Improved survival in myeloma patients-a nationwide registry study of 4,647 patients ≥75 years treated in Denmark and Sweden.

The prevalence of multiple myeloma (MM) is increasing in Nordic countries and the rest of the western world. Patients aged ≥75 years at diagnosis constitute an increasing proportion of all MM patients, but are underrepresented in randomized clinical trials. There is an urgent need for studies of the characteristics, treatment and outcome in this cohort. We present data from two nationwide population-based registries of all MM patients diagnosed in Denmark from January 1, 2005 until February 18, 2020, and in Sweden from January 1, 2008 until December 31, 2019, including treatment data for patients diagnosed until 2018 (Denmark) and 2019 (Sweden). In total 4,647 patients were ≥75 years at diagnosis, compared to 7,378 younger patients. Patients ≥75 years, accounting for approximately 40% of all MM patients, are a distinct cohort with more advanced disease at diagnosis, reflected by higher International Staging System (ISS) stage, and a higher proportion have renal failure and anemia. We found a more gradual introduction of modern medications in the older cohort than in the younger, despite simultaneous changes in guidelines. Compared to the cohorts in randomized controlled trials that guide the treatment of non-transplant eligible patients, we found a higher proportion of patients ≥75 years and presenting with ISS III in the real-world populations. Nevertheless, response rates and survival are increasing, indicating that modern treatment regimens are effective and well tolerated also in elderly MM patients in real-world populations.

Fatigue, health-related quality-of-life and metabolic changes in men treated with enzalutamide or abiraterone acetate plus prednisone for metastatic castration-resistant prostate cancer: A randomised clinical trial (HEAT).

INTRODUCTION: Enzalutamide and abiraterone acetate plus prednisone (AAP) have similar efficacy in metastatic castration-resistant prostate cancer (mCRPC). Herein, we compare fatigue, health-related quality-of-life (HRQoL) and metabolic changes in men with mCRPC treated with enzalutamide and AAP. MATERIALS AND METHODS: In this single-centre, open-labelled, phase IV trial, patients with metastatic prostate cancer progressing on androgen deprivation therapy were randomly assigned to enzalutamide (160 mg daily) or AAP (1000 mg abiraterone acetate and 10 mg prednisone daily) as first-line mCRPC treatment. The primary outcome was the difference in changed fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire). The secondary outcomes were differences in changed HRQoL (Functional Assessment of Cancer Therapy-Prostate questionnaire), body composition, weight, glucose homeostasis, lipid profile and blood pressure. All outcomes were assessed at baseline and at 12-week follow-up. TRIAL REGISTRATION: clinicaltrialsregister.eu (2017-000099-27). RESULTS: 170 patients were randomised (1:1) to enzalutamide or AAP. The primary outcome was positive with a clinically meaningful difference in fatigue, favouring AAP (3.4 points, 95% CI 1.2; 5.6, P = 0.003). The group difference in changed HRQoL did not reach clinical significance. The most important metabolic finding was a higher increase in glycated haemoglobin (HbA1c) for AAP than enzalutamide (3.4 mmol/mol, 95% CI 2.1; 4.8, P = 0.001). Eight patients developed type 2 diabetes (T2D) in the AAP group and none in the enzalutamide group. No treatment-related serious adverse event was observed. CONCLUSIONS: AAP resulted in less fatigue than enzalutamide in a randomised setting. This was at the expense of a higher HbA1c increase and incidence of T2D.

Drug Levels Associated With Optimal Discrimination Between Remission and Nonremission and Comparison of Antibody Assays During First Year of Stable Infliximab Maintenance Therapy in Inflammatory Bowel Disease.

