Externally validated treatment algorithm acceptably predicts nonoperative treatment success in patients with anterior cruciate ligament rupture.

PURPOSE: This study aims to develop and externally validate a treatment algorithm to predict nonoperative treatment success or failure in patients with anterior cruciate ligament (ACL) rupture. METHODS: Data were used from two completed studies of adult patients with ACL ruptures: the Conservative versus Operative Methods for Patients with ACL Rupture Evaluation study (development cohort) and the KNee osteoArthritis anterior cruciate Ligament Lesion study (validation cohort). The primary outcome variable is nonoperative treatment success or failure. Potential predictor variables were collected, entered into the univariable logistic regression model and then incorporated into the multivariable logistic regression model for constructing the treatment algorithm. Finally, predictive performance and goodness-of-fit were assessed and externally validated by discrimination and calibration measures. RESULTS: In the univariable logistic regression model, a stable knee measured with the pivot shift test and a posttrauma International Knee Documentation Committee (IKDC) score <50 were predictive of needing an ACL reconstruction. Age >30 years and a body mass index > 30 kg/m2 were predictive for not needing an ACL reconstruction. Age, pretrauma Tegner score, the outcome of the pivot shift test and the posttrauma IKDC score are entered into the treatment algorithm. The predictability of needing an ACL reconstruction after nonoperative treatment (discrimination) is acceptable in both the development and the validation cohort: area under the curve = resp. 0.69 (95% confidence interval [CI]: 0.58-0.81) and 0.68 (95% CI: 0.58-0.78). CONCLUSION: This study shows that the treatment algorithm can acceptably predict whether an ACL injury patient will have a(n) (un)successful nonoperative treatment (discrimination). Calibration of the treatment algorithm suggests a systematical underestimation of the need for ACL reconstruction. Given the limitations regarding the sample size of this study, larger data sets must be constructed to improve the treatment algorithm further. LEVEL OF EVIDENCE: Level II.

Evaluating Community-Based Intrathecal Baclofen Therapy: Effectiveness, Safety, and Feasibility.

Background: Intrathecal baclofen (ITB) is used for the treatment of intractable spasticity. The burden of traveling for ITB screening and aftercare is problematic for nursing home residents with severe spasticity and seems to result in undertreatment of spasticity. The aim of this study is to evaluate the effectiveness, safety, and feasibility of ITB for nursing home residents treated in their home, describing the selection phase, the initial trial of ITB, and aftercare up to 3 months after implantation of an ITB pump. Methods: This retrospective database study included immobile, adult nursing home residents with severe spasticity, referred to an Ambulatory Care Clinic between 2016 and 2021. When eligible, an ITB trial was performed by ITB experts in the nursing home. If a permanent pump was implanted, dose titration and aftercare were performed on location. Results: A total of 102 patients were referred; 80 underwent an ITB trial on location, and 94% improved significantly on the Modified Ashworth Scale and clonus scale pre-ITB trial versus post-ITB trial, as well as at 3 months post-implantation. There was a low incidence of adverse events, mostly procedure- and drug-related. Conclusions: This study indicates that selection, testing, and aftercare for ITB on location is effective and safe.

Tumor Necrosis Factor Inhibitor Use Increases Birthweight in Pregnant Women With Rheumatoid Arthritis Independently of the Soluble Fms-Like Tyrosine Kinase-1/Placental Growth Factor Ratio.

