Primary total knee replacement for tibial plateau fractures in older patients: a systematic review of 197 patients.

INTRODUCTION: Tibial plateau fractures are typically treated with osteosynthesis. In older patients, osteosynthesis is associated with some complications, risk of post-traumatic osteoarthritis and long partial, or non-weight bearing during the recovery phase. To avoid these problems, primary total knee replacement (TKR) has become an increasingly common treatment option. The aim of this study was to evaluate all the relevant literature and summarize the current evidence-based knowledge on the treatment of tibial plateau fractures with primary TKR in older patients. MATERIALS AND METHODS: A systematic literature search of studies on total knee replacement (TKR) as primary treatment for acute traumatic tibial plateau fracture was conducted using OVID Medline, Scopus, and Cochrane databases from 1946 to 18 November 2019. We included all studies without restrictions regarding total knee replacement (TKR) as primary treatment for acute traumatic tibial plateau fracture. RESULTS: Of the 640 reviewed articles, 16 studies with a total of 197 patients met the inclusion criteria. No controlled trials were available, and the overall quality of the literature was low. The results, using different clinical scoring systems, were good or fair. Four-year follow-up complication (6.1%) and revision (3.6%) rates after primary TKR appeared to be lower than after secondary TKR (complication rate 20-48%, revision rate 8-20%) but higher than after elective primary TKR. CONCLUSION: Based on low-quality evidence, TKR appears to be a useful treatment option for tibial plateau fractures in older patients. Controlled trials are mandatory to determine the relative superiority of these two options as primary treatment of tibial plateau fractures in older patients.

Trends in the Incidence, Etiology, Treatment, and Outcomes of Pleural Infections in Adults Over a Decade in a Finnish University Hospital.

BACKGROUND AND AIMS: The aim of the study was to ascertain changes in the incidence, etiology, treatment, and outcomes of pleural infections over a decade in a Finnish University Hospital. MATERIALS AND METHODS: All patients treated for pleural infections in Tampere University Hospital during 2000-2008 and 2012-2016 were included. The incidence rates and the epidemiologic data and medical history of patients, etiology of infection, and treatment trends and outcomes were compared between the cohorts. RESULTS: The incidence of pleural infections increased from 4.4 during 2000-2008 to 9.9 during 2012-2016 per 100.000 patient-years, p < 0.001. The patients in the latter group were older, 63 versus 57 years, p = 0.001, and the prevalence of chronic lung disease, hypertension, heart failure, dyslipidemia, and immunosuppressive medication were higher. The causes of infection remained similar and pneumonia accounted for 70% of all cases. The identification rate of the microbe pathogens increased from 49% to 64%, p = 0.002, while the distribution of identified pathogens was unchanged. More patients in the latter cohort were treated operatively, 88.3% versus 80.9%, p = 0.005, and, in these, the proportion of thoracoscopic surgery was higher, 57.4% versus 8.0%, p < 0.001, and the delay to surgery shorter, 5 versus 7 days, p < 0.001. Radiologic outcomes were similar. The 30-day mortality rate was 3.1% during 2000-2008 and 5.1% during 2012-2016, p = 0.293. CONCLUSION: The overall incidence of pleural infections has increased significantly while the causes of pleural infections and the distribution of pathogens remain unchanged. Contemporary patients are older with higher prevalence of comorbidities and more frequently undergo thoracoscopic surgery.

Repeated metal ion measurement in patients with bilateral metal on metal (ASR™) hip replacements.

