Additive influence of exercise pressor reflex activation on Valsalva responses in white and black adults.

AIM: This study aimed to determine if activation of the exercise pressor reflex exerts additive or redundant influences on the autonomic responses to the Valsalva maneuver (VL), and if these responses differ between White and Black or African American (B/AA) individuals. METHODS: Twenty participants (B/AA n = 10, White n = 10) performed three separate experimental trials. In the first trial, participants performed two VLs in a resting condition. In a second trial, participants performed 5 min of continuous handgrip (HG) exercise at 35% of the predetermined maximal voluntary contraction. In a third and final trial, participants repeated the 5-min bout of HG while also performing two VLs during the 4th and 5th minutes. Beat by beat blood pressure and heart rate (HR) were recorded continuously and the absolute systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and heart rate (HR) responses were reported for phases I-IV of each VL. RESULTS: No significant group by trial interactions or main effects of group were observed for any phase of the VL (all p ≥ 0.36). However, significant main effects of time were observed for blood pressure and heart rate during phases IIa-IV (all p ≤ 0.02). Specifically, the addition of HG exercise exaggerated the hypertensive responses during phases IIb and IV (all p ≤ 0.04) and blunted the hypotensive responses during phases IIa and III (all p ≤ 0.01). CONCLUSIONS: These results suggest that activation of the exercise pressor reflex exerts an additive influence on autonomic responses to the VL maneuver in both White and B/AA adults.

A 10-mg dose of amiloride increases time to failure during blood-flow-restricted plantar flexion in healthy adults without influencing blood pressure.

Amiloride has been shown to inhibit acid-sensing ion channels (ASICs), which contribute to ischemia-related muscle pain during exercise. The purpose of this study was to determine if a single oral dose of amiloride would improve exercise tolerance and attenuate blood pressure during blood-flow-restricted (BFR) exercise in healthy adults. Ten subjects (4 females) performed isometric plantar flexion exercise with BFR (30% maximal voluntary contraction) after ingesting either a 10-mg dose of amiloride or a volume-matched placebo (random order). Time to failure, time-tension index (TTI), and perceived pain (visual analog scale) were compared between the amiloride and placebo trials. Mean blood pressure, heart rate, blood pressure index (BPI), and BPI normalized to TTI (BPInorm) were also compared between trials using both time-matched (TM50 and TM100) and effort-matched (T50 and T100) comparisons. Time to failure (+69.4 ± 63.2 s, P < 0.01) and TTI (+1,441 ± 633 kg·s, P = 0.02) were both significantly increased in the amiloride trial compared with placebo, despite no increase in pain (+0.4 ± 1.7 cm, P = 0.46). In contrast, amiloride had no significant influence on the mean blood pressure or heart rate responses, nor were there any significant differences in BPI or BPInorm between trials when matched for time (all P ≥ 0.13). When matched for effort, BPI was significantly greater in the amiloride trial (+5,300 ± 1,798 mmHg·s, P = 0.01), likely owing to an increase in total exercise duration. In conclusion, a 10-mg oral dose of amiloride appears to significantly improve the tolerance to BFR exercise in healthy adults without influencing blood pressure responses.

Systemic and regional hemodynamic response to activation of the exercise pressor reflex in patients with peripheral artery disease.

