Long-term survival of 2997 finger metacarpophalanageal joint arthroplasties from the Norwegian Arthroplasty Register.

We present the long-time survival of 2997 primary metacarpophalangeal (MCP) joint implants from the Norwegian Arthroplasty Register from 1994 to 2019. Six different implants were compared in terms of survival and risk of revision. The majority of implants were inserted in patients diagnosed with inflammatory diseases and in women. The overall survival was found to be 94%, 89%, 85% and 84% after 5, 10, 15 and 20 years. The most prevalent reason for revision was a fractured prosthetic component, and the second was pain. Implants inserted in the right hand and in younger patients had a higher risk for revision. Sex, type of implant, finger treated, one- or two-component prosthesis, and inflammatory or non-inflammatory conditions did not influence the survival. The frequency of MCP joint implantations decreased during the observation period. Our data show satisfactory long-term survival of the MCP implants, with no difference found between implant types or concepts.Level of evidence: II.

Preventing adverse events of chemotherapy for gastrointestinal cancer by educating patients about the nocebo effect: a randomized-controlled trial.

BACKGROUND: Adverse events of chemotherapy may be caused by pharmacodynamics or psychological factors such as negative expectations, which constitute nocebo effects. In a randomized controlled trial, we examined whether educating patients about the nocebo effect is efficacious in reducing the intensity of self-reported adverse events. METHODS: In this proof-of-concept study, N = 100 outpatients (mean age: 60.2 years, 65% male, 54% UICC tumour stage IV) starting first-line, de novo chemotherapy for gastrointestinal cancers were randomized 1:1 to a nocebo education (n = 49) or an attention control group (n = 51). Our primary outcome was patient-rated intensity of four chemotherapy-specific and three non-specific adverse events (rated on 11-point Likert scales) at 10-days and 12-weeks after the first course of chemotherapy. Secondary outcomes included perceived control of adverse events and tendency to misattribute symptoms. RESULTS: General linear models indicated that intensity of adverse events differed at 12-weeks after the first course of chemotherapy (mean difference: 4.04, 95% CI [0.72, 7.36], p = .02, d = 0.48), with lower levels in the nocebo education group. This was attributable to less non-specific adverse events (mean difference: 0.39, 95% CI [0.04, 0.73], p = .03, d = 0.44) and a trend towards less specific adverse events in the nocebo education group (mean difference: 0.36, 95% CI [- 0.02, 0.74], p = .07, d = 0.37). We found no difference in adverse events at 10-days follow-up, perceived control of adverse events, or tendency to misattribute non-specific symptoms to the chemotherapy. CONCLUSIONS: This study provides first proof-of-concept evidence for the efficacy of a brief information session in preventing adverse events of chemotherapy. However, results regarding patient-reported outcomes cannot rule out response biases. Informing patients about the nocebo effect may be an innovative and clinically feasible intervention for reducing the burden of adverse events. TRIAL REGISTRATION: Retrospectively registered on March 27, 2018 to the German Clinical Trial Register (ID: DRKS00009501).

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala

The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition. To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window. Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0­7 y; life course, outcome data from 2017­2018 follow-up, ages 40­57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self- Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized. Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress. Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status. Keywords: early childhood nutrition, protein-energy

Age at childbirth and change in BMI across the life-course: evidence from the INCAP Longitudinal Study

Background: Parity has been associated with both short- and long-term weight gain in women. However, it is not clear if timing of parity across the reproductive age has different associations with BMI. Methods: To prospectively assess the association between age at childbirth and maternal change in BMI, we analyzed data from the ongoing INCAP Longitudinal Study, which started in 1969 in four villages in Guatemala. Cohort women (n=778) provided information on reproductive history and anthropometric measures were measured in 1988-89 (adolescence, 15 to 25y), 2002-04 (early adulthood, 26 to 36y) and 2015-17 (mid adulthood, 37 to 55y). We evaluated the associations of number of live births in the period preceding each study wave (1969-77 to 1988-89, 1988-89 to 2002-04 and 2002-04 to 2015-17) with BMI change in the same period using multivariable linear regression models. Results: Number of live births between 1988 and 89 and 2002-04 was positively associated with increased BMI, while there was not an association between number of live births and BMI in the other intervals. Women who had one, two, or three or more children between 1988 and 89 and 2002-04 had 0.90 (kg/m2, 95% CI: -0.55, 2.35), 2.39 (kg/m2, 95% CI: 1.09, 3.70) and 2.54 (kg/m2, 95% CI: 1.26, 3.82) higher BMI, respectively, than women who did not give birth in the same period. Conclusions: Our findings suggest that women who had three or more children during early adulthood gained more weight compared to women who had no children in the same period. In contrast, women who had children earlier or later in their reproductive lives did not gain additional weight compared to those who did not have children during that period. Childbirth may have different

