Machine learning augmented near-infrared spectroscopy: In vivo follow-up of cartilage defects.

OBJECTIVE: To assess the potential of near-infrared spectroscopy (NIRS) for in vivo arthroscopic monitoring of cartilage defects. METHOD: Sharp and blunt cartilage grooves were induced in the radiocarpal and intercarpal joints of Shetland ponies and monitored at baseline (0 weeks) and at three follow-up timepoints (11, 23, and 39 weeks) by measuring near-infrared spectra in vivo at and around the grooves. The animals were sacrificed after 39 weeks and the joints were harvested. Spectra were reacquired ex vivo to ensure reliability of in vivo measurements and for reference analyses. Additionally, cartilage thickness and instantaneous modulus were determined via computed tomography and mechanical testing, respectively. The relationship between the ex vivo spectra and cartilage reference properties was determined using convolutional neural network. RESULTS: In an independent test set, the trained networks yielded significant correlations for cartilage thickness (ρ = 0.473) and instantaneous modulus (ρ = 0.498). These networks were used to predict the reference properties at baseline and at follow-up time points. In the radiocarpal joint, cartilage thickness increased significantly with both groove types after baseline and remained swollen. Additionally, at 39 weeks, a significant difference was observed in cartilage thickness between controls and sharp grooves. For the instantaneous modulus, a significant decrease was observed with both groove types in the radiocarpal joint from baseline to 23 and 39 weeks. CONCLUSION: NIRS combined with machine learning enabled determination of cartilage properties in vivo, thereby providing longitudinal evaluation of post-intervention injury development. Additionally, radiocarpal joints were found more vulnerable to cartilage degeneration after damage than intercarpal joints.

Restored pelvic anatomy is preserved after laparoscopic and robot-assisted ventral rectopexy: MRI-based 5-year follow-up of a randomized controlled trial.

AIM: Our aim was to compare the long-term anatomical outcomes between robot-assisted ventral mesh rectopexy (RVMR) and laparoscopic ventral mesh rectopexy (LVMR) for external or internal rectal prolapse. METHOD: This study is a follow-up of a single-centre randomized controlled trial (RCT). Thirty patients were randomly allocated to RVMR (n = 16) or LVMR (n = 14). The primary end-point was maintenance of the restored pelvic anatomy 5 years after the operation, as assessed by magnetic resonance (MR) defaecography. Secondary outcome measures included the Pelvic Organ Prolapse Quantification (POP-Q) measures and functional results assessed using symptom questionnaires. RESULTS: Twenty-six patients (14 RVMR and 12 LVMR) completed the 5-year follow-up and were included in the study. The MRI results, POP-Q measurements and symptom-specific quality of life measures did not differ between the RVMR and LVMR groups. The MRI measurements of the total study population remained unchanged between 3 months and 5 years. In the Pelvic Floor Distress Inventory (PFDI-20), the RVMR group had lower symptom scores (mean 96.0, SD 70.7) than the LVMR group (mean 160.6, SD 58.9; P = 0.004). In the subscales of pelvic organ prolapse (POPDI-6) (mean 23.2, SD 24.3 vs mean 52.4, SD 22.4; P = 0.001) and the Colorectal-Anal Distress Inventory (CRADI-8) (mean 38.4, SD 23.3 vs mean 58.6, SD 25.4; P = 0.009), the patients in the RVMR group had significantly better outcomes. CONCLUSION: After VMR, the corrected anatomy was preserved. There were no clinically significant differences in anatomical results between the RVMR and LVMR procedures 5 years after surgery based on MR defaecography. However, functional outcomes were better after RMVR.

Evaluation of equine articular cartilage degeneration after mechanical impact injury using cationic contrast-enhanced computed tomography.

