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A review of 75 original articles from clinical cancer research in Norway is presented. Articles published in 1993 and with at least one Norwegian author were included in the review. Sixty papers were observational, whereas 15 were experimental. Of the observational studies 44 were retrospective. Most of the papers concerned prognostic factors. Prior hypotheses were explicitly defined in 16 papers only, and less than half of the articles described inclusion and exclusion criteria. Sample size calculations were performed in four papers only. The choice of statistical method was considered to be suitable in 22 of the 58 articles presenting statistical inferences. Problems related to multiple significance testing were rarely addressed, although the median number of p-values reported was as high as 8. Confidence intervals for main findings were presented in 14 papers. For proper planning of studies, as well as for analysis and interpretation of study results, statistical advice is indeed required. [ABSTRACT FROM AUTHOR]

Background and purpose -- A new periprosthetic joint infection (PJI) definition has recently been proposed by the European Bone and Joint Infection Society (EBJIS). The goals of this paper are to evaluate its diagnostic accuracy and compare it with previous definitions and to assess its accuracy in preoperative diagnosis. Patients and methods -- We retrospectively evaluated a multicenter cohort of consecutive revision total hip and knee arthroplasties. Cases with minimum required diagnostic workup were classified according to EBJIS, 2018 International Consensus Meeting (ICM 2018), Infectious Diseases Society of America (IDSA), and modified 2013 Musculoskeletal Infection Society (MSIS) definitions. 2 years' minimum follow-up was required to assess clinical outcome. Results -- Of the 472 cases included, PJI was diagnosed in 195 (41%) cases using EBJIS; 188 (40%) cases using IDSA; 172 (36%) using ICM 2018; and 145 (31%) cases using MSIS. EBJIS defined fewer cases as intermediate (5% vs. 9%; p = 0.01) compared with ICM 2018. Specificity was determined by comparing risk of subsequent PJI after revision surgery. Infected cases were associated with higher risk of subsequent PJI in every definition. Cases classified as likely/confirmed infections using EBJIS among those classified as not infected in other definitions showed a significantly higher risk of subsequent PJI compared with concordant non-infected cases using MSIS (RR = 3, 95% CI 1-6), but not using ICM 2018 (RR = 2, CI 1-6) or IDSA (RR = 2, CI 1-5). EBJIS showed the highest agreement between preoperative and definitive classification (k = 0.9, CI 0.8-0.9) and was better at ruling out PJI with an infection unlikely result (sensitivity 89% [84-93], negative predictive value 90% [85-93]). Conclusion -- The newly proposed EBJIS definition emerged as the most sensitive of all major definitions. Cases classified as PJI according to the EBJIS criteria and not by other definitions seem to have increased risk of subsequent PJI compared with concordant non-infected cases. EBJIS classification is accurate in ruling out infection preoperatively. [ABSTRACT FROM AUTHOR]

Normative health-related quality of life (HRQoL) data from the general population are regularly used to facilitate the interpretation of HRQoL as reported by cancer patients participating in cancer clinical trials, especially when conducting long-term follow-up studies after treatment. The aim of the present study is to compare two Swedish normative data sets, published in 2000 and 2019 respectively, and explore whether HRQoL as reported by the Swedish general population has changed over time. 'Sample 2000' was comprised of normative data from the Swedish general population who responded to the EORTC QLQ-C30 in a Swedish mail survey in 1999 (n = 3069). 'Sample 2019' consisted of data from the Swedish general population collected as part of a European norm data study using online panels, published in 2019 (n = 1027). Data were analyzed stratified by sex and age (40–49; 50–59; 60–69; 70–79 years). For most of the subscales and single items, no age group differences between the two samples were found, with the exception of the oldest age group (70–79 years), where Sample 2019 generally showed better HRQoL as compared to Sample 2000. Lower (worse) levels of Global quality of life and higher (worse) levels of Dyspnoea were found in Sample 2019 for most age groups. There were no differences found between the samples for most EORTC QLQ-C30 subscales and single items, with the exception of the oldest age group of both sexes in Sample 2019 who reported better HRQoL on many variables. When deciding which normative dataset to use, the mode of data collection and age group have to be considered. [ABSTRACT FROM AUTHOR]

Background and purpose — Long-term rates of knee arthroplasty in patients with anterior cruciate ligament (ACL) injury who undergo ligament reconstruction (ACLr) are unclear. We determined this risk of arthroplasty through comparison with the general population. Patients and methods — All patients undergoing an ACLr in England, 1997–2017, were identified from national hospital statistics. Patients subsequently undergoing a knee arthroplasty were identified and survival analysis was performed (survival without undergoing knee arthroplasty). A Cox proportional hazards model was used to identify factors associated with knee arthroplasty. Relative risk of knee arthroplasty (total or partial) in comparison with the general population was determined. Results — 111,212 ACLr patients were eligible for analysis (mean age 29; 77% male). Overall, 0.46% (95% confidence interval [CI] 0.40–0.52) ACLr patients underwent knee arthroplasty within 5 years, 0.97% (CI 0.82–1.2) within 10 years, and 1.8% (CI 1.4–2.3) within 15 years. Knee arthroplasty risk was greater in older age groups and women. In comparison with the general population, the relative risk of undergoing arthroplasty at a younger age (at time of arthroplasty) was elevated: at 30–39 years (risk ratio [RR] 20; CI 11–35), 40–49 years (RR 7.5; CI 5.5–10), and 50–59 years (RR 2.5; CI 1.8–3.5), but not 60–69 years (RR 1.7; CI 0.93–3.2). Interpretation — Patients sustaining an ACL injury who undergo ACLr are at elevated risk of subsequent knee arthroplasty in comparison with the general population. Although the absolute rate of arthroplasty is low, the risk of arthroplasty at a younger age is particularly elevated. When the outcome of shared decision-making is ACLr, this data will help inform patients and clinicians about the long-term risk of requiring knee arthroplasty. [ABSTRACT FROM AUTHOR]

Background: The treatment options for patients with therapy refractory metastatic colorectal cancer (mCRC) are sparse. TAS-102 (FTD/TPI) is a new oral anti-tumour agent composed of a nucleoside analogue, trifluridine, and a thymidine phosphorylase inhibitor, tipiracil, indicated for patients with mCRC who are refractory to standard therapies. This study summarizes published and unpublished experience with FTD/TPI in clinical practice settings. Patients and methods: The Medline/PubMed, Embase and Cochrane Library databases were searched to identify observational studies on FTD/TPI monotherapy for mCRC. Papers describing use of FTD/TPI monotherapy outside clinical trials in series of patients evaluable for effectiveness were eligible. The outcomes of interest were median progression free survival (mPFS), median overall survival (mOS) as well as mean PFS time restricted to six months (PFS6m) and mean OS time restricted to one year (OS1y). Results of the pooled analyses of observational studies were compared to the results of the Japanese phase II trial and the two phase III trials, RECOURSE and TERRA. Results: Seven published and two unpublished studies with 1008 patients from 64 centres were included for analysis. The pooled mPFS was 2.2 months (95% CI 2.1 to 2.3 months), and the pooled mOS was 6.6 months (95% CI 6.1 to 7.1 months). PFS6m was 2.9 months (95% CI 2.6 to 3.1 months) and OS1y was 6.8 (95% CI 6.0 to 7.5) months. While these results all reflect RECOURSE, the pooled mOS is lower than in the phase II trial and the OS1y is inferior to both the phase II trial and TERRA. Conclusion: This systematic review and a meta-analysis indicates that in real life settings, the survival benefit of FTD/TPI monotherapy in patients with therapy refractory mCRC reflects the outcomes in RECOURSE but is inferior to outcomes in the two Asian efficacy trials. TAS 102 (Lonsurf) is an oral fixed dose combination of trifluridine (FTD) and tipiracil (TPI) indicated as salvage-line treatment in patients with therapy refractory metastatic colorectal cancer (mCRC). A Japanese phase II trial and two phase III trials, RECOURSE and TERRA, demonstrated that FTD/TPI prolonged overall survival. This systematic review and meta-analysis of real life data from 64 sites indicates that the effectiveness in daily clinical practice settings of FTD/TPI monotherapy in late stage mCRC reflects the outcomes in RECOURCE but is inferior to the outcomes in the Japanese phase II trial and TERRA. [ABSTRACT FROM AUTHOR]

The article presents a college thesis which investigated the determinants of the outcomes of lumbar spinal stenosis surgery and is based on several papers previously published by F. G. Sigmundsson, B. Jönsson and B.Strömqvist, including papers which appeared in a 2013 issue of "Acta Orthopaedica", a 2012 issue of "Acta Orthopaedica" and a 2014 issue of "Spine".