Patients with peripheral artery disease (PAD) have an accentuated exercise pressor reflex (EPR) during exercise of the affected limb. The underlying hemodynamic changes responsible for this, and its effect on blood flow to the exercising extremity, are unclear. We tested the hypothesis that the exaggerated EPR in PAD is mediated by an increase in total peripheral resistance (TPR), which augments redistribution of blood flow to the exercising limb. Twelve patients with PAD and 12 age- and sex-matched subjects without PAD performed dynamic plantar flexion (PF) using the most symptomatic leg at progressive workloads of 2-12 kg (increased by 1 kg/min until onset of fatigue). We measured heart rate, beat-by-beat blood pressure, femoral blood flow velocity (FBV), and muscle oxygen saturation (SmO2) continuously during the exercise. Femoral blood flow (FBF) was calculated from FBV and baseline femoral artery diameter. Stroke volume (SV), cardiac output (CO), and TPR were derived from the blood pressure tracings. Mean arterial blood pressure and TPR were significantly augmented in PAD compared with control during PF. FBF increased during exercise to an equal extent in both groups. However, SmO2 of the exercising limb remained significantly lower in PAD compared with control. We conclude that the exaggerated pressor response in PAD is mediated by an abnormal TPR response, which augments redistribution of blood flow to the exercising extremity, leading to an equal rise in FBF compared with controls. However, this increase in FBF is not sufficient to normalize the SmO2 response during exercise in patients with PAD.NEW & NOTEWORTHY In this study, peripheral artery disease (PAD) patients and healthy control subjects performed graded, dynamic plantar flexion exercise. Data from this study suggest that previously reported exaggerated exercise pressor reflex in patients with PAD is driven by greater vasoconstriction in nonexercising vascular territories which also results in a redistribution of blood flow to the exercising extremity. However, this rise in femoral blood flow does not fully correct the oxygen deficit due to changes in other mechanisms that require further investigation.

Central and peripheral modulation of exercise pressor reflex sensitivity after nonfatiguing work.

Autonomic blood pressure control is fundamentally altered during a single bout of exercise, as evidenced by the downward resetting of the baroreflex following exercise (postexercise hypotension). However, it is unclear if an acute bout of exercise is also associated with a change in the sensitivity of the exercise pressor response to a controlled stimulus, such as a static contraction. This study tested the hypothesis that the blood pressure response to a controlled static contraction would be attenuated after unilateral cycling of the contralateral (opposite) leg, but preserved after cycling of the ipsilateral (same) leg. To test this, the blood pressure response to 90 s of isometric plantar flexion [50% maximal voluntary contraction (MVC)] was compared before and after 20 min of contralateral and ipsilateral single-leg cycling at 20% peak oxygen consumption and rest (control) in 10 healthy subjects (three males and seven females). The mean arterial pressure response was significantly attenuated after contralateral single-leg cycling (+9.8 ± 7.5% ∆mmHg vs. +6.7 ± 6.6% ∆mmHg pre and postexercise, respectively, P = 0.04) and rest (+9.0 ± 7.5% ∆mmHg vs. +6.6 ± 5.2% ∆mmHg pre and postexercise, respectively, P = 0.03). In contrast, the pressor response nonsignificantly increased following ipsilateral single-leg cycling (+5.5 ± 5.2% ∆mmHg vs. +8.9 ± 7.2% ∆mmHg pre and postexercise, respectively, P = 0.08). The heart rate, leg blood flow, and leg conductance responses to plantar flexion were not affected by any condition (P ≥ 0.12). These results are consistent with the notion that peripheral, but not central mechanisms promote exercise pressor reflex sensitivity after exercise.

CCTA in patients with positive troponin and low clinical suspicion for ACS: a useful diagnostic option to exclude obstructive CAD.

