Time Points T1 Research Articles

13C-Metabolic flux analysis detected a hyperoxemia-induced reduction of tricarboxylic acid cycle metabolism in granulocytes during two models of porcine acute subdural hematoma and hemorrhagic shock.

Supplementation with increased inspired oxygen fractions has been suggested to alleviate the harmful effects of tissue hypoxia during hemorrhagic shock (HS) and traumatic brain injury. However, the utility of therapeutic hyperoxia in critical care is disputed to this day as controversial evidence is available regarding its efficacy. Furthermore, in contrast to its hypoxic counterpart, the effect of hyperoxia on the metabolism of circulating immune cells remains ambiguous. Both stimulating and detrimental effects are possible; the former by providing necessary oxygen supply, the latter by generation of excessive amounts of reactive oxygen species (ROS). To uncover the potential impact of increased oxygen fractions on circulating immune cells during intensive care, we have performed a 13C-metabolic flux analysis (MFA) on PBMCs and granulocytes isolated from two long-term, resuscitated models of combined acute subdural hematoma (ASDH) and HS in pigs with and without cardiovascular comorbidity. Swine underwent resuscitation after 2 h of ASDH and HS up to a maximum of 48 h after HS. Animals received normoxemia (PaO2 = 80 - 120 mmHg) or targeted hyperoxemia (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation, thereafter PaO2 as in the control group). Blood was drawn at time points T1 = after instrumentation, T2 = 24 h post ASDH and HS, and T3 = 48h post ASDH and HS. PBMCs and granulocytes were isolated from whole blood to perform electron spin resonance spectroscopy, high resolution respirometry and 13C-MFA. For the latter, we utilized a parallel tracer approach with 1,2-13C2 glucose, U-13C glucose, and U-13C glutamine, which covered essential pathways of glucose and glutamine metabolism and supplied redundant data for robust Bayesian estimation. Gas chromatography-mass spectrometry further provided multiple fragments of metabolites which yielded additional labeling information. We obtained precise estimations of the fluxes, their joint credibility intervals, and their relations, and characterized common metabolic patterns with principal component analysis (PCA). 13C-MFA indicated a hyperoxia-mediated reduction in tricarboxylic acid (TCA) cycle activity in circulating granulocytes which encompassed fluxes of glutamine uptake, TCA cycle, and oxaloacetate/aspartate supply for biosynthetic processes. We further detected elevated superoxide levels in the swine strain characterized by a hypercholesterolemic phenotype. PCA revealed cell type-specific behavioral patterns of metabolic adaptation in response to ASDH and HS that acted irrespective of swine strains or treatment group. In a model of resuscitated porcine ASDH and HS, we saw that ventilation with increased inspiratory O2 concentrations (PaO2 = 200 - 250 mmHg for 24 h after treatment initiation) did not impact mitochondrial respiration of PBMCs or granulocytes. However, Bayesian 13C-MFA results indicated a reduction in TCA cycle activity in granulocytes compared to cells exposed to normoxemia in the same time period. This change in metabolism did not seem to affect granulocytes' ability to perform phagocytosis or produce superoxide radicals.

A Structured Training for Trans Anal Irrigation in Pediatric Patients Improves Outcomes and Reduce Failures: Results of an Interventional Multicenter Prospective Study

BackgroundContinence issues due to organic causes including previous colorectal surgery or neurological issues might benefit from Transanal irrigation (TAI) that proved to be highly effective but with a number of limitations including a relatively high discontinuation rates. Our study was aimed at evaluating the efficacy of an advanced protocol tailored to each patient to prevent dropout and increase satisfaction, independence, and quality of life. Materials and methodsThis was a prospective, interventional, multicenter, nonrandomized study involving children aged 4–18 years with bowel dysfunction unresponsive to conventional treatments who required TAI. TAI was performed in accordance to the best standards of care with a total irrigation volume that was determined based on low emission X-Ray barium enemas performed at the very beginning of the study. All patients underwent training and assessments of continence, patients’ perspectives and quality of life were performed at different timepoints from enrollment (T0) up to 6 months since TAI was introduced (T3). ResultsA total of 78 patients were enrolled. Male to female ratio was 1.4:1. Mean age at enrollment was 106.1 ± 42.8 months. Discontinuation was reported by 3 patients (3.8 %). Continence, satisfaction and a number of other outcome measures increased from baseline (T0) to the last visit (T3). In particular, mean Rintala total score increased linearly from 7.8 to 14.8 during the study period (T0 to T3 timepoints). On a multivariate analysis, the only parameter that proved to be inversely associated with continence as well as with other outcome measures was the use of laxatives at enrollment and during the study. ConclusionsThis study has demonstrated the high efficacy of this innovative patient-tailored TAI protocol across all assessed scores. Of note, given the negative impact of laxatives, our findings suggest limiting their use in this patient population to further increase the efficacy of the procedure.

