Distal radius fractures:epidemiology, seasonal variation and results of palmar plate fixation

Abstract Distal radius fractures (DRFs) are the most commonly encountered fall-related fracture in clinical practice. Recognised as a typical fragility fractures, the ageing of the population may increase the occurrence of DRFs in the near future. The aims of this thesis were (I) to describe the epidemiology of DRFs in a cohort of adult patients in the city of Oulu during the year 2008 and to study changes in the incidence of DRFs during the last decades in Finland and other northern countries and the relationship between slippery conditions during the winter and the incidence of DRFs, (II) to compare the results of primary nonoperative treatment and early palmar plating of primarily dislocated DRFs in 80 patients ≥ 50 years old in an randomised controlled study and (III) to investigate the rate and risk factors for plate-related complications after palmar plate fixation of 881 DRFs. The crude incidence rate of DRFs was 258/100 000 person-years in Oulu in 2008, and the age-specific incidence rate in the female population aged ≥ 70 years was increased compared to previous studies in Finland and in Norway. A clear seasonal variation was observed in fall-related DRFs. The number of DRFs was 2.5 times higher on slippery winter days compared to non-winter days. Early palmar plating of DRFs showed favourable DASH (disabilities of the arm, shoulder and hand) scores at two years compared to primary nonoperative treatment. Delayed surgery in the primary nonoperative treatment group did not provide comparable DASH scores to early plating. The overall complication rate in the cohort of 881 plate-fixated DRFs was 15%. These could be regarded as plate-related in 7% of cases. Operations performed by low-volume surgeons and patient ages < 40 years were independent predictors of plate-related complications. In conclusion, the incidence of DRFs has increased during the last decades in Finland in elderly females, and slippery winter conditions increase the risk of DRFs. Early palmar plating of DRFs produces more consistent results compared to primary nonoperative treatment in patients ≥ 50 years old. The complication rate after palmar plating of DRFs is significantly influenced by surgeon experience and patient age.Tiivistelmä Värttinäluun alaosan murtuma (rannemurtuma) on yleisin kaatumistapaturman aiheuttama luunmurtuma, jonka taustalla on monesti ikääntymisestä johtuva luun hauraus. Väestön edelleen ikääntyessä rannemurtumien ilmaantuvuus todennäköisesti lisääntyy. Tämän väitöskirjan tavoitteina oli (1) kuvata rannemurtumien epidemiologiaa ja ilmaantuvuuden muutosta Suomessa ja muissa Pohjoismaissa viimeisten vuosikymmenien aikana, sekä tutkia liukkaiden talvikelien yhteyttä rannemurtumien ilmaantuvuuteen. Lisäksi tavoitteena oli (2) verrata kahden eri hoitokäytännön — varhaisen levykiinnityksen ja ensisijaisen konservatiivisen hoidon — kliinisiä tuloksia ≥ 50-vuotiailla rannemurtumapotilailla. Lopuksi tavoitteena oli (3) selvittää rannemurtuman levytykseen liittyvien komplikaatioiden yleisyys sekä riskitekijät. Rannemurtumien ilmaantuvuus oli oululaisessa aikuisväestössä 258/100 000 henkilövuotta vuonna 2008. Ikä-spesifinen ilmaantuvuus lisääntyi aiempaan suomalaistutkimukseen verrattuna etenkin > 70 vuotiailla naispotilailla ja sama suuntaus todettiin myös aiemmassa norjalaistutkimuksessa. Rannemurtumien ilmaantuvuudessa todettiin selkeä vuodenaikavaihtelu, ja liukkaalla talvikelillä rannemurtuman riski oli 2.5-kertainen verrattuna ei-talvikelin murtumariskiin. Varhaisella rannemurtuman levykiinnityksellä saavutettiin paremmat DASH (Disabilities of the Arm, Shoulder, and Hand) -pisteet kahden vuoden seurannassa verrattuna ensisijaiseen konservatiiviseen hoitoon. Murtuman asennon heikentyessä seurannassa ei myöhäisleikkauksella saavutettu kliinistä hyötyä ensisijaisessa konservatiivisen hoidon ryhmässä. Komplikaatioprosentti 881 levykiinnityksellä hoidetun rannemurtumapotilaan aineistossa oli 15 %. Levytyskomplikaatioita todettiin 7 %:lla potilaista. Itsenäisiä levytyskomplikaatioille altistavia riskitekijöitä olivat kirurgin vähäinen leikkauskokemus ja potilaan matala ikä (< 40 vuotta). Yhteenvetona voidaan todeta, että rannemurtumien ilmaantuvuus on lisääntynyt Suomessa iäkkäillä naispotilailla viimeisten vuosikymmenten aikana ja liukkaudella on selkeä yhteys rannemurtumien ilmaantuvuuteen. Varhaisella leikkaushoidolla saavutetaan yhtenäisemmät hoitotulokset verrattuna ensisijaiseen konservatiiviseen hoitoon ≥ 50-vuotialla rannemurtumapotilailla. Kirurgin leikkauskokemus ja potilaan ikä ovat yhteydessä rannemurtuman levytyskomplikaatioiden riskiin