PURPOSE: It is uncertain whether patients with elevated troponin and non-classical presentation of acute coronary syndrome (ACS) should receive coronary CT angiography (CCTA). A proportion of these patients will have no coronary artery disease (CAD) and would benefit from non-invasive investigations and expedited discharge. Objectives were to determine most common diagnoses and rate of ACS among patients with positive troponin and low clinical suspicion of ACS who received CCTA. METHODS: IRB approved retrospective analysis of 491 consecutive patients in a level I trauma center ED referred for CCTA between April 4, 2015 to April 2, 2017. Patients were included if there was an elevated troponin (TnI > 0.045 µg/L) and atypical chest pain within 24 h prior to imaging. One hundred one patients met inclusion criteria; 17 excluded due to technical factors or history. Scans performed on dual-source CT. RESULTS: Eighty-four patients (47 men, 37 women) with median TnI of 0.11 ± 0.21 µg/L underwent CCTA 8.20 ± 6.41 h after first elevated Tn. Mean age was 53.2 ± 14.6 years. CCTA demonstrated absence of CAD in 39 patients (46.4%; 20 M, 19 F). CAD < 25% stenosis was observed in 24 (28.6%; 9 M, 15 F). CAD with 25-50% stenosis was observed in seven (8.3%; six M, one F). CAD > 50% stenosis was observed in 11 (13.1%; 9 M, 2 F), and non-diagnostic in three (3.6%, 3 M, 0 F). Forty-six (56.8%) were discharged directly from ED with median stay 15.82 ± 6.41 h. CONCLUSIONS: Use of CCTA in ED patients with elevated troponin and low clinical suspicion for ACS allowed obstructive CAD to be excluded in 83%.

How Do Le Fort-Type Fractures Present in a Pediatric Cohort?

PURPOSE: Le Fort-type fractures are very rare in children, and there is a paucity of literature presenting their frequency and characteristics. The purpose of this study was to determine the etiology, frequency, and fracture patterns of children with severe facial trauma associated with pterygoid plate fractures in a pediatric cohort. PATIENTS AND METHODS: We performed a retrospective cohort study of all children aged younger than 16 years with pterygoid plate and facial fractures who presented to our institute between 1990 and 2010. Patient charts and radiologic records were reviewed for demographic and fracture characteristics. Patients were categorized into 2 groups as per facial fracture pattern: non-Le Fort-type fractures (group A) and Le Fort-type fractures (group B). Other variables including dentition age, frontal sinus development, mechanism of injury, injury severity, and concomitant injuries were recorded. Univariate methods were used to compare groups. RESULTS: We identified 24 children; 25% were girls, and 20.8% were of nonwhite race. Most presented with Le Fort-type fracture patterns (group B, 66.7%). Age was significantly different between group A and group B (mean, 5.9 years and 9.9 years, respectively; P = .009). No significant differences in Injury Severity Score, rate of operative repair, and length of stay were found between groups. CONCLUSIONS: Most children with severe facial fractures and pterygoid plate fractures presented with Le Fort-type fracture patterns in our cohort. The mean age of children with Le Fort-type fractures was greater than in those with non-Le Fort-type patterns. However, Le Fort-type fractures did occur in younger children with deciduous and mixed dentition.

Detection of Bone Marrow Edema in Nondisplaced Hip Fractures: Utility of a Virtual Noncalcium Dual-Energy CT Application.

Purpose To quantify the sensitivity and specificity of dual-energy computed tomographic (CT) virtual noncalcium images in the detection of nondisplaced hip fractures and to assess whether obtaining these images as a complement to bone reconstructions alters sensitivity, specificity, or diagnostic confidence. Materials and Methods The clinical research ethics board approved chart review, and the requirement to obtain informed consent was waived. The authors retrospectively identified 118 patients who presented to a level 1 trauma center emergency department and who underwent dual-energy CT for suspicion of a nondisplaced traumatic hip fracture. Clinical follow-up was the standard of reference. Three radiologists interpreted virtual noncalcium images for traumatic bone marrow edema. Bone reconstructions for the same cases were interpreted alone and then with virtual noncalcium images. Diagnostic confidence was rated on a scale of 1 to 10. McNemar, Fleiss κ, and Wilcoxon signed-rank tests were used for statistical analysis. Results Twenty-two patients had nondisplaced hip fractures and 96 did not have hip fractures. Sensitivity with virtual noncalcium images was 77% and 91% (17 and 20 of 22 patients), and specificity was 92%-99% (89-95 of 96 patients). Sensitivity increased by 4%-5% over that with bone reconstruction images alone for two of the three readers when both bone reconstruction and virtual noncalcium images were used. Specificity remained unchanged (99% and 100%). Diagnostic confidence in the exclusion of fracture was improved with combined bone reconstruction and virtual noncalcium images (median score: 10, 9, and 10 for readers 1, 2, and 3, respectively) compared with bone reconstruction images alone (median score: 9, 8, and 9). Conclusion When used as a supplement to standard bone reconstructions, dual-energy CT virtual noncalcium images increased sensitivity for the detection of nondisplaced traumatic hip fractures and improved diagnostic confidence in the exclusion of these fractures. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 17, 2017.