BACKGROUND: To implement therapeutic drug monitoring-based strategies for infliximab (IFX) in inflammatory bowel disease, the authors assessed IFX levels for optimal discrimination between remission and nonremission and compared assays for anti-IFX antibodies (Abs). METHODS: The retrospective cohort comprised 163 bionaive patients with inflammatory bowel disease who received stable IFX maintenance therapy (5 mg/kg every 8 weeks [q8w]) for 1 year. The clinical and biochemical remission status was assessed at all infusions (weeks 14-22-30-38-46-54), and IFX and anti-IFX Abs were estimated using a time-resolved fluorometric assay (n = 690; 88% of infusions). Samples positive for anti-IFX Abs or IFX levels < limit of detection (n = 102) were analyzed by 2 binding assays [enzyme-linked immunosorbent assay (ELISA)] and functional reporter gene assay/drug-tolerant enzyme immunoassay. RESULTS: At all assessed time points, IFX levels were more than double in patients presenting clinical or biochemical remission. An IFX concentration of 4.5 mcg/mL was associated with clinical remission during the entire first year of therapy [sensitivity 54% (49-59), specificity 73% (67-78), AUCROC 0.65 (0.60-0.69), P < 0.0001]; these values were comparable with biochemical remission. Exploratory assessments for endoscopic remission (n = 131) were performed at the discretion of the treating physician. Anti-IFX Abs were associated with undetectable IFX and treatment failure [OR 2.9 (1.4-6.0), P < 0.01], irrespective of persistency or transiency. All performed assays detected anti-IFX Abs were picked up by all assays in ∼2/3 of samples. Binding assays demonstrated a higher sensitivity to anti-IFX Abs. CONCLUSIONS: IFX at ∼5 mcg/mL was associated with clinical and biochemical remission during the first year of maintenance therapy. During this phase of therapy, standard binding assays are appropriate for therapeutic drug monitoring.

Outcome data from >10 000 multiple myeloma patients in the Danish and Swedish national registries.

OBJECTIVE: We describe real-world evidence (RWE) from the nationwide Swedish and Danish registries that provide important information on incidence and outcome in multiple myeloma (MM). METHOD: First line treatment data on more than 10.000 MM patients from Denmark and Sweden between 2005-2018 are presented. Key results from research conducted within the Swedish and Danish myeloma registries are summarized, describing subgroups of patients with comorbidity, myeloma complications, and early relapse. RESULTS: We show that national guidelines, generated on results from randomized clinical trials (RCTs) are rapidly implemented and improve overall survival (OS). We find that both the incidence of MM and the median age at diagnosis is higher in national registries compared to results from referral centres, indicating a more complete coverage. This highlights the need of validation of prognostic scoring systems and indices in e.g., SMM and high-risk MM in a real- world-population. We show that these subgroups are unlikely to be captured in RCTs with narrow inclusion and exclusion criteria, that they have worse survival, and are in need of new treatment approaches. CONCLUSION: National registries that include all MM patients are an important source of knowledge on epidemiology, treatment and outcome with implications for the planning of MM care. Despite the introduction of new and better treatments, rapidly implemented in our countries, our registries uncover subgroups of patients that still have inferior outcome. Our RWE can help to identify important research questions to be studied in further clinical trials also in patients currently not included in RCTs.

Diurnal variation of magnesium and the mineral metabolism in patients with chronic kidney disease.

Increasing levels of magnesium in blood are associated with reduced risk of cardiovascular disease in chronic kidney disease (CKD). Magnesium supplementation may reduce the progression of vascular calcification in CKD. The diurnal pattern and effect of fasting on magnesium in blood and urine in CKD is unknown, and knowledge of this may influence management of magnesium supplementation. We included ten patients with CKD stage four without diabetes mellitus and ten healthy controls. Participants were admitted to our hospital ward for a 24-h study period. Blood and urine samples were collected in a non-fasting state at 8 o'clock in the morning and every third hour hereafter until the final samples in a fasting state at 8 o'clock the following morning. We found no diurnal variation in plasma magnesium (p = 0.097) in either group, but a significant diurnal variation in urinary excretion of magnesium (p = 0.044) in both CKD and healthy controls with no significant interaction between the two groups, and thus no suggestion that CKD affects diurnal variation of plasma magnesium or urinary magnesium excretion. The levels of plasma magnesium were not significantly different in fasting and non-fasting conditions. Magnesium in plasma does not display a significant diurnal variation and can be measured at any time of day and in both fasting and non-fasting conditions. Urinary magnesium excretion displays diurnal variation, which is likely related to increased uptake of magnesium during meals and helps maintain a stable concentration of magnesium in blood.