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

BACKGROUND: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. PATIENTS AND METHODS: In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. RESULTS: In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. CONCLUSION: FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC.

Relationship of polypharmacy to HIV RNA suppression in people aged ≥ 50 years living with HIV.

OBJECTIVES: People living with HIV (PLWH) aged ≥ 50 years face unique challenges regarding their medication therapies, especially antiretroviral therapy (ART). Use of ARTs, along with medications for comorbidities, may lead to adverse events, drug-drug interactions (DDIs) and poor adherence. The objective of this study was to identify the number of medications above which PLWH aged ≥ 50 years are less likely to be virally suppressed and to describe other associated patient-specific risk factors. METHODS: This was a cross-sectional study of PLWH aged ≥ 50 years, prescribed ART, and seen at least once in the Northwestern Infectious Disease Center between 1 June 2013 and 31 May 2015. Variables concerning medication use and comorbidities were collected. The primary outcome was the presence of an undetectable plasma HIV RNA level (viral load). RESULTS: Among the 621 included patients, there was a higher percentage taking ≤ 15 medications with an undetectable plasma HIV RNA (n = 453; 80.6%) vs. patients taking > 15 medications (n = 40; 67.8%; P = 0.03). Taking > 15 medications [odds ratio (OR) 0.49; 95% confidence interval (CI) 0.26-0.96], pulmonary disease (OR 0.54; 95% CI 0.3-0.97) and CD4 T-lymphocyte count < 200 cells/µL (OR 0.39; 95% CI 0.22-0.68) decreased the odds of having an undetectable plasma HIV RNA. CONCLUSIONS: PLWH taking > 15 medications were less likely to have an undetectable HIV RNA. Further studies are needed to evaluate the impact of overall medication economic burden on clinical outcomes among PLWH ≥ 50 years of age.

Thromboprophylaxis in primary shoulder arthroplasty does not seem to prevent death: a report from the Norwegian Arthroplasty Register 2005-2018.

Background and purpose - There is still no consensus on whether to use thromboprophylaxis as a standard treatment in shoulder replacement surgery. We investigated the use of thromboprophylaxis reported to the Norwegian Arthroplasty Register (NAR). The primary endpoint was early mortality after primary shoulder arthroplasty with and without thromboprophylaxis. Secondary endpoints included revisions within 1 year and intraoperative complications.Patients and methods - This observational study included 6,123 primary shoulder arthroplasties in 5,624 patients reported to the NAR from 2005 to 2018. Cox regression analyses including robust variance analysis were performed with adjustments for age, sex, ASA score, diagnosis, type of implant, fixation, duration of surgery, and year of primary surgery. An instrumental variable Cox regression was performed to estimate the causal effect of thromboprophylaxis.Results - Thromboprophylaxis was used in 4,089 out of 6,123 shoulder arthroplasties. 90-day mortality was similar between the thromboprophylaxis and no thromboprophylaxis groups (hazard ratio (HR) = 1.1, 95% CI 0.6-2.4). High age (> 75), high ASA class (≥ 3), and fracture diagnosis increased postoperative mortality. No statistically significant difference in the risk of revision within 1 year could be found (HR = 0.6, CI 0.3-1.2). The proportion of intraoperative bleeding was similar in the 2 groups (0.2%, 0.3%).Interpretation - We had no information on cause of death and relation to thromboembolic events. However, no association of reduced mortality with use of thromboprophylaxis was found. Based on our findings routine use of thromboprophylaxis in shoulder arthroplasty can be questioned.