BACKGROUND: To study whether the use of TNF (tumor necrosis factor) inhibitors (TNFi) by pregnant women with rheumatoid arthritis affects sFlt-1 (soluble Fms-like tyrosine kinase-1), PlGF (placental growth factor), or their impact on birthweight. METHODS AND RESULTS: sFlt-1 and PlGF were measured in all trimesters of pregnancy in the Preconception Counseling in Active Rheumatoid Arthritis study and were compared according to the use of TNFi. The association of sFlt-1 and PlGF with birthweight in relation to TNFi was determined. The study included 158 women, of whom 52.5% used TNFi during pregnancy. Both sFlt-1 and PlGF increased during pregnancy, whereas their ratio declined. Taking into consideration the trimester-related variation in levels of sFlt-1 and PlGF, after correction for relevant confounders, the sFlt-1/PlGF ratio was not significantly different between patients who did or did not use TNFi (sFlt-1/PlGF ratio in the second trimester compared with the first trimester: estimated change 8.17 [95% CI, 2.54-26.29], P=0.79; sFlt-1/PlGF ratio in the third trimester compared with the first trimester: estimated change 6.25 [95% CI, 1.73-22.50], P=0.25). In women who did not use TNFi, birthweight was significantly lower (3180 versus 3302 g; P=0.03), and sFlt-1 displayed a negative correlation with birthweight (r=-0.462, P<0.001) and birthweight percentile (r=-0.332, P=0.008). In TNFi users, these correlations were absent. CONCLUSIONS: TNF inhibitor use increases birthweight in pregnant women with rheumatoid arthritis independently of the sFlt-1/PlGF ratio. REGISTRATION: http://clinicaltrials.gov. Unique identifier: NCT01345071.

Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.

Antibodies against angiotensin II receptor type 1 and endothelin A receptor are increased in COVID-19 patients.

Background: Increased titers of autoantibodies targeting the G-protein-coupled receptors angiotensin II type 1 receptor (AT1R) and endotelin-1 type A receptor (ETAR) are associated with severe coronavirus disease 2019 (COVID-19) infection. The aim of this study was to determine whether 1) these antibodies are specifically related to COVID-19 disease pathogenesis or increased during any severe respiratory illness, 2) if they are formed during illness, and 3) if they correlate with inflammatory markers or long-term symptoms. Methods: Antibodies against AT1R, ETAR, and antinuclear antibodies (ANAs) were measured in n=40 prospectively enrolled COVID-19 patients and n=207 COVID-19 patients included in a biobank. Clinical and laboratory findings were prospectively and retrospectively assessed in both cohorts, and results were combined for analysis. The presence of auto-antibodies against AT1R or ETAR in peripheral blood was compared between hospitalized patients with COVID-19 and controls (n=39). Additionally, AT1R and ETAR titers were compared between patients with an unfavorable disease course, defined as intensive care admission and/or death during hospital admission (n=121), to those with a favorable disease course (n=126). A subset of intubated patients with severe COVID-19 were compared to intubated patients with acute respiratory distress syndrome (ARDS) due to any other cause. Results: Significantly increased AT1R and ETAR antibody titers were found in COVID-19 patients compared to controls, while titers were equal between favorable and unfavorable COVID-19 disease course groups. On ICU, intubated patients with COVID-19 had significantly increased AT1R and ETAR titers compared to patients with ARDS due to any other cause. The titers did not correlate with baseline inflammatory markers during admission or with diffusion capacity, cognitive impairment, or fatigue measured at 3 months follow-up. Conclusions: In patients hospitalized for COVID-19, antibodies against AT1R and ETAR are increased compared to controls and patients with ARDS due to other causes than COVID-19. The baseline antibody titers do not correlate with inflammatory markers or long-term symptoms in this study.

Are serum cobalt and chromium levels predictors for patient-reported outcome measures in the ASR hip resurfacing arthroplasty?

Aims: The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate. Methods: A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model. Results: We found that an increase of one part per billion (ppb) in serum Co and Cr levels correlated significantly with worsening of the HHS in the following year. This significant correlation was also true for the HOOS-Pain and HOOS-quality of life sub scores. The overall ten-year survival rate in our cohort was 65% (95% confidence interval (CI) 52.5 to 77.6). Cox regression analysis showed a significant hazard ratio (HR) of 1.08 (95% CI 1.01 to 1.15; p = 0.028) for serum Co level. No significance was found with sex or inclination angle. Conclusion: This study shows that increasing serum Co and Cr levels measured in patients with an ASR-HRA are predictive for deterioration in HHS and HOOS subscales in the following year. Increasing serum Co and Cr should forewarn both surgeon and patient that there is a heightened risk of failure. Continued and regular review of patients with an ASR-HRA implant by measurement of serum Co/Cr levels and PROMs remains essential.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

OBJECTIVE: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. METHODS: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. RESULTS: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). CONCLUSIONS: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Systemic Metabolomics in a Framework of Genetics and Lifestyle in Age-Related Macular Degeneration.

