Synchronous mode-locking of solid-state lasers by difference frequency generation.

This Letter introduces a novel, to the best of our knowledge, method for achieving mode-locking and synchronization of mode-locked output pulses from two lasers. The proposed technique leverages parametric gain from difference frequency generation. Specifically, a Nd:YAG laser is mode-locked by single-pass mode-locked pulses from a mode-locked Ti:sapphire laser using an intracavity nonlinear crystal. When the continuous-wave laser is not actively pumped, the system functions as a synchronously pumped optical parametric oscillator. This novel approach has the potential to enable new devices, especially for pump-probe applications or for generation of mode-locked pulses in spectral regions where conventional mode-locked devices are typically not available.

Bariatric surgeons' views on pre-operative factors associated with improved health-related quality of life following surgery.

Bariatric surgery is an effective treatment for severe obesity, affording significant improvements in weight loss and health-related quality of life. However, bariatric surgeons' views on whether certain pre-operative factors predict improvements in post-operative health-related quality of life, and if so, which ones, are largely unknown. This cross-sectional survey study examined the views of 58 bariatric surgeons from Australia and New Zealand. A total of 18 factors were selected for exploration based on their mention in the literature. Participants rated the extent to which they thought these pre-operative factors would improve post-operative health-related quality of life. Responses showed that bariatric surgeons held diverse perspectives and revealed a lack of consensus regarding "predictive" factors. Generally, respondents agreed that better than average health literacy, higher socioeconomic status, good physical and psychological health, and positive social support were predictors of improved health-related quality of life following surgery. However, poor eating behaviours, smoking, and the use of alcohol or other substances were deemed negative predictors. Interestingly, aside from higher socioeconomic status, good psychological health, and positive social support, none of the aforementioned views aligned with existing literature. This study offers an initial insight into bariatric surgeons' views on the influence of different pre-operative factors on post-operative health-related quality of life. The array of views identified suggests that there may be an opportunity for medical education, but the findings warrant caution due to the sample size. Replication with a larger survey may be useful, especially as predicted health-related quality of life outcomes could guide decisions regarding surgical (non)progression.

Reduced Cerebrovascular Oxygenation in Individuals with Post-Acute COVID-19 Syndrome (PACS) ("long COVID").

There is evidence that hypoxia occurs in the brain of some individuals who contracted the COVID-19 disease. Furthermore, it has been widely reported that about 13% of individuals who contracted the COVID-19 disease report persistent symptoms after the acute infection stage (>2 months post-acute infection). This is termed post-acute COVID-19 syndrome (PACS) or ("long COVID"). In this study, we aimed to determine if hypoxia measured non-invasively with frequency domain near-infrared spectroscopy (fdNIRS) occurs in asymptomatic and symptomatic individuals with post-acute COVID-19 disease. We show that 26% of our symptomatic group, measured on average 9.6 months post-acute COVID-19 disease, were hypoxic and 12% of the asymptomatic group, measured on average 2.5 months post-acute infection, were hypoxic. Our study indicates that fdNIRS measure of hypoxia in the brain may be a useful tool to identify individuals that are likely to respond to treatments targeted at reducing inflammation and improving oxygenation.

Efficient calculation of electronic coupling integrals with the dimer projection method via a density matrix tight-binding potential.

Designing organic semiconductors for practical applications in organic solar cells, organic field-effect transistors, and organic light-emitting diodes requires understanding charge transfer mechanisms across different length and time scales. The underlying electron transfer mechanisms can be efficiently explored using semiempirical quantum mechanical (SQM) methods. The dimer projection (DIPRO) method combined with the recently introduced non-self-consistent density matrix tight-binding potential (PTB) [Grimme et al., J. Chem. Phys. 158, 124111 (2023)] is used in this study to evaluate charge transfer integrals important for understanding charge transport mechanisms. PTB, parameterized for the entire Periodic Table up to Z = 86, incorporates approximate non-local exchange, allowing for efficient and accurate calculations for large hetero-organic compounds. Benchmarking against established databases, such as Blumberger's HAB sets, or our newly introduced JAB69 set and comparing with high-level reference data from ωB97X-D4 calculations confirm that DIPRO@PTB consistently performs well among the tested SQM approaches for calculating coupling integrals. DIPRO@PTB yields reasonably accurate results at low computational cost, making it suitable for screening purposes and applications to large systems, such as metal-organic frameworks and cyanine-based molecular aggregates further discussed in this work.