BACKGROUND: Blood metal ion measurements have become a cornerstone in the surveillance of metal-on-metal (MoM) hip replacements. Interpretation of these levels in patients with bilateral MoM hip replacements, however, is challenging. We therefore asked (1) if there is a clinically significant change in whole blood (WB) Co or Cr levels in repeated WB assessment in patients operated on with bilateral ASR hip replacements, and (2) what proportion of patients has WB Co or Cr level below the previously established safe upper limits (SUL) (Co<5.0µg/L, Cr<7.4µg/L) in the repeated WB metal ion assessment. HYPOTHESIS: We hypothesized that there is a significant difference between repeated Co and Cr level measurement performed within one year±4 months interval in patients with bilateral ASR hip replacements. MATERIALS AND METHODS: We identified all patients (n=139) who had received bilateral ASR hip replacements (278 hips). Patients (n=76, 152 hips) who had undergone two blood metal ion measurements within eight to sixteen months' time interval were included in the study analysis. Study cohort included 38 patients with bilateral ASR hip resurfacings (mean age 53 years, median follow-up 4.6 years, median femoral diameter 51mm) and 38 patients with bilateral ASR XL total hip replacements (mean age 60 years, median follow-up 3.6 years, median femoral diameter 49mm). RESULTS: There was no significant change in Co and Cr levels between the repeated measurements in the HR cohort. Both Co and Cr were significantly higher in the THR cohort in the repeated measurement (Co: 8.3µg/L vs. 12.6µg/L, Cr: 3.15µg/L vs. 3.4µg/L, both P<0.001). WB Co and Cr levels remained below SUL and within their initial values during a mean one-year measurement interval in the majority of patients with bilateral high risk HR device. In contrast to this, 21.1% of patients with THRs had WB Co ion levels exceeding the SUL in the first measurement. WB Co values significantly increased over the measurement interval in the THR group. DISCUSSION: Annual blood metal ion measurement is not useful in patients with bilateral hip resurfacings who have undergone at least one preliminary screening including both metal ion measurement and cross-sectional imaging. It seems, however, to be beneficial in patients with bilateral high risk MoM THR. LEVEL OF EVIDENCE: Level III (retrospective comparative study).

Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age.

Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.

Monocyte-derived dendritic cells from Crohn's disease patients exhibit decreased ability to activate T helper type 17 responses in memory cells.

An increased activation of interleukin (IL)-17A-producing immune cells is a well-established feature of Crohn's disease (CD). Mechanisms that contribute to this aberrant immune activation are, however, less clear. Given that an enhanced induction of innate-immunity associated cytokines IL-6 and IL-23, which promote IL-17 immunity, is also clearly implicated in CD, we hypothesized that monocyte-derived dendritic cells (moDCs) of CD patient origin would mount exaggerated IL-17A responses in T cells. However, we found a significantly attenuated up-regulation of the IL-17A response in allogeneic T helper memory cells in the presence of culture media from lipopolysaccharide (LPS)-stimulated moDCs of CD patients when compared with moDCs of control subjects (median fold-increase in IL-17A mRNA expression 1·09 versus 1·44, P = 0·038). This was accompanied by a lower expression of IL-1ß and IL-6 transcripts in the LPS-treated moDCs (median 9·55 versus 13·9 relative units, P = 0·042, and 2·66 versus 9·06 relative units, P = 0·049, respectively). In addition, the up-regulation of autophagy-related LC3 transcripts was decreased in moDCs of CD patients (median fold-increase in mRNA expression 1·22 versus 1·52, P = 0·029). Our findings reveal similar immunological aberrancies in CD in the general population as reported in CD patients with mutated intracellular bacterial sensor NOD2, namely attenuated activation of innate cytokines and impaired autophagy, combined with a reduced capacity to up-regulate the T helper type 17 (Th17) response. The results presented here emphasize a defective anti-microbial response in the pathogenesis of CD. The increased mucosal Th1 and Th17 responses, which may contribute to the pathogenesis, could be the consequences of primary defects in the innate immunity.

Orthopaedic reconstruction of complex pelvic bone defects. Evaluation of various treatment methods.

Despite major developments in the field of revision surgery in recent decades, the management of severe acetabular deficiency at revision arthroplasty, complex primary total hip replacement or after pelvic tumour resection remains a complex problem. The options available for the management of severe bone loss include the use of uncemented press-fit cups with or without metal augments, impaction allografts, allograft-prosthesis composites, custom-made triflange cups, hip transposition, reconstruction prostheses or various combinations of these. This paper describes defect classification, various treatment options, clinical outcomes, survival of reconstruction, and typical complications in relation to treatment.

A small-molecule inhibitor of integrin alpha2 beta1 introduces a new strategy for antithrombotic therapy.