Factors associated with melanoma-related limb lymphoedema.

BACKGROUND: Melanoma-related limb lymphoedema is a well-known late effect following sentinel node biopsy (SNB), and lymph node dissection (LND) in patients treated of melanoma. However, data on associated risk factors are sparse. This study aimed to investigate factors associated with melanoma-related limb lymphoedema. METHODS: The present cross-sectional single-center clinical study included patients between 18 and 75 years with American Joint Committee on Cancer Stages I-III melanoma treated with wide local excision (WLE) and unilateral axillary or inguinal SNB and/or completion LND (CLND) or therapeutic LND (TLND). The diagnosis of secondary unilateral limb lymphoedema was based on the history, symptoms, and physical examination and staged according to the International Society of Lymphology (ISL). Data on factors associated with lymphoedema were analysed with binary logistic regression models. RESULTS: In total, 642 patients were eligible, of which 435 (68%) patients participated in the study. Among these 431 patients, 109 (25%) had lymphoedema of which 48 (44%), and 61 (56%) were classified with ISL Stages I and II-III, respectively. Multivariate analyses identified primary tumour on the limb (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.17-4.56; p value .017), inguinal surgery (OR, 6.91; 95% CI, 3.49-14.11; p value <.0001), LND (OR, 6.45; 95% CI, 3.18-13.57; p value <.0001), and persistent pain at the site of lymph node surgery as factors associated with lymphoedema (OR, 3.52; 95% CI, 1.54-8.19; p value .003). Multivariable analysis of ISL Stage II-III lymphoedema further identified limb cellulitis to be associated with lymphoedema (OR 5.74; 95% CI, 2.11-15.99; p value .0006). CONCLUSIONS: Melanoma-related limb lymphoedema is associated with inguinal surgery, LND, primary tumour on the limb, persistent pain at the site of lymph node surgery, and cellulitis of the limb. This study highlights the importance of increasing awareness, improving prevention, and treatment of melanoma-related limb lymphoedema.

Peripheral nerve block anaesthesia and postoperative pain in acute ankle fracture surgery: the AnAnkle randomised trial.

BACKGROUND: Peripheral nerve blocks (PNBs) are increasingly popular in acute ankle fracture surgery but rebound pain may outweigh the benefits. The AnAnkle Trial was designed to assess the postoperative pain profile of PNB anaesthesia compared with spinal anaesthesia (SA). METHODS: The AnAnkle Trial was a randomised, two-centre, blinded outcome analysis trial. Eligible adults booked for primary ankle fracture surgery were randomised to PNB or SA. The PNBs were ultrasound-guided popliteal sciatic and saphenous blocks with ropivacaine and SAs were with hyperbaric bupivacaine. Postoperatively, all subjects received paracetamol, ibuprofen, and patient-controlled i.v. morphine for pain. The primary endpoint was 27 h Pain Intensity and Opioid Consumption (PIOC) score. Secondary endpoints included longitudinal pain scores and morphine consumption separately, and questionnaires on quality of recovery. RESULTS: This study enrolled 150 subjects, and the PNB success rate was >94%. PIOC was lower with PNB anaesthesia (median, -26.5% vs +54.3%; P<0.001) and the probability of a better PIOC score with PNB than with SA was 74.8% (95% confidence interval, 67.0-82.6). Pain scores and morphine consumption analysed separately also yielded a clear benefit with PNB, despite substantial rebound pain when PNBs subsided. Quality of recovery scores were similar between groups, but 99% having PNB vs 90% having SA would choose the same anaesthesia form again (P=0.03). CONCLUSIONS: PNB anaesthesia was efficient and provided a superior postoperative pain profile compared with SA for acute ankle fracture surgery, despite potentially intense rebound pain after PNB. CLINICAL TRIAL REGISTRATION: Clinicaltrialsregister.eu, EudraCT number: 2015-001108-76.

High-grade B-cell lymphomas with MYC and BCL2 translocations lack tumor-associated macrophages and PD-L1 expression: A possible noninflamed subgroup.

