When are patients with osteoarthritis referred for surgery?

Current treatment strategies in hip and knee osteoarthritis (OA) involve a combined approach that includes not only modification of risk factors and conservative treatment but also joint-preserving surgical therapy in the early stages, or joint replacement in late OA. With the recent development of new etiological concepts (i.e. hip dysplasia and femoroacetabular impingement as major risk factors for hip OA), treatment alternatives for joint preservation could be extended significantly. Satisfactory results of osteotomies and other reconstructive procedures around hip and knee joints can only be expected in early OA (Kellgren/Lawrence grade 0-II). If patients with advanced radiographic OA grades III-IV do not respond to conservative treatment over at least 3 months and express a relevant burden of disease, joint replacement might be considered. Prior to surgery, potential contraindications must be excluded, patient expectations need to be discussed, and modifiable risk factors, which may negatively influence the outcome, should be optimized.

Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

[Partial or full component exchange in hip revision? : The relevance of off-label use and mix & match]. / Partieller oder vollständiger Wechsel in der Hüftrevisionsendoprothetik? : Bedeutung von Off-Label-Anwendung und Mix & Match.

Off-label use is frequently practiced in hip revision arthroplasty, as there may be indications for the application of implants for purposes outside the one the manufacturers intended (i.e. large bone and soft tissue defects, obesity). Patients may also benefit from selective application of mix & match in hip revision, when the exchange of one component only is necessary and the invasiveness of surgery can be reduced. Currently, there are no formal guidelines for these situations. Therefore, within a recent EFORT initiative, evidence- and consensus-based recommendations have been developed for the safe application of off-label use and mix & match in revision hip and knee arthroplasty.

Social inequality in tooth loss: separate and joint effects of household income and dental visits.

OBJECTIVE: The aim of the study was to investigate the separate and joint effects of household income and dental visits on tooth loss. BASIC RESEARCH DESIGN: Participants from the Social Inequality in Cancer Cohort (SIC) were followed in registers for household income (2000), dental visits (2002-2009) and tooth loss (2010-2016). Logistic regression was used to assess the effect of household income and dental visits on tooth loss, and linear models were applied to assess the separate and joint effects of household income and dental visits. RESULTS: In total, 10.8% of the participants had tooth loss (⟨15 teeth present). Low household income and irregular dental visits showed significantly higher odds ratios for tooth loss. Compared to regular dental visits, irregular dental visits accounted for 923 (95% CI 840 - 1,005) extra cases of tooth loss per 10,000 persons, and compared to high household income, low household income accounted for 1,294 (95% CI 1,124 - 1,464) additional cases of tooth loss per 10,000 persons. Further, due to household income-dental visit interaction, we observed 581 (95% CI 233 - 928) extra cases of tooth loss per 10,000 persons. CONCLUSION: Low household income and irregular dental visits are important in relation to social inequality in tooth loss. Irregular dental visits are associated with higher risk of tooth loss among persons with low household income compared to persons with high household income. Such interaction may be explained by differences in susceptibility to tooth loss across household income groups.

Correction: Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1.

Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear. This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph + ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10-3 and 36/67 (53%) and 53/67 (79%) at 10-4BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph + ALL.

Differences in regional cerebral oximetry during cardiac surgery for patients with or without postoperative cerebral ischaemic lesions evaluated by magnetic resonance imaging.

