Virtual reality for postsurgical pain management: An explorative randomized controlled study.

BACKGROUND: Virtual reality (VR) is a promising tool in a multimodal analgesic approach; however, evidence regarding virtual reality for postsurgical pain is limited. This study investigates the initial effectiveness and feasibility of self-administered virtual reality in postsurgical pain management. METHODS: Patients reporting a postsurgical pain score ≥4 were randomized for control or VR, stratified for 3 interventions with varying levels of immersion and interaction. Subjects were instructed to use virtual reality as add-on treatment at least 3 times a day for 10 minutes on days 2 till 4 postoperatively. Primary outcome was the mean daily pain intensity. Results of pain scores were related to patient and intervention characteristics, to explore which characteristics interact with virtual reality effects. Secondary outcomes were analgesic use, anxiety, stress, and feasibility. RESULTS: One hundred patients were included in the analyses: 37 in the control group and 63 for VR. VR did not demonstrate a significant effect on self-reported pain scores (P = .43), nor were specific patient or intervention characteristics associated with greater VR effects. Analgesic usage did not differ between groups. However, there was a trend toward greater cumulative percentages of patients achieving a 30% pain reduction, and significantly lower daily experienced stress (P = .01) and anxiety (P = .03) levels in VR intervention groups. VR was used less than prescribed, mainly because of illness and pain. Adverse events included disorientation, nausea, and fatigue. CONCLUSIONS: This explorative study did not demonstrate initial effectiveness of VR as add-on pain treatment regarding pain and analgesic use; however, VR positively affected stress and anxiety. VR is safe and suitable for a wide target audience, and feasibility differed between interventions. Personalizing and improving VR technology may enhance its effectiveness.

Serum Calcification Propensity Is Increased in Myocardial Infarction and Hints at a Pathophysiological Role Independent of Classical Cardiovascular Risk Factors.

BACKGROUND: Vascular calcification is associated with increased mortality in patients with cardiovascular disease. Secondary calciprotein particles are believed to play a causal role in the pathophysiology of vascular calcification. The maturation time (T50) of calciprotein particles provides a measure of serum calcification propensity. We compared T50 between patients with ST-segment-elevated myocardial infarction and control subjects and studied the association of T50 with cardiovascular risk factors and outcome. METHODS: T50 was measured by nephelometry in 347 patients from the GIPS-III trial and in 254 matched general population controls from PREVEND (Prevention of Renal and Vascular End-Stage Disease). We also assessed the association between T50 and left ventricular ejection fraction, as well as infarct size, the incidence of ischemia-driven reintervention during 5 years of follow-up, and serum nitrite as a marker of endothelial dysfunction. RESULTS: Patients with ST-segment-elevated myocardial infarction had a significantly lower T50 (ie, higher serum calcification propensity) compared with controls (T50: 289±63 versus 338±56 minutes; P<0.001). In patients with ST-segment-elevated myocardial infarction, lower T50 was associated with female sex, lower systolic blood pressure, lower total cholesterol, lower LDL (low-density lipoprotein) cholesterol, lower triglycerides, and higher HDL (high-density lipoprotein) cholesterol but not with circulating nitrite or nitrate. Ischemia-driven reintervention was associated with higher LDL (P=0.03) and had a significant interaction term for T50 and sex (P=0.005), indicating a correlation between ischemia-driven reintervention and T50 above the median in men and below the median in women, between 150 days and 5 years of follow-up. CONCLUSIONS: Serum calcification propensity is increased in patients with ST-segment-elevated myocardial infarction compared with the general population, and its contribution is more pronounced in women than in men. Its lack of/inverse association with nitrite and blood pressure confirms T50 to be orthogonal to traditional cardiovascular disease risk factors. Lower T50 was associated with a more favorable serum lipid profile, suggesting the involvement of divergent pathways of calcification stress and lipid stress in the pathophysiology of myocardial infarction.

Inhibition of endogenous hydrogen sulfide production reduces activation of hepatic stellate cells via the induction of cellular senescence.