Insights into the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness, point towards a complex interplay of genetic and lifestyle factors triggering various systemic pathways. This study aimed to characterize metabolomic profiles for AMD and to evaluate their position in the trias with genetics and lifestyle. This study included 5923 individuals from five European studies. Blood metabolomics were assessed using a nuclear magnetic resonance platform of 146 metabolites. Associations were studied using regression analyses. A genetic risk score (GRS) was calculated using ß-values of 49 AMD variants, a lifestyle risk score (LRS) using smoking and diet data, and a metabolite risk score (MRS) using metabolite values. We identified 61 metabolites associated with early-intermediate AMD, of which 94% were lipid-related, with higher levels of HDL-subparticles and apolipoprotein-A1, and lower levels of VLDL-subparticles, triglycerides, and fatty acids (false discovery rate (FDR) p-value < 1.4 × 10-2). Late AMD was associated with lower levels of the amino acids histidine, leucine, valine, tyrosine, and phenylalanine, and higher levels of the ketone bodies acetoacetate and 3-hydroxybutyrate (FDR p-value < 1.5 × 10-3). A favorable lifestyle characterized by a healthy diet was associated with higher levels of amino acids and lower levels of ketone bodies, while an unfavorable lifestyle, including smoking, showed opposite effects (FDR p-value < 2.7 × 10-2). The MRS mediated 5% of the effect of the GRS and 20% of that of the LRS on late AMD. Our findings show that metabolomic profiles differ between AMD stages and show that blood metabolites mostly reflect lifestyle. The severity-specific profiles spur further interest into the systemic effects related to disease conversion.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2).

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. METHODS: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. DISCUSSION: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022. PROTOCOL VERSION: Version 3, February 2022.

Ipsilateral Aorto-Iliac Calcification is Not Directly Associated With eGFR After Kidney Transplantation: A Prospective Cohort Study Analyzed Using a Linear Mixed Model.

Aorto-iliac calcification (AIC) is a well-studied risk factor for post-transplant cardiovascular events and mortality. Its effect on graft function remains unknown. The primary aim of this prospective cohort study was to assess the association between AIC and estimated glomerular filtration rate (eGFR) in the first year post-transplant. Eligibility criteria were: ≥50 years of age or ≥30 years with at least one risk factor for vascular disease. A non-contrast-enhanced CT-scan was performed with quantification of AIC using the modified Agatston score. The association between AIC and eGFR was investigated with a linear mixed model adjusted for predefined variables. One-hundred-and-forty patients were included with a median of 31 (interquartile range 26-39) eGFR measurements per patient. No direct association between AIC and eGFR was found. We observed a significant interaction between follow-up time and ipsilateral AIC, indicating that patients with higher AIC scores had lower eGFR trajectory over time starting 100 days after transplant (p = 0.014). To conclude, severe AIC is not directly associated with lower post-transplant eGFR. The significant interaction indicates that patients with more severe AIC have a lower eGFR trajectory after 100 days in the first year post-transplant.

Multimarker Analysis of Serially Measured GDF-15, NT-proBNP, ST2, GAL-3, cTnI, Creatinine, and Prognosis in Acute Heart Failure.

BACKGROUND: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. METHODS: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. RESULTS: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78-2.57) unadjusted, 1.96 (1.49-2.53) after adjustment for clinical confounders and 1.44 (1.05-1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78-3.33) and 1.52 (1.15-2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). CONCLUSIONS: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. REGISTRATION: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.).