The article reports on studies about orthopedic trauma surgery in low and middle-income countries (LMIC). Topics discussed include the history of femoral intramedullary nailing, the problems faced by LMICs in providing trauma care and the occurrence of infection after trauma surgery in LMICs. Also discussed are the effects of HIV and AIDS on orthopedic trauma surgery in LMICs and the assistance offered by the nonprofit organization SIGN Fracture International to hospitals in LMICs.

Background and purpose - There is debate as to the relative merits of unicompartmental and total knee arthroplasty (UKA, TKA). Although the designer surgeons have achieved good results with the Oxford UKA there is concern over the reproducibility of these outcomes. Therefore, we evaluated published long-term outcomes of the Oxford Phase 3 UKA. Patients and methods - We searched databases to identify studies reporting ≥10 year outcomes of the medial Oxford Phase 3 UKA. Revision, non-revision, and re-operation rates were calculated per 100 component years (% pa). Results - 15 studies with 8,658 knees were included. The annual revision rate was 0.74% pa (95% CI 0.67--0.81, n = 8,406) corresponding to a 10-year survival of 93% and 15-year survival of 89%. The non-revision re-operation rate was 0.19% pa (95% CI 0.13--0.25, n = 3,482). The re-operation rate was 0.89% pa (95% CI 0.77--1.02, n = 3,482). The most common causes of revision were lateral disease progression (1.42%), aseptic loosening (1.25%), bearing dislocation (0.58%), and pain (0.57%) (n = 8,658). Average OKS scores were 40 at 10 years (n = 3,417). The incidence of medical complications was 0.83% (n = 1,443). Interpretation - Very good outcomes were achieved by both designer and non-designer surgeons. The PROMs, medical complication rate, and non-revision re-operation rate were better than those found in meta-analyses and publications for TKA but the revision rate was higher. However, if failure is considered to be all re-operations and not just revisions, then the failure rate of UKA was less than that of TKA. [ABSTRACT FROM AUTHOR]

Background. Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds. Methods. After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers. Results. Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02). Conclusions. Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined. [ABSTRACT FROM AUTHOR]

Background. Radical prostatectomy (RP) is worldwide probably the most common procedure to treat localized prostate cancer (PC). Due to a more widespread use of Prostate-Specific Antigen (PSA) testing, patients operated today are often younger and have organ confined disease justifying a more preservative surgery. At the same time, surgical technique has improved resulting in lower risk of permanent side-effects. This paper aims to give an overview of results from modern surgery regarding cancer control and side-effects. A brief overview of the history is given. Material and Methods. A literature research identified recently published papers focusing on outcome and side-effects after RP. Results. One large randomized study (SPCG-4) compared RP and watchful waiting (WW). The study showed that RP was superior to WW in preventing local progression (RR 0.36), distant metastasis (RR 0.65) and death from PC (RR 0.65). Observational studies also show a better outcome for men treated with RP compared to WW. Peri-operative mortality after RP is low in most material around 0.1%. The risk of stricture of the vesico-urethral anastomosis has decreased with improved technique from historically 10-20% to a low incidence of around 2-9% today. Also the risk of incontinence has declined with improved technique. However, while the rates of severe incontinence is usually very low, as many as 30% still report light incontinence after long-term follow-up. Erectile dysfunction (ED) is still a frequent side-effect after RP. This risk is dependent on age, pre-operative sexual function, surgical technique and other risk factors for ED such as smoking, diabetes, etc. In selected subgroups the risk of ED is low. Inguinal hernia is a more recently described complication after open retropubic RP with a post-operative incidence of 15-20% within three years of surgery. Conclusion. RP is an effective method to achieve cancer control in selected patients. With modern technique it is a safe procedure with a low risk of permanent side-effects except for ED. [ABSTRACT FROM AUTHOR]

Background:The clinical feasibility of using pseudo-computed tomography (pCT) images derived from magnetic resonance (MR) images for external bean radiation therapy (EBRT) planning for prostate cancer patients has been well demonstrated. This paper investigates the feasibility of applying an MR-derived, pCT planning approach to additional types of cancer in the pelvis. Material and methods:Fifteen patients (five prostate cancer patients, five rectal cancer patients, and five gynecological cancer patients) receiving EBRT at Turku University Hospital (Turku, Finland) were included in the study. Images from an MRCAT (Magnetic Resonance for Calculating ATtenuation, Philips, Vantaa, Finland) pCT method were generated as a part of a clinical MR-simulation procedure. Dose calculation accuracy was assessed by comparing the pCT-based calculation with a CT-based calculation. In addition, the degree of geometric accuracy was studied. Results:The median relative difference of PTV mean dose between CT and pCT images was within 0.8% for all tumor types. When assessing the tumor site-specific accuracy, the median [range] relative dose differences to the PTV mean were 0.7 [−0.11;1.05]% for the prostate cases, 0.3 [−0.25;0.57]% for the rectal cases, and 0.09 [−0.69;0.25]% for the gynecological cancer cases. System-induced geometric distortion was measured to be less than 1 mm for all PTV volumes and the effect on the PTV median dose was less than 0.1%. Conclusions:According to the comparison, using pCT for clinical EBRT planning and dose calculation in the three investigated types of pelvic cancers is feasible. Further studies are required to demonstrate the applicability to a larger cohort of patients. [ABSTRACT FROM PUBLISHER]

Background and purpose — The use of a cemented cup together with an uncemented stem in total hip arthroplasty (THA) has become popular in Norway and Sweden during the last decade. The results of this prosthetic concept, reverse hybrid THA, have been sparsely described. The Nordic Arthroplasty Register Association (NARA) has already published 2 papers describing results of reverse hybrid THAs in different age groups. Based on data collected over 2 additional years, we wanted to perform in depth analyses of not only the reverse hybrid concept but also of the different cup/stem combinations used. Patients and methods — From the NARA, we extracted data on reverse hybrid THAs from January 1, 2000 until December 31, 2013. 38,415 such hips were studied and compared with cemented THAs. The Kaplan-Meier method and Cox regression analyses were used to estimate the prosthesis survival and the relative risk of revision. The main endpoint was revision for any reason. We also performed specific analyses regarding the different reasons for revision and analyses regarding the cup/stem combinations used in more than 500 cases. Results — We found a higher rate of revision for reverse hybrids than for cemented THAs, with an adjusted relative risk of revision (RR) of 1.4 (95% CI: 1.3–1.5). At 10 years, the survival rate was 94% (CI: 94–95) for cemented THAs and 92% (95% CI: 92–93) for reverse hybrids. The results for the reverse hybrid THAs were inferior to those for cemented THAs in patients aged 55 years or more (RR =1.1, CI: 1.0–1.3; p < 0.05). We found a higher rate of early revision due to periprosthetic femoral fracture for reverse hybrids than for cemented THAs in patients aged 55 years or more (RR =3.1, CI: 2.2–4.5; p < 0.001). Interpretation — Reverse hybrid THAs had a slightly higher rate of revision than cemented THAs in patients aged 55 or more. The difference in survival was mainly caused by a higher incidence of early revision due to periprosthetic femoral fracture in the reversed hybrid THAs. [ABSTRACT FROM PUBLISHER]

The article reports on studies concerning sacroiliac joint movements and pelvic joint fusion outcomes. Topics discussed include the accuracy of radiostereometrics in analyzing sacroiliac joint movement, the outcomes for patients with severe pelvic girdle pain (PGP) who underwent pelvic joint fusion and the possible causes of PGP. Also discussed are the tests to diagnose PGP and the biomechanical considerations for sacroiliac joint movement.