A study protocol outlining the development and evaluation of a training program for frontline managers on leading well-being and the psychosocial work environment in Danish hospital settings - a cluster randomized waitlist controlled trial.

BACKGROUND: Hospital staff are often exposed to stressful psychosocial working conditions and report high levels of stress and burnout, which may negatively impact the safety of employees and patients. Managers hold unique knowledge of workplace conditions and needs of employees, but leadership interventions to improve the well-being of managers and employees in hospital settings are scarce. This study evaluates the effects of a leadership intervention based on a health-oriented leadership approach on the well-being and psychosocial work environment aspects of managers and employees. METHODS/DESIGN: The study is designed as a randomized, waitlist-controlled trial with two groups (intervention and waitlist control group) and measurements at baseline, 6- and 12-month follow-up. We aim to include 200 frontline managers in Danish hospital settings and their approximately 5,000 employees. The leadership training comprises five full day modules and four smaller group-training sessions over a period of 5 months. The main aim is to improve stress, burnout, self-care, and perceived level of staff-care among managers and employees. Sickness absence will also be assessed at both manager and employee level. In addition, several psychosocial factors will be assessed at the employee level. A quantitative and qualitative process evaluation will also be conducted. DISCUSSION: Action towards supporting the mental health of hospital employees is important to maintain a strong healthcare system. There is increasing recognition that best practice in workplace mental health requires an integrated approach that prevents harm and promotes positive mental health. There is also increasing understanding of the key role managers' play in maintaining well-being within the workplace, however they often report a lack of knowledge and skills to promote employee mental health. The current leadership training program has been developed for frontline managers working in a hospital setting. The aim is to increase managers' application of strategies to facilitate a healthy psychosocial work environment to benefit well-being and mental health among staff and managers themselves. TRIAL REGISTRATION: The study was retrospectively registered on November 21, 2022 in Clinical Trial.gov with identifier: NCT05623371.

First-in-class Microbial Ecosystem Therapeutic 4 (MET4) in combination with immune checkpoint inhibitors in patients with advanced solid tumors (MET4-IO trial).

BACKGROUND: The intestinal microbiome has been associated with response to immune checkpoint inhibitors (ICIs) in humans and causally implicated in ICI responsiveness in animal models. Two recent human trials demonstrated that fecal microbiota transplant (FMT) from ICI responders can rescue ICI responses in refractory melanoma, but FMT has specific limitations to scaled use. PATIENTS AND METHODS: We conducted an early-phase clinical trial of a cultivated, orally delivered 30-species microbial consortium (Microbial Ecosystem Therapeutic 4, MET4) designed for co-administration with ICIs as an alternative to FMT and assessed safety, tolerability and ecological responses in patients with advanced solid tumors. RESULTS: The trial achieved its primary safety and tolerability outcomes. There were no statistically significant differences in the primary ecological outcomes; however, differences in MET4 species relative abundance were evident after randomization that varied by patient and species. Increases in the relative abundance of several MET4 taxa, including Enterococcus and Bifidobacterium, taxa previously associated with ICI responsiveness, were observed and MET4 engraftment was associated with decreases in plasma and stool primary bile acids. CONCLUSIONS: This trial is the first report of the use of a microbial consortium as an alternative to FMT in advanced cancer patients receiving ICI and the results justify the further development of microbial consortia as a therapeutic co-intervention for ICI treatment in cancer.

Systematic review with meta-analysis: Current and emerging models of preoperative psychological preparation for individuals undergoing stoma surgery.

OBJECTIVE: Stoma surgery is a profoundly life changing event that can result in a range of negative psychological and mental health outcomes, often requiring significant postoperative adaption. While postoperative avenues of support to address these outcomes exist, there remains a lack of preoperative psychological preparation for surgical candidates in standard models of care. The present systematic review and meta-analysis aims to examine the current and emerging models of psychological preparation available to stoma surgery candidates during the preoperative period. METHODS: A systematic search of PubMed, Embase, Emcare, PsycINFO, CINAHL, and SCOPUS was conducted. All studies examining the effects of preoperative psychological interventions targeting postoperative psychological adjustment and/or mental health outcomes for individuals planning to undergo or who had undergone stoma surgery were included. RESULTS: Overall, 15 publications meeting inclusion criteria were identified, encompassing 1565 total participants. Intervention types ranged from psychoeducational, counselling, and practical based skills, examining the postoperative outcomes of anxiety, depression, quality of life, adjustment, self-efficacy, and systematic improvements to standard models of care. Five studies examining postoperative anxiety were included for meta-analysis, demonstrating an overall significant effect (SMD = -1.13, 95% CI -1.96 to -0.30, p = .008). Due to the high level of heterogeneity between remaining studies, articles examining postoperative outcomes other than anxiety were synthesised in narrative form. CONCLUSION: Despite some promising advancements in the field, there remains insufficient evidence to judge the overall effectiveness of current and emerging models of preoperative psychological preparation on postoperative psychological outcomes for individuals facing stoma surgery.