[Reconstruction by thoracodorsal perforator flap after petrosectomy]. / Comblement de cavité d'évidement après pétrectomie.

Petrosectomy is a debilitating intervention, consisting of a resection of the bone forming the external auditory canal, the middle ear and sometimes the internal ear as well. The cavity formed after this surgery can lead to infectious complications. Reconstruction is an essential element for patients' rehabilitation. Most cases require local rotation flaps such as temporal muscle flap. However, when the remaining defect is too large or when the structures have been altered by radiotherapy, free flaps are the most adequate solution for repair. Upon review of the literature, there are very few articles providing options regarding reconstruction possibilities post-petrosectomy. Plastic surgeons are often unfamiliar with this indication, therefore, it is essential to call their attention in order to provide the best options of care in these difficult and complicated cases where possibilities are limited. That is why, it is important for us to share our experience in this domain through the example of our patient presenting with a large osteoradionecroses of the petrous bone, requiring resection and immediate reconstruction using a free flap.

Risk factors for surgical site infections using a data-driven approach.

OBJECTIVE: The objective of this study was to identify risk factors for surgical site infection from digestive, thoracic and orthopaedic system surgeries using clinical and data-driven cut-off values. A second objective was to compare the identified risk factors in this study to risk factors identified in literature. SUMMARY BACKGROUND DATA: Retrospective data of 3 250 surgical procedures performed in large tertiary care hospital in The Netherlands during January 2013 to June 2014 were used. METHODS: Potential risk factors were identified using a literature scan and univariate analysis. A multivariate forward-step logistic regression model was used to identify risk factors. Standard medical cut-off values were compared with cut-offs determined from the data. RESULTS: For digestive, orthopaedic and thoracic system surgical procedures, the risk factors identified were preoperative temperature of ≥38°C and antibiotics used at the time of surgery. C-reactive protein and the duration of the surgery were identified as a risk factors for digestive surgical procedures. Being an adult (age ≥18) was identified as a protective effect for thoracic surgical procedures. Data-driven cut-off values were identified for temperature, age and CRP which can explain the SSI outcome up to 19.5% better than generic cut-off values. CONCLUSIONS: This study identified risk factors for digestive, orthopaedic and thoracic system surgical procedures and illustrated how data-driven cut-offs can add value in the process. Future studies should investigate if data-driven cut-offs can add value to explain the outcome being modelled and not solely rely on standard medical cut-off values to identify risk factors.

Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study.

BACKGROUND: Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes. METHODS: Ten patients received intravenous BTZ 1.3 mg/m2 on days 1, 4, and 7 during each 4th weekly TMZ-chemotherapy starting on day 3 and escalated from 150 mg/m2 per oral 5 days/wk via 175 to 200 mg/m2 in cycles 1, 2, and 3, respectively. Adverse events and quality of life were evaluated by CTCAE and EQ-5D-5L questionnaire, and immunological biomarkers evaluated by flow cytometry and Luminex enzyme-linked immunosorbent assay. RESULTS: Sequential BTZ + TMZ therapy was safe and well tolerated. Pain and performance of daily activities had greatest impact on patients' self-reported quality of life and were inversely correlated with Karnofsky performance status. Patients segregated a priori into three groups, where group 1 displayed stable clinical symptoms and/or slower magnetic resonance imaging radiological progression, expanded CD4+ effector T-cells that attenuated cytotoxic T-lymphocyte associated protein-4 and PD-1 expression and secreted interferon γ and tumor necrosis factor α in situ and ex vivo upon stimulation with PMA/ionomycin. In contrast, rapidly progressing group 2 patients exhibited tolerised T-cell phenotypes characterized by fourfold to sixfold higher interleukin 4 (IL-4) and IL-10 Th-2 cytokines after BTZ + TMZ treatment, where group 3 patients exhibited intermediate clinical/radiological responses. CONCLUSION: Sequential BTZ + TMZ treatment is safe and promotes Th1-driven immunological responses in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)).

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Anatomy transformed.