Poorer survival in cancer patients with vs. without comorbidity has been reported for various cancer sites. For patients with colorectal cancer (CRC), limited data are available so far. Patients with CRC diagnosed between 2010 and 2018 were identified in a health claims database covering 20% of the German population. We assessed the prevalence of comorbidities at cancer diagnosis and categorized the patients into the groups: 'none', 'somatic only', 'mental only' or 'both' types of comorbidities. Hazard ratios (HR, with 95% confidence intervals) for five-year overall survival were estimated by Cox proportional hazard models, adjusted for age, sex and stage at diagnosis (advanced vs. non-advanced). We included 92,991 patients (females: 49.1%, median age: 72 years) with a median follow-up of 30 months. The proportions assigned to the groups 'none', 'somatic only', 'mental only' or 'both' were 24.7%, 65.5%, 1.4% and 8.4%. Overall, 32.8% of the patients died during follow-up. Compared to patients without comorbidities ('none'), the adjusted HR regarding death from any cause was 1.11 (95% CI: 1.07–1.14) in the group 'somatic only', 1.74 (95% CI: 1.58–1.92) in the group 'mental only' and 1.92 (95% CI: 1.84–2.00) in the group 'both'. For patients with 'mental only' comorbidities, the adjusted HR was higher in males than in females (HR = 2.19, 95% CI: 1.88–2.55 vs. HR = 1.55, 95% CI: 1.37–1.75). Our results suggest that patients with CRC and with mental comorbidities, particularly males, have a markedly lower overall survival compared to those without any or only somatic comorbidities. [ABSTRACT FROM AUTHOR]

Compared to non-smokers, smokers have reduced effects of cancer treatment, and increased risk of treatment-related toxicity. Quitting smoking can improve treatment effects and reduce side effects. This study reports on the potential impact of a smoking cessation program on smoking cessation rates among patients in cancer treatment. Cancer patients 18 years and older who smoked, with survival prognosis ≥12 months, not suffering dementia or other mental illness, and who were referred to cancer treatment at six Norwegian hospitals were invited to participate. The study took place from 2017 to 2020 and used a pre-test-posttest non-equivalent control group design. The intervention group received structured smoking cessation guidance based on Motivational Interviewing combined with cost-free nicotine replacement products, while the control group received standard smoking cessation treatment. Self-reported smoking status were registered at baseline and at 6 months' follow up. 76% of patients smoked at baseline and 44% at follow-up in the intervention group, correspondingly 72% and 49% in the control group. In an analysis of differences in within-person change, the reduction in the intervention group was 13 percentage points larger (95% CI = (0.25, −0.005), p = 0.041). Adjusting for gender, age, education, labour market participation and partnership status did not attenuate the estimated effect (18 percentage point difference, 95% CI = (−0.346, −0.016), p = 0.032). Demographic factors and dropout rate differed somewhat between the groups with a higher dropout rate in the intervention group, 54% vs. 51%, respectively). Offering a structured smoking cessation program based on Motivational Interviewing and cost-free nicotine replacement products to cancer patients can increase cessation rates in comparison to standard smoking cessation care. [ABSTRACT FROM AUTHOR]

The aim was to investigate the distribution of health problems in general practice (GP) among adolescent and young adult (AYA) survivors of lymphoma and to compare problem rates with the general population. All GP consultations between 2006 and 2020 were identified from the national GP claims register. Diseases and complaints presented 3–10 years after the cancer diagnosis were identified using the International Classification of Primary Care codes (ICPC-2) and compared by applying logistic regression models, presented with odds ratio (OR) and 95%CI. A total of 2,500,557 AYAs, of whom 1105 were diagnosed with lymphoma, and over 50 million GP consultations were included. The most common causes of consultation among AYA survivors of lymphoma were related to Hodgkin's disease (13%), pregnancy (11%), respiratory diseases (9%), psychological problems (8%), musculoskeletal system (6%) and fatigue (4%). Almost all these problems were significantly higher among AYA lymphoma survivors compared to the general population (OR ranging from 1.1 to 1.5). Compared to the general population, young lymphoma survivors have increased contact with the GP for a considerable number of health problems for up to 10 years post-diagnosis. This emphasizes the importance of robust follow-up and a good flow of information between hospital and primary care. [ABSTRACT FROM AUTHOR]

There are two main coping styles regarding information seeking under medical threat; monitoring (information-seeking) and blunting (information-avoiding). The aim of this study is to (1) determine factors associated with a monitoring or blunting coping style in gastro-intestinal stromal tumour (GIST) patients and (2) investigate its association with psychological distress, cancer-related concerns, health-related quality of life and satisfaction with healthcare. In a cross-sectional study, Dutch GIST patients completed the shortened version of the Threatening Medical Situations Inventory to determine their coping style, the Hospital Anxiety and Depression Scale, Cancer Worry Scale, EORTC QLQ-C30 and part of the EORTC QLQ-INFO25. A total of 307 patients were classified as blunters (n = 175, 57%) or monitors (n = 132, 43%). Coping style was not associated with tumour or treatment variables, but being a female (OR 2.5; 95%CI 1.5–4.1; p= <.001) and higher educated (OR 5.5; 95%CI 2.5–11.9, p= <.001) were associated with higher odds of being a monitor. Monitors scored significantly lower on emotional functioning (mean = 86.8 vs mean = 90.9, p=.044), which is considered a trivial difference, more often experienced severe fear of cancer recurrence or progression (53.0% vs 37.7%, p=.007), and had more concerns about dying from GIST in the future (60.6% vs 47.4%, p=.025). Compared to blunters, monitors were less satisfied with the received healthcare and information, and would have liked to receive more information. GIST patients with a monitoring coping style experience a higher emotional burden. Additionally, monitors exhibit a greater need for information. Although this need for information could potentially result in fears and concerns, recognising it may also create an opening for tailored communication and information. [ABSTRACT FROM AUTHOR]

Using real-world (RW) data from registries to mimic or substitute a comparator arm of clinical trials is increasingly investigated. The feasibility of using data sources for this purpose depends on the source's completeness of the wide spectrum of a disease characteristics and relevant endpoints, which could allow for proper matching of important variables. This is a Norwegian study using data from three population-based registries, the Cancer Registry (CRN), the National Patient Registry (NPR), and the Norwegian Prescribed Drug Registry (LMR). We assessed if the registries contained the information necessary for selecting a RW cohort of patients with characteristics that mimicked the inclusion and exclusion criteria from the control arm of the phase 3 trial (KeyNote-407) on patients with stage IV, squamous NSCLC. We did this both on an aggregated - and individual data level. We also described the survival in the RW-cohorts and compared it with the survival in the control arm of the KN-407 trial. Using aggregated data from the CRN allowed us to find the patients based on some clinically relevant inclusion criteria, but only to a limited extent could we apply the exclusion criteria of KN-407. When we used individual data from the CRN, NPR and the LMR we could create a patient cohort that shared more criteria corresponding to the eligibility criteria from KN-407, including exclusion criteria. Compared to the 11.3 months (CI 95% 9.5, 14.8) median survival in the control arm of KN-407, both RW-cohorts had a shorter median survival, 7.07 months (CI 95% 6.7, 9.5) (individual) and 8.0 months (CI 95% 5.8, 10.5) (aggregated). Even if we demonstrated that the registries contain clinically relevant information necessary to mimic the eligibility criteria of a selected RCT, the survival is shorter for RW patients compared to their control arm counterpart in the RCT. [ABSTRACT FROM AUTHOR]

Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML. Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment. Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25–2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75–2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53–2.90]), bosutinib (1.41 [1.07–1.86]), and radotinib (1.87 [1.33–2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs. [ABSTRACT FROM AUTHOR]