In chronic liver injury, quiescent hepatic stellate cells (HSCs) transdifferentiate into activated myofibroblast-like cells and produce large amounts of extracellular matrix components, e.g. collagen type 1. Cellular senescence is characterized by irreversible cell-cycle arrest, arrested cell proliferation and the acquisition of the senescence-associated secretory phenotype (SASP) and reversal of HSCs activation. Previous studies reported that H2S prevents induction of senescence via its antioxidant activity. We hypothesized that inhibition of endogenous H2S production induces cellular senescence and reduces activation of HSCs. Rat HSCs were isolated and culture-activated for 7 days. After activation, HSCs treated with H2S slow-releasing donor GYY4137 and/or DL-propargylglycine (DL-PAG), an inhibitor of the H2S-producing enzyme cystathionine γ-lyase (CTH), as well as the PI3K inhibitor LY294002. In our result, CTH expression was significantly increased in fully activated HSCs compared to quiescent HSCs and was also observed in activated stellate cells in a in vivo model of cirrhosis. Inhibition of CTH reduced proliferation and expression of fibrotic markers Col1a1 and Acta2 in HSCs. Concomitantly, DL-PAG increased the cell-cycle arrest markers Cdkn1a (p21), p53 and the SASP marker Il6. Additionally, the number of ß-galactosidase positive senescent HSCs was increased. GYY4137 partially restored the proliferation of senescent HSCs and attenuated the DL-PAG-induced senescent phenotype. Inhibition of PI3K partially reversed the senescence phenotype of HSCs induced by DL-PAG. Inhibition of endogenous H2S production reduces HSCs activation via induction of cellular senescence in a PI3K-Akt dependent manner. Our results show that cell-specific inhibition of H2S could be a novel target for anti-fibrotic therapy via induced cell senescence.

Serum carnosinase 1, an early indicator for incident microalbuminuria in type 1 diabetes.

Aims: Carnosinase (CN1) polymorphisms have been linked to diabetic kidney disease (DKD), as CN1 degrades dipeptides which scavenge oxidative metabolites and prevent the formation of advanced glycation end-products. In this work, we studied the association between serum CN1, the systemic redox status and long-term renal outcome in type 1 diabetes. Methods: Serum CN1 was measured in a prospective type 1 diabetes cohort (n = 218) with a 16-year follow-up. A total of 218 patients treated at the Diabetes Outpatient Clinic of the Weezenlanden Hospital (nowadays Isala Hospital, Zwolle, The Netherlands) were included in this analysis. We assessed whether serum CN1 was associated with renal function and development of DKD as well as other diabetic complications. Results: At baseline, age, systemic redox status and N-terminal pro brain-natriuretic peptide (NT-proBNP) were associated with serum CN1 concentration (p < 0.05). During follow-up, CN1 concentration in the middle tertile was associated with less incident microalbuminuria (odds ratio = 0.194, 95% C.I.: 0.049-0.772, p = 0.02) after adjustment for age, systemic redox status, NT-proBNP and sex. Discussion: Serum CN1 could predict incident microalbuminuria and may be used as a novel parameter to identify patients at risk for DKD.

Oxidative stress biomarkers for fetal growth restriction in umbilical cord blood: A scoping review.

Fetal growth restriction and underlying placental insufficiency are associated with increased oxidative stress. Current diagnostics fail to identify all growth restricted fetuses and newborns, due to focus on small size. This scoping review aims to summarize the available evidence on usefulness of cord blood oxidative stress biomarkers for identification of growth restricted newborns in need of monitoring and support because of associated health risks. MEDLINE and EMBASE were searched from inception to May 2024. Studies were included if oxidative stress biomarkers were measured in cord blood collected immediately after delivery in newborns suspected to be growth restricted. Biomarkers were categorized based on the origin and/or biological function and their interrelationships. Oxidative stress was determined for each individual biomarker and category. Literature search identified 78 studies on 39 different biomarkers, with a total of 2707 newborns with suspected growth restriction, and 4568 controls. Total oxidant/antioxidant status, catalase, glutathione, ischemia-modified albumin, and nucleated red blood cells were most consistently associated with suspected growth restriction. Reactive oxygen species/reactive nitrogen species, factors in their production, antioxidant enzymes, non-enzymatic antioxidants, and products of oxidative stress were not consistently associated. This review collates the evidence of associations between cord blood oxidative stress biomarkers and growth restriction. Total oxidant/antioxidant status, catalase, glutathione, ischemia-modified albumin, and nucleated red blood cells could potentially be candidates for developing a cord blood diagnostic tool for future clinical use.