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. MATERIALS AND METHODS: This study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. RESULTS: In total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. CONCLUSIONS: Standard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research. ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma.

PURPOSE: Lurbinectedin is a promising new drug being investigated in pre-treated patients with small cell lung cancer (SCLC) or malignant pleural mesothelioma (MPM). Its clinical activity in the real-world setting has not been investigated yet. PATIENTS AND METHODS: Clinical data of patients with SCLC and MPM who were treated with lurbinectedin were prospectively collected. Comprehensive immune cell profiling by flow cytometry was performed on screening and treating peripheral blood samples. RESULTS: A total of 95 patients (43 SCLC and 52 MPM) were treated, mostly as ≥3-line of therapy. In the SCLC cohort, a median progression-free survival (mPFS) was 1.5 months (95% CI: 1.4-3.0), and median overall survival was 7.0 months (95% CI: 4.7-not reached). Objective radiological response and disease control rate after 12 weeks were 16% and 28%, respectively. In the MPM cohort, median progression-free survival was 2.8 months (95% CI: 1.4-4.2), and median overall survival was 7.2 months (95% CI: 5.9-not reached). Disease control rate after 12 weeks was 29%, whereas no partial responses were registered. No new safety signals were observed. Lurbinectedin treatment was significantly associated with the depletion of circulating classical monocytes, which correlated with a better PFS in patients with SCLC. Lurbinectedin increased the proliferation of CD4+ and CD8+ T cells (SCLC) and natural killer and natural killer T cells (SCLC and MPM) and altered co-stimulatory and co-inhibitory receptor expression on circulating lymphocytes. CONCLUSION: Lurbinectedin has a manageable safety profile and shows clinical activity in pre-treated patients with SCLC and MPM. Its immune-modulatory functions make lurbinectedin a potential platform for immunotherapy combinations.

Development and validation of a multivariable prediction model for early prediction of chronic postsurgical pain in adults: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of developing chronic postsurgical pain (CPSP) is an essential step in reducing pain chronification in postsurgical patients. We aimed to develop and validate a prognostic model for the early prediction of CPSP including pain characteristics indicating altered pain processing within 2 weeks after surgery. METHODS: A prospective cohort study was conducted in adult patients undergoing orthopaedic, vascular, trauma, or general surgery between 2018 and 2019. Multivariable logistic regression models for CPSP were developed using data from the University Medical Centre (UMC) Utrecht and validated in data from the Erasmus UMC Rotterdam, The Netherlands. RESULTS: In the development (n=344) and the validation (n=150) cohorts, 28.8% and 21.3% of patients reported CPSP. The best performing model (area under the curve=0.82; 95% confidence interval [CI], 0.76-0.87) included preoperative treatment with opioids (odds ratio [OR]=4.04; 95% CI, 2.13-7.70), bone surgery (OR=2.01; 95% CI, 1.10-3.67), numerical rating scale pain score on postoperative day 14 (OR=1.57; 95% CI, 1.34-1.83), and the presence of painful cold within the painful area 2 weeks after surgery (OR=4.85; 95% CI, 1.85-12.68). Predictive performance was confirmed by external validation. CONCLUSIONS: As only four easily obtainable predictors are necessary for reliable CPSP prediction, the models are useful for the clinician to be alerted to further assess and treat individual patients at risk. Identification of the presence of painful cold within 2 weeks after surgery as a strong predictor supports altered pain processing as an important contributor to CPSP development.

Home monitoring of lung function, symptoms and quality of life after admission with COVID-19 infection: The HOMECOMIN' study.

