2020-27-item checklist and keywords Related to the objectives of the study, it was carried out from 2013 to January 2024. The prevalence was equivalent to the rate ratio of bone formation. A model with fixed effect and inverse–variance method was used. All statistical analyses are done using STATA/MP software. v17 was done considering the significance of less than 0.05. Results: Nine studies were selected according to the inclusion criteria. The fixed-effects rate ratio of bone formation meta-analysis showed that ES = 0.39, 95% CI; 0.34-0.45, p-value

Abstract Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure–activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

Abstract Most established clinical walking tests assess specific aspects of movement function (velocity, endurance, etc.) but are generally unable to determine specific biomechanical or neurological deficits that limit an individual’s ability to walk. Recently, inertial measurement units (IMU) have been used to collect objective kinematic data for gait analysis and could be a valuable extension for clinical assessments (e.g., functional walking measures). This study assesses the reliability of an IMU-based overground gait analysis during the 2-min walk test (2mWT) in individuals with spinal cord injury (SCI). Furthermore, the study elaborates on the capability of IMUs to distinguish between different gait characteristics in individuals with SCI. Twenty-six individuals (aged 22–79) with acute or chronic SCI (AIS: C and D) completed the 2mWT with IMUs attached above each ankle on 2 test days, separated by 1 to 7 days. The IMU-based gait analysis showed good to excellent test–retest reliability (ICC: 0.77–0.99) for all gait parameters. Gait profiles remained stable between two measurements. Sensor-based gait profiling was able to reveal patient-specific gait impairments even in individuals with the same walking performance in the 2mWT. IMUs are a valuable add-on to clinical gait assessments and deliver reliable information on detailed gait pathologies in individuals with SCI. Trial registration: NCT04555759.

Abstract Background Metabolic side effects of psychotropic medications are a major drawback to patients’ successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip. Results A global methylation increase was noted after the first month of treatment, which was more pronounced (p

Abstract Meteorological factors play a crucial role in affecting air quality in the urban environment. Peshawar is the capital city of the Khyber Pakhtunkhwa province in Pakistan and is a pollution hotspot. Sources of PM10 and the influence of meteorological factors on PM10 in this megacity have yet to be studied. The current study aims to investigate PM10 mass concentration levels and composition, identify PM10 sources, and quantify links between PM10 and various meteorological parameters like temperature, relative humidity (RH), wind speed (WS), and rainfall (RF) during the winter months from December 2017 to February 2018. PM10 mass concentrations vary from 180 – 1071 µg m−3, with a mean value of 586 ± 217 µg m−3. The highest concentration is observed in December, followed by January and February. The average values of the mass concentration of carbonaceous species (i.e., total carbon, organic carbon, and elemental carbon) are 102.41, 91.56, and 6.72 μgm−3, respectively. Water-soluble ions adhere to the following concentration order: Ca2+ > Na+ > K+ > NH4 + > Mg2+. Twenty-four elements (Al, Si, S, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Co, Zn, Ga, Ge, As, Se, Kr, Ag, Pb, Cu, and Cd) are detected in the current study by PIXE analysis. Five sources based on Positive Matrix Factorization (PMF) modeling include industrial emissions, soil and re-suspended dust, household combustion, metallurgic industries, and vehicular emission. A positive relationship of PM10 with temperature and relative humidity is observed (r = 0.46 and r = 0.56, respectively). A negative correlation of PM10 is recorded with WS (r = − 0.27) and RF (r = − 0.46). This study’s results motivate routine air quality monitoring owing to the high levels of pollution in this region. For this purpose, the establishment of air monitoring stations is highly suggested for both PM and meteorology. Air quality standards and legislation need to be revised and implemented. Moreover, the development of effective control strategies for air pollution is highly suggested.