Interaction of blood platelets with vascular collagen is an initiating event in haemostasis and thrombus formation. Based on molecular modelling of human integrin alpha2I domain and cell-based screening assays we have developed sulfonamide derivatives, a mechanistically novel class of molecules. These molecules show antiplatelet efficacy by selectively inhibiting alpha2beta1 integrin-mediated collagen binding. One sulfonamide derivative, named BTT-3016, showed inhibitory capacity in several assessments of human platelet interaction with collagen. It inhibited about 90% of the aggregation of gel-filtered magnesium-supplemented platelets and 70% of aggregation in PPACK-anticoagulated platelet-rich plasma when stimulated with collagen but not with ADP. The antiplatelet activity of BTT-3016 was dependent on alpha2beta1 integrin, since in collagen binding test BTT-3016 had no effect on the platelets derived from alpha2 integrin null mice. When tested in an in vivo model in mice, BTT-3016 clearly reduced thrombus formation on the vessel wall after vascular injury. Furthermore, BTT-3016 prolonged tail-bleeding time in a manner comparable to aspirin. We show that new alpha2beta1 inhibitors exert collagen-specific antiplatelet activity and regulate thrombus growth in vivo without compromising primary haemostasis more than aspirin. We suggest that the alpha2beta1 inhibiting strategy could be further developed for the prevention and treatment of arterial thrombosis.

Randomized clinical trial of Lichtenstein patch or Prolene Hernia System for inguinal hernia repair.

BACKGROUND: In this randomized prospective study the short- and long-term outcomes of patients undergoing inguinal hernia repair with either Lichtenstein mesh or the Prolene Hernia System (PHS) were evaluated. METHODS: Postoperative pain and time to return to work, driving and sporting hobbies were recorded after 300 inguinal hernia repairs done by one of the two methods. Long-term sequelae and complications were assessed at follow-up visits 1 week, 1 month and 1 year after the operation. RESULTS: The median duration of operation for unilateral primary hernia was 37 min for the Lichtenstein operation and 27 min for the PHS procedure (P < 0.001). Postoperative pain was similar after both operations. Median sick leave was 7 days in both groups. Time to driving a car was 4 versus 3 days, and time to return to sporting hobbies 13 versus 11 days, in the Lichtenstein and PHS groups, respectively. Apart from a residual femoral hernia after Lichtenstein repair, no recurrent inguinal hernias were detected. CONCLUSION: Both Lichtenstein and PHS methods resulted in rapid recovery and low recurrence rates. The PHS operation was significantly quicker.

Abnormal response to physical activity in femurs after heterozygous inactivation of one allele of the Col2a1 gene for type II collagen in mice.

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Functional treatment of closed humeral shaft fractures.

We treated 93 consecutive patients, average age 53 (16-90) years, with closed humeral shaft fractures applying a functional brace immediately after injury. Seventy-two (77%) fractures healed without problems. There were significantly more consolidation problems in fractures in the proximal third (46% consolidated) compared to those at the middle (81% consolidated) and distal third (86% consolidated) of the shaft. Logistic regression analysis revealed the only predictive factor in respect to successful brace treatment was fracture location. No significant difference was found in respect to healing between different AO-type fractures.

Premature vertebral endplate ossification and mild disc degeneration in mice after inactivation of one allele belonging to the Col2a1 gene for Type II collagen.

STUDY DESIGN: Skeletal tissues of mice with an inactivated allele of the Col2a1 gene for Type II collagen ("heterozygous knockout") were studied. OBJECTIVE: To determine whether a heterozygous inactivation of the Col2a1 gene has a role in the etiology of spine disorders such as disc degeneration. SUMMARY OF BACKGROUND DATA: Mutations in the COL2A1, COL11A1, COL11A2, and COL9A2 genes have been linked to spine disorders. However, the mechanism by which genetic factors lead to disc degeneration still are largely unknown. METHODS: Spine tissues were studied using radiograph analyses; conventional, quantitative, and polarized light microscopy; immunohistochemistry for the major extracellular components, and in situ hybridization for procollagens alpha1(I) and alpha1(II). Voluntary running activity also was monitored in half of the mice. RESULTS: As the findings showed, 1-month-old heterozygous knockout mice had shorter limb bones, skulls, and spines, as well as thicker and more irregular vertebral endplates, which calcified earlier than in the control mice. They also had a lower concentration of glycosaminoglycans in the anulus fibrosus, in the endplates, and in the vertebral bone than the controls. These features in the heterozygous knockout mice were compensated by the age of 15 months. However, the long bones and skulls of the mature heterozygous mice remained shorter than those of the controls. Gene-deficient mice used the running wheel less. However, physical exercise did not induce any marked structural changes in the skeleton. CONCLUSION: Mice with heterozygous knockout of Col2a1 show subtle early skeletal manifestations that bear some resemblance to those of human spine disorders.