Proof-of-principle of a lung sealant based on functionalized polyoxazolines: experiments in an ovine acute aerostasis model.

OBJECTIVES: More effective lung sealants are needed to prevent prolonged pulmonary air leakage (AL). Polyoxazoline-impregnated gelatin patch (N-hydroxysuccinimide ester functionalized poly(2-oxazoline)s; NHS-POx) was promising for lung sealing ex vivo. The aim of this study is to confirm sealing effectiveness in an in vivo model of lung injury. METHODS: An acute aerostasis model was used in healthy adult female sheep, involving bilateral thoracotomy, amputation lesions (bronchioles Ø > 1.5 mm), sealant application, digital chest tube for monitoring AL, spontaneous ventilation, obduction and bursting pressure measurement. Two experiments were performed: (i) 3 sheep with 2 lesions per lung (N = 4 NHS-POx double-layer, N = 4 NHS-POx single-layer, N = 4 untreated) and (ii) 3 with 1 lesion per lung (N = 3 NHS-POx single-layer, N = 3 untreated). In pooled linear regression, AL was analysed per lung (N = 7 NHS-POx, N = 5 untreated) and bursting pressure per lesion (N = 11 NHS-POx, N = 7 untreated). RESULTS: Baseline AL was similar between groups (mean 1.38-1.47 l/min, P = 0.90). NHS-POx achieved sealing in 1 attempt in 8/11 (72.7%) and in 10/11 (90.9%) in >1 attempt. Application failures were only observed on triangular lesions requiring 3 folds around the lung. No influences of methodological variation between experiments was detected in linear regression (P > 0.9). AL over initial 3 h of drainage was significantly reduced for NHS-POx [median: 7 ml/min, length of interquartile range: 333 ml/min] versus untreated lesions (367 ml/min, length of interquartile range: 680 ml/min, P = 0.036). Bursting pressure was higher for NHS-POx (mean: 33, SD: 16 cmH2O) versus untreated lesions (mean: 19, SD: 15 cmH2O, P = 0.081). CONCLUSIONS: NHS-POx was effective for reducing early AL, and a trend was seen for improvement of bursting strength of the covered defect. Results were affected by application characteristics and lesion geometry.

Converting cell death into senescence by PARP1 inhibition improves recovery from acute oxidative injury.

Excessive amounts of reactive oxygen species (ROS) lead to macromolecular damage and high levels of cell death with consequent pathological sequelae. We hypothesized that switching cell death to a tissue regenerative state could potentially improve the short-term and long-term detrimental effects of ROS-associated acute tissue injury, although the mechanisms regulating oxidative stress-induced cell fate decisions and their manipulation for improving repair are poorly understood. Here, we show that cells exposed to high oxidative stress enter a poly (ADP-ribose) polymerase 1 (PARP1)-mediated regulated cell death, and that blocking PARP1 activation promotes conversion of cell death into senescence (CODIS). We demonstrate that this conversion depends on reducing mitochondrial Ca2+ overload as a consequence of retaining the hexokinase II on mitochondria. In a mouse model of kidney ischemia-reperfusion damage, PARP inhibition reduces necrosis and increases transient senescence at the injury site, alongside improved recovery from damage. Together, these data provide evidence that converting cell death into transient senescence can therapeutically benefit tissue regeneration.

Exploring the kynurenine pathway in mild traumatic brain injury: A longitudinal study.