Background: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. Methods: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. Results: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p=0.010), while patients with non-malignant lung pathology showed a reduction in distress (p=0.070). Both urinary epinephrine (p=0.001) and norepinephrine (p=0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. Conclusion: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis. Abbreviations: HADS: Hospital Anxiety and Depression scale; HADS-A: Hospital Anxiety and Depression scale - anxiety score; HADS-D: Hospital Anxiety and Depression scale - depression score; HADS-T: Hospital Anxiety and Depression scale - total score; IQR: Interquartile range; LUCASS study: Lung Cancer, Stress and Survival study; NSCLC: Non-small cell lung cancer; PTSD: Post Traumatic Stress Disorder; SCLC: Small-cell lung cancer; SD: Standard Deviation; SNS: the Sympathetic Nervous System. [ABSTRACT FROM AUTHOR]

Introduction: Professional visual artists constitute a heterogeneous vocational group, including, but not limited to painters, photographers, textile artists, and sculptors who may face exposure to workplace hazardous substances and lifestyle factors that may contribute to the development of selected cancers. The objective of this registry-based cohort study was to assess the cancer incidence among Nordic visual artists. Materials and methods: This study is based on data from the Nordic Occupational Cancer (NOCCA) project that combines census data of 15 million people from all Nordic countries and cancer registries from 1961 to 2005. For the present study we selected a cohort of visual artists from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. Results: In male visual artists, there were statistically significant excesses in cancers of the tongue (SIR 2.91, 95% confidence interval 1.74-4.55), oral cavity (2.09, 1.26-3.27), pharynx (2.18, 1.45--3.15), testis (1.91, 1.11-3.05), renal pelvis (2.48, 1.42-4.03) and bladder (1.33, 1.14-1.55). The risk was significantly decreased for cancers of the lip (0.45, 0.18-0.93) and stomach (0.65, 0.50-0.84). In female visual artists, the only significantly increased risk was observed for breast cancer (1.29, 1.13-1.48) and the only significantly decreased risk for stomach cancer (0.43, 0.17-0.88). The incidence of lung cancer was close to the population average in both sexes. Conclusions: The non-elevated incidence of lung cancer suggests a similar prevalence of smoking between visual artists and the general population, while the elevated risk of cancers of mouth and pharynx among male visual artists is suggestive of more widespread alcohol drinking. The excess risk of urogenital cancers might be associated with exposure to solvents. NOVELTY & IMPACT The exposure of visual artists to carcinogens remains unstudied and equivocal. The current study suggests that visual artists carry an overall cancer risk that is slightly above the risk among the general population of the four Nordic countries. We observed in men over two-fold excess risks of cancers of the tongue, oral cavity, pharynx, and renal pelvis, and also a significant risk of testis and bladder cancers. [ABSTRACT FROM AUTHOR]

Background. Understanding the dose-response of the lung in order to minimize the risk of radiation pneumonitis (RP) is critical for optimization of lung cancer radiotherapy. We propose a method to combine the dose-response relationship for RP in the landmark QUANTEC paper with known clinical risk factors, in order to enable individual risk prediction. The approach is validated in an independent dataset. Material and methods. The prevalence of risk factors in the patient populations underlying the QUANTEC analysis was estimated, and a previously published method to adjust dose-response relationships for clinical risk factors was employed. Effect size estimates (odds ratios) for risk factors were drawn from a recently published meta-analysis. Baseline values for D50 and γ50 were found. The method was tested in an independent dataset (103 patients), comparing the predictive power of the dose-only QUANTEC model and the model including risk factors. Subdistribution cumulative incidence functions were compared for patients with high/low-risk predictions from the two models, and concordance indices (c-indices) for the prediction of RP were calculated. Results. The reference dose- response relationship for a patient without pulmonary co-morbidities, caudally located tumor, no history of smoking, < 63 years old, and receiving no sequential chemotherapy was estimated as D500 = 34.4 Gy (95% CI 30.7, 38.9), γ500 = 1.19 (95% CI 1.00, 1.43). Individual patient risk estimates were calculated. The cumulative incidences of RP in the validation dataset were not significantly different in high/low-risk patients when doing risk allocation with the QUANTEC model (p = 0.11), but were significantly different using the individualized model (p = 0.006). C-indices were significantly different between the dose-only and the individualized model. Conclusion. This study presents a method to combine a published dose-response function with known clinical risk factors and demonstrates the increased predictive power of the combined model. The method allows for individualization of dose constraints and individual patient risk estimates. [ABSTRACT FROM AUTHOR]

The article discusses diseases, including osteoarthritis, lunate malacia and inflammatory arthritis, for which total wrist arthroplasty is used and discusses the different types of wrist arthroplasty, including Volz wrist arthroplasty, the meuli wrist arthroplasty system and trispherical wrist arthroplasty, which are available to orthopaedic professionals. A discussion of research which investigated several papers concerned with wrist arthroplasty, including "Promising 1-6 Years Results With the Motec Wrist Arthroplasty in SN AC and SL AC patients" by O. Reigstad, T.Lütken, C. Grimsgaard et al., "New Concept for Total Wrist Replacement" by A. Reigstad, O. Reigstad, C. Grimsgaard et al. and "Improved Bone Ingrowth and Fixation With a Thin Calcium Phosphate Coating Intended for Complete Resorption" by O. Reigstad, V. Franke-Stenport, C. Johansson et al, is presented.

Purpose. To study if partnership modifies the effect of gastrointestinal symptoms on quality of life after radiation therapy for prostate cancer. Material and methods. Using a study-specific questionnaire we conducted a cross-sectional follow-up of the occurrence gastrointestinal symptoms and quality of life after radiation therapy for prostate cancer. We obtained information from 874 prostate cancer survivors treated with radiation therapy at the Sahlgrenska University Hospital, Sweden between 1994 and 2006. In this paper we describe how partnership status affects the association between gastrointestinal symptoms and quality of life. Results. We found that unpartnered men with gastrointestinal symptoms reported a lower quality of life than unpartnered men without such symptoms. Unpartnered men with symptoms had an excess risk of low quality of life compared with unpartnered men without symptoms for those experiencing altered composition of stools, prevalence ratio 3.8 (95% CI 1.1-13.1), leakage, 3.6 (1.3-10.1), sensory bowel symptoms, 4.5 (1.6-12.8), and for urgency, 4.2 (1.2-15.1). We also found that unpartnered men with symptoms had an excess risk of low quality of life compared with partnered men with symptoms for those experiencing altered composition of stools, prevalence ratio 2.9 (95% CI 1.4-5.8), leakage 2.8 (1.2-6.4), sensory bowel symptoms 3.4 (1.5-7.4), urgency 2.6 (1.2-5.8), and for any gastrointestinal symptom 2.5 (1.3-4.9). Conclusion. Unpartnered men may represent a group that is specifically vulnerable to the distressful effects of gastrointestinal symptoms after radiation therapy for prostate cancer. [ABSTRACT FROM AUTHOR]

Background. Survival from breast cancer (BC) in Estonia has been consistently among the lowest in Europe. The aim of this study was to examine most recent trends in BC survival in Estonia by age and stage. The trends in overall BC incidence and mortality are also shown in the paper. Material and methods. Estonian Cancer Registry data on all cases of BC, diagnosed in women in Estonia during 1995-2007 (n = 7424) and followed up for vital status through 2009, were used to estimate relative survival ratios (RSR). Period hybrid approach was used to obtain the most recent estimates (2005-2009). Stage was classified as localized, local/regional spread or distant. Results. BC incidence continued to rise throughout the study period, but mortality has been in steady decline since 2000. The distribution of patients shifted towards older age and earlier stage at diagnosis. Overall age-standardized five-year RSR increased from 63% in 1995-1999 to 74% in 2005-2009. Younger age groups experienced a more rapid improvement compared to women over 60. Significant survival increase was observed for both localized and locally/regionally spread BC with five-year RSRs reaching 96% and 70% in 2005-2009, respectively; the latest five-year RSR for distant BC was 11%. Survival for T4 tumors was poor and large age difference was seen for locally/regionally spread BC. Conclusions. Considerable improvement in BC survival was observed over the study period. Women under 60 benefited most from both earlier diagnosis and treatment advances of locally/regionally spread cancers. However, the survival gap with more developed countries persists. Further increase in survival, but also decline in BC mortality in Estonia could be achieved by facilitating early diagnosis in all age groups, but particularly among women over 60. Investigations should continue to clarify the underlying mechanisms of the stage-specific survival deficit in Estonia. [ABSTRACT FROM AUTHOR]

The article reports on research which was conducted as part of a higher educational thesis and investigated the epidemiology, radiology and histology of atypical femoral fractures which were linked to the use of drugs called bisphosphonates. In the article the author offers his opinions on the use of bisphosphonates and on the need for additional research on the treatment of atypical femoral fractures.