We investigated the intratumoral source of PD-L1 expression and the infiltration of tumor-associated macrophages (TAMs) in large B-cell lymphomas (LBCLs) with or without MYC-translocation, as well as possible correlations to BCL2-and BCL6-translocations and cell of origin (COO). One-hundred and twenty-six patient samples were studied in a cohort enriched for MYC-translocated tumors with 34 samples carrying this translocation. Demonstration of intratumoral distribution and cellular source of PD-L1 was enabled by immunohistochemical (IHC) dual staining specifically highlighting PD-L1 expression in lymphoma B-cells with antibodies against PD-L1 and PAX5. Additional IHC with antibodies against CD68 and CD163 identified TAMs. We found that CD68-positive TAMs were the main source of PD-L1 protein expression in contrast to lymphoma B cells which rarely expressed PD-L1. Semiquantitative IHC demonstrated a significant correlation between CD68 and PD-L1 protein expression. Unsupervised hierarchical analysis of PD-L1, CD68, and CD163 IHC data subsequently demonstrated three potential clusters defined by expression of the three biomarkers. Cluster A consisted of patient samples with significantly lower expression of PD-L1, CD68, and CD163, but also significantly higher prevalence of BCL2-translocation and MYC-BCL2-double-hit (DH) compared to the other two clusters. In cluster C we found a significant accumulation of BCL6 translocated tumors. This cluster in contrast had the highest protein expression of PD-L1, CD68, and CD163. Cluster B tumors had an intermediate expression of the three biomarkers, but no accumulation of the specific genetic translocations. Our data, which were based on morphological analysis, immunophenotyping and genotyping by fluorescence in situ hybridization were in line with new concepts of LBCL taxonomy integrating genetic, phenotypical, and immunological characteristics with identification of new subgroups where MYC translocation and MYC-BCL2 DH may identify a noninflamed subtype. These findings may furthermore hold significant predictive value especially regarding immune checkpoint blockade therapy, but further molecular characterization should be done to substantiate this hypothesis.

Myocardial Ischemia Induced by 5-Fluorouracil: A Prospective Electrocardiographic and Cardiac Biomarker Study.

BACKGROUND: Cardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity. SUBJECTS, MATERIALS, AND METHODS: Patients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention). RESULTS: A total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p = .001). The ischemic burden per day (p = .001), the number of ST depression episodes per day (p = .003), and the total duration of ischemic episodes per day (p = .003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p < .001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment. CONCLUSION: 5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%-6% of the patients developed acute coronary syndromes during treatment with 5-FU. IMPLICATIONS FOR PRACTICE: Symptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%-19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.

Validation of the UK myeloma research alliance risk profile, a new clinical prediction model for outcome in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation; a population-based study from the Danish national multiple myeloma registry.

In 2019 the UK Myeloma Research Alliance introduced the Myeloma Risk Profile (MRP) for prediction of outcome in patients with newly diagnosed multiple myeloma (MM), ineligible for autologous stem cell transplantation. To validate the MRP in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients above 65 years in the Danish National MM Registry. Our data confirmed the value of the MRP. In a cohort of 1,377 patients, the MRP score separated patients into three distinct risk-groups with an observed hazard ratio of 2.91 for early death in high-risk versus low-risk patients.

Bone turnover biomarkers in COPD patients randomized to either a regular or shortened course of corticosteroids: a substudy of the randomized controlled CORTICO-COP trial.

