Shock wave lithotripsy, for the treatment of kidney stones, results in changes to routine blood tests and novel biomarkers: a prospective clinical pilot-study.

BACKGROUND: The number of patients undergoing shock wave lithotripsy (SWL) for kidney stones is increasing annually, and as such the development of post-operative complications, such as haematuria and acute kidney injury (AKI) following SWL, is likely to increase. The aim of the study was to evaluate changes in routine blood and novel biomarkers following SWL, for the treatment of kidney stones. METHODS: Twelve patients undergoing SWL for solitary unilateral kidney stones were recruited. From patients (8 males and 4 females) aged between 31 and 72 years (median 43 years), venous blood samples were collected pre-operatively (baseline), at 30, 120 and 240 min post-operatively. Routine blood tests were performed using a Sysmex XE-5000, and Beckman Coulter AU5800 and AU680 analysers. NGAL, IL-18, IL-6, TNF-α, IL-10 and IL-8 concentrations were determined using commercially available ELISA kits. RESULTS: Significant (p ≤ 0.05) changes were observed in several blood parameters following SWL. NGAL concentration significantly increased, with values peaking at 30 min post-treatment (p = 0.033). Although IL-18 concentration increased, these changes were not significant (p = 0.116). IL-6 revealed a statistically significant rise from pre-operative up to 4 h post-operatively (p < 0.001), whilst TNF-α significantly increased, peaking at 30 min post-SWL (p = 0.05). There were no significant changes to IL-10 and IL-8 concentrations post-SWL (p > 0.05). CONCLUSIONS: Changes to routine blood tests and specific biomarkers, in the future, may be more useful for clinicians. In turn, identification of a panel of biomarkers could provide valuable data on "normal" physiological response after lithotripsy. Ultimately, studies could be expanded to identify or predict those patients at increased risk of developing post-operative complications, such as acute kidney injury or. These studies, however, need validating involving larger cohorts.

Safety and efficacy of Holmium laser enucleation of the prostate (HoLEP) in patients with previous transperineal biopsy (TPB): outcomes from a dual-centre case-control study.

BACKGROUND: We investigated the surgical feasibility, safety and effectiveness of 50 W (low power) Holmium Laser enucleation of the prostate (HoLEP) in patients who have undergone previous template biopsy of the prostate (TPB). METHODS: Data encompassing pre-operative baseline characteristics, intra-operative measures and post-operative outcomes was collected for 109 patients undergoing HoLEP across two UK centres. Patients were stratified into two groups; group 1 (n = 24) had undergone previous TPB were compared with 'controls' (no previous TPB) in group 2 (n = 85). The primary outcome was successful HoLEP. RESULTS: There were no statistically significant differences in either key baseline characteristics or mass of prostate enucleated between groups 1 and 2. There was no statistically significant difference in enucleation or morcellation times parameters between the two groups other than enucleation efficiency in favour of group 1 (p = 0.024). Functional outcomes improved, without any statistically significant difference, in both groups. CONCLUSIONS: In patients with a previous TPB, HoLEP is surgically feasible, safe and effective. TPB should not be considered a contraindication to HoLEP. Our work provides a strong foundation for further research in this area.

Prolonged and Increased Usage of a Flexible Ureterorenoscope: The Maelor FURS Protocol.

We present our point of technique detailing the specific preoperative and postoperative steps used in our institution to prolong the use of a flexible ureterorenoscope, and discuss the potential cost-effectiveness of this protocol. We have used a single flexible ureterorenoscope, for 145 consecutive cases to date, using the protocol described in this article. This prolonged use has resulted in a calculated cost per case of £273.48 GBP. We have described our experience of a dedicated protocol to prolong the usage of a single flexible ureterorenoscope. We would consider recommending the technique described in this article, to prolong flexible ureterorenoscope usage in a cost-effective manner.

Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review.

This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect.

The effects of physical contact type on the internal and external demands during a rugby league match simulation protocol.