Abstract Obstructive sleep apnea syndrome (OSAS) and obesity go hand in hand in the majority of patients and both are associated with a systemic inflammation, immune disturbance and comorbidities such as cardiovascular disease. However, the unambiguous impact of OSAS and obesity on the individual inflammatory microenvironment and the immunological consequences of human monocytes has not been distinguished yet. Therefore, aim of this study was to investigate the impact of OSAS and obesity related factors on the inflammatory microenvironment by performing flow cytometric whole blood measurements of CD14/CD16 monocyte subsets in normal weight OSAS patients, patients with obesity but without OSAS, and patients with OSAS and obesity, compared to healthy donors. Moreover, explicitly OSAS and obesity related plasma levels of inflammatory mediators adiponectin, leptin, lipocalin and metalloproteinase-9 were determined and the influence of different OSAS and obesity related factors on cytokine secretion and expression of different adhesion molecules by THP-1 monocytes was analysed. Our data revealed a significant redistribution of circulating classical and intermediate monocytes in all three patient cohorts, but differential effects in terms of monocytic adhesion molecules CD11a, CD11b, CD11c, CX3CR1, CD29, CD49d, and plasma cytokine levels. These data were reflected by differential effects of OSAS and obesity related factors leptin, TNFα and hypoxia on THP-1 cytokine secretion patterns and expression of adhesion molecules CD11b and CD49d. In summary, our data revealed differential effects of OSAS and obesity, which underlines the need for a customized therapeutic regimen with respect to the individual weighting of these overlapping diseases.

Abstract Proteins exert their function through protein–protein interactions. In Drosophila, G protein-coupled receptors like rhodopsin (Rh1) interact with a G protein to activate visual signal transduction and with arrestins to terminate activation. Also, membrane proteins like Rh1 engage in protein–protein interactions during folding within the endoplasmic reticulum, during their vesicular transport and upon removal from the cell surface and degradation. Here, we expressed a Rh1-TurboID fusion protein (Rh1::TbID) in Drosophila photoreceptors to identify in vivo Rh1 interaction partners by biotin proximity labeling. We show that Rh1::TbID forms a functional rhodopsin that mediates biotinylation of arrestin 2 in conditions where arrestin 2 interacts with rhodopsin. We also observed biotinylation of Rh1::TbID and native Rh1 as well as of most visual signal transduction proteins. These findings indicate that the signaling components in the rhabdomere approach rhodopsin closely, within a range of ca. 10 nm. Furthermore, we have detected proteins engaged in the maturation of rhodopsin and elements responsible for the trafficking of membrane proteins, resembling potential interaction partners of Rh1. Among these are chaperons of the endoplasmic reticulum, proteins involved in Clathrin-mediated endocytosis as well as previously unnoticed contributors to rhodopsin transportation, such as Rab32, Vap33, or PIP82.

The number of highly pathogenic avian influenza (HPAI) H5-related infections and deaths of wild birds in Europe was high during October 1, 2020–September 30, 2022. To quantify deaths among wild species groups with known susceptibility for HPAI H5 during those epidemics, we collected and recorded mortality data of wild birds in the Netherlands. HPAI virus infection was reported in 51 bird species. The species with the highest numbers of reported dead and infected birds varied per epidemic year; in 2020–21, they were within the Anatidae family, in particular barnacle geese (Branta leucopsis) and in 2021–22, they were within the sea bird group, particularly Sandwich terns (Thalasseus sandvicensis) and northern gannet (Morus bassanus). Because of the difficulty of anticipating and modeling the future trends of HPAI among wild birds, we recommend monitoring live and dead wild birds as a tool for surveillance of the changing dynamics of HPAI.

Key Clinical Message Hydatid cyst is a sly disease that can manifest with a spectrum of symptoms in almost every part of the human body, so it is crucial to be familiar with different scenarios that a patient may present. Abstract The echinococcus granulosus parasite causes hydatid disease and is common in areas with animal husbandry and agriculture. Here, we report a middle age woman who presented with abdominal pain that further investigation revealed a cyst in subdiaphragmatic area.