Chronic hand eczema in Europe: Patient experiences and perspectives (CHEPEP) in qualitative interviews.

BACKGROUND: Chronic hand eczema (CHE) is a very common skin disease among the European population. It causes itch and pain and, in more severe cases, seriously impairs hand functioning at work and in private life. OBJECTIVES: To explore perspectives of people with lived experience on CHE-related problems, wishes and goals. METHODS: Following a qualitative approach, we conducted topic-guided interviews in five European countries and applied template analysis to identify recurrent themes among patients with CHE. RESULTS: We interviewed 60 patients in seven outpatient dermatological and occupational medicine clinics in Croatia, Denmark, Germany, the Netherlands and Spain. Five main themes were identified: (1) knowledge about the disease and its course, (2) preventive behaviour, (3) hand eczema therapy, (4) impact on everyday life and (5) attitudes towards CHE and healthcare. Participants did not feel well informed about CHE, especially about causes, triggers and treatment options. Preventive measures were experienced as more or less effective but also cumbersome. Experiences with therapy were diverse. Treatment satisfaction depended on the results and on the perceived support from the treatment teams. Participants found it important to be taken seriously, to receive practical advice, to try out additional treatments or examinations, find new hope and have occupational perspectives. They wished that others could better understand the physical and emotional burden of CHE. Patient support groups were not mentioned. Participants found it important to learn to take care of themselves and accept life with CHE. CONCLUSIONS: Due to its annoying symptoms, high visibility and impaired functioning at work and in private life, CHE has a high emotional and social impact. Some people may require support to learn coping with CHE and its prevention. Patients wish for information about causes and triggers. They value physicians who listen to them and keep looking for solutions.

Postural and longitudinal variability in seismocardiographic signals.

Objective. Low frequency cardiovascular vibrations detectable on the chest surface (termed seismocardiography or SCG) may be useful for non-invasive diagnosis and monitoring of various cardiovascular conditions. A potential limitation of using SCG for longitudinal patient monitoring is the existence of intra-subject variability, which can contribute to errors in calculating SCG features. Improved understanding of the contribution of intra-subject variability sources may lead to improved SCG utility. This study aims to quantify postural and longitudinal SCG variability in healthy resting subjects during normal breathing.Approach. SCG and ECG signals were longitudinally acquired in 19 healthy subjects at different postures (supine, 45° head up, and sitting) during five recording sessions over five months. SCG cycles were segmented using the ECG R wave. Unsupervised machine learning was used to reduce SCG variability due to respiration by grouping the SCG signals into two clusters with minimized intra-cluster waveform heterogeneity. Several SCG features were assessed at different postures and longitudinally.Main results. SCG waveform morphological variability was calculated within each cluster (intra-cluster) and between two clusters (inter-cluster) at each posture and data collection session. The variabilities were significantly different between the supine and sitting but not between supine and 45° postures. For the 45° and sitting postures, the intra-cluster variability was not significantly different, while the inter-cluster variability difference was significant. The energy ratio between different frequency bands to total spectral energy in 0.5-50 Hz were calculated and were comparable for all postures. The combined cardiac timing intervals from the two clusters showed significant variation with postural changes. There was significant heart rate difference between the clusters and between postural positions. The SCG features were compared between longitudinal sessions and all features were not significantly different,Significance. Several SCG features significantly varied with posture suggesting that posture needs to be specified when comparing SCG changes over time. Longitudinally comparable SCG feature values suggests that significant longitudinal differences, if observed, may reflect true alternations in the cardiac functioning over time.

Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Baseline serum levels of IgA anti-cyclic citrullinated protein antibodies in early rheumatoid arthritis predict radiographic progression after 11 years of treatment: a secondary analysis of the CIMESTRA study.