Connective tissue growth factor (CTGF/CCN2) in haemophilic arthropathy and arthrofibrosis: a histological analysis.

INTRODUCTION: Joint haemorrhage is the principal clinical manifestation of haemophilia frequently leading to advanced arthropathy and arthrofibrosis, resulting in severe disability. The degree and prevalence of arthrofibrosis in hemophilic arthropathy is more severe than in other forms of arthropathy. Expression of connective tissue growth factor (CTGF) has been linked to many fibrotic diseases, but has not been studied in the context of haemophilic arthropathy. AIM: We aim to compare synovial tissues histologically from haemophilia and osteoarthritis patients with advanced arthropathy in order to compare expression of proteins that are possibly aetiologic in the development of arthrofibrosis. METHODS: Human synovial tissues were obtained from 10 haemophilia and 10 osteoarthritis patients undergoing joint surgery and processed for histology and immunohistochemistry. RESULTS: All samples from haemophilia patients had synovitis with hypertrophy and hyperplasia of synovial villi. Histologically, synovial tissues contained hyperplastic villi with increased cellularity and abundant haemosiderin- and ferritin-pigmented macrophage-like cells (HMCs), with a perivascular localization in the sub-surface layer. CTGF staining was observed in the surface layer and sub-surface layer in all haemophilia patients, exclusively co-localizing with HMCs. Quantification showed that the extent of CTGF-positive areas was correlated with the degree of detection of HMCs. CTGF was not observed in any of the samples from osteoarthritis patients. CONCLUSION: Using histological analysis, we showed that CTGF expression is elevated in haemophilia patients with arthrofibrosis and absent in patients with osteoarthritis. Additionally, we found that CTGF is always associated with haemosiderin-pigmented macrophage-like cells, which suggests that CTGF is produced by synovial A cells following the uptake of blood breakdown products.

The Impact of Financial Conflicts of Interest in Plastic Surgery: Are They All Created Equal?

BACKGROUND: Recently, several studies have demonstrated that articles that disclose conflicts of interests (COI) are associated with publication of positive results. The purpose of this study was to learn more about the different types of COI as they relate to the general topic of COI in plastic surgery. Specifically, we aimed to examine whether different types of COI are more likely than others to be associated with the presentation of positive findings. METHODS: We reviewed all original articles in Annals of Plastic Surgery, Journal of Plastic, Reconstructive, and Aesthetic Surgery, and Plastic & Reconstructive Surgery from January 1, 2012, to December 31, 2013. All scientific articles were analyzed, and several article characteristics were extracted. Disclosed COI were categorized into the following categories: consultant/employee, royalties/stock options, and research support. The findings reported in each article abstract were blindly graded as reporting a positive, negative, neutral, or not applicable result. A multivariable analysis was performed to determine whether an association existed between certain types of COI and publication of positive conclusions. RESULTS: A total of 3124 articles were identified of which 1185 fulfilled the inclusion criteria. Financial COI were reported in 153 studies (12.9%). The most common type of COI was "research support" (7.3%), whereas the least common was "royalties/stock options" (1.2%). Rates of different types of COI varied significantly by plastic surgery subspecialty field (P < 0.001). In the multivariable analysis, authors who disclosed COI related to research support, consultant/employee, and royalties/stock options were 1.31, 6.62, and 8.72 times more likely, respectively, to publish positive findings when compared with authors that disclosed no COI after correcting for potential confounding factors. However, consultancy/employee status was the only COI category statistically associated with publication of positive results (P < 0.001). CONCLUSIONS: Self-reported COI are uncommon in plastic surgery research. Our results provide evidence that certain types of financial COI are more likely than others to be associated with the presentation of positive findings. This analysis suggests that certain investigators may be more biased, consciously or unconsciously, by the type of financial benefit offered by industry.