Algorithms for predicting COVID outcome using ready-to-use laboratorial and clinical data.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging crisis affecting the public health system. The clinical features of COVID-19 can range from an asymptomatic state to acute respiratory syndrome and multiple organ dysfunction. Although some hematological and biochemical parameters are altered during moderate and severe COVID-19, there is still a lack of tools to combine these parameters to predict the clinical outcome of a patient with COVID-19. Thus, this study aimed at employing hematological and biochemical parameters of patients diagnosed with COVID-19 in order to build machine learning algorithms for predicting COVID mortality or survival. Patients included in the study had a diagnosis of SARS-CoV-2 infection confirmed by RT-PCR and biochemical and hematological measurements were performed in three different time points upon hospital admission. Among the parameters evaluated, the ones that stand out the most are the important features of the T1 time point (urea, lymphocytes, glucose, basophils and age), which could be possible biomarkers for the severity of COVID-19 patients. This study shows that urea is the parameter that best classifies patient severity and rises over time, making it a crucial analyte to be used in machine learning algorithms to predict patient outcome. In this study optimal and medically interpretable machine learning algorithms for outcome prediction are presented for each time point. It was found that urea is the most paramount variable for outcome prediction over all three time points. However, the order of importance of other variables changes for each time point, demonstrating the importance of a dynamic approach for an effective patient's outcome prediction. All in all, the use of machine learning algorithms can be a defining tool for laboratory monitoring and clinical outcome prediction, which may bring benefits to public health in future pandemics with newly emerging and reemerging SARS-CoV-2 variants of concern.

Application of remimazolam transversus abdominis plane block in gastrointestinal tumor surgery.

Transversus abdominis plane block (TAPB) is a block of the abdominal afferent nerve fibers between the internal oblique muscle and the transverse abdominal muscle achieved with local anesthetics. It can effectively block the conduction of the anterior nerve of the abdominal wall and exert a good analgesic effect. However, the effect of combining the block with remimazolam on anesthesia in patients undergoing gastrointestinal tumor surgery is still unclear. To examine the effects of combining TAPB with remimazolam on the stress response and postoperative recovery of gastrointestinal tumor surgery patients. A retrospective analysis was conducted on the clinical data of 102 individuals diagnosed with gastrointestinal malignancies who underwent laparoscopic surgery under general anesthesia between April 2020 and June 2023. The patients were categorized into a control group (n = 51), receiving remimazolam for general anesthesia, and an observation group (n = 51), receiving TAPB combined with remimazolam for general anesthesia. A comparison was made between both groups in terms of hemodynamic parameters, stress markers, pain levels, recovery quality, analgesic effects, and adverse reactions during the perioperative period. The observation group had significantly higher heart rates at time points 1 min after induction and upon leaving the operating room than the control group (P < 0.05). The mean arterial pressure at time point T1 in the observation group was significantly higher than that in the control group (P < 0.05). Five minutes after extubation, the levels of the hormones adrenaline and noradrenaline in the observation group were considerably lower than those in the control group (P < 0.05). At 12 h, 24 h, and 48 h following surgery, the visual analog scale scores of the observation group were considerably lower than those of the control group (P < 0.05). The observation group had shorter awakening and extubation times and lower Riker sedation-agitation scale scores than the control group (P < 0.05). The observation group exhibited considerably fewer effective pump presses, lower fentanyl dosages, and lower incidences of rescue analgesia within 24 h following surgery than the control group (P < 0.05). The application effect of TAPB combined with remimazolam general anesthesia in anesthesia of patients undergoing gastrointestinal tumor surgery is good, which is helpful to promote faster recovery after operation.

Expanded nursing roles to promote person-centred care for people with cognitive impairment in acute care (ENROLE-acute): study protocol for a controlled clinical trial, process and economic evaluation