Background Numerous papers have been published on the medium- and long-term results of hemiarthroplasties (HAs) after femoral neck fracture in the elderly. We were not aware of any articles that describe the outcome of HA until the patient dies. Methods Between 1975 and 1989, 307 bipolar hemiarthroplasties were performed in 302 consecutive patients with a displaced femoral neck facture. Patients with osteoarthritis of the hip, rheumatoid arthritis (RA), or senile dementia were not included in the study. All patients were followed annually until they died or until they needed a revision operation. Results The mortality rate was 28% after 1 year, and 63% after 5 years. The last patient who did not need a revision operation died in October 2010. Revision operations for aseptic loosening, protrusion, or both had to be performed in 34 patients (16%). A difference in reoperation rate was observed between patients less than 75 years of age (38%) and those who were older (6%). Interpretation Apart from age below 75 years, male sex appeared to be predictive of a revision operation. HA is a safe and relatively inexpensive treatment for patients over 75 years of age with a displaced femoral neck fracture. [ABSTRACT FROM AUTHOR]

Background. Two conceptually different morbidity outcomes unmet needs and health-related quality of life are used to identify cancer patients in need of clinical attention and to evaluate rehabilitation programmes. The knowledge on the interrelation between unmet needs and health-related quality of life is scarce. This paper studies the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. Material and methods. Based on registers, a Danish population-based cohort of adult, incident, mixed-site cancer patients diagnosed between 1 October 2007 and 30 September 2008 was established. At 14 months following diagnosis participants completed a questionnaire including health-related quality of life (EORTC QLQ C-30), psychological distress (POMS-SF), and unmet needs with regard to physical, emotional, family-oriented, sexual, work-related, and financial problems. Unmet needs were assessed through six ad hoc questions. Results. Questionnaires were received from 3439 of 4947 patients, resulting in a response rate of 70%. The three most frequent cancer types were breast (28.4%), prostate (14.6%) and colorectal cancer (15.2%). Overall, 60.1% expressed an unmet need of rehabilitation in at least one area, physical and emotional problems being the most frequent (40.0% and 37.5%). For all scales of the EORTC QLQ C-30 and POMS, significant adjusted mean differences were observed between patients with unmet needs in at least one area and patients with no unmet needs (p-values < 0.001). These differences were well above levels usually considered clinically relevant. Further, impairment increased with increasing number of areas in which unmet needs were reported. Discussion. We confirmed the hypothesis that patient-perceived unmet needs of rehabilitation during the cancer trajectory are associated with decreased quality of life. This study supports the use of unmet needs questions to identify patients in need of clinical attention. Interventions reducing cancer patients' perceived needs of rehabilitation may enhance quality of life. [ABSTRACT FROM AUTHOR]

Background and purpose The properties and performance of a new low-monomer cement were examined in this prospective randomized, controlled RSA study. 5-year data have already been published, showing no statistically significant differences compared to controls. In the present paper we present the 10-year results. Methods 44 patients were originally randomized to receive total hip replacement with a Lubinus SPII titanium-aluminum-vanadium stem cemented either with the new Cemex Rx bone cement or with control bone cement, Palacos R. Patients were examined using RSA, Harris hip score, and conventional radiographs. Results At 10 years, 33 hips could be evaluated clinically and 30 hips could be evaluated with RSA (16 Cemex and 14 Palacos). 9 patients had died and 4 patients were too old or infirm to be investigated. Except for 1 hip that was revised for infection after less than 5 years, no further hips were revised before the 10-year follow-up. There were no statistically significant clinical differences between the groups. The Cemex cement had magnitudes of migration similar to or sometimes lower than those of Palacos cement. In both groups, most hips showed extensive radiolucent lines, probably due to the use of titanium alloy stems. Interpretation At 10 years, the Cemex bone cement tested performed just as well as the control (Palacos bone cement). [ABSTRACT FROM AUTHOR]

Background and purpose In January 2008, we established the Norwegian Register for Shoulder Instability Surgery. We report on the establishment, the baseline data, and the results at 1-year follow-up. Methods Primary and revision shoulder stabilization is reported by the surgeon on a 1-page paper form containing the patient's history of shoulder injury, clinical findings, and perioperative findings. The WOSI questionnaire for self-assessment of shoulder function is completed at baseline and at follow-up after 1, 2, and 5 years. To evaluate the completeness of registration, we compared our data with those in the Norwegian Patient Registry (NPR). Results The NPR reported 39 hospitals performing shoulder stabilizations. 20 of these started to report to our register during 2009, and 464 procedures (404 primary, 59 revisions) were included up to December 31, 2009, which represented 54% of the procedures reported to NPR. Of the 404 primary procedures, 83% were operations due to anterior instability, 10% were operations due to posterior instability, and 7% were operations due to multidirectional instability. Arthroscopic soft tissue techniques were used in 88% of the patients treated for primary anterior instability and open coracoid transfer was used in 10% of such patients. At 1-year follow-up of 213 patients, we found a statistically significantly improved WOSI score in all types of instability. 10% of the patients treated with arthroscopic anterior labral repair and 16% treated with arthroscopic posterior labral repair reported recurrent instability. No statistically significant difference in functional improvement or rate of recurrence was found between these groups. Interpretation The functional results are in accordance with those in previous studies. However, the incidence of recurrent instability 1 year after arthroscopic labral repair is higher than expected. [ABSTRACT FROM AUTHOR]

Background and purpose Modular cementless revision prostheses are being used with increasing frequency. In this paper, we review risk factors for the outcome of the Link MP stem and report implant survival compared to conventional cemented long-stem hip revision arthroplasties. Patients and methods We used data recorded in the Swedish Hip Arthroplasty Register. 812 consecutive revisions with the MP stem (mean follow-up time 3.4 years) and a control group with 1,073 cemented long stems (mean follow-up time 4.2 years) were included. Kaplan-Meier analysis was used to determine implant survival. The Cox regression model was used to study risk factors for reoperation and revision. Results The mean age at revision surgery for the MP stem was 72 (SD 11) years. Decreasing age (HR == 1.1, 95% CI: 1--1.1), multiple previous revisions (HR == 2.6, 95% CI: 1.1--6.2), short stem length (HR == 2.4, 95% CI: 1.1--5.2), standard neck offset (HR == 5, 95% CI: 1.5--17) and short head-neck length (HR == 5.3, 95% CI 1.4--21) were risk factors for reoperation. There was an overall increased risk of reoperation (HR == 1.7, 95% CI: 1.3--2.4) and revision (HR == 1.9, 95% CI: 1.2--3.1) for the MP prostheses compared to the controls. Interpretation The cumulative survival with both reoperation and revision as the endpoint was better for the cemented stems with up to 3 years of follow-up. Thereafter, the survival curves converged, mainly because of increasing incidence of revision due to loosening in the cemented group. We recommend the use of cemented long stems in patients with limited bone loss and in older patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature. Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration. In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p < 0.001. This association corresponded to an absolute risk difference of 14%. 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it. [ABSTRACT FROM AUTHOR]