Dual-source CT in blunt trauma patients: elimination of diaphragmatic motion using high-pitch spiral technique.

The purpose of this study was to compare diaphragmatic motion on dual-source high-pitch (DS-HP) and conventional single-source (SS) CT scans in trauma patients. Seventy-five consecutive trauma patients who presented to a level one trauma center over a 6-month period were scanned with a standardized whole body trauma CT protocol including both DS-HP chest (pitch = 2.1-2.5) and SS abdominal CT scans. Subjective analysis of diaphragmatic motion was performed by two readers using a four-point motion scale in seven regions of the diaphragm on coronal and axial slices. An overall confidence score to exclude a diaphragmatic tear was determined (1 to 10, 10: completely confident and 1: impossible to exclude). Wilcoxon rank sum tests were used for statistical analysis, and p < 0.05 was considered significant. Mean confidence score of 9.85 for DS-HP was significantly better than the mean score of 7.66 for SS images (p < 0.0001). Diaphragmatic motion scores and subjective diaphragmatic motion artifact on coronal and axial images were significantly better for DS-HP images in all areas when compared individually (p < 0.0001) and overall (p < 0.0001). Regions of DS-HP (99.2 %) were diagnostic, whereas only 87.0 % % regions on SS were. Complete agreement of motion scores was present in 92 % of cases, with moderate overall agreement for confidence to exclude a diaphragmatic tear (κ = 0.45). Dual-source high-pitch CT scanning is advantageous as it allows for significantly better evaluation of diaphragmatic structures by minimizing motion artifacts on images of freely breathing trauma patients.

Ankle fusion in patients with haemophilia.

Ankle fusion in patients with haemophilia is a well-accepted treatment for end-stage arthropathy. However, current published outcome data are based on small sample sizes and generally short-term follow-up. The aim of this study was to evaluate the long-term results of ankle fusion in a large group of haemophilic patients treated at a single institution. The results of 57 ankle fusions performed on 45 patients between 1971 and 2010 were reviewed retrospectively. Data were gathered for type and severity of haemophilia, HIV status, fixation technique, postoperative complications and requirement of additional surgeries. A modified American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score was calculated for 20 ankles available for follow-up. Patients were followed for a mean of 6.6 years. There were no intra-operative or immediate postoperative complications related to fusion of the ankle. The overall non-union rate was 10.4% for tibio-talar fusion and 8.3% for sub-talar fusion. This rate was reduced to 3.7% and 5.6%, respectively, after the introduction of newer surgical techniques in 1995. None of these non-unions required revision surgery. The modified AOFAS scale demonstrated that 75% had no pain in the operated ankle a mean of 7.2 years following surgery. The remaining 25% scored their average pain as 3 of 10. The functional portion of the score suggested that patients have good alignment, minimal activity limitations or gait abnormalities, and can walk long distances. We conclude that ankle fusion successfully relieves pain and provides a good functional outcome. It is an appropriate treatment for end-stage haemophilic arthropathy of the ankle.

Agreement between multiparametric MRI (PIVOT), Doppler ultrasound, and near-infrared spectroscopy-based assessments of skeletal muscle oxygenation and perfusion.