OBJECTIVE: Smoking and periodontitis are risk factors for developing rheumatoid arthritis (RA), suggesting a break of tolerance on mucosal surfaces. Immunoglobulin A (IgA) antibodies are part of the mucosal immune system. The dominant autoantibodies in RA are anti-cyclic citrullinated protein antibodies (ACPAs), and IgG and IgA subclasses exist simultaneously. This study aimed to investigate the association of ACPA IgA subtypes with disease activity and long-term radiographic outcomes in RA, compared with ACPA IgG. METHOD: Total ACPA IgG, IgA, IgA1, and IgA2 were quantified in serum from patients with early RA (n = 97). Patient characteristics, IgM rheumatoid factor (IgM-RF) status, clinical and biochemical disease activity scores, and radiographic status evaluated by total Sharp score (TSS), were assessed at baseline and after 2 and 11 years of treatment. RESULTS: All patients with ACPA IgA also had ACPA IgG. ACPA IgA positivity was associated with IgM-RF and male gender. Both ACPA IgA and IgG levels at baseline were weakly associated with disease activity markers. Baseline ACPA IgA and IgG did not show a linear correlation with radiographic status after 10 years, but could predict radiographic progression (ΔTSS ≥ 5 from 0 to 11 years), with positive likelihood ratios of 3.7 and 4.0, respectively. CONCLUSION: ACPA IgA and IgG were weakly associated with disease activity in early RA. RA patients with a ΔTSS ≥ 5 after 11 years of treatment had higher ACPA IgG and ACPA IgA levels at baseline; however, none of the ACPA subtypes was superior in predicting long-term radiographic progression.

Monocyte secretory profiling in a clinical and MEFV genotype-characterized cohort of Danish familial Mediterranean fever patients: diagnostic potential of CCL1 and CXCL1.

OBJECTIVE: The autoinflammatory disease familial Mediterranean fever (FMF), characterized by recurrent attacks of sterile fever, serosal, and/or synovial inflammation, is caused by variants in the Mediterranean fever gene, MEFV, coding for the pyrin inflammasome sensor. The diagnosis of FMF is mainly based on clinical symptoms and confirmed by detection of disease-associated MEFV variants. However, the diagnosis is challenging among patients carrying variants of uncertain clinical significance (VUS). In this study, we aimed to identify potential FMF discriminatory diagnostic markers in a cohort of clinically characterized FMF patients. METHOD: We established a cohort of clinically and MEFV genotype-characterized FMF patients by enrolling patients from major Danish hospitals (n = 91). The secretory profile of pyrin inflammasome-activated monocytes from healthy donors (HDs) and MEFV-characterized FMF patients (n = 28) was assessed by analysing cell supernatants for a custom-designed panel of 23 cytokines, chemokines, and soluble tumour necrosis factor receptors associated with monocyte and macrophage function. RESULTS: MEFV genotypes in Danish FMF patients were associated with age at symptom onset (p < 0.05), FMF among relatives (p < 0.01), proportion of patients in colchicine treatment (p < 0.01), and treatment response (p < 0.05). Secretion of chemokines CCL1 and CXCL1 from pyrin-activated FMF monocytes was significantly decreased compared to HDs (p < 0.05), and could discriminate FMF patients with 'non-confirmatory' MEFV genotypes from HDs with 80.0% and 70.0% sensitivity for CCL1 and CXCL1, respectively (p < 0.05). CONCLUSION: Our data suggest that a functional diagnostic assay based on CCL1 or CXCL1 levels in pyrin-activated patient monocytes may contribute to FMF diagnosis in patients with VUS.

The association between migraine and dementia - a national register-based matched cohort study.

OBJECTIVES: Migraine and dementia, two major public health challenges, are associated, but more knowledge is needed to understand their relationship. Objectives of this study were to investigate 1) the association between non-self-reported measures of migraine and dementia, and whether dementia was associated with 2) migraine without aura (MO) and with aura (MA) in combination with migraine medication use, and 3) migraine severity operationalized as the number of migraine prescriptions. STUDY DESIGN: Matched cohort study. METHODS: National register data were obtained from individuals born between 1934 and 1958. Migraine cases (aged 25-58 years) were identified by migraine diagnoses and redeemed migraine medication. Migraine cases were matched with non-cases (N = 340,850) and date of diagnosis or medication redemption was defined as index year. Dementia was identified by dementia diagnoses and redeemed dementia medication. RESULTS: We observed a 1.46 (95% CI: 1.26-1.69) times higher dementia rate in individuals with a migraine diagnosis and a 0.86 (95% CI: 0.76-0.97) times lower rate when using migraine medication. We found the highest dementia rate among individuals with MA, who also used migraine medication (HR = 2.23; 95% CI: 1.19-4.17), and the lowest rate among individuals with MO, who also used medication (HR = 1.25; 95% CI: 0.75-2.10). The number of migraine medication prescriptions was not associated with dementia. CONCLUSIONS: Being registered with a migraine diagnosis was associated with a higher dementia rate, while use of prescribed migraine medication was not. The differences in the dementia rate among migraine cases identified via diagnoses versus medications warrants further investigation.