BackgroundFor people with cognitive impairment, hospitalisation is challenging and associated with adverse events as well as negative outcomes resulting in a prolonged hospital stay. Person-centred care can improve the quality of care and the experience of people with cognitive impairment during hospitalisation. However, current care processes in German hospitals are rarely person-centred. To enable successful implementation of person-centred care on hospital wards, change agents within the interprofessional team are key. The aim of this study is to test the feasibility and initial effects of a newly developed complex person-centred care intervention for people with cognitive impairment provided by expanded practice nurses in acute care.MethodsWe will conduct an exploratory non-randomised controlled clinical trial with accompanying process and cost evaluation with three intervention and three control wards at one university hospital. The person-centred care intervention consists of 14 components reflecting the activities of expanded practice nurses within the interprofessional team on the intervention wards. The intervention will be implemented over a six-month period and compared with optimised care on the control wards. We will include people aged 65 years and older with existing cognitive impairment and/or at risk of delirium. The estimated sample size is 720 participants. The primary outcome is length of hospital stay. Secondary outcomes include prevalence of delirium, prevalence of agitation, sleep quality, and person-centred care. We will collect patient level data at six time points (t1 admission, t2 day 3, t3 day 7, t4 day 14, t5 discharge, t6 30 days after discharge). For secondary outcomes at staff level, we will collect data before and after the intervention period. The process evaluation will examine degree and quality of implementation, mechanisms of change, and the context of the complex intervention. The economic evaluation will focus on costs from the hospital’s perspective.DiscussionThe ENROLE-acute study will provide insights into the effectiveness and underlying processes of a person-centred care intervention for people with cognitive impairment provided by expanded practice nurses on acute hospitals wards. Results may contribute to intervention refinement and evidence-based decision making.Trial registrationCurrent controlled trials: ISRCTN81391868. Date of registration: 12/06/2023. URL: https://doi.org/10.1186/ISRCTN81391868

Understanding the relationship between marketing analytics, customer agility, and customer satisfaction: A longitudinal perspective.

Shifting towards a more data-driven culture is a key antecedent of business success in today's digital era. Previous research has paid attention to exploring the influence of marketing analytics on business performance, and rarely examined how the use of marketing analytics influences customer agility and satisfaction. According to the dynamic capabilities view and using previous studies, we developed a conceptual framework to explore the effect of marketing analytics use on customer agility and customer satisfaction. In Study 1, we utilised cross-sectional data collected from 468 managers from various industries. In study 2, we employed longitudinal data in a three-wave longitudinal utilising a cross-lagged panel model. Study 1 indicated that data acquisition and tool acquisition are key drivers in adopting marketing analytics. Marketing analytics use has stronger effect on customer agility when market turbulence is high. They also revealed that the influence of customer agility on customer satisfaction in such conditions is stronger. Study 2 revealed that marketing analytics use at time point T1 has a significant and positive influence on customer agility at time point T2, while customer agility at time point T2 has a significant and positive influence on customer satisfaction at time point T3. These findings indicate strong temporal effects between marketing analytics use, customer agility, and customer satisfaction. The findings suggest that researchers should look beyond direct effects of marketing analytics use and shift their attention on how a marketing analytics can be leveraged to enable and support dynamic capabilities and customer satisfaction.

Effect of methoxymine on prevention and treatment of myocardial injury and cardiac function in elderly patients with hypotension during intraspinal anesthesia.

We aimed to investigate the effects of methoxamine to prevent hypotension in the elderly with intraspinal anesthesia (IA) on myocardial injury and cardiac function. A retrospective study was conducted by enrolling sixty elderly patients who underwent femoral head replacement (FHR) under IA in our hospital from August 2019 to August 2020. The patients were divided into two groups according to the random number table method. In the control group (CG) (30 patients), 5 mg of ephedrine was administered sedately when patients developed hypotension (20% below basal blood pressure). In the research group (RG) (30 cases), 2 μg/(kg·h) of methoxamine hydrochloride was given as a constant-rate pump before anesthesia, and 1 mg of methoxamine hydrochloride was administered intraoperatively if hypotension occurred. The hemodynamic [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR)], myocardial injury indexes [cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), fatty acid binding protein (FABP), plasma amino-terminal brain natriuretic peptide precursor (NT-proBNP)], cardiac function indexes [systemic vascular resistance (SVR), stroke volume (SV), net percentage ejection time (ET)] were observed before anesthesia (T1), at the end of surgery (T2), and 6 h after surgery (T3) in both groups. The Bruggemann Comfort Score (BCS) and Visual Analog Scale (VAS) scores at T3, 12 h postoperatively (T4) and 24 h postoperatively (T5) in both groups were observed, and the incidence of adverse reactions to intralesional anesthesia in both groups was counted. SBP, DBP and HR at T2 were lower than those at T1 in both groups, and SBP, DBP and HR at T3 were higher than those at T2, and SBP, DBP and HR at T2 and T3 in the RG were higher than those in the CG (p<0.05). In both groups, cTnⅠ, CK-MB and FABP were higher at T2 and T3 than at T1, higher at T3 than at T2, and NT-proBNP was higher at T2 than at T1 and T3, and lower in the RG than in the CG (p<0.05). In both groups, SVR and SV at time point T2 were lower than at time point T1 and ET was higher than at time point T1, SVR and SV at time point T3 were higher than at time point T2 and ET was lower than at time point T2, SVR and SV in the RG were higher than in the CG and ET was lower than in the CG (p<0.05). VAS scores were higher in both groups at T4 and T5 than at T3, and lower in the RG than in the CG (p<0.05). Methoxamine can effectively reduce the risk of hypotension in geriatric endotracheal anesthesia, which can reduce myocardial injury and stabilize cardiac function in patients.