Skeletal muscle perfusion and oxygenation are commonly evaluated using Doppler ultrasound and near-infrared spectroscopy (NIRS) techniques. However, a recently developed magnetic resonance imaging (MRI) sequence, termed PIVOT, permits the simultaneous collection of skeletal muscle perfusion and T2* (an index of skeletal muscle oxygenation). PURPOSE: To determine the level of agreement between PIVOT, Doppler ultrasound, and NIRS-based assessments of skeletal muscle perfusion and oxygenation. METHODS: Twelve healthy volunteers (8 females, 25 ± 3 years, 170 ± 11 cm, 71.5 ± 8.0 kg) performed six total reactive hyperemia protocols. During three of these reactive hyperemia protocols, Tissue Saturation Index (TSI) and oxygenated hemoglobin (O2Hb) were recorded from the medial gastrocnemius (MG) and tibialis anterior (TA), and blood flow velocity was recorded from the popliteal artery (BFvpop) via Doppler Ultrasound. The other three trials were performed inside the bore of a 3 T MRI scanner, and the PIVOT sequence was used to assess perfusion (PIVOTperf) and oxygenation (T2*) of the medial gastrocnemius and tibialis anterior muscles. Positive incremental areas under the curve (iAUC) and times to peak (TTP) were calculated for each variable, and the level of agreement between collection methods was evaluated via Bland-Altman analyses and Spearman's Rho correlation analyses. RESULTS: The only significant bivariate relationships observed were between the T2* vs. TSI iAUC and PIVOTperf vs. BFvpop values recorded from the MG. Significant mean differences were observed for all comparisons (all P ≤ 0.038), and significant proportional biases were observed for the PIVOTperf vs. tHb TTP (R2 = 0.848, P < 0.001) and T2* vs. TSI TTP comparisons in the TA (R2 = 0.488, P = 0.011), and the PIVOTperf vs. BFvpop iAUC (R2 = 0.477, P = 0.013) and time to peak (R2 = 0.851, P < 0.001) comparisons in the MG. CONCLUSIONS: Our findings suggest that the PIVOT technique has, at best, a moderate level of agreement with Doppler ultrasound and NIRS assessment methods and is subject to significant proportional bias. These findings do not challenge the accuracy of either measurement technique but instead reflect differences in the vascular compartments, sampling volumes, and parameters being evaluated.

Autonomic and vascular function testing in collegiate athletes following SARS-CoV-2 infection: an exploratory study.

Introduction: Recent studies suggest that SARS-CoV-2 infection alters autonomic and vascular function in young, otherwise healthy, adults. However, whether these alterations exist in young competitive athletes remains unknown. This study aimed to assess the effects of COVID-19 on cardiac autonomic control and vascular function in collegiate athletes who tested positive for COVID-19, acknowledging the limitations imposed by the early stages of the pandemic. Methods: Sixteen collegiate athletes from various sports underwent a battery of commonly used autonomic and vascular function tests (23 ± 9, range: 12-44 days post-infection). Additionally, data from 26 healthy control participants were included. Results: In response to the Valsalva maneuver, nine athletes had a reduced early phase II blood pressure response and/or reduced Valsalva ratio. A depressed respiratory sinus arrhythmia amplitude was observed in three athletes. Three athletes became presyncopal during standing and did not complete the 10-min orthostatic challenge. Brachial artery flow-mediated dilation, when allometrically scaled to account for differences in baseline diameter, was not different between athletes and controls (10.0% ± 3.5% vs. 7.1% ± 2.4%, p = 0.058). Additionally, no differences were observed between groups when FMD responses were normalized by shear rate (athletes: 0.055% ± 0.026%/s-1, controls: 0.068% ± 0.049%/s-1, p = 0.40). Discussion: Few atypical and borderline responses to autonomic function tests were observed in athletes following an acute SARS-CoV-2 infection. The most meaningful autonomic abnormality being the failure of three athletes to complete a 10-min orthostatic challenge. These findings suggest that some athletes may develop mild alterations in autonomic function in the weeks after developing COVID-19, while vascular function is not significantly impaired.

Gastropulmonary fistula following sleeve gastrectomy: use of dual-energy CT following oral contrast administration to confirm diagnosis.