FT-IR breath test in the diagnosis and control of treatment of methanol intoxications.

A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was tested for the diagnosis of methanol intoxications. Breath analysis with FT-IR was fast and easy, and no sample preparation was needed. The analyzer was adequately sensitive and accurate in detecting and quantitating clinically relevant amounts of ethanol and methanol in the breath of seriously ill patients. FT-IR spectrometry was also suitable for nearly on-line monitoring of the exhaled ethanol and methanol during hemodialysis. The breath analysis results correlated well with blood samples. The FT-IR method used also has a traceable calibration to physical properties of the analyte, and the measured spectra can be saved for later analysis.

Efficacy and tolerability of fluticasone propionate nasal drops 400 microgram once daily compared with placebo for the treatment of bilateral polyposis in adults.

BACKGROUND: Chronic eosinophilic rhinosinusitis underlies a range of respiratory disorders including nasal polyposis. Surgical and medical methods are used to control polyps, with topical steroids commonly being used for their anti-inflammatory properties. Fluticasone propionate nasal drops (FPND) is a formulation developed specifically for an effective and well tolerated corticosteroid treatment of nasal polyposis. OBJECTIVES: To assess efficacy and tolerability of FPND in the treatment of bilateral nasal polyposis in adults. METHODS: This multicentre, randomized, parallel-group study compared FPND 400 microgram once daily (o.d.) with placebo for 12 weeks in adult patients with mild to moderate bilateral polyposis. The primary efficacy endpoint was visual assessment of polyp size by the physician at monthly clinic visits. Nasal blockage, rhinitis, peak nasal inspiratory flow (PNIF), olfactory function and requirement for polypectomy were also assessed at visits. The patients kept diary card records of symptoms, PNIF, and use of rescue antihistamine. Additional safety data were provided by a 12-week open extension, when all patients received FPND 400 microgram o.d. RESULTS: After 12 weeks double-blind treatment with FPND (n = 52) or placebo (n = 52), polyp size was reduced in 27% and 16% of patients, respectively; clinical reduction of nasal blockage significantly favoured FPND over placebo (55% vs 22%; P = 0.002), and clinic PNIF had increased significantly with FPND (by 52 L/min vs -3 L/min for placebo; P < 0.001). Diary card measurements showed significant benefits of FPND vs placebo for daily PNIF, nasal blockage, rhinitis and use of loratadine rescue medication. Both treatments were well tolerated and no serious adverse events occurred during randomized treatment. Epistaxis was more frequent with FPND than placebo but was generally mild and did not result in withdrawals. Mean serum cortisol levels did not change significantly with either treatment. CONCLUSION: This study showed FPND 400 microgram o.d. to be an effective and well tolerated treatment for bilateral nasal polyposis in adults.

The use of low-resolution FT-IR spectrometry for the analysis of alcohols in breath.

Fast and reliable diagnostic methods are needed for detection or exclusion of industrial solvents as a cause of intoxication. Analyzing human breath reveals the presence of any volatile substance. A portable Fourier transform infrared (FT-IR) multicomponent point-of-care analyzer was developed for exhaled breath. The analyzer proved to be accurate and precise in laboratory tests for simultaneous measurement of methanol and ethanol in water. Ethanol, in addition to normal contents of breath, was simultaneously analyzed in human experiments, and the results correlated well with blood samples. FT-IR method has a traceable calibration to physical properties of the analyte. The measured spectra can also be saved and analyzed later. Breath analysis with FT-IR is fast and easy, and no preparation of the sample is needed.