Longitudinal dynamics of gut microbiota in the pathogenesis of acute graft-versus-host disease.

The gut microbiota has been reported to be associated with acute graft-versus-host disease (aGvHD) in hematopoietic stem cell transplantation (HSCT). Dynamic surveillance of the microbiota is required to understand the detailed pathogenesis involved in the process of aGvHD. Fecal samples were collected prospectively at four timepoints, including pre-HSCT (T1), graft infusion (T2), neutrophil engraftment (T3), and 30 days after transplantation (T4). Fecal samples were profiled by 16S ribosomal RNA gene sequencing to assess the microbiota composition. From the T1 to T4 timepoint, the diversity of the gut microbiota decreased, and the dominant species also changed, with a decrease in the obligate anaerobic bacteria and a shift toward a "pathogenic community". Compared with non-aGvHD patients, aGvHD patients had a lower abundance of Roseburia at T1 and a higher abundance of Acinetobacter johnsonii at T2. Furthermore, Acinetobacter johnsonii was negatively correlated with the secretion of IL-4 and TNF-α. At T3, Rothia mucilaginos was demonstrated to be linked with a decreased risk of aGvHD, which was accompanied by decreased secretion of IL-8. At T4, higher abundances of Lactobacillus paracasei and Acinetobacter johnsonii were identified to be related with aGvHD. Lactobacillus paracasei was associated with the downregulation of IL-10, and Acinetobacter johnsonii was associated with the downregulation of IL-2 and TNF-α. Dynamic changes in gut microbiota composition and related cytokines were found to be related to aGvHD, including pathogenic or protective changes. These findings suggested that manipulation of gut microbiota at different timepoints might be a promising avenue for preventing or treating this common complication.

New Pattern of Emerging Somatic Mutations in Optimal Responders Following Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia Patients Evidenced from Mutational Kinetic Analysis Based on Pairwise Comparison

Introduction Recent advances in genomics in chronic myeloid leukemia (CML) patients (pts) provide new insights in understanding somatic mutation (SM) and their prognostic implications following tyrosine kinase inhibitor (TKI) therapy. DNMT3A, TET2, or ASXL1 (DTA) mutations are most frequently detected following TKI therapy and have adverse prognosis. Five longitudinal patterns of changes in SM after TKI therapy were suggested with its clinical significance (Kim, Blood 2017): Pattern 1, persistent mutation burden despite optimal TKI response; Pattern 2, emerging mutation which correlates with TKI resistance/CML progression; Pattern 3, mutational clearance with mixed clinical outcomes; and Pattern 4 and 5 having some mutation in germline control as well as CML cells. Clonal evolution (CE) in Philadelphia negative (Ph -) clone is found in up to 10% of CML pts who respond to TKI therapy optimally but develop +8 or -7 changes in Ph - clone. This is diagnosed only by metaphase cytogenetic test on bone marrow samples. Alternatively, fluorescence in situ hybridization (FISH) test can be used. With recent advances in next-generation sequencing (NGS), we hypothesize that SM profiling can capture a clone carrying a SM in the Ph - population. We sequenced and analyzed mutation profiles in paired samples taken prior to TKI therapy and at longitudinal follow-up. Patients and methods The present study adopted single molecule-tagging and molecular inversion probe (smMIP)-based sequencing methods to analyze the DNA extracted from the mononuclear cell fraction of peripheral blood samples collected from CML pts at initial diagnosis and during follow-up. While conventional NGS has a relatively high intrinsic sequencing error rate and is limited in detecting mutations with a variant allele frequency (VAF) of less than 2%, smMIP-based sequencing overcomes this issue by tracking all sequence reads from a single strand and can detect mutations with a limit of detection up to 0.1%. The in-house CML-specific smMIP panel used in this study included 40 genes with 332 amplicon probes covering genes involved in epigenetic modifiers, activation signaling, myeloid transcription factor, spliceosome, tumor suppressor, cohesion, and miscellaneous functions. To evaluate kinetics of mutations, we calculated doubling time of mutations. Using the mutational VAFs from 2 time points, t1 and t2, the doubling time was calculated according to the following equation: = (-2 -1) log(2) /log(-2) - log(-1), where VAF1 and VAF2 is the VAF of the mutant at time points t1 and t2, respectively. Results We performed targeted deep sequencing on a total of 119 serial samples from 51 CML pts (median of 405.5 days following TKI therapy). 41 pts had an optimal response, 7 were non-responders, and 3 were non-evaluable for response. Pattern 2 was observed in 1 of 7 non-responders. In 12 pts pattern 3 (mutation clearance with mixed clinical outcomes) was observed. 22 pts carried 36 mutations. At baseline 9 pts had somatic mutations. Emergence of somatic mutations in optimal responders was observed in 13 out of total 51 (25%) pts, with DNMT3A (n=5), TET2 (n=4), ASXL1 (n=4), and EZH2 (n=2). While JAK2, SF3B1, U2AF1, PHF6, TP53, BRAF, and CBL were observed in one patient each (Figure 1). Particularly, those with emerging DTA mutation were all optimal responders to TKI therapy. This pattern of mutational change is novel and has never been described before. The median doubling time was 77 days (range 21-1909 days) in the group with emergence of somatic mutation in follow-up samples. The doubling time was 56.1, 93.7, 74.8 days in DNMT3A, ASXL1, and TET2 mutations, respectively. Based on kinetics of mutations (doubling time), to capture 10-fold increase (i.e. 1 log increase) of certain mutation, NGS profile can be monitored every 6-7 months. This pattern of emergence of mutations (mostly DTA mutation) in pts responding optimally to TKI therapy is new and does not fit into the five patterns mentioned in our previous paper (Kim, Blood 2017). Thus, we propose this sixth novel pattern called “Emerging mutational clones in CML pts responding optimally to TKI therapy”. Conclusion We suggest a new pattern of emerging mutations in optimal responders to TKI therapy, which could derive from expansion of Ph- clone carrying some clones with emerging mutations. Longitudinal NGS monitoring in CML patients is feasible with frequency every 6-7 months.