The aim of this study was to investigate how the type of contact influences physiological, perceptual and locomotive load during a simulated rugby league match. Eleven male university rugby league players performed two trials of the rugby league movement simulation protocol for interchange forwards with a traditional soft tackle bag and a weighted tackle sled to replicate contact demands. The interchange forward-specific simulation was chosen given the contact frequency is higher for this group of players compared to whole match players. Locomotive rate, sprint speed, tackle intensity, heart rate (HR) and rating of perceived exertion were analysed during the first and second bouts that replicated two ~23 min on-field passages. Countermovement jump (CMJ) was measured before and immediately after each trial. More time was spent in heart rate zone between 91 and 100% HRpeak during the first (effect size ± 90% confidence interval: 0.44 ± 0.49) and second bouts (0.44 ± 0.43), and larger (0.6 ± 0.69) decrements in CMJ performance were observed during the sled trial (5.9, s = 4.9%) compared to the bag trial (2.6, s = 5.4%). Changing the type of contact during the match simulation subtly altered both the internal and external loads on participants. Using a standard tackle bag results in faster sprint speed to contact, but lower overall high-intensity running. Conversely, a heavier tackle object increases the internal load and results in greater lower limb neuromuscular fatigue as reflected by the decrease in CMJ performance.

Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures.

BACKGROUND: With an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective). METHODS: Test subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever. RESULTS: THR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections. CONCLUSIONS: The most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.

Tourniquet-applied upper limb orthopaedic surgery results in increased inflammation and changes to leukocyte, coagulation and endothelial markers.

PURPOSE: During this pilot clinical study, patients scheduled for elective tourniquet-applied upper limb orthopaedic surgery were recruited to investigate the effects of surgery on various biological markers (n = 10 patients). METHODS: Three venous blood samples were collected from the arm at the ante-cubital fossa, at baseline (pre-operatively), 5 and 15 minutes after reperfusion (post-operatively). Neutrophil and monocyte leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte activation was investigated by measuring the cell surface expression of CD62L (L-selectin), CD11b (Mac-1) and the intracellular production of hydrogen peroxide (H2O2), via flow cytometry. C-reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma concentrations of protein C and von Willebrand factor (vWF) were measured using enzyme-linked fluorescent assays (ELFA). RESULTS: Following tourniquet-applied upper limb orthopaedic surgery, there was a decrease in neutrophil CD62L expression (p = 0.001), an increase in CD11b expression and in the intracellular production of H2O2 by neutrophils and monocytes (p<0.05). An increase in CRP concentration (p<0.001), a decrease in protein C concentration (p = 0.004), with a trend towards elevated vWF levels (p = 0.232) were also observed during this time. CONCLUSIONS: Conventionally, patients undergoing orthopaedic surgery have been monitored in the peri-operative period by means of CRP, which is a non-specific marker of inflammation. This test cannot differentiate between inflammation due to current or pre-existing disease processes and the development of ischaemia-reperfusion injury surgery. The findings from this study suggest that markers such as CD11b, protein C and H2O2 may provide alternative ways of assessing leukocyte and coagulation activation peri-operatively. It is proposed that by allowing orthopaedic surgeons access to laboratory markers such as CD11b, protein C and H2O2, an accurate assessment of the extent of inflammation due to surgery per se could be made.

Total hip and knee replacement surgery results in changes in leukocyte and endothelial markers.