Gastropulmonary fistula represents a late complication of sleeve gastrectomy and, if untreated, has high morbidity and mortality. We present a case report of a 29-year-old female who developed a gastropulmonary fistula 3 years after a sleeve gastrectomy. Dual energy CT of the chest and upper abdomen demonstrated a cavitary left lower lobe lesion associated with a focal complex pleural effusion; iodinated oral contrast confirmed the presence of a fistulous connection through the left hemidiaphragm. The patient underwent a thoracotomy, left lower lobectomy, resection of the infected segment of the left hemidiaphragm with primary repair, drainage of a subphrenic abscess and a gastric repair; the patient was discharged 2-weeks postprocedure.

Opinions on radiosynovectomy for chronic haemophilic synovitis: point/counterpoint.

Joint bleeding is the hallmark of severe haemophilia and the major cause of disability in patients with this coagulopathy. Repeated bleeding into the same joint can lead to chronic synovitis and progressive arthropathy. Radiosynovectomy is one option for the treatment of chronic haemophilic synovitis, but concerns about the risks of exposure to ionizing radiation have divided clinicians as to the safety and appropriate use of the procedure. This article presents two differing viewpoints, one from a pair of orthopaedic surgeons who collectively have performed more than 300 radiosynovectomies in patients with haemophilia. They maintain that radiosynovectomy is a simple, effective, safe and low-cost technique children and adults with chronic haemophilic synovitis. The other perspective is from an experienced haemophilia treater who directs a major US haemophilia treatment centre. She believes that unresolved questions about the safety of radiation exposure in children argue against the use of radiosynovectomy in paediatric patients with haemophilia.

Knee arthropathy: when things go wrong.

Joint bleeding, or haemarthrosis, is the most common type of bleeding episode experienced by individuals with haemophilia A and B. This leads to changes within the joints, including synovial proliferation, which results in further bleeding and chronic synovitis. Blood in the joint can also directly damage the cartilage, and with repeated bleeding, there is progressive destruction of both cartilage and bone. The end result is known as haemophilic arthropathy which is characterized by pain, stiffness and deformity. The joint most commonly affected is the knee. Haemophilic arthropathy can be prevented through regular prophylaxis and physiotherapy. However, when necessary, there are multiple surgical and non-surgical options available. These procedures are indicated to improve the joint function and quality of life for haemophilic patients worldwide. In this review, the role of surgical and non-surgical treatment of advanced knee arthropathy and its complications will be described.

Phylogenetic relationships among global populations of Pseudomonas syringae pv. actinidiae.

ABSTRACT Pseudomonas syringae pv. actinidiae, the causal agent of canker in kiwifruit (Actinidia spp.) vines, was first detected in Japan in 1984, followed by detections in Korea and Italy in the early 1990s. Isolates causing more severe disease symptoms have recently been detected in several countries with a wide global distribution, including Italy, New Zealand, and China. In order to characterize P. syringae pv. actinidiae populations globally, a representative set of 40 isolates from New Zealand, Italy, Japan, South Korea, Australia, and Chile were selected for extensive genetic analysis. Multilocus sequence analysis (MLSA) of housekeeping, type III effector and phytotoxin genes was used to elucidate the phylogenetic relationships between P. syringae pv. actinidiae isolates worldwide. Four additional isolates, including one from China, for which shotgun sequence of the whole genome was available, were included in phylogenetic analyses. It is shown that at least four P. syringae pv. actinidiae MLSA groups are present globally, and that marker sets with differing evolutionary trajectories (conserved housekeeping and rapidly evolving effector genes) readily differentiate all four groups. The MLSA group designated here as Psa3 is the strain causing secondary symptoms such as formation of cankers, production of exudates, and cane and shoot dieback on some kiwifruit orchards in Italy and New Zealand. It is shown that isolates from Chile also belong to this MLSA group. MLSA group Psa4, detected in isolates collected in New Zealand and Australia, has not been previously described. P. syringae pv. actinidiae has an extensive global distribution yet the isolates causing widespread losses to the kiwifruit industry can all be traced to a single MLSA group, Psa3.