BACKGROUND AND OBJECTIVE: To develop targeted and efficient follow-up programmes for patients hospitalized with coronavirus disease 2019 (COVID-19), structured and detailed insights in recovery trajectory are required. We aimed to gain detailed insights in long-term recovery after COVID-19 infection, using an online home monitoring programme including home spirometry. Moreover, we evaluated patient experiences with the home monitoring programme. METHODS: In this prospective multicentre study, we included adults hospitalized due to COVID-19 with radiological abnormalities. For 6 months after discharge, patients collected weekly home spirometry and pulse oximetry measurements, and reported visual analogue scales on cough, dyspnoea and fatigue. Patients completed the fatigue assessment scale (FAS), global rating of change (GRC), EuroQol-5D-5L (EQ-5D-5L) and online tool for the assessment of burden of COVID-19 (ABCoV tool). Mixed models were used to analyse the results. RESULTS: A total of 133 patients were included in this study (70.1% male, mean age 60 years [SD 10.54]). Patients had a mean baseline forced vital capacity of 3.25 L (95% CI: 2.99-3.44 L), which increased linearly in 6 months with 19.1% (Δ0.62 L, p < 0.005). Patients reported substantial fatigue with no improvement over time. Nevertheless, health status improved significantly. After 6 months, patients scored their general well-being almost similar as before COVID-19. Overall, patients considered home spirometry useful and not burdensome. CONCLUSION: Six months after hospital admission for COVID-19, patients' lung function and quality of life were still improving, although fatigue persisted. Home monitoring enables detailed follow-up for patients with COVID-19 at low burden for patients and for the healthcare system.

Clinical and Molecular Profiling to Develop a Potential Prediction Model for the Response to Alemtuzumab Therapy for Acute Kidney Transplant Rejection.

Alemtuzumab, a monoclonal antibody that depletes CD52-bearing immune cells, is an effective drug for the treatment of severe or glucocorticoid-resistant acute kidney transplant rejection (AR). Patient-specific predictions on treatment response are, however, urgently needed, given the severe side effects of alemtuzumab. This study developed a multidimensional prediction model with the aim of generating clinically useful prognostic scores for the response to alemtuzumab. Clinical and histological characteristics were collected retrospectively from patients who were treated with alemtuzumab for AR. In addition, targeted gene expression profiling of AR biopsy tissues was performed. Least absolute shrinkage and selection operator (LASSO) logistic regression modeling was used to construct the ALEMtuzumab for Acute Rejection (ALEMAR) prognostic score. Response to alemtuzumab was defined as patient and allograft survival and at least once an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 during the first 6 months after treatment. One hundred fifteen patients were included, of which 84 (73%) had a response to alemtuzumab. The ALEMAR-score accurately predicted the chance of response. Gene expression analysis identified 13 differentially expressed genes between responders and nonresponders. The combination of the ALEMAR-score and selected genes resulted in improved predictions of treatment response. The present preliminary prediction model is potentially helpful for the development of stratified alemtuzumab treatment for acute kidney transplant rejection but requires validation.

Fractionated stereotactic radiotherapy for uveal melanoma: Long-term outcome and control rates.

PURPOSE: The aim of our study is to evaluate local tumour control rates, radiation side-effects, visual preservation and disease-free survival (DFS) of uveal melanoma (UM) patients treated with fractionated stereotactic radiotherapy (fSRT). METHODS: A retrospective study of UM patients, who were treated with fSRT (N = 189), was performed by the Rotterdam Ocular Melanoma Study group (ROMS), the Netherlands, between 1999 and 2014 with a follow-up of at least 5 years. RESULTS: The 1-, 3-, 5-, 10- and 15-year local tumour control rates were as follows: 99.4%, 92.8%, 92.2%, 89.3% and 89.3%, respectively. Cataract (67.8%) was the most common side-effect of fSRT followed by retinopathy (35.1%), maculopathy (23.8%), vitreous haemorrhage (20.1%), neovascular glaucoma (NVG) (20.0%) and optic neuropathy (12.4%). Patients with anterior located UMs developed cataract more frequently (p = 0.047, multivariable analysis). By multivariable analysis, significant factors for secondary enucleation were tumour recurrence (p < 0.001) and NVG (p < 0.001). In multivariable analysis, risk factors for a worse DFS were larger UM (p = 0.024) and tumours with subretinal fluid (SRF) at baseline (p = 0.038). The 5-year DFS was 77.0% and the best corrected visual acuity decreased significantly after treatment. After 5 years, 22.0% of patients and after 10 years 17.6% of patients had a visual acuity of ≤0.3 logMAR. CONCLUSION: Fractionated stereotactic radiotherapy is a good treatment option for small-, medium- and large-sized tumours with 5-year local tumour control of 92.2%. After 5 years, 22.0% of the patients had a good vision. Independently of tumour location, the visual acuity decreased significantly after treatment. Overall, the 5-year DFS was 77.0%.