BACKGROUND: Near infrared spectroscopy (NIRS) is widely used to monitor regional cerebral tissue oxygenation (rScO2). We compared rScO2 values during cardiac surgery in patients with or without new cerebral ischaemic lesions on diffusion weighted magnetic resonance imaging (DWI). We hypothesised patients with new cerebral lesions would have impaired tissue oxygenation reflected in their rScO2 values. METHODS: NIRS and DWI data were collected in 152 elective cardiac surgery patients. Absolute rScO2 values, duration of desaturation below thresholds (baseline, 10%, and 20%), and accumulated cerebral desaturation load were compared between patients with or without new cerebral lesions on DWI. Primary outcome was time below 10% from rScO2 baseline. RESULTS: The time below 10% from rScO2 baseline was significantly longer for patients with new cerebral lesions than for patients without [median (inter-quartile range): 11.0 (0.4; 37.5) min vs 1.8 inter-quartile range: (0.05; 20.9) min, P=0.02]. Furthermore, they had a higher accumulated desaturation load below baseline (P=0.02) and 10% below baseline (P=0.02). Finally, their absolute minimum rScO2 value was significantly lower (P=0.01). However, the frequency of patients with desaturation below 10% and 20% was comparable between patients with and without new cerebral lesions. Receiver-operating characteristic curve analysis did not identify a clear-cut critical threshold among the investigated rScO2 variables. CONCLUSIONS: Use of NIRS identified significant group differences in rScO2 values between patients with or without new ischaemic lesions. However, a critical threshold could not be identified because of a high variation in NIRS values across both groups. CLINICAL TRIAL REGISTRATION: NCT 02185885.

[The S2k guideline: Indications for knee endoprosthesis : Evidence and consent-based indications for total knee arthroplasty]. / S2k-Leitlinie: Indikation Knieendoprothese : Evidenz- und konsensbasierte Indikationsstellung in der Knie-Endoprothetik (EKIT-Knie).

Total knee arthroplasty (TKA) is one of the most frequent surgical procedures in orthopaedic surgery. Until now there have not been any standardized indication criteria, which might contribute to the large geographical differences in the frequency of TKA. This guideline aims to consent minimal requirements (main criteria), additional important aspects (minor criteria), as well as relative and absolute contraindications for TKA. The following main criteria have been consented: knee pain, radiological confirmation of osteoarthritis or osteonecrosis, inadequate response to conservative treatment, adverse impact of knee disease on the patient's quality of life and the burden of suffering due to the knee disease. Relative contraindications have been consented as severe general disease with reduced life expectancy and a BMI ≥40; absolute contraindications are an active infection and if the patient is not able to undergo major surgery.

Exploring the effect of a lifestyle intervention on cancer risk: 43-year follow-up of the randomized Oslo diet and antismoking study.

BACKGROUND/OBJECTIVES: The Oslo diet and antismoking study showed that counselling for a healthy lifestyle reduced lifelong coronary mortality in high-risk men. We explored whether the same counselling reduced also cancer risk. METHODS: The study randomly allocated males at high coronary risk to either a 5-year intervention for lifestyle changes (cholesterol-lowering dietary changes, weight loss and stopping smoking) or a control group (1 : 1) in 1972/73. We explored the incidence and mortality of all cancers and cancer forms related to smoking, BMI or diet up to 43 years after randomization. RESULTS: A total of 595 men in the intervention and 621 in the control group were included. At inclusion median age was 45 years, 588 (48.4%) subjects were overweight (BMI > 25 kg m-2 ) and 925 (76.1%) current smokers. The intervention did not reduce the risk of cancer after 43 years (adjusted hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.80-1.15). In the first 25 years of follow-up, among the 1088 (89.5%) men who were overweight/obese and/or smokers, the intervention reduced the incidence of those cancer forms related to smoking, BMI or diet (including carcinoma of the respiratory, digestive and urinary tracts; adjusted HR 0.69; 95% CI 0.49-0.99). The intervention had no significant effect on incidence beyond 25 years, or on mortality. CONCLUSIONS: The 5-year counselling for a healthy lifestyle did not reduce the overall cancer risk in the very long term. However, in the first 25 years, the counselling reduced the risk of relevant cancer types in overweight/obese subjects and smokers.

Administration of platelets to ruptured abdominal aortic aneurysm patients before open surgery: a prospective, single-blinded, randomised study.