BACKGROUND: Long-term treatment with corticosteroids causes loss of bone density, but the effects of using short-term high-dose systemic-corticosteroid therapy to treat acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are unclear. Our aim was to determine whether high-dose corticosteroid therapy affected bone turnover markers (BTMs) to a greater extent compared to low-dose corticosteroid therapy. METHODS: The CORTICO-COP trial (NCT02857842) showed that an eosinophil-guided corticosteroid intervention led to approximately 60% lower accumulated corticosteroid dose for hospitalized patients with AECOPD (low-dose group) compared with 5-day standard corticosteroid treatment (high-dose group). We compared the levels of BTMs C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP) in 318 participants during AECOPD and at 1- and 3-month follow-up visits. RESULTS: CTX decreased and P1NP increased significantly over time in both treatment groups. There were no significant differences between the groups at 1- or 3-months follow-up for P1NP. A significant drop in CTX was seen at 3 months (down Δ24% from the baseline, p = 0.017) for the high dose group. CONCLUSION: Short-term, high-dose systemic corticosteroid treatment caused a rapid suppression of biomarkers of bone resorption. Corticosteroids did not suppress biomarkers of bone formation, regardless of patients receiving low or high doses of corticosteroids. This therapy was, therefore, harmless in terms of bone safety, in our prospective series of COPD patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02857842 . Submitted August 2nd, 2016.

Protein supplementation combined with low-intensity resistance training in geriatric medical patients during and after hospitalisation: a randomised, double-blind, multicentre trial.

Sarcopenia (loss of muscle mass/strength) burdens many older adults - hospitalised older adults being particularly vulnerable. Treating the condition, protein supplementation (PrS) and resistance training (RT) may act synergistically. Therefore, this block-randomised, double-blind, multicentre intervention study, recruiting geriatric patients > 70 years from three medical departments, investigated the effect of PrS combined with RT during hospitalisation and 12 weeks after discharge. Participants were randomly allocated (1:1) to receive PrS (totally 27·5 g whey protein/d, about 2000 kJ/d) or isoenergetic placebo-products (< 1·5 g protein/d) divided into two servings per d to supplement the habitual diet. Both groups were engaged in a standardised, progressive low-intensity RT programme for the lower extremities (hospital: supervised daily/after discharge: self-training 4×/week). From April 2016 to September 2017, 2351 patients were screened, 462 were eligible, and 165 included. Fourteen were excluded and ten dropped out, leaving 141 participants in the intention-to-treat analysis. The average total protein intake during hospitalisation/after discharge was 1·0 (interquartile range (IQR) 0·8, 1·3)/1·1 (IQR 0·9, 1·3) g/kg per d (protein-group) and 0·6 (IQR 0·5, 0·8)/0·9 (IQR 0·6, 1·0) g/kg per d (placebo group). Both groups improved significantly for the primary and secondary endpoints of muscle mass/strength, functional measurements and quality of life, but no additional effect of PrS was seen for the primary endpoint (30-s chair stand test, repetitions, median changes from baseline: (standard test: 0 (IQR 0, 5) (protein group) v. 2 (IQR 0, 6) (placebo group) and modified test: 2 (IQR 0, 5) (protein group) v. 2 (IQR -1, 5) (placebo group)) or any secondary endpoints (Mann-Whitney U tests, P > 0·05). In conclusion, PrS increasing the total protein intake by 0·4 and 0·2 g/kg per d during hospitalisation and after discharge, respectively, does not seem to increase the adaptive response to low-intensity RT in geriatric medical patients.

Increased use of total shoulder arthroplasty for osteoarthritis and improved patient-reported outcome in Denmark, 2006-2015: a nationwide cohort study from the Danish Shoulder Arthroplasty Registry.

Background and purpose - Osteoarthritis has become the most common indication for shoulder arthroplasty in Denmark, and the treatment strategies have changed towards the use of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty. We investigated whether changes in the use of arthroplasty types have changed the overall patient-reported outcome from 2006 to 2015. Patients and methods - We included 2,867 shoulder arthroplasties performed for osteoarthritis between 2006 and 2015 and reported to the Danish Shoulder Arthroplasty Registry. The Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 1 year was used as patient-reported outcome. The raw score was converted to a percentage of a maximum score. General linear models were used to analyze differences in WOOS. Results - The proportion of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty increased from 3% and 7% in 2006 to 53% and 27% in 2015. The mean WOOS score was 70 (SD 26) after resurfacing hemiarthroplasties (n = 1,258), 68 (SD 26) after stemmed hemiarthroplasty (n = 500), 82 (SD 23) after anatomical total shoulder arthroplasties (n = 815), and 74 (SD 23) after reverse shoulder arthroplasties (n = 213). During the study period, the overall WOOS score increased with 18 (95% CI 12-22) in the univariate model and 10 (CI 5-15) in the multivariable model, and the WOOS scores for anatomical total shoulder arthroplasty increased by 14 (CI 5-23). Interpretation - We found an increased WOOS score from 2006 to 2015, which was primarily related to a higher proportion of anatomical total shoulder arthroplasty and reverse shoulder arthroplasty towards the end of the study period, and to improved outcome of anatomical total shoulder arthroplasty.