Early palmar plate fixation of distal radius fractures may benefit patients aged 50 years or older:a randomized trial comparing 2 different treatment protocols

Abstract Background and purpose: There is no consensus regarding optimal treatment of displaced distal radius fractures (DRFs). We compared the results of 2 treatment protocols: early palmar plating vs. primary nonoperative treatment of displaced DRFs. Patients and methods: We performed a prospective randomized controlled study including 80 patients aged ≥ 50 years with dorsally displaced DRFs, excluding AO type C3 fractures. Patients were randomized to undergo either immediate surgery with palmar plating (n = 38), or initial nonoperative treatment (n = 42) after successful closed reduction in both groups. Delayed surgery was performed in nonoperatively treated patients showing early loss of alignment (n = 16). The primary outcome measure was Disabilities of the Arm, Shoulder, and Hand (DASH) score. Results: Mean DASH scores at 24 months in the early surgery group were 7.9 vs. 14 in the initial nonoperative group (difference between means 6, 95% CI 0.1–11, p = 0.05). Delayed operation was performed on 16/42 of patients due to secondary displacement in the initial nonoperative group. In “as treated” analysis, DASH scores were 7 in the early surgery group, 13 in the nonoperative group, and 17 after delayed surgery (p = 0.02). The difference in DASH scores between early and delayed surgery was 9 points (CI 0.3–19, p = 0.02). Interpretation: Treatment of DRFs with early palmar plating resulted in better 2-year functional outcomes for ≥50-year-old patients compared with a primary nonoperative treatment protocol. Delayed surgery in case of secondary displacement was not beneficial in terms of function

Long-term results of arthroscopic Bankart repair:minimum 10 years of follow-up

Abstract Purpose: This study investigated the long-term results of arthroscopic Bankart repair in terms of rates and timelines of recurrence of instability, with special interest in young adult patients aged ≤20 years. Methods: Between 2000 and 2005, 186 shoulders [182 patients, 50 women, median age 26 (range 15–58) years] were operated on at a university hospital using arthroscopic Bankart repair because of instability after traumatic anteroinferior shoulder dislocation. Medical records were retrospectively reviewed and patients were assessed using postal questionnaires or telephone interview after a minimum of 10 years of follow-up [median 12.2 (range 10–16) years]. The primary outcome measure was recurrence of instability (assessed from 167 shoulders), other outcome measures included Oxford instability score (OIS), subjective shoulder value (SSV), and Western Ontario instability index (WOSI) (assessed from 157 shoulders). Results: At the end of follow-up, 50/167 shoulders (30%) had recurrence of instability and 30/167 (18%) were subjected to reoperation due to instability symptoms. Twenty-six (52%) failures occurred within ≤2 years, 11 (22%) within 2–5 years, and 13 (26%) >5 years after surgery. Failure rate was 19/35 (54%) for patients aged ≤20 years and 31/132 (24%) for patients aged >20 years; reoperation rates were 11/35 (31%) and 19/132 (14%), respectively. Mean OIS was 20 (SD 9, range 12–50), SSV 83% (SD 21, range 10–100), and WOSI score 80 (SD 22, range 33–100). Conclusions: Nearly one-third of patients had recurrence of instability after arthroscopic Bankart repair after a minimum of 10-year follow-up. Patients aged ≤20 years did poorly with more than half of the patients having recurrence; alternative stabilization techniques should probably be considered for these patients. Level of evidence: IV

Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer

Abstract Recent studies have reported of an association between high serum apolipoprotein A1 (APOA1) levels and favorable prognosis in several malignancies, while the significance of apolipoprotein B (APOB) in cancer is less well-known. In this study, we analyzed the correlation between serum APOA1 and APOB levels, and APOB/APOA1 ratio, and their associations with clinicopathologic parameters, the levels of twenty systemic inflammatory markers, and survival in 144 colorectal cancer (CRC) patients. We demonstrated that low serum APOA1 levels associated with advanced T-class and TNM-stage but low serum APOB levels did not significantly correlate with tumor characteristics. Serum APOA1 levels showed strong negative correlation with the markers of systemic inflammation including serum CRP and interleukin (IL)-8 levels and blood neutrophil count, whereas high serum APOB levels associated with high serum CCL2 levels. High APOA1 and APOB levels and low APOB/APOA1 ratio associated with improved cancer specific and overall survival. APOA1 had independent prognostic value in Cox regression analysis. In conclusion, low serum APOA1 levels are associated with advanced stage and systemic inflammation, while serum APOB does not significantly correlate with tumor stage. Serum APOA1 represents a promising additional prognostic parameter in CRC

Sarcopenia and Myosteatosis Are Associated with Neutrophil to Lymphocyte Ratio but Not Glasgow Prognostic Score in Colorectal Cancer Patients

Cancer patients commonly present sarcopenia, myosteatosis, and systemic inflammation, which are risk factors of poor survival. In this study, sarcopenia and myosteatosis were defined from preoperative body computed tomography scans of 222 colorectal cancer (CRC) patients and analyzed in relation to tumor and patient characteristics, markers of systemic inflammation (modified Glasgow prognostic score (mGPS), neutrophil–lymphocyte ratio (NLR), serum levels of C-reactive protein (CRP), albumin, and 13 cytokines, and survival. Of the systemic inflammation markers, sarcopenia and/or myosteatosis associated with elevated NLR (p = 0.005) and low albumin levels (≤35 g/L) (p = 0.018), but not with mGPS or serum cytokine levels. In addition, myosteatosis was associated with a proximal tumor location (p = 0.039), serrated tumor subtype (p < 0.001), and severe comorbidities (p = 0.004). Multivariable analyses revealed that severe comorbidities and serrated histology were independent predictors of myosteatosis, and older age and elevated NLR were independent indicators of sarcopenia. Myosteatosis associated with shorter overall survival in univariable analysis (HR 1.959, 95% CI 1.24–3.10, p = 0.004) but not in multivariable analysis (p = 0.075). We conclude that sarcopenia and myosteatosis were associated with inflammatory marker NLR, but not with mGPS. Moreover, patients with serrated CRC may have an increased risk of myosteatosis. Myosteatosis or sarcopenia were not independent predictors of patient survival

Alterations in serum amino-acid profile in the progression of colorectal cancer:associations with systemic inflammation, tumour stage and patient survival

Abstract Background: Cancer cachexia is a complex wasting syndrome affecting patients with advanced cancer, with systemic inflammation as a key component in pathogenesis. Protein degradation and release of amino acids (AAs) in skeletal muscle are stimulated in cachexia. Here, we define factors contributing to serum AA levels in colorectal cancer (CRC). Methods: Serum levels of nine AAs were characterised in 336 CRC patients and their relationships with 20 markers of systemic inflammatory reaction, clinicopathological features of cancers and patient survival were analysed. Results: Low serum glutamine and histidine levels and high phenylalanine levels associated with indicators of systemic inflammation, including high modified Glasgow Prognostic Score, high blood neutrophil/lymphocyte ratio and high serum levels of CRP, IL-6 and IL-8. Low levels of serum glutamine, histidine, alanine and high glycine levels also associated with advanced cancer stage and with poor cancer-specific survival in univariate analysis. Conclusions: In CRC, serum AA levels are associated with systemic inflammation and disease stage. These findings may reflect muscle catabolism induced by systemic inflammation in CRC

Serum enterolactone concentrations are low in colon but not in rectal cancer patients