Exploration of key factors in Gingival Crevicular fluids from patients undergoing Periodontally Accelerated Osteogenic Orthodontics (PAOO) using proteome analysis

BackgroundThe aims of this study are to explore protein changes in gingival crevicular fluid at different time points after PAOO by proteomics method and to select significant bone metabolization-related biomarkers.MethodsThis study included 10 adult patients experiencing PAOO. After orthodontic alignment and leveling, the maxillary anterior teeth were treated with PAOO, which is classified as the experimental area. The traditional orthodontic treatment was performed in the mandibular dentition as the control. Gingival crevicular fluid samples were collected at the following time points: the day before the PAOO (T1) and at 1 week, 2 weeks, 1 month, 2 months and 6 months after PAOO (T2, T3, T4, T5 and T6, respectively). The label-free quantitative proteomic assay was used to evaluate the gingival crevicular fluid in PAOO and control areas at time point T1, T2, and T4. Bioinformatics analysis was carried out to categorize proteins based on biological processes, cellular component and molecular function, which is in compliance with gene ontology (GO) standards. The changes of proteins were confirmed by ELISA.ResultsA total of 134 proteins were selected by keywords (Osteoblast markers, Osteoclast markers, Osteoclastogenesis regulating genes and inflammatory marker). 33 of them were statistically different between groups, and 12 were related to bone metabolism. 5 proteins selected by label-free quantitative proteomics were KLF10, SYT7, APOA1, FBN1 and NOTCH1. KLF10 decreased after PAOO, hitting a trough at T4, and then leveled off. SYT7 increased after PAOO, reaching a peak at T3, and then stabilized until T6. APOA1 ascended to a peak at T4 after PAOO, and then remained stable until T6. The FBN1 rose after PAOO, reaching a peak at T4, and then went down slowly. NOTCH1 ascended rapidly in the first two weeks after PAOO and continued its slow growth trend.ConclusionIn this study, protein changes in gingival crevicular fluid were detected by proteomics method, and significant bone metabolization-related proteins were selected. It is speculated that APOA1, FBN1, NOTCH1, SYT7 and KLF10 played key roles in regulating bone metabolic balance and in reversible osteopenia after PAOO, which might be involved in the accelerated tooth movement.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (Clinical trial registration number: ChiCTR-ONRC-13,004,129) (26/04/2013).

Multivariate analysis of alveolar bone dehiscence and fenestration in anterior teeth after orthodontic treatment: A retrospective study.