Electron spin resonance (ESR) probe for interventional MRI instrument localization.

This article presents a miniaturized electron spin resonance (ESR) probe for deducing the position of a surgical instrument on an MR image. The ESR probe constructed was small enough to fit inside a 14-G biopsy needle sheath, and position information of the sheath could be acquired using a simple gradient sequence. The position accuracy was estimated from needle trajectories as inferred from the needle artifact, the actual physical trajectory, and measured coordinates. The probe was able to track the tip of a biopsy needle quickly (10 samples/sec) and precisely with accuracy better than +/-2 mm. J. Magn. Reson. Imaging 1999;10:216-219.

Do more highly organized collagen fibrils increase bone mechanical strength in loss of mineral density after one-year running training?

The aim of this study was to evaluate the effects of long-term running training on the structural properties of bone. Ten beagle dogs ran according to a strenuous progressive program (up to 40 km/day) for 1 year. At the end of the training program, there was a significant reduction in bone mineral density (up to 9.7%) in the vertebrae of the runner dogs as compared with 10 sedentary control dogs. Polarized light microscopy of the vertebral trabecular bone, however, displayed proportionally higher retardation values of the collagen network of the runner dogs than of the sedentary dogs, suggesting a reorganization in a more parallel manner in the collagen fibrils. The concentration and cross-linking of collagen in the bones remained similar in both groups. No differences were observed in the force to failure of bones of the two groups nor in the histomorphometric analysis of the bones. We suggest that the collagen network in the bones accounted for the maintenance of the strength properties in the bones of the runner dogs despite the loss of mineral density.

Subchondral bone remodeling increases in early experimental osteoarthrosis in young beagle dogs.

We evaluated subchondral bone remodeling and structure in the condyles of the femur and the patellar surface of the femur in early experimental osteoarthrosis of young female beagle dogs. 14 littermate (twin) dogs were divided into operation (n 7) and control groups (n 7). The dogs in the operation group underwent surgically a 30 degrees valgus angulation of the right tibia to induce osteoarthrotic articular cartilage lesions in the knee (stifle) joint. 7 months postoperatively, bone samples were harvested from both condyles and the patellar surface of the femur and evaluated by histomorphometry of subchondral bone. Cartilage samples from the same areas were taken for histology. In the operated dogs, subchondral bone remodeling increased strikingly in the patellar surface of the femur; osteoid thickness and osteoblast surface/bone surface increased up to 42% and 94% (p < 0.05), as compared to controls. Total and active erosion depths increased by 14% and 30% in the same area (p < 0.05). However, in bone structural parameters no significant difference could be observed between the groups. In the medial condyle of the femur, the trabecular number decreased in operated dogs, as compared to controls (p < 0.05). The lateral condyle of the femur in operated animals did not differ from controls in the parameters tested. In the operated dogs, histology from cartilage samples showed initial osteoarthrotic changes in the patellar surface and the medial condyle of the femur. Histologic changes were greatest in the patellar surface of the femur, as assessed by the Mankin scores. At the very onset of osteoarthrosis, subchondral bone remodeling increases, but the bone structural changes are indistinct. It seems that in this osteoarthrosis model, cartilage lesions precede major subchondral changes in the structure of the bone.

Estimation of spinal bone density using conventional MRI. Comparison between MRI and DXA in 32 subjects.

We evaluated the usefulness of MRI T1 and T2 relaxation times in assessing bone mineral status. T1 and T2 relaxation times of L3 were measured in 16 pairs of identical twins (24 men, 8 women), aged 25-69 years. Bone mineral density (BMD), bone mineral content (BMC) and apparent volumetric bone mineral density (BMDvol) of L3 were measured from the same subjects using dual x-ray absorptiometry (DXA). T2 relaxation time correlated inversely with BMD and BMC (r -0.40 and r -0.47, respectively), whereas a significant positive correlation between T1 relaxation time and BMDvol was found (r 0.36). The measurement of T1 may give some information on bone mineral status in clinical MRI measurements when DXA is not available. It is possible that T1 and T2 reflect not only bone density, but also other factors related to bone structure.