This paper arose from exhibitions in Oxford and Dublin and comprises three experiments which look at the relationship between anatomy and art. In the first experiment, a passport photograph, photographic portrait and portrait in oils, all of the same sitter, show how artistic input transforms anatomy from a mere likeness into works of art. In the second, the reverse is true, as computer techniques render idealized old master images anatomically accurate. The third experiment addresses the biomechanical consequences of anatomical variation and shows that vehicular design is based on mean body shapes, and so it is the average, rather than the idealized, form that is safer in a collision.

Paraoxonase 1 (PON1) attenuates sperm hyperactivity and spontaneous acrosome reaction.

BACKGROUND: Sperm capacitation is essential for proper fertilization and is associated with increased sperm hyperactivity (HA) and acrosome reaction (AR). For successful fertilization, AR timing is critical; accordingly, early spontaneous AR may not facilitate fertilization. Paraoxonase 1 (PON1) possesses antioxidant properties which affect sperm capacitation. The association between PON1, semen parameters, and capacitation is not fully understood. OBJECTIVE: To study PON1 activity in relation to human sperm hyperactivity and AR. MATERIALS AND METHODS: Semen samples were collected, and parameters were determined (volume, concentration, total sperm count, percentage total motility, and percentage normal morphology) according to World Health Organization (WHO) guidelines. AR and hyperactivity were evaluated using FITC-PSA, staining, and computer-aided sperm analysis (CASA). PON1 activity was assessed using arylesterase activity assay. RESULTS: Purified PON1 inhibited both sperm hyperactivity and AR in a dose-dependent manner. Native semen PON1 activity was positively associated with higher sperm concentration and negatively associated with spontaneous acrosome reaction (sAR). DISCUSSION AND CONCLUSION: PON1 may have a positive effect on fertility via its ability to prevent early spontaneous sperm capacitation and AR before reaching the female genital tract.

[Late effects following childhood cancer treatment : A special challenge for transition medicine]. / Spätfolgen einer Krebsbehandlung im Kindes- und Jugendalter : Eine Herausforderung für die Transitionsmedizin.

BACKGROUND: Childhood cancer survivors are at risk of cancer- and treatment-related chronic health conditions. Since these sequelae may occur years after the end of treatment, many patients are already adults and have completed pediatric oncological care. Thus, successful transition is essential in order to ensure long-term surveillance. OBJECTIVES: The present review outlines the most frequent late effects of childhood cancer treatment. Moreover, difficulties in transition of these patients are discussed and interdisciplinary models of care are presented. RESULTS: Late effects following childhood cancer treatment occur in over two thirds of patients 30 years after the end of the oncological treatment and can affect different organs. The most frequent sequelae are endocrine disturbances, cardiac conditions, and subsequent neoplasms. Many late effects are effectively manageable if detected early. This necessitates an interdisciplinary approach as well as life-long surveillance. CONCLUSIONS: Transition from pediatric to internal medicine care as well as a change in the focus of care, shifting from relapse centered follow-up to late-effects centered surveillance, constitute a special challenge for a successful transition of long-term childhood cancer survivors. Specialized late-effects survivorship clinics offering interdisciplinary care from pediatric oncologists, specialists of internal medicine, and further disciplines enable the early diagnosis and treatment of late-effects.

Prenatal exposure to dental amalgam and risk of symptoms of attention-deficit and hyperactivity disorder (ADHD).

BACKGROUND: ADHD is multifactorial, including both genetic and environmental factors. The safety of amalgam used in dental treatment has been discussed due to its content of mercury and potential risks for negative neurodevelopmental consequences in the offspring. The aim of the study was to investigate possible associations between symptoms related to ADHD in children of three and five years of age and prenatal exposure to mercury from mothers' amalgam fillings. METHODS: Data from the Norwegian Mother and Child Cohort Study (MoBa) were used. Data were collected by questionnaires sent to participating women in week 17 (Q1) and 30 (Q3) of pregnancy and when the child was three (Q6) and five years of age (Q7). Information about exposure to amalgam during pregnancy was obtained from Q3. Information about symptoms related to ADHD was obtained from Q6 and Q7. Valid data were obtained for 42 163 children at three years of age and 23 392 children at five years of age. Logistic regression models, including mothers' age, education, body mass index, parity, smoking and alcohol consumption during pregnancy, were used to estimate the association between ADHD symptoms and prenatal exposure to amalgam fillings. RESULTS: No significant associations between number of teeth with amalgam filling, amalgam fillings placed or removed during pregnancy, and symptoms related to ADHD in children of three and five years of age were found. CONCLUSIONS: In a large, prospective cohort study, we found no indication of increased risk of ADHD-related symptoms in children prenatally exposed to mother's amalgam fillings.