To compare the prevalence of fenestration and dehiscence between pre- and post-orthodontic treatment and to explore the factors related to fenestration and dehiscence in the anterior teeth after treatment. This study included 1000 cone-beam computed tomography (CBCT) scans of 500 patients before (T1) and after (T2) orthodontic treatment. These images were imported into Dolphin 11.9 software to detect alveolar fenestration and dehiscence in the anterior teeth area. The chi-square test and Fisher's exact test were performed to compare the prevalence of alveolar bone defects between time points T1 and T2. A total of 499 patients were selected for logistic regression analysis to examine the correlation among age, sex, crowding, sagittal facial type, extraction, miniscrew use and fenestration or dehiscence post-treatment. Except for the maxillary lingual fenestration and labial fenestration of mandibular canines, a significant change in the prevalence of fenestration and dehiscence was noted between time points T1 and T2 (P < .025). Multinomial logistic regression showed that age, miniscrew use and extraction highly influenced the prevalence of anterior lingual dehiscence (P < .05). Dehiscence of the mandibular labial side (skeletal Class III vs. I, OR = 2.368, P = .000) and fenestration of the mandibular lingual side (skeletal Class II vs. I, OR = 2.344, P = .044) were strongly correlated with the sagittal facial type. Dehiscence of the maxillary labial side (moderate vs. mild, OR = 1.468, P = .017) was significantly associated with crowding. Older age, maxillary moderate crowding, skeletal Class III, extraction and miniscrew potentially significantly affect the prevalence of anterior teeth dehiscence. Adult females, skeletal Class III patients on the mandibular labial side and skeletal Class II patients on the mandibular lingual side should be monitored for anterior teeth fenestration.

Self-reported childhood family adversity is linked to an attenuated gain of trust during adolescence

A longstanding proposal in developmental research is that childhood family experiences provide a template that shapes a capacity for trust-based social relationships. We leveraged longitudinal data from a cohort of healthy adolescents (n = 570, aged 14–25), which included decision-making and psychometric data, to characterise normative developmental trajectories of trust behaviour and inter-individual differences therein. Extending on previous cross-sectional findings from the same cohort, we show that a task-based measure of trust increases longitudinally from adolescence into young adulthood. Computational modelling suggests this is due to a decrease in social risk aversion. Self-reported family adversity attenuates this developmental gain in trust behaviour, and within our computational model, this relates to a higher ‘irritability’ parameter in those reporting greater adversity. Unconditional trust at measurement time point T1 predicts the longitudinal trajectory of self-reported peer relation quality, particularly so for those with higher family adversity, consistent with trust acting as a resilience factor.

Changes in care utilization by patients in low-income neighborhoods during two Covid-19 waves

Abstract Background During the COVID-19 pandemic, general practitioners’ face-to-face consultations were replaced by remote (telephone or digital) consultations. This study aims to gain insight into the impact of the COVID-19 pandemic on GP care and the suitability of remote GP care for patients living in low-income neighborhoods. Methods A follow-up study of GP patients in disadvantaged neighborhoods of Rotterdam, using questionnaires at T1, the outbreak of COVID-19 (N = 213) and T2, after one year with gradual easing of COVID-19 measures (N = 133). At T1 and T2, 56% and 61% respectively were female, 61% and 65% 50 years and over, 48% and 53% had low health literacy. Results The proportion of patients who used remote or other care, i.e. face-to-face care or contact with assistant (56% and 44% respectively) was at T2 similar to T1. A positive attitude toward remote care declined from T1 to T2 from 71% to 58%. At T1 use of remote care was associated with sex and age, with significantly more females using remote care (OR = 3.22, 95% C.I. 1.57 - 6.59) and less respondents 50 years and over using remote care (OR = 0.46, 95% C.I. 0.22 - 0.97). At T2, remote care use was associated with having a migration background (OR = 2.18, 95% 1.00 - 4.74), financial difficulties (OR = 0.30, 95% 0.11 - 0.81), lack of digital skills (OR = 2.73, 95% 1.19 - 6.26) and a chronic disease (OR = 0.40, 95% 0.19 - 0.87). At multivariate level, the associations of age and digital skills with remote care at both time points T1 and T2, compared to remote care only at T1 or T2 or no remote care, were confounded by chronic disease, with lower remote care use by those with a chronic disease (OR = 0.33, 95% 0.13 - 0.87). Conclusions The COVID-19 pandemic rapidly accelerated the use of remote care in Dutch general practices. Experience after one year showed provision of GP remote care should be advised selectively for patients showing vulnerability, such as financial difficulties, low digital skills and chronic diseases. Key messages • At the start of the COVID-19 pandemic, patients were willing to receive GP care remotely and provision was depending on general characteristics sex and age. • Remote GP care is less suitable for vulnerable older patients, patients with financial difficulties and those with low digital skills or chronic diseases living in low-income neighborhoods.

