Clinical outcomes following surgical management of insertional Achilles tendinopathy using a double-row suture bridge technique with mean two-year follow-up.

BACKGROUND: The clinical outcomes following surgical management of insertional Achilles tendinopathy (IAT) vary depending on the surgical technique used to reattach the Achilles tendon following debridement. The aim of this study was to investigate the clinical outcomes of patients with IAT who underwent surgical management with a double-row suture bridge technique used to reattach the Achilles tendon. METHODS: A retrospective review of consecutive patients diagnosed with IAT, who underwent surgical management utilising a double-row suture bridge technique (Arthex Speedbridge), and a minimum of 3-month follow-up were included. The primary outcome was the Manchester-Oxford Foot Questionnaire (MOXFQ) Index score which is a patient reported outcome measure (PROM). Secondary outcomes included EuroQol EQ-5D-5L health-related quality of life PROM and complication rates. RESULTS: Between July 2013 and June 2020, 50 consecutive patients (23 male; 27 female) were included. The mean age (± standard deviation) was 52.3 ± 11.3 (range 29.0-84.3). Pre- and post-operative PROM data were available for all cases. The mean follow-up was 2.4 ± 1.9 years. The MOXFQ Index score improved from 48.5 to 12.4 (p < 0.01), EQ-5D-5L improved from 2.7 ± 0.46 to 1.2 ± 0.37 (p < 0.01), and EQ-VAS improved from 48.0 ± 18.4 to 84.1 ± 12.6 (p < 0.01). Four patients had complications which were of minimal clinical relevance and caused no deviation from routine recovery. There were no cases of tendon rupture. CONCLUSION: This study has demonstrated that surgical management of IAT is safe and effective with clinical improvement in both clinical and general health-related quality of life outcome PROMs. LEVEL OF EVIDENCE: IV.

Health-related quality of life in patients with Achilles tendinopathy: Comparison to the general population of the United Kingdom.

BACKGROUND: There is little evidence available regarding the impact of Achilles Tendinopathy (AT) on health-related quality of life (HRQOL). The primary aim of this study was to quantify the clinical and health-related quality-of-life patient-reported outcome measures for a population presenting with either mid-substance or insertional Achilles tendinopathy. METHODS: A prospective comparative observational study of consecutive patients with AT presenting for extracorporeal shockwave therapy (ESWT) at a large teaching hospital. The primary outcome was assessment of a validated health-related quality of life PROMs (Euroqol EQ-5D-5L) and comparison to 2 general UK population datasets. The secondary outcomes were Visual Analogue Pain Scale (VAS-Pain) and two validated foot-specific patient reported outcome measures (Foot Function Index (FFI) and Victorian Institute of Sports Assessment-Achilles (VISA-A)). RESULTS: Between March 2014 and June 2021, 320 consecutive patients (125 male; 195 female) were diagnosed with AT and referred for a first course of ESWT. EQ-5D-5L PROMs were prospectively collected for 303 of these patients (94.7%). The mean age (± standard deviation(SD)) was 52.1 ± 11.4 years. The mean EQ-5D-5L Index score (mean±SD) for the AT cohort was 0.783 ± 0.131. Patients less than 55 years with AT had a statistically significantly worse quality of life compared with members of the same age group in the general population. The mean VAS-Pain, FFI, VISA-A clinical outcome scores were 6.0 ± 2.3, 49.5 ± 21.2 and 34.1 ± 14.4 respectively. There was a statistically significant moderate correlation between HRQOL and clinical PROMs (VAS-Pain and FFI vs EQ-5D) however there was no correlation with age. CONCLUSION: This study demonstrates that patients under the age of 55 with AT have a significantly reduced quality of life compared with the general population. LEVEL OF EVIDENCE: III.

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies.

OBJECTIVE: Symptomatic long-term hypoparathyroidism following thyroid surgery requires an alternative and permanent therapy that would effectively restore parathyroid function and eliminate the need for substitution drug therapy. The aim of this study was to systematically review the literature on the efficacy and safety of parathyroid allotransplantation to treat post-operative hypoparathyroidism. METHODS: MEDLINE, Embase, BIOSIS and the Cochrane Library were searched for published articles (from inception of each database to September 30, 2018). A total of 9 studies comprising 146 patients (177 allotransplantations) with post thyroidectomy hypoparathyroidism were identified. RESULTS: Parathyroid tissues used for allotransplant were cultured parathyroid cells, cryopreserved parathyroid cells and encapsulated microspheres. Post-transplant immunosuppression was only reported in three studies, mainly with oral prednisolone for 2 weeks to 6 months. Mean graft survival following allotransplantation was 47% (95% CI 24%-71%) when patients were followed-up to 6 months and 41% (95% CI 2.3%-80%) at 12 months. There was significant unexplained heterogeneity observed between studies in both these groups (I2 > 50%). Parathyroid hormone (PTH) levels, and serum calcium levels post intervention was not reported in all studies, but available evidence suggests the levels remains higher (PTH level around 12 pg/ml; Ca level around 8 mg/dl) post-allotransplantation for up to 24 months. CONCLUSIONS: Long-term benefit and harms of allotransplantation is still unclear due to the clinical and statistical heterogeneity observed among the studies. Therefore, conduct of a well-designed controlled clinical trial in the immediate future on allotransplantation is of paramount importance.