Adherence to dietary guidelines and risk of dementia: a prospective cohort study of 94 184 individuals.

AIMS: Recent estimates suggest that 40% of dementia cases could be avoided by treating recognised cardiovascular risk factors such as hypertension, diabetes, smoking and physical inactivity. Whether diet is associated with dementia remains largely unknown. We tested if low adherence to established dietary guidelines is associated with elevated lipids and lipoproteins and with increased risk of Alzheimer's disease and non-Alzheimer's dementia ­ a dementia subtype with a high frequency of cardiovascular risk factors. METHODS: We used the prospective Copenhagen General Population Study including 94 184 individuals with dietary information and free of dementia at baseline. Mean age at study entry was 58 years, and 55% (N = 51 720) were women and 45% (N = 42 464) were men. Adherence to dietary guidelines was grouped into low, intermediate and high adherence based on food frequency questionnaires. Main outcomes were non-Alzheimer's dementia and Alzheimer's disease. RESULTS: Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and plasma triglyceride levels were higher in individuals with intermediate and low adherence to dietary guidelines compared with individuals with high adherence (all p for trends <0.001). Age and sex-adjusted hazard ratios (HRs) for non-Alzheimer's dementia v. individuals with high adherence were 1.19 (95% confidence interval 0.97­1.46) for intermediate adherence, and 1.54 (1.18­2.00) for low adherence. Corresponding HRs in multivariable-adjusted models including APOE genotype were 1.14 (0.92­1.40) and 1.35 (1.03­1.79). These relationships were not observed in individuals on lipid-lowering therapy. CONCLUSIONS: Low adherence to national dietary guidelines is associated with an atherogenic lipid profile and with increased risk of non-Alzheimer's dementia ­ the subtype of dementia with a high frequency of vascular risk factors. This study suggests that implementation of dietary guidelines associated with an anti-atherogenic lipid profile could be important for prevention of non-Alzheimer's dementia.

Direct Measurement of the Return Current Instability in a Laser-Produced Plasma.

Measurements were made of the return current instability growth rate, demonstrating its concurrence with nonlocal transport. Thomson scattering was used to measure a maximum growth rate of 5.1×10^{9} Hz, which was 3 times less than classical Spitzer-Härm theory predicts. The measured plasma conditions indicate the heat flux was nonlocal, and Vlasov-Fokker-Planck simulations that account for nonlocality reproduce the measured growth rates. Furthermore, the threshold for the return current instability was measured (δ_{T}=0.017±0.002) to be in good agreement with previous theoretical models.

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study.

OBJECTIVE: Pembrolizumab demonstrated a clinically meaningful objective response rate in patients with previously treated, advanced MSI-H/dMMR endometrial cancer in the multicohort phase 2 KEYNOTE-158 study (ClinicalTrials.gov, NCT02628067). We present health-related quality of life (HRQoL) results for these patients. METHODS: This analysis included patients from cohorts D (endometrial cancer with any MSI status) and K (any MSI-H/dMMR solid tumor except colorectal) who had previously treated, advanced MSI-H/dMMR endometrial cancer. Patients received pembrolizumab 200 mg Q3W for 35 cycles. EORTC QLQ-C30 and EQ-5D-3L questionnaires were administered at baseline, at regular intervals during treatment, and 30 days after treatment discontinuation. Pre-specified exploratory analyses included changes from baseline to week 9 in QLQ-C30 global health status (GHS)/QoL and EQ-5D-3L visual analog scale (VAS) score for all patients and by best overall response. RESULTS: 84 of 90 enrolled patients completed ≥1 HRQoL questionnaire and were included in the analysis. QLQ-C30 and EQ-5D-3L compliance rates were 90% and 94%, respectively, at baseline, and 92% and 93% at week 9. Mean (95% CI) QLQ-C30 GHS/QoL scores improved from baseline to week 9 by 6.08 (0.71-11.46) points in the overall population, with greater improvement in patients who achieved complete or partial response (11.67 [5.33-18.00]-point increase). Mean (95% CI) EQ-5D-3L VAS scores improved by 6.00 (2.25-9.75) points in the overall population and 9.11 (5.24-12.98) points in patients with CR/PR. CONCLUSIONS: Pembrolizumab maintained or improved HRQoL in patients with previously treated, advanced MSI-H/dMMR endometrial cancer, further supporting efficacy and safety results from KEYNOTE-158 and pembrolizumab use in this setting.