Determinants of implementing the ID ROLL OUT study's interventions: qualitative results

Abstract Issue Antimicrobial stewardship programmes (ASP) and infectious disease (ID) specialists aim to ensure the rational use of antimicrobials and to improve patient outcomes. Whilst ASPs are established to varying degrees, ID specialists are rarely available in secondary and tertiary care hospitals in Germany. Description of the problem With the ID ROLL OUT study, we implemented and evaluated an intervention, which comprises ASP with and without ID specialists’ consultation in ten hospitals (excl. university hospitals) in south-west Germany. Little has been reported on the medical and pharmaceutical staff's perspectives on the implementations. This study describes barriers, facilitators, and suggestions for improvement to successfully establish a large-scale multicentre intervention. The participants responsible for implementing the intervention were interviewed using semi-structured, guided interviews at two time-points (t1: n = 17; t2: n = 18). The recorded interviews were analysed for content, following Kuckartz. Results A high level of acceptance and a positive attitude towards the intervention are conducive to the intervention's successful implementation. The teams find extra time for the study and a close staff collaboration at a local team level to be helpful. The main barriers identified are a high workload, lack of acceptance by colleagues in key roles, and the Covid-19 pandemic. Lack of digitalisation and entrenched internal structures were identified as major barriers. To further improve implementation, more infectious disease training should be provided, along with support from superiors and extension of the intervention phase. Moreover, government-mandated ASP guidelines and quality management by the German Medical Association are desired and expected to contribute in the future. Lessons The identified determinants provide much-needed key information, which is important for the efficient, targeted and successful implementation of future similar interventions. Key messages • Acceptance, positive attitude and staff collaboration help to implement the intervention. • Heavy workloads and lack of support from key colleagues hinder the intervention’s implementation.

Index of consciousness monitoring during general anesthesia may effectively enhance rehabilitation in elderly patients undergoing laparoscopic urological surgery: a randomized controlled clinical trial

BackgroundBased on electroencephalogram (EEG) analysis, index of consciousness (IoC) monitoring is a new technique for monitoring anesthesia depth. IoC is divided into IoC1 (depth of sedation) and IoC2 (depth of analgesia). The potential for concurrent monitoring of IoC1 and IoC2 to expedite postoperative convalescence remains to be elucidated. We investigated whether combined monitoring of IoC1 and IoC2 can effectively enhances postoperative recovery compared with bispectral index (BIS) in elderly patients undergoing laparoscopic urological surgery under general anesthesia.MethodsIn this prospective, controlled, double-blinded trail, 120 patients aged 65 years or older were arbitrarily assigned to either the IoC group or the control group (BIS monitoring). All patients underwent blood gas analysis at T1 (before anesthesia induction) and T2 (the end of operation). The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were administered to all patients at T0 (1 day before surgery) and T4 (7 days after surgery). Serum concentrations of C-reactive protein (CRP) and glial fibrillary acid protein (GFAP) were assessed at T1, T2, and T3 (24 h after surgery). Postoperative complications and the duration of hospitalization were subjected to comparative evaluation.ResultsThe incidence of postoperative cognitive dysfunction (POCD) was notably lower in the IoC group (10%) than in the control group (31.7%) (P = 0.003). Postoperative serum CRP and GFAP concentrations exhibited significant differences at time points T2 (CRP: P = 0.000; GFAP: P = 0.000) and T3 (CRP: P = 0.003; GFAP: P = 0.008). Postoperative blood glucose levels (P = 0.000) and the overall rate of complications (P = 0.037) were significantly lower in Group IoC than in Group control.ConclusionThe employment of IoC monitoring for the management of elderly surgical patients can accelerate postoperative convalescence by mitigating intraoperative stress and reducing peripheral and central inflammatory injury.Trial registrationChinese Clinical Trial Registry Identifier: ChiCTR1900025241 (17/08/2019).

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Health-related quality of life and its determinants during and after treatment for paediatric acute lymphoblastic leukaemia: a national, prospective, longitudinal study in the Netherlands

ObjectivesHealth-related quality of life (HRQoL) is impaired in paediatric patients with acute lymphoblastic leukaemia (ALL). Over the past decades, ALL treatment has successfully been adjusted to the risk of relapse,...

Quality of Life with Respect to Surgically Treated Vertebral Osteomyelitis and Degenerative Spondylolisthesis.

Vertebral osteomyelitis (VO) and degenerative spondylolisthesis (SL) are 2 commonly treated spinal conditions. Therefore, in the presented work, the quality of life after surgical therapy of these 2 entities is compared using established scores.In a monocentric study, all patients with VO and SL were prospectively enrolled using the Spine Tango Registry. Surgical procedures included one- or two-stage fusion of the affected segments. Quality of life was assessed using the Core Outcome Measures Index (COMI) and the Oswestry Disability Index (ODI) at time points t0 (0 months), t1 (12 months), and t2 (24 months). Statistical analysis was performed using SPSS. The level of significance was set at 5%.52 patients with VO and 48 patients with SL were included in the analysis. There were no significant differences in age and gender distribution. The length of stay in the SL group was significantly shorter (p<0.001). ODI at time t0 was significantly higher in the VO group (p<0.001), whereas COMI scores did not differ significantly (p=0.155). At time points t1 and t2, the differences between the VO and SL groups were not significantly different for either the ODI score (p=0.176; p=0.250) or the COMI score (p=0.682; p=0.640).Postoperative quality of life scores after lumbar fusion surgery in SL and VO are comparable despite different indications and medical conditions. In both groups, similar quality of life with in patient with chronic back pain was achieved. This should be considered for the preoperative assessment, as well as for the indication for surgery in SL.