A potential source of novel biomarkers for mTBI is the kynurenine pathway (KP), a metabolic pathway of tryptophan (Trp), that is up-regulated by neuroinflammation and stress. Considering that metabolites of the KP (kynurenines) are implicated in various neuropsychiatric diseases, exploration of this pathway could potentially bridge the gap between physiological and psychological factors in the recovery process after mTBI. This study, therefore, set out to characterize the KP after mTBI and to examine associations with long-term outcome. Patients were prospectively recruited at the emergency department (ED), and blood samples were obtained in the acute phase (<24 h; N = 256) and at 1-month follow-up (N = 146). A comparison group of healthy controls (HC; N = 32) was studied at both timepoints. Trp, kynurenines, and interleukin (IL)-6 and IL-10 were quantified in plasma. Clinical outcome was measured at six months post-injury. Trp, xanthurenic acid (XA), and picolinic acid (PA) were significantly reduced in patients with mTBI relative to HC, corrected for age and sex. For Trp (d = -0.57 vs. d = -0.29) and XA (d = -0.98 vs. d = -0.32), larger effects sizes were observed during the acute phase compared to one-month follow-up, while for PA (d = -0.49 vs. d = -0.52) effect sizes remained consistent. Findings for other kynurenines (e.g., kynurenine, kynurenic acid, and quinolinic acid) were non-significant after correction for multiple testing. Within the mTBI group, lower acute Trp levels were significantly related to incomplete functional recovery and higher depression scores at 6 months post-injury. No significant relationships were found for Trp, XA, and PA with IL-6 or IL-10 concentrations. In conclusion, our findings indicate that perturbations of the plasma KP in the hyperacute phase of mTBI and 1 month later are limited to the precursor Trp, and glutamate system modulating kynurenines XA and PA. Correlations between acute reductions of Trp and unfavorable outcomes may suggest a potential substrate for pharmacological intervention.

A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population.

Introduction: Systemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study. Methods: Individuals without CKD at baseline (n = 4662) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma calprotectin levels were assessed in samples that had been stored at -80 °C. Occurrence of new-onset CKD was defined as a composite outcome of an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2, urinary albumin excretion (UAE) >30 mg/24h, or both. Results: Baseline median (interquartile range) plasma calprotectin levels were 0.49 (0.35-0.68) mg/l and baseline median eGFR was 95.9 (interquartile range: 85.0-105.7) ml/min per 1.73 m2. After median follow-up of 8.3 (7.8-8.9) years, 467 participants developed new-onset CKD. Baseline plasma calprotectin levels were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.28 [95% confidence interval, CI: 1.14-1.44], P < 0.001), independent of potentially confounding factors (HR 1.14 [95% CI: 1.01-1.29], P = 0.034), except for baseline high-sensitive C-reactive protein (hs-CRP) (HR 1.05 [0.91-1.21], P = 0.494). In secondary analyses, the association between plasma calprotectin and occurrence of UAE >30 mg/24h remained significant (HR 1.17 [1.02-1.34], P = 0.027), but not significantly so for the incidence of eGFR <60 ml/min per 1.73 m2 as individual outcome (HR 1.15 [0.92-1.43], P = 0.218). Conclusion: Higher plasma calprotectin levels are associated with an increased risk of developing CKD in the general population. This association is mitigated after adjustment for hs-CRP, and more pronounced with new-onset CKD defined by UAE.

Clinical Safety and Performance of GATT-Patch for Hemostasis in Minimal to Moderate Bleeding During Open Liver Surgery.

INTRODUCTION: Intraoperative blood loss and postoperative hemorrhage affect outcomes after liver resection. GATT-Patch is a new flexible, pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with N-hydroxy-succinimide polyoxazoline. We evaluated safety and performance of the GATT-Patch for hemostasis at the liver resection plane. METHODS: Adult patients undergoing elective open liver surgery were recruited in three centers. GATT-Patch was used for minimal to moderate bleeding at the liver resection plane. The primary endpoint was hemostasis of the first-treated bleeding site at 3 min versus a prespecified performance goal of 65.4%. RESULTS: Two trial stages were performed: I (n = 8) for initial safety and II (n = 39) as the primary outcome cohort. GATT-Patch was applied in 47 patients on 63 bleeding sites. Median age was 60.0 (range 25-80) years and 70% were male. Most (66%) surgeries were for colorectal cancer metastases. The primary endpoint was met in 38 out of 39 patients (97.4%; 95% confidence interval: 84.6%-99.9%) versus 65.4% (P < 0.001). Of all the 63 bleeding sites, hemostasis was 82.7% at 30, 93.7% at 60, and 96.8% at 180 s. No reoperations for rebleeding or device-related issues occurred. CONCLUSIONS: When compared to a performance goal derived from state-of-the-art hemostatic agents, GATT-Patch for the treatment of minimal to moderate bleeding during liver surgery successfully and quickly achieved hemostasis with acceptable safety outcomes. (ClinicalTrials.gov Identifier: NCT04819945).