Abstract The dietary lignan metabolite, enterolactone, has been suggested to have anti-cancer functions, and high serum enterolactone concentrations have been associated with decreased risk of breast and prostate cancers. We hypothesized that serum enterolactone concentrations as a marker of plant-based foods are associated with decreased risk in colorectal cancer (CRC). We measured serum enterolactone glucuronide and sulfate concentrations by liquid chromatography-tandem mass spectrometry in 115 CRC patients and 76 sex- and age-matched controls and analyzed the results with respect to tumor parameters, clinical parameters, and systemic inflammatory markers. Patients with colon cancer had significant lower serum enterolactone glucuronide and sulfate concentrations than controls (glucuronide: median 3.14 nM vs. 6.32 nM, P < 0.001; sulfate: median 0.13 nM vs. 0.17 nM, P = 0.002), whereas rectal cancer patients had similar enterolactone levels as controls (glucuronide: median 5.39 nM vs. 6.32 nM, P = 0.357; sulfate: median 0.19 nM vs. 0.17 nM, P = 0.452). High serum enterolactone concentrations were associated with low tumor grade, high serum creatinine levels, and concomitant diabetes. In summary, our results suggest that serum enterolactone concentrations are decreased in colon but not in rectal cancer. Further investigations are required to assess whether this reflects an altered lignan metabolism by the colon microbiome

Systemic inflammation is associated with circulating cell death released keratin 18 fragments in colorectal cancer

Abstract Systemic inflammation is a stage-independent marker of poor prognosis in colorectal cancer (CRC), activated in a complex, multifactorial process. It has been proposed that one of the main factors driving systemic inflammation may be tumor necrosis. Keratin 18 (KRT18) fragments are released from dead cells and their serum levels are markers for apoptotic and necrotic cell death. In CRC, high KRT18 levels associate with advanced disease, but their relationship with tumor necrosis and systemic inflammation is unknown. In this study, serum total soluble KRT18 (tKRT18) and apoptosis-related, caspase-cleaved fragment (aKRT18) levels were measured preoperatively from 328 CRC patients, and their difference was calculated to assess necrosis related KRT18 (nKRT18) levels. The relationships of these markers with tumor necrosis, clinicopathologic features, systemic inflammation markers (C-reactive protein, albumin, and 13 cytokines), and survival were analyzed. High serum tKRT18, aKRT18, and nKRT18 levels showed association with a higher extent of tumor necrosis, distant metastasis, and increased levels of several markers of systemic inflammation, including CXCL8. High serum tKRT18 (multivariable HR 1.94, 95% CI 1.28–2.95, p = 0.002) and nKRT18 (multivariable HR 1.87, 95% CI 1.24–2.82, p = 0.003) levels were associated with poor overall survival independent of potential confounding factors. Our results show that tumor necrosis in CRC contributes to serum levels of KRT18 fragments, and both necrosis and KRT18 levels associate with systemic inflammation. Moreover, we show that serum tKRT18 and nKRT18 levels have independent prognostic value in CRC. Our observations confirm the link between cell death and systemic inflammation

Platelet count, aspirin use, and characteristics of host inflammatory responses in colorectal cancer

Abstract Background: Platelets not only contribute to hemostasis but also to the regulation of inflammatory reactions and cancer pathogenesis. We hypothesized that blood platelet count would be associated with systemic inflammation, the densities of tumor infiltrating immune cells, and survival in colorectal cancer (CRC), and these relationships could be altered by aspirin use. Methods: We measured blood platelet count in a cohort of 356 CRC patients and analyzed its relationships with tumor and patient characteristics including aspirin use, markers of systemic inflammation (modified Glasgow Prognostic Score, mGPS; serum levels of CRP, albumin, and 13 cytokines), blood hemoglobin levels, five types of tumor infiltrating immune cells (CD3, CD8, FoxP3, Neutrophil elastase, mast cell tryptase), and survival. Results: Platelet count inversely correlated with blood hemoglobin levels (p < 0.001) and positively correlated with serum levels of CRP and multiple cytokines including IL-1RA, IL-4, IL-6, IL-7, IL-8, IL-12, IFNγ, and PDGF-BB (p < 0.001 for all), while aspirin use was not associated with the levels of systemic inflammatory markers. High platelet count was also associated with high mGPS (p < 0.001) but did not show statistically significant multivariable adjusted associations with the densities of tumor infiltrating immune cells. Higher platelet counts were observed in higher tumor stage (p < 0.001), but platelet count or aspirin use were not associated with patient survival. Conclusions: High platelet count is associated with systemic inflammation in CRC. This study could not demonstrate statistically significant associations between platelet count, aspirin use, and the densities of tumor infiltrating immune cells