Immune monitoring of SARS-CoV-2-specific T cell and B cell responses in patients with multiple sclerosis treated with ocrelizumab.

Since the development of the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there has been significant interest in determining the effectiveness of SARS-CoV-2 vaccines in patients under immunomodulatory or immunosuppressive therapies. The aim of this study was to evaluate the impact of ocrelizumab, a monoclonal anti-CD20 antibody, on SARS-CoV-2-specific T cell and B cell responses in patients with relapsing-remitting multiple sclerosis (RRMS). To this end, peripheral blood mononuclear cells (PBMCs) were isolated from n = 23 patients with RRMS. Of these patients, n = 17 were tested before (time point t0) and one month after (time point t1) their first dose of ocrelizumab. In addition, we studied n = 9 RRMS patients that got infected with SARS-CoV-2 over the course of ocrelizumab therapy (time point t2). PBMCs were also isolated from n = 19 age- and gender-matched healthy controls (HCs) after vaccination or infection with SARS-CoV-2, respectively. Interferon-γ (IFN-γ)/interleukin-2 (IL-2) and granzyme B (GzB)/perforin (PFN) double-color enzyme-linked immunospot (ELISPOT) assays or single-color ELISPOT assays were performed to measure SARS-CoV-2 antigen-specific T cell and B cell responses. Anti-viral antibody titers were quantified in the serum by chemiluminescence immunoassay. Our data indicate a significant difference in the SARS-CoV-2 specific IFN-γ (P = 0.0119) and PFN (P = 0.0005) secreting T cell compartment in the MS cohort at t0 compared to HCs. Following the first dose of ocrelizumab treatment, a significant decrease in the number of SARS-CoV-2 spike protein-specific B cells was observed (P = 0.0012). Infection with SARS-CoV-2 in MS patients under ocrelizumab therapy did not significantly alter their existing immune response against the virus. Kaplan-Meier survival analysis suggested that the spike S1 protein-specific immunoglobulin (Ig)G response might be a key parameter for predicting the probability of (re)infection with SARS-CoV-2. Our results call for a critical discussion regarding appropriate vaccination intervals and potential biomarkers for the prediction of (re)infection with SARS-CoV-2 in patients with MS receiving ocrelizumab. DRKS00029110; URL: http://apps.who.int/trialsearch/.

Lung Magnetic Resonance Imaging for Prediction of Progression in Patients With Nonidiopathic Pulmonary Fibrosis Interstitial Lung Disease: A Pilot Study.

Correlate magnetic resonance imaging (MRI) parameters at baseline with disease progression in nonidiopathic pulmonary fibrosis interstitial lung disease (ILD). Prospective observational cohort study, in which patients with non-idiopathic pulmonary fibrosis ILD underwent MRI at baseline (1.5 T). T2-weighted images (T2-WI) were acquired by axial free-breathing respiratory-gated fat-suppressed "periodically rotated overlapping parallel lines with enhanced reconstruction" and T1-weighted images (T1-WI) by coronal end-expiratory breath-hold fat-suppressed "volumetric interpolated breath-hold examination" sequences, before and at time points T1, T3, T5, and T10 minutes after gadolinium administration. After MRI segmentation, signal intensity values were extracted by dedicated software. Percentage of the ILD volume and a ratio between signal intensity of ILD (SIILD) and normal lung (SInormal lung) were calculated for T2-WI; percentage of signal intensity (%SI) at each time point, time to peak enhancement, and percent relative enhancement of ILD in comparison with normal lung (%SIILD/normal lung) were calculated for T1-WI. MRI parameters at baseline were correlated with diagnosis of disease progression and variation in percent predicted forced vital capacity (%FVC) and diffusing capacity of the lung for carbon monoxide after 12 months. Comprehensive MRI evaluation (T2-WI and T1-WI) was performed in 21 of the 25 patients enrolled (68% females; mean age: 62.6 y). Three of the 24 patients who completed follow-up fulfilled criteria for disease progression. Baseline T2-WI SIILD/SInormal lung was higher for the progression group (P = 0.052). T2-WI SIILD/SInormal lung and T1-WI %SIILD/normal lung at T1 were positively correlated with the 12-month variation in %FVC (r = 0.495, P = 0.014 and r = 0.489, P= 0.034, respectively). Baseline MRI parameters correlate with %FVC decline after 12 months.