Beyond second-line therapy in patients with metastatic colorectal cancer: a systematic review.

Background: The optimal chemotherapeutic regimen for use beyond the second line for patients with metastatic colorectal cancer (mCRC) remains unclear. Materials and methods: We systematically searched the Cochrane Database of Systematic Reviews, EMBASE and Medline for records published between January 2002 and May 2017, and cancer congress databases for records published between January 2014 and June 2017. Eligible studies evaluated the efficacy, safety and patient-reported outcomes of monotherapies or combination therapies at any dose and number of treatment cycles for use beyond the second line in patients with mCRC. Studies were assessed for design and quality, and a qualitative data synthesis was conducted to understand the impact of treatment on overall survival and other relevant cancer-related outcomes. Results: The search yielded 938 references of which 68 were included for qualitative synthesis. There was limited evidence to support rechallenge with chemotherapy, targeted therapy or both. Compared with placebo, an overall survival benefit for trifluridine/tipiracil (also known as TAS-102) or regorafenib has been shown for patients previously treated with conventional chemotherapy and targeted therapy. There was no evidence to suggest a difference in efficacy between these treatments. Patient choice and quality of life at this stage of treatment should also be considered when choosing an appropriate therapy. Conclusions: These findings support the introduction of an approved agent such as trifluridine/tipiracil or regorafenib beyond the second line before any rechallenge in patients with mCRC who have failed second-line treatment.

A survivorship study of 838 total elbow replacements: a report from the Norwegian Arthroplasty Register 1994-2016.

BACKGROUND: The aim of this study was to present the long-term survivorship (20 years) of total elbow arthroplasty (TEA) for a relatively large population and to compare different prosthesis brands and patient subgroups. METHODS: Between 1994 and 2017, a total of 838 primary TEAs were reported to the Norwegian Arthroplasty Register. Implant survival was calculated using the Kaplan-Meier method. Risk differences were examined using Cox regression analyses and exact Cox regression for rare events. We compared the survivorship of the 8 most frequently used implant brands, the different diagnoses leading to TEA, and the influence of the fixation technique. RESULTS: The overall 5-, 10-, 15-, and 20-year survival rates for all elbow arthroplasties were 92%, 81%, 71%, and 61%, respectively. Risk factors for revision were a diagnosis of sequelae after trauma and cementless fixation of the ulna component. There were some differences between the implant brands. The Norway prostheses had higher survival compared with the Kudo after 15 years of follow-up (78% and 66%, respectively; P < .001). Among the implants with shorter follow-up, the IBP and NES had inferior survivorship compared with the Norway. The frequently used Discovery had promising survivorship up to 5 years. The most frequent reason for revision surgery was aseptic loosening, followed by defective polyethylene, infection, and dislocation. The revision causes were to some degree implant specific. CONCLUSION: Fairly good results in terms of prosthesis survival were obtained with TEA, although results were poorer than for knee and hip arthroplasties.

Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion.

Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth. Conversely, disruption of exosome secretion in AML cells through targeting Rab27a, an important regulator involved in exosome release, significantly delayed leukemia development. In BM stromal cells, AML-derived exosomes induced the expression of DKK1, a suppressor of normal hematopoiesis and osteogenesis, thereby contributing to osteoblast loss. Conversely, treatment with a DKK1 inhibitor delayed AML progression and prolonged survival in AML-engrafted mice. In addition, AML-derived exosomes induced a broad downregulation of hematopoietic stem cell-supporting factors (for example, CXCL12, KITL and IGF1) in BM stromal cells and reduced their ability to support normal hematopoiesis. Altogether, this study uncovers novel features of AML pathogenesis and unveils how AML cells create a self-strengthening leukemic niche that promotes leukemic cell proliferation and survival, while suppressing normal hematopoiesis through exosome secretion.