OBJECTIVE: Cationic agent contrast-enhanced computed tomography (cationic CECT) characterizes articular cartilage ex vivo, however, its capacity to detect post-traumatic injury is unknown. The study objectives were to correlate cationic CECT attenuation with biochemical, mechanical and histological properties of cartilage and morphologic computed tomography (CT) measures of bone, and to determine the ability of cationic CECT to distinguish subtly damaged from normal cartilage in an in vivo equine model. DESIGN: Mechanical impact injury was initiated in equine femoropatellar joints in vivo to establish subtle cartilage degeneration with site-matched controls. Cationic CECT was performed in vivo (clinical) and postmortem (microCT). Articular cartilage was characterized by glycosaminoglycan (GAG) content, biochemical moduli and histological scores. Bone was characterized by volume density (BV/TV) and trabecular number (Tb.N.), thickness (Tb.Th.) and spacing (Tb.Sp.). RESULTS: Cationic CECT attenuation (microCT) of cartilage correlated with GAG (r = 0.74, P < 0.0001), compressive modulus (Eeq) (r = 0.79, P < 0.0001) and safranin-O histological score (r = -0.66, P < 0.0001) of cartilage, and correlated with BV/TV (r = 0.37, P = 0.0005), Tb.N. (r = 0.39, P = 0.0003), Tb.Th. (r = 0.28, P = 0.0095) and Tb.Sp. (r = -0.44, P < 0.0001) of bone. Mean [95% CI] cationic CECT attenuation at the impact site (2215 [1987, 2443] Hounsfield Units [HUs]) was lower than site-matched controls (2836 [2490, 3182] HUs, P = 0.036). Clinical cationic CECT attenuation correlated with GAG (r = 0.23, P = 0.049), Eeq (r = 0.26, P = 0.025) and safranin-O histology score (r = -0.32, P = 0.0046). CONCLUSIONS: Cationic CECT (microCT) reflects articular cartilage properties enabling segregation of subtly degenerated from healthy tissue and also reflects bone morphometric properties on CT. Cationic CECT is capable of characterizing articular cartilage in clinical scanners.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts.

OBJECTIVE: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. DESIGN: Individual participant data meta-analysis of 39 cohorts. SETTING: Europe, North America, and Oceania. POPULATION: 265 270 births. METHODS: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. RESULTS: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. CONCLUSIONS: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. TWEETABLE ABSTRACT: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Cost-analysis and quality of life after laparoscopic and robotic ventral mesh rectopexy for posterior compartment prolapse: a randomized trial.

BACKGROUND: The aim of this study was to assess, whether robotic-assistance in ventral mesh rectopexy adds benefit to laparoscopy in terms of health-related quality of life (HRQoL), cost-effectiveness and anatomical and functional outcome. METHODS: A prospective randomized study was conducted on patients who underwent robot-assisted ventral mesh rectopexy (RVMR) or laparoscopic ventral mesh rectopexy (LVMR) for internal or external rectal prolapse at Oulu University Hospital, Finland, recruited in February-May 2012. The primary outcomes were health care costs from the hospital perspective and HRQoL measured by the 15D-instrument. Secondary outcomes included anatomical outcome assessed by pelvic organ prolapse quantification method and functional outcome by symptom questionnaires at 24 months follow-up. RESULTS: There were 30 females (mean age 62.5 years, SD 11.2), 16 in the RVMR group and 14 in the LVMR group. The surgery-related costs of the RVMR were 1.5 times higher than the cost of the LVMR. At 3 months the changes in HRQoL were 'much better' (RVMR) and 'slightly better' (LVMR) but declined in both groups at 2 years (RVMR vs. LVMR, p > 0.05). The cost-effectiveness was poor at 2 years for both techniques, but if the outcomes were assumed to last for 5 years, it improved significantly. The incremental cost-effectiveness ratio for the RVMR compared to LVMR was €39,982/quality-adjusted life years (QALYs) at 2 years and improved to €16,707/QALYs at 5 years. Posterior wall anatomy was restored similarly in both groups. The subjective satisfaction rate was 87% in the RVMR group and 69% in the LVMR group (p = 0.83). CONCLUSIONS: Although more expensive than LVMR in the short term, RVMR is cost-effective in long-term. The minimally invasive VMR improves pelvic floor function, sexual function and restores posterior compartment anatomy. The effect on HRQoL is minor, with no differences between techniques.