Virtual reality to reduce periprocedural anxiety during invasive coronary angiography: rationale and design of the VR InCard trial.

INTRODUCTION: Patients undergoing invasive coronary angiography (ICA) experience anxiety due to various reasons. Procedural anxiety can lead to physiological and psychological complications, compromising patient comfort and overall procedural outcomes. Benzodiazepines are commonly used to reduce periprocedural anxiety, although the effect is modest. Virtual reality (VR) is a promising non-pharmacological intervention to reduce anxiety in patients undergoing ICA. METHODS AND ANALYSIS: A single-centre open-label randomised controlled trial is conducted assessing the effectiveness of add-on VR therapy on anxiety in 100 patients undergoing ICA and experiencing anxiety in a periprocedural setting. The primary outcome is the Numeric Rating Scale (NRS) anxiety score measured just before obtaining arterial access. Secondary outcomes include postarterial puncture and postprocedural anxiety, patient-reported outcome measures (PROMs) of anxiety and physiological measurements associated with anxiety. The NRS anxiety level and physiological measurements are assessed five times during the procedure. The PROM State-Trait Anxiety Inventory and Perceived Stress Scale are completed preprocedure, and the PROM STAI and the Igroup Presence Questionnaire are performed postprocedure. ETHICS AND DISSEMINATION: The protocol of this study has been approved by the Research Ethics Committee of the Radboud University Medical Centre, the Netherlands (CMO Arnhem-Nijmegen, 2023-16586). Informed consent is obtained from all patients. The trial is conducted according to the principles of the Helsinki Declaration and in accordance with Dutch guidelines, regulations, and acts (Medical Research involving Human Subjects Act, WMO). REGISTRATION DETAILS: Trial registration number: NCT06215456.

Plasma calprotectin and new-onset type 2 diabetes in the general population: a prospective cohort study.

BACKGROUND: Systemic inflammation plays a pivotal role in the development of type 2 diabetes (T2D). Here we hypothesized that circulating levels of calprotectin, a myeloid cell-derived biomarker of inflammation, is associated with the development of new-onset T2D in the general population. METHODS: A total of 4,815 initially non-diabetic participants of the Prevention of Renal and Vascular ENd-stage Disease (PREVEND), a prospective population-based cohort study, were assessed for plasma levels of calprotectin at baseline. Circulating levels of calprotectin were investigated for potential associations with the risk of new-onset T2D, defined as a fasting plasma glucose level ≥7.0 mmol/l, a random plasma glucose level ≥11.1 mmol/l, a self-reported physician-based diagnosis of T2D, the use of glucose-lowering drugs, or any combinations thereof. RESULTS: Median plasma calprotectin levels were 0.49 [0.35-0.69] mg/l. Plasma calprotectin levels were significantly associated with the risk of new-onset T2D (hazard ratio [HR] per doubling 1.42 [95% confidence interval: 1.22-1.66], P<0.001). The association remained independent of adjustment for age and sex (HR 1.34 [95%CI: 1.14-1.57], P<0.001), but not after further adjustment for potentially confounding factors (HR 1.11 [95% CI: 0.90-1.37], P=0.326), with adjustment for hyperlipidemia and high-sensitivity C-reactive protein explaining the loss of significance. Stratified analyses showed significant effect modification by hypertension, history of cardiovascular disease and HOMA-IR (Pinteraction≤0.001 for each), with higher HRs in individuals without hypertension, without history of cardiovascular disease and with below-median HOMA-IR. CONCLUSIONS: Elevated plasma levels of calprotectin are associated with a higher risk of developing T2D in the general population and may represent a moveable inflammatory biomarker. This association, however, does not represent a direct effect, and seems dependent on hyperlipidemia and systemic inflammation.

Outpatient Video Visits During the COVID-19 Pandemic: Cross-Sectional Survey Study of Patients' Experiences and Characteristics.