Improving management of needle distress during the journey to dialysis through psychological education and training-the INJECT study feasibility pilot protocol.

BACKGROUND: Needle-related distress is a common yet poorly recognised and managed problem among haemodialysis (HD) patients. The aim of this pilot study is to test the feasibility and acceptability of the INJECT Intervention-an innovative psychology-based intervention to empower patients to self-manage needle distress with the support of dialysis nurses. METHODS: This investigator-initiated, single-arm, non-randomised feasibility study will take place in a large dialysis service in Adelaide, Australia. Participants will include patients aged ≥ 18 years, commencing or already receiving maintenance HD, recruited through dialysis physicians and nursing staff as individuals believed to be at risk of needle distress. They will be screened for inclusion using the Dialysis Fear of Injection Questionnaire (DFIQ) and enrolled into the study if the score is ≥ 2. The multi-pronged intervention encompasses (i) psychologist review, (ii) patient self-management program and (iii) nursing education program. The primary aim is to evaluate feasibility and acceptability of the intervention from patient and dialysis nurse perspectives, including recruitment, retention, engagement with the intervention and completion. Secondary exploratory outcomes will assess suitability of various tools for measuring needle distress, evaluate acceptability of the nursing education program and measure cannulation-related trauma and vascular access outcomes. CONCLUSION: The results will inform the protocol for larger trials addressing needle distress in HD patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000229875, approved 4 April 2021, https://www.anzctr.org.au/ .

Robotic retroperitoneal lymph node dissection for primary and post-chemotherapy testis cancer.

The role of retroperitoneal lymph node dissection (RPLND) in testicular cancer is well established in both the primary and post-chemotherapy setting. The aim of this study was to report our 2 years oncological outcomes of robotic RPLND. A retrospective review was performed of all patients undergoing robotic RPLND by a single surgeon at Princess Margaret Cancer Centre. Demographic, perioperative, and oncologic data were analyzed using descriptive statistics. Between September 2014 and June 2020, 141 patients underwent an RPLND [33 (23.4%) were primary, 108 (76.6%) were post-chemotherapy]. 27 (19.1%) patients underwent a robotic bilateral template nerve-sparing RPLND. RPLND indication was primary (i.e. pre-chemotherapy) in 18 (66.7%), and post-chemotherapy in 9 (33.3%) patients. Stage at RPLND was 2A (n = 15, 55.6%), 2B (n = 9, 33.3%), 2C (n = 1, 3.7%) and 3 (n = 2, 7.4%). Median OR time (incision to closure) was 525 min and blood loss was 200 ml. Nerve sparing was performed in all but one case. Six (22.2%) adjuvant procedures were performed including two (7.4%) vascular repairs. Median length of stay was 2 days. Viable tumor was detected in 17 (63%) and teratoma in 9 (33.3%). Median follow-up was 31.3 months. No adjuvant chemotherapy was given. Three patients (11.1%) relapsed: 2 out-of-field and 1 with both in-field and out-of-field disease. Robotic RPLND can be performed safely. Long-term follow-up of series such as ours, enriched with patients with viable disease and/or teratoma, and not treated with adjuvant chemotherapy is required to ensure oncological outcomes are comparable to the open approach.

Can Shunt Response in Patients with Idiopathic Normal Pressure Hydrocephalus Be Predicted from Preoperative Brain Imaging? A Retrospective Study of the Diagnostic Use of the Normal Pressure Hydrocephalus Radscale in 119 Patients.