Functional effects of an interpenetrating polymer network on articular cartilage mechanical properties.

OBJECTIVE: Depletion of glycosaminoglycans (GAGs) and degradation of collagen network are early hallmarks of osteoarthritis (OA). Currently, there are no chondroprotective therapies that mitigate the loss of GAGs or effectively restore the collagen network. Recently, a novel polymeric cartilage supplement was described that forms a charged interpenetrating polymer network (IPN) reconstituting the hydrophilic properties of the extracellular matrix (ECM). To investigate the mechanism by which this hydrophilic IPN improves articular cartilage material properties, a finite element (FE) model is used to evaluate the IPN's effect on the fibrillar collagen network, nonfibrillar matrix, and interstitial fluid flow. METHODS: Bovine osteochondral plugs were degraded with chondroitinase ABC to selectively decrease GAG content. Samples were mechanically tested before and after IPN treatment using unconfined testing geometry and stress-relaxation protocol. Every measurement was modeled separately using a fibril-reinforced poroviscoelastic FE model. Measurement replication was achieved by optimizing the following model parameters: initial and strain-dependent fibril network modulus (Ef0, Efε, respectively), nonfibrillar matrix modulus (Enf), initial permeability (k0) and strain-dependent permeability factor (M). RESULTS: Based on the FE model results, treatment of native and GAG depleted cartilage with the hydrophilic IPN increases the ECM stiffness and impedes fluid flow. The IPN did not alter the stiffness of fibrillary network. Cartilage permeability and the strain-dependent permeability factor decreased with increasing IPN w/v%. CONCLUSIONS: The IPN reconstitutes cartilage material properties primarily by augmenting the hydrophilic ECM. This reinforcement of the solid phase also affects the fluid phase reestablishing low permeability.

Robot-assisted vs laparoscopic ventral rectopexy for external or internal rectal prolapse and enterocele: a randomized controlled trial.

AIM: The purpose of this prospective randomized study was to compare robot-assisted and laparoscopic ventral rectopexy procedures for posterior compartment procidentia in terms of restoration of the anatomy using magnetic resonance (MR) defaecography. METHOD: Sixteen female patients (four with total prolapse, twelve with intussusception) underwent robot-assisted ventral mesh rectopexy (RVMR) and 14 female patients (two with prolapse, twelve with intussusception) laparoscopic ventral mesh rectopexy (LVMR). Primary outcome measures were perioperative parameters, complications and restoration of anatomy as assessed by MR defaecography, which was performed preoperatively and 3 months after surgery. RESULTS: Patient demographics, operation length, operating theatre times and length of in-hospital stay were similar between the groups. The anatomical defects of rectal prolapse, intussusception and rectocele and enterocele were similarly corrected after rectopexy in either technique as confirmed with dynamic MR defaecography. A slight residual intussusception was observed in three patients with primary total prolapse (two RVMR vs one LVMR) and in one patient with primary intussusception (RVMR) (P = 0.60). Rectocele was reduced from a mean of 33.0 ± 14.9 mm to 5.5 ± 8.4 mm after RVMR (P < 0.001) and from 24.7 ± 17.5 mm to 7.2 ± 3.2 mm after LVMR (P < 0.001) (RVMR vs LVMR, P = 0.10). CONCLUSION: Robot-assisted laparoscopic ventral rectopexy can be performed safely and within the same operative time as conventional laparoscopy. Minimally invasive ventral rectopexy allows good anatomical correction as assessed by MR defaecography, with no differences between the techniques.

Laparoscopic ventral rectopexy in male patients with external rectal prolapse is associated with a high reoperation rate.