BACKGROUND: In patients undergoing open surgery for a ruptured abdominal aortic aneurysm (rAAA), survivors demonstrate a high platelet count, and proactive administration of platelets (and fresh frozen plasma) appears to influence mortality. OBJECTIVES: This trial investigated the effect of platelets administered before transport to surgery. METHODS: In a prospective study design, patients were randomised to receive platelets (intervention; n = 61) or no platelets (control; n = 61) before transport to vascular surgery from 11 local hospitals. The study was terminated when one of the vascular surgical centres implemented endovascular repair for rAAA patients. RESULTS: Thirty days after surgery, mortality was 36% for patients with intervention vs 31% for controls (P = 0·32). Post-operative thrombotic events (14 vs 15; P = 0·69), renal failure (11 vs 10; P = 0·15) and pulmonary insufficiency (34 vs 39; P = 0·15) were similar in the two groups of patients. No adverse reactions to platelet administration were observed. In addition, length of stay in the intensive care unit was unaffected by intervention. CONCLUSIONS: For patients planned for open repair of a rAAA, we observed no significant effect of early administration of platelets with regard to post-operative complications and stay in the ICU or in hospital and also no significant effect on mortality.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

This corrects the article DOI: 10.1038/leu.2017.9.

Effects of hydroxyethyl starch 130/0.42 vs. Ringer's acetate on cytokine levels in severe sepsis.

BACKGROUND: The Scandinavian Starch for Severe Sepsis/Septic Shock (6S) trial showed increased 90-day mortality with hydroxyethyl starch (HES) 130/0.42 vs. Ringer's acetate. To explore the underlying pathophysiology, we compared early changes in plasma cytokine concentrations between patients resuscitated with HES vs. Ringer's acetate. METHODS: In a subgroup of 226 patients from the 6S trial, we calculated delta plasma concentrations of tumour necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-10 from randomization to day 2. We used multiple linear and logistic regression analyses to assess differences between the groups and associations between delta cytokine concentrations and 90-day mortality, respectively. RESULTS: Baseline characteristics and day 2 mortality were comparable between the groups. We observed similar delta cytokine concentrations in the HES vs. Ringer's group (mean difference in delta TNF-α: -1.5 pg/ml (95% CI, -4.9 to 1.9), P = 0.39; IL-6: 36.0 pg/ml (-24.1 to 96.1), P = 0.24; IL-10: -3.9 pg/ml (-21.1 to 28.9), P = 0.76). In all included patients, we observed a linear relationship between increases in TNF-α and 90-day mortality (P = 0.005). CONCLUSION: Resuscitation with HES 130/0.42 vs. Ringer's acetate did not appear to affect plasma concentrations of TNF-α, IL-6 or IL-10 differently during the first days after randomization into the 6S trial. In the overall cohort, increases in TNF-α were associated with increased 90-day mortality. Although interpretation should be done with caution, it seems unlikely that the increased mortality observed with the use HES in the 6S trial is signalled by early changes in three biomarkers of systemic inflammation.

Expression of the CTLA-4 ligand CD86 on plasmacytoid dendritic cells (pDC) predicts risk of disease recurrence after treatment discontinuation in CML.

It is unknown, why only a minority of chronic myeloid leukemia (CML) patients sustains treatment free remission (TFR) after discontinuation of tyrosine kinase inhibitor (TKI) therapy in deep molecular remission (MR). Here we studied, whether expression of the T-cell inhibitory receptor (CTLA-4)-ligand CD86 (B7.2) on plasmacytoid dendritic cells (pDC) affects relapse risk after TKI cessation. CML patients in MR displayed significantly higher CD86+pDC frequencies than normal donors (P<0.0024), whereas TFR patients had consistently low CD86+pDC (n=12). This suggested that low CD86+pDC might be predictive of TFR. Indeed, in a prospective analysis of 122 patients discontinuing their TKI within the EURO-SKI trial, the one-year relapse-free survival (RFS) was 30.1% (95% CI 15.6-47.9) for patients with >95 CD86+pDC per 105 lymphocytes, but 70.0% (95% CI 59.3-78.3) for patients with <95 CD86+pDC (hazard ratio (HR) 3.4, 95%-CI: 1.9-6.0; P<0.0001). Moreover, only patients with <95 CD86+pDC derived a significant benefit from longer (>8 years) TKI exposure before discontinuation (HR 0.3, 95% CI 0.1-0.8; P=0.0263). High CD86+pDC counts significantly correlated with leukemia-specific CD8+ T-cell exhaustion (Spearman correlation: 0.74, 95%-CI: 0.21-0.92; P=0.0098). Our data demonstrate that CML patients with high CD86+pDC counts have a higher risk of relapse after TKI discontinuation.