BACKGROUND: During the first lockdown of the COVID-19 pandemic, an exponential increase in video consultations replacing in-person outpatient visits was observed in hospitals. Insight into patients' experiences with this type of consultation is helpful for a broad, sustainable, and patient-centered implementation of video consultation. OBJECTIVE: This study aims to examine patients' experiences with video consultation during the COVID-19 pandemic and identify discriminative patient and consultation characteristics to determine when video consultation is most feasible. METHODS: A cross-sectional survey study was conducted. Patients aged ≥18 years and scheduled for a video consultation at the outpatient clinic of a Dutch university medical center from August 2020 to December 2020 for all medical specialties were eligible. Patients' experiences were explored through a study-specific survey using descriptive quantitative statistics. Open-ended questions were qualitatively analyzed and thematically categorized into appreciated aspects and aspects for improvement. Discriminative patient and consultation characteristics were identified using 3 distinctive survey items. Characteristics of patients who scored and those who did not score all 3 items positively were analyzed using binary logistic regression. RESULTS: A total of 1054 patients were included in the analysis. Most patients (964/1054, 91.46%) were satisfied with their video consultation, with a mean overall grade of 8.6 (SD 1.3) of 10. In the qualitative analyses, 70.02% (738/1054) of the patients cited aspects they appreciated and 44.97% (474/1054) mentioned aspects for improvement during their consultation. Patients with better self-rated health reported a positive evaluation significantly more often (P=.001), which also held true for other medical specialties (vs surgical and nonsurgical specialties; P<.001). CONCLUSIONS: Video consultation was perceived as highly satisfactory by patients during the COVID-19 pandemic, with the best experience reported by healthy participants and those undergoing their first consultation. Appreciated aspects are mainly at the individual professional level, organizational level, and innovation level itself. The aspects that were mentioned for improvement can be changed for the better.

Development of a Multimodal, Personalized Intervention of Virtual Reality Integrated Within Physiotherapy for Patients With Complex Chronic Low-Back Pain.

Background: Chronic low-back pain (CLBP) is the leading cause of years lived with disability. Physiotherapy is the most common treatment option for CLBP, but effects are often unsatisfactory. Virtual reality (VR) offers possibilities to enhance the effectiveness of physiotherapy treatment. Primary aim was to develop and test a personalized VR intervention integrated within a physiotherapy treatment for patients with CLBP. Methods: This study describes an intervention development process using mixed methods design that followed the Medical Research Council (MRC) framework. This involved a cocreation process with patients, physiotherapists, and researchers. A draft intervention was constructed based on a literature review and focus groups, and subsequently tested in a feasibility study and evaluated in focus groups. Focus group data were analyzed using thematic analysis. This intervention development process resulted in a final intervention. Results: Focus group data showed that VR and physiotherapy can strengthen each other when they are well integrated, and that VR needs to be administered under the right conditions including flawless technology, physiotherapists with sufficient affinity and training, and the right expectations from patients. The draft intervention was considered feasible after evaluation by four patients and three physiotherapists and was further complemented by expanding the training for physiotherapists and improving the protocols for physiotherapists and patients. The final intervention consisted of a 12-week physiotherapy treatment with three integrated VR modules: pain education, physical exercise, and relaxation. Conclusion: Using the MRC framework in cocreation with the end users, a personalized VR intervention integrated within a physiotherapy treatment for patients with CLBP was developed. This intervention was found to be feasible and will subsequently be evaluated for (cost-)effectiveness in a cluster randomized controlled trial.

Serum T50 predicts cardiovascular mortality in individuals with type 2 diabetes: A prospective cohort study.

BACKGROUND AND AIMS: Individuals with type 2 diabetes (T2D) have a higher risk of cardiovascular disease, compared with those without T2D. The serum T50 test captures the transformation time of calciprotein particles in serum. We aimed to assess whether serum T50 predicts cardiovascular mortality in T2D patients, independent of traditional risk factors. METHODS: We analyzed 621 individuals with T2D in this prospective cohort study. Cox regression models were performed to test the association between serum T50 and cardiovascular and all-cause mortality. Causes of death were categorized according to ICD-10 codes. Risk prediction improvement was assessed by comparing Harrell's C for models without and with T50. RESULTS: The mean age was 64.2 ± 9.8 years, and 61% were male. The average serum T50 time was 323 ± 63 min. Higher age, alcohol use, high-sensitive C-reactive protein, and plasma phosphate were associated with lower serum T50 levels. Higher plasma triglycerides, venous bicarbonate, sodium, magnesium, and alanine aminotransferase were associated with higher serum T50 levels. After a follow-up of 7.5[5.4-10.7] years, each 60 min decrease in serum T50 was associated with an increased risk of cardiovascular (fully adjusted HR 1.32, 95% CI 1.08-1.50, and p = 0.01) and all-cause mortality (HR 1.15, 95%CI 1.00-1.38, and p = 0.04). Results were consistent in sensitivity analyses after exclusion of individuals with estimated glomerular filtration rate <45 or <60 mL/min/1.73 m2 and higher plasma phosphate levels. CONCLUSIONS: Serum T50 improves prediction of cardiovascular and all-cause mortality risk in individuals with T2D. Serum T50 may be useful for risk stratification and to guide therapeutic strategies aiming to reduce cardiovascular mortality in T2D.