BACKGROUND: Laparoscopic ventral rectopexy has been used to treat male patients with external rectal prolapse, but evidence to support this approach is scarce. The aim of this study was to evaluate the results of this new abdominal rectopexy surgical technique in men. METHODS: This was a retrospective multicenter study. Adult male patients who were operated on for external rectal prolapse using ventral rectopexy in five tertiary hospitals in Finland between 2006 and 2014 were included in the study. Patient demographics, detailed operative, postoperative and short-term follow-up data were collected from patient registers in participating hospitals. A questionnaire and informed consent form was sent to all patients. The questionnaire included scores for anal incontinence, obstructed defecation syndrome, urinary symptoms and sexual dysfunction. The main outcome measure was the incidence of recurrent rectal prolapse. Surgical morbidity, the need for surgical repair due to recurrent symptoms and functional outcomes were secondary outcome measures. RESULTS: A total of 52 adult male patients with symptoms caused by external rectal prolapse underwent ventral rectopexy. The questionnaire response rate was 64.4 %. Baseline clinical characteristics and perioperative results were similar in the responder and non-responder groups. A total of 9 (17.3 %) patients faced complications. There were two (3.8 %) serious surgical complications during the 30-day period after surgery that necessitated reoperation. None of the complications were mesh related. Recurrence of the prolapse was noticed in nine patients (17 %), and postoperative mucosal anal prolapse symptoms persisted in 11 patients (21 %). As a result, the reoperation rate was high. Altogether, 17 patients (33 %) underwent reoperation during the follow-up period due to postoperative complications or recurrent rectal or mucosal prolapse. According to the postoperative questionnaire data, patients under 40 had good functional results in terms of anal continence, defecation, urinary functions and sexual activity. CONCLUSIONS: Laparoscopic ventral rectopexy is a safe surgical procedure in male patients with external prolapse. However, a high overall reoperation rate was noticed due to recurrent rectal and residual mucosal prolapse. This suggests that the ventral rectopexy technique should be modified or combined with other abdominal or perineal methods when treating male rectal prolapse patients.

Alterations in subchondral bone plate, trabecular bone and articular cartilage properties of rabbit femoral condyles at 4 weeks after anterior cruciate ligament transection.

OBJECTIVE: To quantify early osteoarthritic-like changes in the structure and volume of subchondral bone plate and trabecular bone and properties of articular cartilage in a rabbit model of osteoarthritis (OA) induced by anterior cruciate ligament transection (ACLT). METHODS: Left knee joints from eight skeletally mature New Zealand white rabbits underwent ACLT surgery, while the contralateral (CTRL) right knee joints were left unoperated. Femoral condyles were harvested 4 weeks after ACLT. Micro-computed tomography imaging was applied to evaluate the structural properties of subchondral bone plate and trabecular bone. Additionally, biomechanical properties, structure and composition of articular cartilage were assessed. RESULTS: As a result of ACLT, significant thinning of the subchondral bone plate (P < 0.05) was accompanied by significantly reduced trabecular bone volume fraction and trabecular thickness in the medial femoral condyle compartment (P < 0.05), while no changes were observed in the lateral compartment. In both lateral and medial femoral condyles, the equilibrium modulus and superficial zone proteoglycan (PG) content were significantly lower in ACLT than CTRL joint cartilage (P < 0.05). Significant alterations in the collagen orientation angle extended substantially deeper into cartilage from the ACLT joints in the lateral femoral condyle relative to the medial condyle compartment (P < 0.05). CONCLUSIONS: In this model of early OA, significant changes in volume and microstructure of subchondral bone plate and trabecular bone were detected only in the femoral medial condyle, while alterations in articular cartilage properties were more severe in the lateral compartment. The former finding may be associated with reduced joint loading in the medial compartment due to ACLT, while the latter finding reflects early osteoarthritic changes in the lateral compartment.