A targeted assessment and intervention at the time of discharge reduced the risk of readmissions for short-term hospitalized older patients: a randomized controlled study.

OBJECTIVE: The aim of this study was to test and compare the effect of (1) a systematic discharge assessment with targeted advice and (2) a motivational interview followed by a home visit. DESIGN: This was a three-armed randomized controlled study. SETTING: This study was conducted in the Medical department in a university hospital. SUBJECTS: Patients ⩾65 years of age with health problems at discharge participated in the study. INTERVENTIONS: Group A (n = 117): patients were informed of health problems and self-care interventions; Group B (n = 116): a motivational conversation targeting activities of daily living with a home care nurse and a home visit. MAIN MEASURES: The main measures of this study were readmissions, handgrip strength, chair-to-stand test, health-related quality of life, depression signs, mortality, and call on municipality services. RESULTS: Risk of readmission was reduced for intervention groups by 30% (A; P = 0.26) and 22 % (B; P = 0.46). Mean number of days to first readmission was 49.5 (±51.0) days for the control group (n = 116) and 57.9 (±53.6) and 67.2 (±58.1) days for the intervention groups A (P = 0.43) and B (P = 0.10), respectively. Mean loss of handgrip strength was 10.6 (±16.6) kg for men in the control group and 7 (±19.2) and 1.4 (±17.1) kg for the intervention groups A (P = 0.38) and B (P = 0.01), respectively. Health-related quality of life improved with 0.3 (±23.7) points in the control group and 7.4 (±24.4) and 3.2 (±22.3) points in the intervention groups A (P = 0.04) and B (P = 0.37), respectively. In total, 17 (16.3%) in the control group were provided with assistive devices after three months and 8 (7.3%) and 19 (17.6%) in the intervention groups A (P = 0.04) and B (P = 0.81), respectively. CONCLUSION: The interventions reduced the risk of readmission and improved handgrip strength, quality of life, and use of assistive devices.

Risk factors for infections in newly diagnosed Multiple Myeloma patients: A Danish retrospective nationwide cohort study.

OBJECTIVES: Infections pose the greatest risk of early death in patients with Multiple Myeloma. However, few studies have analyzed the risk factors for infections in Multiple Myeloma patients. The aim of this study was to analyze the risk factors infections within a population-based MM cohort. METHODS: Using Danish registries (from 2005 to 2013), we analyzed all ICD-10 codes for infections within the first 6 months of Multiple Myeloma diagnosis in 2557 patients. RESULTS: Pneumonia and sepsis represented 46% of infections. Multivariable regression analysis showed that risk factors for pneumonia were male gender (HR 1.4; P = 0.001), ISS II (HR 1.6; P = 0.0004) and ISSIII (HR 1.8; P = 0.0004) and elevated LDH (HR 2.6; P = 0.0008). Risk factors for sepsis were high bone marrow plasma cell % (HR 1.1; P = 0.038), ISS II (HR 1.7; P = 0.007) ISS III (HR 2.0; P = 0.002) and creatinine (HR 2.1; P = 0.002). Neither immunoparesis (hypogammaglobulinemia) nor comorbidity was significant risk factors. CONCLUSIONS: Our study suggests that tumor burden and renal impairment are risk factors for pneumonia and sepsis in the early phase of Multiple Myeloma.

Patient-and observer-reported long-term scar quality of wide local excision scars in melanoma patients.