Electrical neurostimulation for the treatment of chronic pruritus: A systematic review.

Approximately one fifth of the world population experiences continuous itch for 6 weeks or more during their life, that is chronic itch. It is diverse in its aetiologies, and it is notoriously hard to treat. Because itch and pain have largely overlapping pathophysiology and the demonstrated efficacy of neurostimulation in treatment of selected chronic pain conditions, we conducted a systematic review to investigate whether neurostimulation could be an effective treatment for chronic itch. We identified two randomized controlled trials and 17 open label studies or case reports investigating various neurostimulation modalities for the treatment of refractory itch of various aetiologies. Transcutaneous electrical nerve stimulation (TENS) was the most investigated modality (n = 17), and in the largest number of conditions. Other modalities were cutaneous field stimulation (n = 2), painscrambler (n = 1), transcranial direct current stimulation (n = 1) and peripheral nerve field stimulation (n = 1). Atopic dermatitis was the most studied condition (n = 5). Despite the large heterogeneity in used stimulation paradigms and outcome parameters, all studies reported a positive effect of at least one neurostimulation modality. Our review indicates that electrical neurostimulation could be considered for the treatment of refractory chronic itch of selected aetiologies, such as atopic dermatitis or burn pruritus. However, better understanding of the mechanisms of action of the neurostimulation modalities and regimens in various pruritic conditions is necessary.

Persistent Health Problems beyond Pulmonary Recovery up to 6 Months after Hospitalization for COVID-19: A Longitudinal Study of Respiratory, Physical, and Psychological Outcomes.

Rationale: Data on longitudinal recovery after hospitalization for coronavirus disease (COVID-19) currently remain scarce, just as outcomes beyond 3 months of follow-up do. Objectives: To evaluate the sequelae up to 6 months after hospitalization for COVID-19 by considering 1) recovery as it relates to pulmonary function, radiological abnormalities, physical and mental health status, and health-related quality of life (HR-QoL) and 2) the predictors of the most clinically relevant sequelae. Methods: Patients were evaluated at 6 weeks, 3 months, and 6 months after hospitalization by using pulmonary function testing, radiological evaluation, and online questionnaires on the physical and mental health status and HR-QoL. Outcomes were analyzed using repeated-measurement analyses. Results: Ninety-two patients were included (mean age, 58.2 ± 12.3 yr; 58 [63.0%] men). The estimated percentage of patients with impaired forced vital capacity improved from 25% at 6 weeks to 11% at 6 months; for impaired diffusion capacity, this percentage improved from 63% to 46%. Radiologically, ground-glass opacity decreased but fibrosis persisted. The majority of patients (89.1%) still reported one or more symptoms 6 months after discharge. Fatigue decreased significantly over time (P = 0.006). Nonetheless, fatigue remained in 51% of the patients at 6 months. HR-QoL (nearly) normalized in most domains at 6 months, except for physical role functioning, with persistent fatigue and the length of hospitalization being the most important predictors. Conclusions: During the first 6 months after hospitalization for COVID-19, most patients demonstrated continuing recovery across all health domains, but persistent sequelae were frequent. Fatigue was the most frequent residual and persistent symptom up to 6 months after hospitalization, importantly impacting HR-QoL.