Estimation of articular cartilage properties using multivariate analysis of optical coherence tomography signal.

OBJECTIVE: The aim was to investigate the applicability of multivariate analysis of optical coherence tomography (OCT) information for determining structural integrity, composition and mechanical properties of articular cartilage. DESIGN: Equine osteochondral samples (N = 65) were imaged with OCT, and their total attenuation and backscattering coefficients (µt and µb) were measured. Subsequently, the Mankin score, optical density (OD) describing the fixed charge density, light absorbance in amide I region (Aamide), collagen orientation, permeability, fibril network modulus (Ef) and non-fibrillar matrix modulus (Em) of the samples were determined. Partial least squares (PLS) regression model was calculated to predict tissue properties from the OCT signals of the samples. RESULTS: Significant correlations between the measured and predicted mean collagen orientation (R(2) = 0.75, P < 0.0001), permeability (R(2) = 0.74, P < 0.0001), mean OD (R(2) = 0.73, P < 0.0001), Mankin scores (R(2) = 0.70, P < 0.0001), Em (R(2) = 0.50, P < 0.0001), Ef (R(2) = 0.42, P < 0.0001), and Aamide (R(2) = 0.43, P < 0.0001) were obtained. Significant correlation was also found between µb and Ef (ρ = 0.280, P = 0.03), but not between µt and any of the determined properties of articular cartilage (P > 0.05). CONCLUSION: Multivariate analysis of OCT signal provided good estimates for tissue structure, composition and mechanical properties. This technique may significantly enhance OCT evaluation of articular cartilage integrity, and could be applied, for example, in delineation of degenerated areas around cartilage injuries during arthroscopic repair surgery.

Is Inferior Mesenteric Artery Embolization Indicated Prior to Endovascular Repair of Abdominal Aortic Aneurysm?

Type II endoleak is a common condition occurring after endovascular repair of abdominal aortic aneurysms (EVAR), and may result in aneurysm sac growth and/or rupture in a small number of patients. A prophylactic strategy of inferior mesenteric artery (IMA) embolization before EVAR has been advocated, however, the benefits of this strategy are controversial. A clinical vignette allows the authors to summarize the available data about this issue and discuss the possible benefits and risks of prophylactic IMA embolization before EVAR. The authors performed a meta-analysis of available data which showed that the pooled rate of type II endoleak after IMA embolization was 19.9% (95% CI 3.4-34.7%, I2 93%) whereas it was 41.4% (95% CI 30.4-52.3%, I2 76%) in patients without IMA embolization (5 studies including 596 patients: p < .0001, OR 0.369, 95% CI 0.22-0.61, I2 27%). Since treatment for type II endoleaks is needed in less than 20% of cases and this complication can be treated successfully in 60-70% of cases resulting in an aneurysm rupture risk of 0.9%, these data indicate that embolization of patent IMA may be of no benefit in patients undergoing EVAR.

Lithography-free oxide patterns as templates for self-catalyzed growth of highly uniform GaAs nanowires on Si(111).

We report self-catalyzed growth of GaAs nanowires (NWs) on Si/SiOx patterns fabricated by a lithography-free method. The patterns are defined using droplet epitaxy of GaAs nanocrystals, spontaneous oxidation, and thermal annealing. We investigate the influence of the size and density of the nucleation sites on the NW growth process and show that this approach enables the fabrication of highly uniform GaAs NWs with controllable density. The pattern fabrication and NW growth process are studied and discussed in relation to the surface morphology and chemical properties of the Si/SiOx patterns. Furthermore, the optical quality of the NWs is investigated by photoluminescence experiments performed for GaAs­AlGaAs core­shell NWs.

Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers.

BACKGROUND: Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC). METHODS: Serum endostatin levels were measured by enzyme-linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels. RESULTS: Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall. CONCLUSIONS: Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin.

Site-dependent changes in structure and function of lapine articular cartilage 4 weeks after anterior cruciate ligament transection.