Bowel dysfunction after colon cancer (CC) surgery is widely neglected in current follow up programmes. This study explored changes in bowel function and quality of life (QoL) from three (3 m) to twelve months (12 m) after surgery in CC patients undergoing right- or left-sided colon resection (RightSCR/LeftSCR) and investigated differences between the two groups 12 m after surgery. CC patients undergoing surgical resection in 2018–2020 at five surgical departments were included in this population-based prospective cohort study. Included patients completed electronic surveys consisting of a collection of validated scores 3 m and 12 m after surgery. A total of 708 CC patients (423 RightSCR, 285 LeftSCR) were included. In RightSCR, no improvement was observed from 3 m to 12 m in most scores/items, on the contrary, symptom worsening in flatus- and faecal incontinence and urgency was observed (p < 0.05). Also, the proportion of patients rating their bowel function as very good/good decreased (p < 0.05) in this group. In LeftSCR improvement was found in flatus and faecal incontinence, urgency and night-time defaecation (p < 0.02), while no improvement was observed in the remaining scores/items. At 12 m, higher proportions of RightSCR than LeftSCR reported loose stools, incontinence and urgency (all p < 0.001), whereas LeftSCR more often reported hard stools and flatus incontinence (p < 0.05). Among all CC patients 18.3% reported bowel-related impairment of QoL at 12 m with no differences between the two groups. From 3 m to 12 m no significant change was observed in the majority of bowel function and QoL scores/items, however, some symptoms worsened in RightSCR, while a few improved in LeftSCR. Bowel dysfunction and impaired QoL were still common in both groups at 12 m, although the symptom pattern differed between the groups. These findings call for a systematic screening for bowel dysfunction to ensure early treatment of symptoms. [ABSTRACT FROM AUTHOR]

Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan–Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. Median time of follow-up (FU) was 48.7 months (IQR 37.2–54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5–45.0) compared to 11.4 months (IQR 4.6–27.1) in ≥2nd line (HR 1.48, 95% CI 1.25–1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22–0.43) compared to 5% (95% CI 0.01–0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates. [ABSTRACT FROM AUTHOR]

Given the scarcity of evidence concerning the long-term sexual health of breast cancer (BC) survivors (BC-Pop), we aimed to assess how BC treatments affect short- and long-term sexual functioning, sexual enjoyment, and body image, and compare with aged-matched women in the Norwegian general population (F-GenPop). The 349 patients in BC-Pop treated at Trondheim University Hospital in 2007–2014, were assessed in clinical controls at the hospital; before starting radiotherapy (T1, baseline), immediately after ending radiotherapy (T2), and after 3, 6, and 12 months (T3–T5), and at a long-term follow-up 7–12 years after baseline (T6). Meanwhile, F-GenPop included 2254 age-matched women in the Norwegian general population. The impact of BC treatment on sexual functioning was examined using a Linear Mixed Model. Sexual functioning, sexual enjoyment, and body image were assessed with the EORTC′s QLQ-BR23 scales and compared between the populations in the four age groups (30–49, 50–59, 60–69, and 70+ years) using means with 95% confidence intervals and Student t-test. Linear regression, adjusted for age and comorbidity was applied to estimate individual scores. BC survivors treated with mastectomy had overall lower sexual functioning than patients who had received breast-conserving surgery (p = 0.017). Although BC survivors treated with chemotherapy had lower sexual functioning than those treated without chemotherapy at T1–T5 (p = 0.044), both groups showed the same level of functioning at T6. BC-Pop exhibited significantly poorer sexual functioning (p < 0.001), lower sexual enjoyment (p < 0.05), and better body image (p < 0.001) than F-GenPop in all age groups. The impact of specific BC treatments on sexual functioning was modest; only mastectomy had a persistent negative influence. Nevertheless, all age groups in BC-Pop displayed significantly poorer sexual functioning than F-GenPop at both 12 months and up to 12 years after treatment. [ABSTRACT FROM AUTHOR]

Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort. [ABSTRACT FROM AUTHOR]

Background and purpose-Immediate postoperative pain management offered in knee arthroplasty is suboptimal in up to one-third of patients resulting in high opiate consumption and delayed discharge. In this meta-analysis we investigate the analgesic effect and safety of perioperative adjuvant corticosteroids in knee arthroplasty. Methods-Databases Medline, Embase, and Central were searched for randomized studies comparing the analgesic effect of adjuvant perioperative corticosteroids in knee arthroplasty. Our primary outcome was pain score at 24 hours postoperatively. Secondary outcomes included pain at 12, 48, and 72 hours, opiate consumption, postoperative nausea and vomiting, infection, and discharge time. Systemic (intravenous) and local (intra-articular) corticosteroids were analyzed separately. Results-14 randomized controlled trials (1,396 knees) were included. Mean corticosteroid dosages were predominantly 50-75mg oral prednisolone equivalents for both systemic and local routes. Systemic corticosteroids demonstrated statistically significant and clinically modest reductions in pain at 12 hours by -1.1 points (95%CI -2.2 to 0.02), 24 hours by -1.3 points (CI -2.3 to -0.26) and 48 hours by -0.4 points (CI -0.67 to -0.04). Local corticosteroids did not reduce pain. Opiate consumption, postoperative nausea and vomiting, infection, or time till discharge were similar between groups. Interpretation-Corticosteroids modestly reduce pain postoperatively at 12 and 24 hours when used systemically without any increase in associated risks for dosages between 50 and 75 mg oral prednisolone equivalents. [ABSTRACT FROM AUTHOR]

The article focuses on assessing severe pneumococcal disease risks in splenectomized Hodgkin lymphoma patients from 1973 to 1995 in Sweden. Topics include the historical context of splenectomy, varying prophylactic measures in different countries, and the decreasing incidence of severe pneumococcal infections in more recent decades among splenectomized patients in Sweden.

The purpose was to investigate the treatment flow of patients with HER2-positive metastatic breast cancer (mBC), progression-free survival (PFS) and overall survival (OS) across treatment lines and adherence to guidelines (defined as trastuzumab, pertuzumab and chemotherapy first line, where 85% received vinorelbine as backbone and T-DM1 second line). Furthermore, we identified clinical markers to predict the risk of developing brain metastases. Patients with HER2-positive mBC, diagnosed between 01.01.2014–31.12.2019, registered in the database of the Danish Breast Cancer Group were included in this real-word study. Clinical follow-up was assessed until 01.10.2020 and complete follow-up for overall survival until 01.10.2021. Survival data were analyzed using the Kaplan-Meier method with guidelines adherence analyzed as a time-varying covariate, and the risk of CNS metastasis was estimated by the cumulative incidence function. 631 patients were included. 329 (52%) patients followed the guidelines. The median OS for all patients was 42.3 months (95% Cl, 38.2–48.4), and significantly higher for the patients who followed guidelines; NA (95% CI, 78.2–NA). The median PFS for all patients was 13.4 months (95% Cl, 12.1–14.8), 6.6 (95% Cl, 5.8–7.6) and 5.8 (95% Cl, 4.9–6.9) for first, second and third line of treatment, respectively. Patients with ER-negative mBC had a higher risk of developing brain metastases and patients with high tumor burden had a higher risk of developing brain metastases with an adjusted HR of 0.69 (95% CI, 0.49–0.98), p = 0.047 and 2.69 (95% CI, 1.45–5.00), p = 0.002, respectively. We found that only half of the patients with HER2-positive mBC, received first and second-line treatment according to national guidelines. Patients receiving treatment according to guidelines had a significantly higher median OS compared to patients who did not. We also found that patients with ER-negative disease or high tumor burden had a significantly higher risk of developing brain metastases. [ABSTRACT FROM AUTHOR]