Wide local excision of the primary tumour is the mainstay of treatment for melanoma patients. The aims of this study were to assess the patient- and observer-reported long-term scar quality after surgery using the patient and observer scar assessment scale (POSAS) in melanoma patients, to assess the reliability and validity of POSAS, and to identify factors influencing the scar assessment. This cross-sectional clinical study included 320 melanoma patients with primary tumours on the trunk and limbs. Data regarding patients, treatment, scar characteristics and functional outcomes was analysed. Internal consistency, inter-rater reliability, and convergent validity were examined. Factors influencing the patient- and observer-reported scar quality were tested using regression analyses. Results of the POSAS showed an overall good scar quality. The internal consistency of POSAS was good, and the convergent validity was strong. The inter-rater reliability was only moderate. The patients were influenced by the POSAS sub-items: colour, irregularity, thickness and pain. The observer was influenced by the POSAS sub-items: vascularity, surface area, thickness, relief and pliability. Both patient- and observer-reported scar qualities were influenced by age, location, type of superficial suture, keloids and widened scars. Moreover, the patients were influenced by the scar tightness while the observer was influenced by postoperative complications, hypertrophic scars, suture marks and dog ears. In conclusion POSAS is a reliable and valid scar assessment tool. The factors influencing patient- and observer-reported scar quality differed, and better understanding of this may improve treatment and hence patient-reported scar quality.

Knee Osteoarthritis Patients Can Provide Useful Estimates of Passive Knee Range of Motion: Development and Validation of the Copenhagen Knee ROM Scale.

BACKGROUND: Knee arthroplasty does not always require extensive long-term follow-up. If knee range of motion (ROM) could be assessed reliably by patients, some follow-up visits might be replaced by patient-reported outcome measures, and this additional information could be reported directly to registers. We developed and tested the validity and reliability of a simple scale for patients to self-report their passive knee ROM. METHODS: Through an iterative process, we created a 2-item scale with 11 illustrations of knee motion in 15° increments. The validity and reliability was tested in knee osteoarthritis and arthroplasty patients at different treatment stages, many with poor ROM. Patient estimates were compared to passive goniometer measurements performed blindly by a physiotherapist and a junior orthopedic surgeon. RESULTS: The mean difference between 100 patients' (70.9 years) estimates and goniometer measurements was -0.7° (standard deviation, 12.3°) for flexion and 1.1° (standard deviation, 11.6°) for extension, both not significant. Correlation was 0.79 and 0.63, and kappa values at retest were 0.84 and 0.66. For flexion < 110°, sensitivity of patient estimates was 88% and specificity was 88%. For a limit of 100°, values were 95% and 81%. For extension deficits >10°, sensitivity was 78% and specificity 70%. Values were 100% and 66% for a 15° limit. CONCLUSION: The Copenhagen Knee ROM Scale is a patient-friendly and feasible alternative to passive ROM measurement for registers, research, and selected clinical use. This scale appears reliable and valid compared to reports of similar tools, and patient estimates are better correlated to goniometer measurements.

Chronic pain after mesh versus nonmesh repair of inguinal hernias: A systematic review and a network meta-analysis of randomized controlled trials.

BACKGROUND: Chronic pain affects 10%-12% of patients after inguinal hernia repairs. Some have suggested that less foreign material may theoretically prevent pain. If the prevalence of chronic pain is less after nonmesh repairs, selected hernias might be repaired without mesh. Our aim was to clarify if nonmesh repairs are superior to mesh repairs regarding chronic pain. METHODS: For this systematic review, searches were conducted in five databases. The main outcome was chronic pain reported a minimum of six months after mesh and nonmesh repair in adult patients with a primary inguinal hernia. Only randomized controlled trials (RCTs) were included. RESULTS: A total of 23 RCTs with 5,444 patients were included. The median follow up was 1.4 years (range 0.5-10). Twenty-one studies reported crude chronic pain rates, and when considering moderate and severe pain, the prevalences of pain after nonmesh repairs and mesh repairs were similar: median 3.5% (0%-16.2%) versus median 2.9% (0%-27.6%), respectively. Both the meta-analyses and the network meta-analysis indicated no difference in chronic pain rates when comparing nonmesh repairs with open- and laparoscopic mesh repairs. CONCLUSION: Mesh may be used without fear of causing a greater rate of chronic pain.