OBJECTIVE: The aim of this study was to investigate the site-dependent changes in the structure and function of articular cartilage in the lapine knee joint at a very early stage of osteoarthritis (OA), created experimentally by anterior cruciate ligament transection (ACLT). METHODS: Unilateral ACLT was performed in eight mature New Zealand white rabbits. ACL transected and contralateral (C-L) joints were prepared for analysis at 4 weeks after ACLT. Three rabbits with intact joints were used as a control group (CNTRL). Femoral groove, medial and lateral femoral condyles, and tibial plateaus were harvested and used in the analysis. Biomechanical tests, microscopy and spectroscopy were used to determine the biomechanical properties, composition and structure of the samples. A linear mixed model was chosen for statistical comparisons between the groups. RESULTS: As a result of ACLT, the equilibrium and dynamic moduli were decreased primarily in the femoral condyle cartilage. Up to three times lower moduli (P < 0.05) were observed in the ACLT group compared to the control group. Significant (P < 0.05) proteoglycan (PG) loss in the ACLT joint cartilage was observed up to a depth of 20-30% from the cartilage surface in femoral condyles, while significant PG loss was confined to more superficial regions in tibial plateaus and femoral groove. The collagen orientation angle was increased (P < 0.05) up to a cartilage depth of 60% by ACLT in the lateral femoral condyle, while smaller effects, but still significant, were observed at other locations. The collagen content was increased (P < 0.05) in the middle and deep zones of the ACLT group compared to the control group samples, especially in the lateral femoral condyle. CONCLUSION: Femoral condyle cartilage experienced the greatest structural and mechanical alterations in very early OA, as produced by ACLT. Degenerative alterations were observed especially in the superficial collagen fiber organization and PG content, while the collagen content was increased in the deep tissue of femoral condyle cartilage. The current findings provide novel information of the early stages of OA in different locations of the knee joint.

Robotic-assisted and laparoscopic ventral rectopexy in the treatment of rectal prolapse: a matched-pairs study of operative details and complications.

BACKGROUND: Laparoscopic ventral rectopexy has been proven to be safe and effective in the treatment of rectal prolapse or intussusception. Robotic-assisted surgery may offer potential benefits to this operation. This study describes the comparison of robotic-assisted and conventional laparoscopic ventral rectopexy in terms of clinical parameters, operative details, postoperative complications and short-term outcomes. METHODS: Twenty patients operated on for rectal prolapse or intussusception using the Da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale CA, USA) were prospectively followed for 3 months. The cases were pair-matched with laparoscopically operated controls from registry files. RESULTS: Mean operating time was 159 min (standard deviation; ±37 SD) and 153 min (±33 SD) and mean total time in the operating theatre 231 min (±39 SD) and 234 min (±41 SD) for robotic-assisted and laparoscopic operations, respectively. Mean blood loss was 25 ml (±49 SD) in robotic-assisted and 37 ml (±50 SD) in laparoscopic procedures. There was one (5 %) significant complication in each group. Mean length of hospital stay was 3.1 (±2 SD) and 3.3 (±1.3 SD) days for the robotic-assisted and laparoscopic groups, respectively. The subjective benefit rate was the same in both groups: 16/20 (80 %). One patient in the robotic-assisted group continued to have symptoms of obstructed defecation, and there was one recurrence of prolapse in the laparoscopic group. CONCLUSIONS: Robotic-assisted laparoscopic ventral rectopexy is safe, feasible and not more time consuming than the laparoscopic technique even at the beginning of the learning curve. The short-term results are comparable with those of laparoscopy. We found no arguments to support the routine use of robotic assistance in rectopexy operations.

Detailed analysis of inflammatory cell infiltration in colorectal cancer.