Fear of cancer recurrence (FCR) in breast cancer survivors (BCSs) is common, associated with reduced quality of life and effective interventions exist. There are knowledge gaps concerning FCR among long-term, early-stage BCSs and its associations with other late effects. Within a national cohort, we explored these knowledge gaps, with the ultimate aim of improved care for BCSs experiencing long-term FCR. In this cross-sectional study, all BCSs aged 20–65 years with early-stage breast cancer in 2011–2012 (n = 2803), were identified by the Cancer Registry of Norway in 2019 and mailed a survey including the Assessment of Survivor Concerns used to measure FCR. Factors associated with moderate/high FCR (defined as a sum score of ≥ 6 of a possible range 3–12, or a single score on one of the items of ≥ 3) were explored using a three-block regression analyses including relevant sociodemographic-, health- and cancer-related variables. In total, 1311 BCSs were included (47%). Median age at survey was 60 years. Fifty-six % reported moderate-to-high FCR, associated with younger age (OR 0.96, 95% CI 0.95–0.97) and receiving chemo- and endocrine therapy (OR 1.59, 95% CI 1.15–2.20). After adding late effects into the model, FCR remained significantly associated with these variables, in addition to sleep disturbances (OR 1.58, 95% CI 1.18–2.10). In the final block, adding mental distress, FCR remained significantly associated with younger age (OR 0.97, 95% CI 0.96–0.99), receiving chemo- and endocrine therapy (OR 1.14, 95% CI 1.00–1.97), sleep disturbances (OR 1.44, 95% CI 1.08–1.94) and anxiety (OR 2.67, 95% CI 1.38–5.19). FCR was prevalent eight years after early-stage breast cancer. Being younger, receiving intensive treatment, experiencing sleep disturbances and/or anxiety were associated with moderate/high FCR. Addressing FCR should be part of standard follow-up care of long-term BCSs. [ABSTRACT FROM AUTHOR]

We hypothesised that the use of the anti-androgenic drug 5α-reductase inhibitors (5-ARIs) improves survival in patients with oesophago-gastric cancer. This nationwide Swedish population-based cohort study included men who underwent surgery for oesophageal or gastric cancer between 2006-2015, with follow-up until the end of 2020. Multivariable Cox regression estimated hazard ratios (HR) for associations between 5-ARIs use and 5-year all-cause mortality (main outcome) and 5-year disease-specific mortality (secondary outcome). The HR was adjusted for age, comorbidity, education, calendar year, neoadjuvant chemo(radio)therapy, tumour stage, and resection margin status. Among 1769 patients with oesophago-gastric cancer, 64 (3.6%) were users of 5-ARIs. Compared to non-users, users of 5-ARIs were not at any decreased risk of 5-year all-cause mortality (adjusted HR 1.13, 95% CI 0.79-1.63) or 5-year disease-specific mortality (adjusted HR 1.10, 95% CI 0.79-1.52). Use of 5-ARIs was not associated with any decreased risk of 5-year all-cause mortality in subgroup analyses stratified by categories of age, comorbidity, tumour stage, or tumour subtype (oesophageal or cardia adenocarcinoma, non-cardia gastric adenocarcinoma, or oesophageal squamous cell carcinoma). This study did not support the hypothesis of improved survival among users of 5-ARIs after curatively intended treatment for oesophago-gastric cancer. [ABSTRACT FROM AUTHOR]

To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time. [ABSTRACT FROM AUTHOR]

Insulin resistance is a critical cause of metabolic dysfunctions. Metabolic dysfunction is common in patients with cancer and is associated with higher cancer recurrence rates and reduced overall survival. Yet, insulin resistance is rarely considered in the clinic and thus it is uncertain how frequently this condition occurs in patients with cancer. To address this knowledge gap, we performed a systematic review and a meta-analysis guided by the Preferred Items for Systematic Review and Meta-Analyses (PRISMA) statement. We included studies assessing insulin resistance in patients with various cancer diagnoses, using the gold-standard hyperinsulinemic–euglycemic clamp method. Studies eligible for inclusion were as follows: (1) included cancer patients older than 18 years of age; (2) included an age-matched control group consisting of individuals without cancer or other types of neoplasms; (3) measured insulin sensitivity using the hyperinsulinemic–euglycemic clamp method. We searched the databases MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published from database inception through March 2023 with no language restriction, supplemented by backward and forward citation searching. Bias was assessed using funnel plot. Fifteen studies satisfied the criteria. The mean insulin-stimulated rate of glucose disposal (Rd) was 7.5 mg/kg/min in control subjects (n = 154), and 4.7 mg/kg/min in patients with a cancer diagnosis (n = 187). Thus, the Rd mean difference was −2.61 mg/kg/min [95% confidence interval, −3.04; −2.19], p<.01). Heterogeneity among the included studies was insignificant (p=.24). These findings suggest that patients with a cancer diagnosis are markedly insulin resistant. As metabolic dysfunction in patients with cancer associates with increased recurrence and reduced overall survival, future studies should address if ameliorating insulin resistance in this population can improve these outcomes thereby improving patient care. Metabolic dysfunction increases cancer recurrence rates and reduces survival for patients with cancer. Insulin resistance is a critical cause of metabolic dysfunctions. To date, no comprehensive compilation of research investigating insulin resistance in cancer patients has been produced. In this meta-analysis, we found that patients with various cancers were markedly insulin-resistant. [ABSTRACT FROM AUTHOR]

Background and purpose -- Robotic-assisted total knee arthroplasty (RATKA) is an alternative surgical treatment method to conventional total knee arthroplasty (COTKA) that may deliver better surgical accuracy. However, its impact on patient outcomes is uncertain. The aim of this systematic review of randomized controlled trials (RCTs) is to evaluate whether RATKA could improve functional and radiological outcomes compared with COTKA in adult patients with primary osteoarthritis of the knee. Methods -- We searched Ovid MEDLINE, EMBASE, Scopus, and the Cochrane Library to identify published RCTs comparing RATKA with COTKA. 2 reviewers independently screened eligible studies, reviewed the full texts, assessed risk of bias using the Risk of Bias 2.0 tool, and extracted data. Outcomes were patient-reported outcomes, range of motion, and mechanical alignment (MA) deviation and outliers, and complications. Results -- We included 12 RCTs involving 2,200 patients. RATKA probably results in little to no effect on patient-reported outcomes (mean difference (MD) in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score of -0.35 (95% confidence interval [CI] -0.78 to 0.07) and range of motion (MD -0.73°; CI -7.5° to 6.0°) compared with COTKA. However, RATKA likely results in a lower degree of MA outliers (risk ratio 0.43; CI 0.27 to 0.67) and less deviation from neutral MA (MD -0.94°; CI -1.1° to -0.73°). There were no differences in revision rate or major adverse effects associated with RATKA. Conclusion -- Although RATKA likely results in higher radiologic accuracy than COTKA, this may not be clinically meaningful. Also, there is probably no clinically important difference in clinical outcomes between RATKA and COTKA, while it is as yet inconclusive regarding the revision and complication rates due to insufficient evidence. [ABSTRACT FROM AUTHOR]

Background and purpose -- We conducted a systematic review and meta-analysis of RSA studies to investigate the early and long-term migration patterns of acetabular cups and the influence of implant factors on cup migration over time. Methods -- We performed a systematic search of PubMed, Embase, and Scopus databases to identify all RSA studies of cup migration following primary total hip replacement (THR). Proximal migration at 3 and 6 months, 1, 2, 5, and 10 years were considered for analysis. Implant factors investigated included fixation type, head size, bearing surface, uncemented coating design, and the decade of RSA introduction. Results -- 47 studies reported the proximal migration of 83 cohorts (2,328 cups). Besides 1 threaded cup design, no implant factor investigated was found to significantly influence proximal migration. The mean pooled 2-year proximal migration of cemented cups (0.14 mm, 95% confidence interval [CI] 0.08-0.20) was not significantly different from uncemented cups (0.12 mm, CI 0.04-0.19). The mean pooled proximal migration at 6 months was 0.11 mm (CI 0.06-0.16) and there was no significant increase between 6 months and 2 years (0.015 mm, CI 0.000-0.030). 27 of 75 cohorts (36%) reported mean proximal migration greater than 0.2 mm at 2 years, which has previously been identified as a predictor of implants at risk of long-term loosening. Conclusion -- Our meta-analysis demonstrated that the majority of cup migration occurs within the first 6 months. With one exception, no implant factors influenced the 2-year proximal migration of acetabular cups. 36% of studies with 2-year migration were considered at risk of long-term loosening. Further investigation and comparison against longterm survivorship data would validate 6-month and/or 1-year proximal migration measurements as an earlier predictor of long-term loosening than the current 2-year threshold. [ABSTRACT FROM AUTHOR]