BACKGROUND AND PURPOSE: The Normal Pressure Hydrocephalus Radscale is a combined scoring of 7 different structural imaging markers on preoperative brain CT or MR imaging in patients with idiopathic normal pressure hydrocephalus: callosal angle, Evans Index, Sylvian fissure dilation, apical sulcal narrowing, mean temporal horn diameter, periventricular WM lesions, and focal sulcal dilation. The purpose of this retrospective study was to assess the performance of the Normal Pressure Hydrocephalus Radscale in distinguishing idiopathic normal pressure hydrocephalus shunt responders from nonresponders. MATERIALS AND METHODS: The preoperative MR imaging and CT scans of 119 patients with idiopathic normal pressure hydrocephalus were scored using the Normal Pressure Hydrocephalus Radscale. A summary shunt-response score assessed within 6 months from ventriculoperitoneal shunt surgery, combining the effect on cognition, gait, and urinary incontinence, was used as a reference. The difference between the mean Normal Pressure Hydrocephalus Radscale for responders and nonresponders was tested using the Student t test. The area under the curve was calculated for the Normal Pressure Hydrocephalus Radscale to assess shunt response. To ascertain reproducibility, we assessed the interobserver agreement between the 2 independent observers as intraclass correlation coefficients for the Normal Pressure Hydrocephalus Radscale for 74 MR imaging scans and 19 CT scans. RESULTS: Ninety-four (79%) of 119 patients were shunt responders. The mean Normal Pressure Hydrocephalus Radscale score for shunt responders was 8.35 (SD, 1.53), and for nonresponders, 7.48 (SD, 1.53) (P = .02). The area under the curve for the Normal Pressure Hydrocephalus Radscale was 0.66 (range, 0.54-0.78). The intraclass correlation coefficient for the Normal Pressure Hydrocephalus Radscale was 0.86 for MR imaging and 0.82 for CT. CONCLUSIONS: The Normal Pressure Hydrocephalus Radscale showed moderate discrimination for shunt response but cannot, on its own, be used for selecting patients with idiopathic normal pressure hydrocephalus for shunt surgery.

Nitro-fatty acids decrease type I interferons and monocyte chemoattractant protein 1 in ex vivo models of inflammatory arthritis.

BACKGROUND: Inflammatory arthritis including rheumatoid arthritis (RA) and spondyloarthritis (SpA) is characterized by inflammation and destruction of the joints. Approximately one third of patients do not respond to first-line treatments. Nitro-fatty acids are bioactive lipids with anti-inflammatory properties and tissue-protective functions. The nitro-fatty acid 10-NO2-oleic acid (10-NO2-OA) is being tested in clinical trials for patients with fibrotic and inflammatory conditions. Here, we tested whether 10-NO2-OA could inhibit immune reactions involved in the inflammatory and joint destructive processes in inflammatory arthritis. METHODS: Synovial fluid and blood samples were obtained from 14 patients with active RA or SpA. The in vitro models consisted of synovial fluid mononuclear cells (SFMCs) cultured for 48 h, SFMCs cultured for 21 days, and fibroblast-like synovial cells (FLSs) co-cultured with peripheral blood mononuclear cells (PBMCs) for 48 h. Cells were treated with or without 10-NO2-OA or the tumor necrosis factor alpha (TNFα) inhibitor etanercept. Supernatants were analyzed for type I interferon, monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase 3 (MMP3) and tartrate resistant acid phosphatase (TRAP). RESULTS: In SFMCs cultured for 48 h, 10-NO2-OA dose-dependently decreased the secretion of bioactive type I interferons and MCP-1 but not MMP3 (P = 0.032, P = 0.0001, and P = 0.58, respectively). Both MCP-1 and MMP3 were decreased by etanercept (P = 0.0031 and P = 0.026, respectively). In SFMCs cultured for 21 days, 10-NO2-OA significantly decreased the production of MCP-1 but not TRAP (P = 0.027 and P = 0.1523, respectively). Etanercept decreased the production of TRAP but not MCP-1 (P < 0.001 and P = 0.84, respectively). In co-cultures of FLSs and PBMCs, 10-NO2-OA decreased the production of MCP-1 (P < 0.0001). This decrease in MCP-1 production was not seen with etanercept treatment (P = 0.47). CONCLUSION: 10-NO2-OA decreased the release of MCP-1 in three models of inflammatory arthritis. Of particular interest, 10-NO2-OA inhibited type I interferon, and 10-NO2-OA was more effective in reducing MCP-1 production in cultures dominated by FLSs compared with etanercept. Our results encourage clinical investigations of 10-NO2-OA in patients with inflammatory arthritis.