BACKGROUND: Higher-grade inflammatory infiltrate is a promising marker for better prognosis in colorectal cancer (CRC). However, the knowledge on the interrelationships between different inflammatory cells and classifications is fragmentary. METHODS: We analysed the densities of eight types of inflammatory cells in a prospectively recruited group of 117 CRC patients and determined their interrelationships and contributions to Klintrup-Mäkinen (K-M) score of overall peritumoural inflammation. We characterised the inflammatory infiltrate in relation to stage and recurrences in 24-month follow-up. RESULTS: There were high positive correlations between the inflammatory cell densities, with the exception of mast cells and CD1a+ immature dendritic cells. High K-M score associated with high peri- and intratumoural densities of CD3+, CD8+, CD68+, CD83+, and FoxP3+ cells and neutrophils. Advanced stage associated with low K-M score, as well as low CD3+, CD8+, CD83+, and FoxP3+ cell counts, of which low K-M score, low CD3(+) T-cell count, and low FoxP3+ T-cell count were linked to higher recurrence rate. CONCLUSION: The density of CRC inflammatory infiltrate declines as stage advances. Especially, low K-M score and low T-cell counts predict higher recurrence rate. The high positive correlations between the individual inflammatory markers support the value of overall inflammatory reaction scoring.

Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma.

BACKGROUND: Inflammation contributes to the pathogenesis of colorectal cancer (CRC), and cytokine levels are altered during colorectal carcinogenesis. METHODS: The serum levels of 13 cytokines and their relation to clinical and pathological parameters, and systemic inflammatory response (mGPS, CRP and neutrophil-lymphocyte ratio), were analysed from a prospective series of 148 CRC patients and 86 healthy age- and sex-matched controls. RESULTS: CRC patients had higher serum platelet-derived growth factor, interleukin (IL)-6, IL-7, and IL-8 levels and lower monocyte chemotactic protein-1 (MCP-1) levels than the controls. A logistic regression model for discriminating the patients from the controls - including the five most predictive cytokines (high IL-8, high IL-6, low MCP-1, low IL-1ra, and low IP-10) - yielded an area under curve value of 0.890 in receiver operating characteristics analysis. Serum cytokines showed distinct correlation with other markers of systemic inflammatory response, and advanced CRCs were associated with higher levels of IL-8, IL-1ra, and IL-6. A metastasised disease was accompanied by an orientation towards Th2 cytokine milieu. CONCLUSION: CRC is associated with extensive alterations in serum cytokine environment, highlighting the importance of studying relative cytokine level alterations. Serum cytokine profile shows promise in separating CRC patients from healthy controls but its clinical value is yet to be confirmed.

Structure-function relationships in osteoarthritic human hip joint articular cartilage.

OBJECTIVES: It is currently poorly known how different structural and compositional components in human articular cartilage are related to their specific functional properties at different stages of osteoarthritis (OA). The objective of this study was to characterize the structure-function relationships of articular cartilage obtained from osteoarthritic human hip joints. METHODS: Articular cartilage samples with their subchondral bone (n = 15) were harvested during hip replacement surgeries from human femoral necks. Stress-relaxation tests, Mankin scoring, spectroscopic and microscopic methods were used to determine the biomechanical properties, OA grade, and the composition and structure of the samples. In order to obtain the mechanical material parameters for the samples, a fibril-reinforced poroviscoelastic model was fitted to the experimental data obtained from the stress-relaxation experiments. RESULTS: The strain-dependent collagen network modulus (E(f)(ε)) and the collagen orientation angle exhibited a negative linear correlation (r = -0.65, P < 0.01), while the permeability strain-dependency factor (M) and the collagen content exhibited a positive linear correlation (r = 0.56, P < 0.05). The nonfibrillar matrix modulus (E(nf)) also exhibited a positive linear correlation with the proteoglycan content (r = 0.54, P < 0.05). CONCLUSION: The study suggests that increased collagen orientation angle during OA primarily impairs the collagen network and the tensile stiffness of cartilage in a strain-dependent manner, while the decreased collagen content in OA facilitates fluid flow out of the tissue especially at high compressive strains. Thus, the results provide interesting and important information of the structure-function relationships of human hip joint cartilage and mechanisms during the progression of OA.