Systemic oxidative stress may be associated with reduced IgG antibody titers against SARS-CoV-2 in vaccinated kidney transplant recipients: A post-hoc analysis of the RECOVAC-IR observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) poses an increased risk for severe illness and suboptimal vaccination responses in patients with kidney disease, in which oxidative stress may be involved. Oxidative stress can be reliably measured by determining circulating free thiols (R-SH, sulfhydryl groups), since R-SH are rapidly oxidized by reactive species. In this study, we aimed to examine the association between serum free thiols and the ability to mount a humoral immune response to SARS-CoV-2 vaccination in kidney patients. METHODS: Serum free thiol concentrations were measured in patients with chronic kidney disease stages 4/5 (CKD G4/5) (n = 46), on dialysis (n = 43), kidney transplant recipients (KTR) (n = 73), and controls (n = 50). Baseline serum free thiol and interferon-γ-induced protein-10 (IP-10) - a biomarker of the interferon response - were analyzed for associations with seroconversion rates and SARS-CoV-2 spike (S1)-specific IgG concentrations after two doses of the mRNA-1273 vaccine. RESULTS: Albumin-adjusted serum free thiol concentrations were significantly lower in patients with CKD G4/5 (P < 0.001), on dialysis (P < 0.001), and KTR (P < 0.001), as compared to controls. Seroconversion rates after full vaccination were markedly reduced in KTR (52.1%) and were significantly associated with albumin-adjusted free thiols (OR = 1.76, P = 0.033). After adjustment for MMF use, hemoglobin, and eGFR, this significance was not sustained (OR = 1.49, P = 0.241). CONCLUSIONS: KTR show suboptimal serological responses to SARS-CoV-2 vaccination, which is inversely associated with serum R-SH, reflecting systemic oxidative stress. Albeit this association was not robust to relevant confounding factors, it may at least partially be involved in the inability of KTR to generate a positive serological response after SARS-CoV-2 vaccination.

Experiences of physiotherapists considering virtual reality for shoulder rehabilitation: A focus group study.

Introduction: Shoulder pain is common and associated with substantial morbidity. Different treatment strategies are being prescribed with equivocal results. Virtual reality (VR) is a novel technology and emerging research suggests that VR may be a promising alternative to current treatments. Prior to effectiveness research or any large-scale introduction, VR-applications require appropriate scrutiny including feasibility- and acceptability of clinicians and patients. Therefore, the aim of this study was to collect experiences of physiotherapists after using immersive VR. Methods: A qualitative interpretive design was used to explore physiotherapists' experiences related to the use of VR for people with shoulder symptoms. 17 physiotherapists were asked to use VR at home for five days prior to a focus group interview. Data from the focus group interviews were analyzed using a six-phase process of thematic analysis. Results: Three main themes were identified, each divided into subthemes. The main themes were: 1. VR as an extension of contemporary physiotherapy care: physiotherapists were positive about the potential of VR and its applicability in daily care. 2. Physiotherapist uncertainties of future care using VR: participants expressed concerns about their professional identity, particularly as patients engage in independent home exercises. 3. Physiotherapist's requirements for implementation of VR: participants shared their needs for evidence regarding the effectiveness and parameters such as frequency, dosage and intensity of the VR intervention. Conclusion: Physiotherapists were positive about VR as an intervention tool. However, they felt more knowledge is needed about parameters of VR. The findings of this study inform researchers and technology developers about optimal design of interventions and applications using VR.