[Utilization of Physical Therapy Services in Germany from 2004 until 2014: Analysis of Statutory Health Insurance Data]. / Physiotherapeutische Versorgungssituation in Deutschland von 2004 bis 2014. Analyse des Verordnungsverhaltens bei Versicherten der Gesetzlichen Krankenversicherung.

Background: Both at the national and international levels, direct access for patients to physical therapy services is currently under debate. Direct access for patients seeking physical therapy care might reduce waiting time and costs, and thus be of benefit for patients and health insurance companies. To critically evaluate this situation, reliable and valid data are needed, but currently lacking. The aim of this study is to evaluate the health care situation for physical therapy services included in the catalogue of remedies from 2004 up to 2014 in Germany. Methods: To obtain information regarding physical therapy services included in the catalogue of remedies, the freely available "Heilmittel-Informations-System (GKV-HIS)" was used. Data from the regional Associations of Statutory Health Insurance Physicians as well as data from federal reports were extracted for the years from 2004 up to 2014. Results: Prescription of physical therapy increased continuously from 2004 and 2014. In 2004, 155 677 860 and in 2014, 254 695 514 physical therapies were prescribed (increase of 61%). The highest number of physical therapies was prescribed in Saxony for all years, whereas in North Rhine-Westphalia and Hessen the lowest number per 1 000 GKV insured persons. Gross sales from physical therapy services differed between federal states and were the highest in Saxony (2004: 59.8; 2009: 54.6, 2014: 76.7) and Baden-Wuerttemberg (2004: 60.0; 2009: 57.6; 2014: 68.0). Discussion: The results of this study show utilization of physical therapy services as defined in the catalogue of remedies in Germany to be heterogeneous. However, causal relationship cannot be identified on the basis of the analyzed data highlighting the need for further research. Criteria for structural-, process- and outcome-quality are needed to be able to evaluate the quality of physical therapy services. To ensure the quality of physical therapy services, interprofessional and patient relevant research is needed.

[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Quality of life assessment in patients with metastatic colorectal cancer receiving maintenance therapy after first-line induction treatment: a preplanned analysis of the phase III AIO KRK 0207 trial.

BACKGROUND: First-line maintenance strategies are a current matter of debate in the management of mCRC. Their impact on patient's health-related quality of life (HRQOL) has not yet been evaluated. The objective of this study was to assess whether differences in HRQOL during any active maintenance treatment compared with no maintenance treatment exist. PATIENT AND METHODS: Eight hundred and thirty-seven patients were enrolled in the AIO KRK 0207 trial. Four hundred and seventy-two underwent randomization (after 24 weeks of induction treatment) into one of the maintenance arms: FP plus Bev (arm A), Bev alone (arm B), or no active treatment (arm C). HRQOL were assessed every 6 weeks during induction and maintenance treatment independent from treatment stop, delay, or modification, and also continued after progression, using the EORTC QLQ-C30, QLQ-CR29. The mean value of the global quality of life dimension (GHS/QoL) of the EORTC QLQ-C30, calculated as the average of all available time points after randomization was considered as pre-specified main endpoint. Additionally, EORTC QLQ-C30 response scores were analyzed. RESULTS: For HRQOL analysis, 413 patients were eligible (arm A: 136; arm B: 142, arm C: 135). Compliance rate with the HRQOL questionnaires was 95% at time of randomization and remained high during maintenance (98%, 99%, 97% and 97% at week 6, 12, 18 and 24). No significant differences between treatment arms in the mean GHS/QoL scores were observed at any time point. Also, rates of GHS/QoL score deterioration were similar (20.5%; 17.2% and 20.7% of patients), whereas a score improvement occurred in 36.1%; 43.8% and 42.1% (arms A, B and C). CONCLUSION: Continuation of an active maintenance treatment with FP/Bev after induction treatment was neither associated with a detrimental effect on GHS/QoL scores when compared with both, less active treatment with Bev alone or no active treatment. CLINICAL TRIALS NUMBER: NCT00973609 (ClinicalTrials.gov).

Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations.

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.