Computed tomography detects changes in contrast agent diffusion after collagen cross-linking typical to natural aging of articular cartilage.

OBJECTIVE: The effect of threose-induced collagen cross-linking on the mechanical and diffusive properties of cartilage was investigated in vitro. In particular, we investigated the potential of Contrast Enhanced Computed Tomography (CECT) to detect changes in articular cartilage after increased collagen cross-linking, which is an age-related phenomenon. METHODS: Osteochondral plugs (Ø=6.0 mm, n=28) were prepared from intact bovine patellae (n=7). Two of the four adjacent samples, prepared from each patella, were treated with threose to increase the collagen cross-linking, while the other two specimen served as paired controls. One sample pair was mechanically tested and then mechanically injured using a material testing device. Contrast agent [ioxaglate (Hexabrix™)] diffusion was imaged in the other specimen pair for 25 h using CECT. Water fraction, collagen and proteoglycan content, collagen network architecture and the amount of cross-links [hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP) and pentosidine (Pent)] of the samples were also determined. RESULTS: Cartilage collagen cross-linking, both Pent and LP, were significantly (P<0.001) increased due to threose treatment. CECT could detect the increased cross-links as the contrast agent penetration and the diffusion flux were significantly (P<0.05) lower in the threose treated than in untreated samples. The equilibrium modulus (+164%, P<0.05) and strain dependent dynamic modulus (+47%, P<0.05) were both significantly greater in the threose treated samples than in reference samples, but there was no association between the initial dynamic modulus and the threose treatment. The water fraction, proteoglycan and collagen contents, as well as collagen architecture, were not significantly altered by the threose treatment. CONCLUSIONS: To conclude, the CECT technique was found to be sensitive at detecting changes in cartilage tissue due to increased collagen cross-linking. This is important since increased cross-linking has been proposed to be related to the increased injury susceptibility of tissue.

Disparity of innate immunity-related gene effects on asthma and allergy on Karelia.

BACKGROUND: We investigated the interactive effects of 11 innate immunity-related genes (IL10, IL12b, IL8, TLR2, TLR4, CD14, IFNGR, CC16, IFNg, CMA1, and TGFB) and four IgE response genes (IL4, IL13, IL4RA, and STAT6) with 'Western' or 'Eastern' environments/lifestyles on asthma and allergy in Karelian children. METHODS: Karelian children (412 Finnish and 446 Russian) were recruited and assessed for a range of allergic conditions, with 24 single-nucleotide polymorphisms genotyped in 15 genes. RESULTS: The genotype-phenotype relationships differed in Finnish and Russian Karelian children. The interaction between polymorphisms and the variable representing 'Western' and 'Eastern' environments/ lifestyles was significant for IL10-1082 (p = 0.0083) on current rhinitis, IL12b 6408 on current conjunctivitis (p = 0.016) and atopy (p = 0.034), IL8 781 on atopic eczema (p = 0.0096), CD14 -550 on current rhinitis (p = 0.022), IFNgR1 -56 on atopic eczema(p = 0.038), and STAT6 2964 on current itchy rash (p = 0.037) and total serum IgE (p = 0.042). In addition, the G allele of IL13 130 was associated with a lower level of total serum IgE in Finnish (p = 0.003) and Russian (p = 0.01) children and overall (pooling the two populations together, p = 0.00006). After adjusting for multiple tests, the association between IL13 130 and IgE and the interactive effects of IL10-1082 on current rhinitis and IL8 781 on atopic eczema were significant by controlling a false-positive rate of 0.05 and 0.10, respectively. CONCLUSIONS: Living in an Eastern vs. Western environment was associated with a different genetic profile associated with asthma and allergy in the Karelian populations.