BACKGROUND: It is estimated that over 8 million people in the United Kingdom suffer from osteoarthritis. These patients may require orthopaedic surgical intervention to help alleviate their clinical condition. Investigations presented here was to test the hypothesis that total hip replacement (THR) and total knee replacement (TKR) orthopaedic surgery result in changes to leukocyte and endothelial markers thus increasing inflammatory reactions postoperatively. METHODS: During this 'pilot study', ten test subjects were all scheduled for THR or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1) and CD62L cell surface expression, intracellular production of H(2)O(2 )and elastase were measured as markers of leukocyte function. Von Willebrand factor (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured as markers of endothelial activation. RESULTS: The results obtained during this study demonstrate that THR and TKR orthopaedic surgery result in similar changes of leukocyte and endothelial markers, suggestive of increased inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in a leukocytosis, this being demonstrated by an increase in the total leukocyte concentration following surgery. Evidence of leukocyte activation was demonstrated by a decrease in CD62L expression and an increase in CD11b expression by neutrophils and monocytes respectively. An increase in the intracellular H(2)O(2 )production by neutrophils and monocytes and in the leukocyte elastase concentrations was also evident of leukocyte activation following orthopaedic surgery. With respect to endothelial activation, increases in vWF and sICAM-1 concentrations were demonstrated following surgery. CONCLUSION: In general it appeared that most of the leukocyte and endothelial markers measured during these studies peaked between days 1-3 postoperatively. It is proposed that by allowing orthopaedic surgeons access to alternative laboratory markers such as CD11b, H(2)O(2 )and elastase, CD62L, vWF and sICAM-1, an accurate assessment of the extent of inflammation due to surgery per se could be made. Ultimately, the leukocyte and endothelial markers assessed during this investigation may have a role in monitoring potential infectious complications that can occur during the postoperative period.

Mild episodes of tourniquet-induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers.

BACKGROUND: Monocytes and neutrophils are examples of phagocytic leukocytes, with neutrophils being considered as the 'chief' phagocytic leukocyte. Both monocytes and neutrophils have been implicated to play a key role in the development of ischaemia-reperfusion injury, where they are intrinsically involved in leukocyte-endothelial cell interactions. In this pilot study we hypothesised that mild episodes of tourniquet induced forearm ischaemia-reperfusion injury results in leukocyte activation and changes in inflammatory and coagulation markers. METHODS: Ten healthy human volunteers were recruited after informed consent. None had any history of cardiovascular disease with each subject volunteer participating in the study for a 24 hour period. Six venous blood samples were collected from each subject volunteer at baseline, 10 minutes ischaemia, 5, 15, 30, 60 minutes and 24 hours reperfusion, by means of a cannula from the ante-cubital fossa. Monocyte and neutrophil leukocyte sub-populations were isolated by density gradient centrifugation techniques. Leukocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. The cell surface expression of CD62L (L-selectin), CD11b and the intracellular production of hydrogen peroxide (H2O2) were measured via flow cytometry. C-reactive protein (CRP) was measured using a clinical chemistry analyser. Plasma concentrations of D-dimer and von Willebrand factor (vWF) were measured using enzyme-linked fluorescent assays (ELFA). RESULTS: During ischaemia-reperfusion injury, there was a decrease in CD62L and an increase in CD11b cell surface expression for both monocytes and neutrophils, with changes in the measured parameters reaching statistical significance (p =< 0.05). A significant decrease in peripheral blood leukocyte concentration was observed during this process, which was measured to assess the degree of leukocyte trapping in the micro-circulation (p =< 0.001). There was an increase in the intracellular production of H2O2 production by leukocyte sub-populations, which was measured as a marker of leukocyte activation. Intracellular production of H2O2 in monocytes during ischaemia-reperfusion injury reached statistical significance (p = 0.014), although similar trends were observed with neutrophils these did not reach statistical significance. CRP was measured to assess the inflammatory response following mild episodes of ischaemia-reperfusion injury and resulted in a significant increase in the CRP concentration (p =< 0.001). There were also increased plasma concentrations of D-dimer and a trend towards elevated vWF levels, which were measured as markers of coagulation activation and endothelial damage respectively. Although significant changes in D-dimer concentrations were observed during ischaemia-reperfusion injury (p = 0.007), measurement of the vWF did not reach statistical significance. CONCLUSION: Tourniquet induced forearm ischaemia-reperfusion injury results in increased adhesiveness, trapping and activation of leukocytes. We report that, even following a mild ischaemic insult, this leukocyte response is immediately followed by evidence of increased inflammatory response, coagulation activity and endothelial damage. These results may have important implications and this pilot study may lead to a series of trials that shed light on the mechanisms of ischaemia-reperfusion injury, including potential points of therapeutic intervention for pathophysiological conditions.