Background and purpose -- Radiostereometric analysis (RSA) is the gold standard for evaluation of migration of implants. CT-RSA has been shown to have precision at the level of RSA in hip, shoulder, and knee joint replacements. We aimed to assess the impact of dose reduction on precision of CT-RSA on tibial implants, comparing it with previously published data on precision of standard dose CT-RSA on tibial implants. Material and methods -- We performed a total knee arthroplasty on a porcine knee cadaver, and subsequent CT-RSA with low effective doses (0.02 mSv). We compared the results with previously published CT-RSA data with standard (0.08 mSv) dose. The primary outcome variable was the difference in precision of the maximum total translation (MTT). Secondary variables included ratios of variances and standard deviations, and precision of peripheral point translations, center-of-mass translations, and rotations. A difference of more than 0.1 mm in precision was defined as clinically relevant. Our hypothesis was that precisions of low and standard CT-RSA doses were equal. Results -- Low dose (mean 0.07, 95% confidence interval [CI] 0.06-0.08) and standard dose CT-RSA (0.08, CI 0.07-0.09) achieve similar precision, with difference in precision of MTT of 0.01, CI 0.00-0.02 mm. The F-statistic (0.99, CI 0.63-1.55) and sdtest (1.05, CI 0.43-2.58) also supported this. Conclusion -- We conclude that the precision of low dose CT-RSA for tibial implants on a porcine cadaver is equal to standard dose CT-RSA. However, these findings should be confirmed in clinical trials. [ABSTRACT FROM AUTHOR]

Background and purpose -- Despite usage of the ATTUNE total knee arthroplasty (TKA) for about 10 years, few randomized trials exist. We evaluated whether the ATTUNE CR design showed improved clinical results compared with the PFC Sigma CR after 2 years and if there was a difference in tibial component migration. Patients and methods -- 96 patients with knee osteoarthritis were randomly treated with cemented ATTUNE or PFC Sigma TKA. 42 patients with the ATTUNE and 48 with the PFC Sigma attended the 2-year follow-up. Patient-reported outcome measurements (PROMs), migration measured with RSA, implant position, and the development of radiolucent zones were studied. Non-parametric tests and repeated measures analysis were used at the statistical evaluation. Results -- The Oxford Knee Score (OKS) at 2 years (primary outcome) and neither of the secondary PROM outcomes differed between the groups (mean difference OKS ATTUNE - PFC: -0.08, 95% confidence interval [CI] -2.9 to 2.7). RSA showed posterior tilt of the tibial component in the ATTUNE group with proximal lift-off anteriorly and subsidence of the tibial tray posteriorly. In contrast, the PFC Sigma tibial component tilted forward (mean difference ATTUNE - PFC: -0.7°, CI -1.1° to -0.4°) with maximum subsidence in the front and maximum lift-off of the posterior edge. The postoperative implant positions and the extension of radiolucent lines around the tibial component at 2 years did not differ. Conclusion -- We found no significant differences in clinical outcome between the 2 groups but minor differences in migration pattern of the tibial component. The clinical long-term significance of this finding if any is not known. [ABSTRACT FROM AUTHOR]

Background and purpose -- The direct superior approach (DSA) is a modification of the posterolateral approach (PLA) for total hip arthroplasty (THA). Patient-reported outcome measures (PROMs) of the DSA have not been investigated previously using nationwide data. Our aim was to assess PROMs after THA using the DSA compared with the PLA and, secondarily, with the anterior approach (DAA). Patients and methods -- In this population-based cohort study we included 37,976 primary THAs performed between 2014 and 2020 (PLA: n = 22,616; DAA: n = 15,017; DSA: n = 343) using Dutch Arthroplasty Registry data. PROMs (NRS pain, EQ-5D, HOOS-PS, and OHS) were measured preoperatively, and at 3 and 12 months postoperatively. Repeated measurements were analyzed using mixed-effects models, adjusted for confounders, to investigate the association between surgical approach and PROMs over time. Results -- From baseline to 3 and 12 months, improvements for NRS pain scores, EQ-5D, and OHS were comparable for the DSA compared with the PLA or DAA. No difference was found in HOOS-PS improvement 3 months postoperatively between DSA and PLA (-0.2, 95% confidence interval [CI] -2.4 to 1.9) and between DSA and DAA (-1.7, CI -3.9 to 0.5). At 12 months postoperatively, patients in the DSA group had improved -2.8 points (CI -4.9 to -0.6) more in HOOS-PS compared with the DAA, but not with the PLA group (-1.0, CI -3.2 to 1.1). Conclusion -- Our study showed no clinically meaningful differences between the DSA and either PLA or DAA. [ABSTRACT FROM AUTHOR]

Background and purpose -- Surgery for bone metastases in the appendicular skeleton (aBM) is a trade-off between limb function and survival. A previous study from a highly specialized center found that extended surgery is not a risk for 30-day mortality and hypothesized that wide resection and reconstruction might reduce postoperative mortality. The study aimed to investigate whether parameters describing the surgical trauma (blood loss, duration of surgery, and degree of bone resection) pose a risk for 30-day mortality in patients treated with endoprostheses (EPR) or internal fixation (IF) in a population-based cohort. Patients and methods -- A population-based cohort having EPR/IF for aBM in the Capital Region of Denmark 2014-2019 was retrospectively assessed. Intraoperative variables and patient demographics were evaluated for association with 30-day mortality by logistic regression analysis. Kaplan-Meier estimate was used to evaluate survival with no loss to follow-up. Results -- 437 patients had aBM surgery with EPR/IF. No parameters describing the magnitude of the surgical trauma (blood loss/duration of surgery/degree of bone resection) were associated with mortality. Overall 30-day survival was 85% (95% confidence interval [CI] 81-88). Univariate analysis identified ASA group 3+4, Karnofsky score < 70, fast-growth primary cancer, and visceral and multiple bone metastases as risk factors for 30-day mortality. Male sex (OR 2.8, CI 1.3-6.3), Karnofsky score < 70 (OR 4.2, CI 2.1-8.6), and multiple bone metastases (OR 3.4, CI 1.2-9.9) were independent prognostic factors for 30-day-mortality in multivariate analysis. Conclusion -- The parameters describing the surgical trauma were not associated with 30-day mortality but, instead, general health status and extent of primary cancer influenced survival post-surgery. [ABSTRACT FROM AUTHOR]

Background and purpose -- In patients around retirement age controversy exists as to whether to treat displaced femoral neck fracture (dFNF) with internal fixation (IF) or arthroplasty. An arthroplasty in this age group may need revision due to a long expected remaining lifetime. IF carries a higher risk of early failure but a maintained native hip if healing occurs. We aimed to determine the cumulative 5-year rate of conversion to arthroplasty after IF and implant revision after primary total hip arthroplasty (THA), respectively. Patients and methods -- In this longitudinal cohort study, patients aged 60-69 years registered with a dFNF in the Swedish Fracture Register (SFR) 2012-2018 were cross-referenced with available data from the Swedish Arthroplasty Register (SAR) until December 31, 2019. Conversion to arthroplasty or revision were analyzed utilizing competing risk, with death as competing event. Results -- At 5 years, the cumulative rate of conversion to arthroplasty after IF was 31% (95% confidence interval [CI] 26-37). For primary THA, the 5-year rate of revision was 4.0% (CI 2.8-5.8). The 5-year mortality did not differ, being 20% (CI 16-27) and 23% (CI 20-28) after IF and THA, respectively. Regression analyses did not identify any risk factors for conversion arthroplasty based on the variables in the register. Conclusion -- A follow-up of 5 years catches most reoperations after IF, resulting in a 31% conversion rate. The 4% revision rate at 5 years after primary THA should be seen as an intermediate result, as late complications may occur. [ABSTRACT FROM AUTHOR]