Kinesin superfamily: roles in breast cancer, patient prognosis and therapeutics.

Breast cancer pathobiology is known to be influenced by the differential expression of a group of proteins called the kinesin superfamily (KIFs), which is instrumental in the intracellular transport of chromosomes along microtubules during mitosis. During cellular division, kinesins are strictly regulated through temporal synthesis so that they are present only when needed. However, their misregulation may contribute to uncontrolled cell growth owing to premature sister chromatid separation, highlighting their importance in cancer. This review covers the functions of kinesins in normal and breast cancer cells, the use of kinesins for breast cancer patient prognosis, and the targeting of these molecules for therapeutics. A better understanding of KIF proteins may be pivotal to improved disease outcomes for breast cancer patients.

Microfluidic Imaging Flow Cytometry by Asymmetric-detection Time-stretch Optical Microscopy (ATOM).

Scaling the number of measurable parameters, which allows for multidimensional data analysis and thus higher-confidence statistical results, has been the main trend in the advanced development of flow cytometry. Notably, adding high-resolution imaging capabilities allows for the complex morphological analysis of cellular/sub-cellular structures. This is not possible with standard flow cytometers. However, it is valuable for advancing our knowledge of cellular functions and can benefit life science research, clinical diagnostics, and environmental monitoring. Incorporating imaging capabilities into flow cytometry compromises the assay throughput, primarily due to the limitations on speed and sensitivity in the camera technologies. To overcome this speed or throughput challenge facing imaging flow cytometry while preserving the image quality, asymmetric-detection time-stretch optical microscopy (ATOM) has been demonstrated to enable high-contrast, single-cell imaging with sub-cellular resolution, at an imaging throughput as high as 100,000 cells/s. Based on the imaging concept of conventional time-stretch imaging, which relies on all-optical image encoding and retrieval through the use of ultrafast broadband laser pulses, ATOM further advances imaging performance by enhancing the image contrast of unlabeled/unstained cells. This is achieved by accessing the phase-gradient information of the cells, which is spectrally encoded into single-shot broadband pulses. Hence, ATOM is particularly advantageous in high-throughput measurements of single-cell morphology and texture - information indicative of cell types, states, and even functions. Ultimately, this could become a powerful imaging flow cytometry platform for the biophysical phenotyping of cells, complementing the current state-of-the-art biochemical-marker-based cellular assay. This work describes a protocol to establish the key modules of an ATOM system (from optical frontend to data processing and visualization backend), as well as the workflow of imaging flow cytometry based on ATOM, using human cells and micro-algae as the examples.

Mechanisms, patterns and outcomes of paediatric polytrauma in a UK major trauma centre.

Introduction Paediatric trauma is a significant burden to healthcare worldwide and accounts for a large proportion of deaths in the UK. Methods This retrospective study examined the epidemiological data from a major trauma centre in the UK between January 2012 and December 2014, reviewing all cases of moderate to severe trauma in children. Patients were included if aged ≤16 years and if they had an abbreviated injury scale score of ≥2 in one or more body region. Results A total of 213 patients were included in the study, with a mean age of 7.8 years (standard deviation [SD]: 5.2 years). The most common cause of injury was vehicle related incidents (46%). The median length of hospital stay was 5 days (interquartile range [IQR]: 4-10 days). Approximately half (52%) of the patients had to stay in the intensive care unit, for a median of 1 day (IQR: 0-2 days). The mortality rate was 6.6%. The mean injury severity score was 19 (SD: 10). Pearson's correlation coefficient showed a positive correlation for injury severity score with length of stay in hospital (p<0.001). Conclusions There is significant variation in mechanism of injury, severity and pattern of paediatric trauma across age groups. A multidisciplinary team approach is imperative, and patients should be managed in specialist centres to optimise their care and eventual functional recovery. Head injury remained the most common, with significant mortality in all age groups. Rib fractures and pelvic fractures should be considered a marker for the severity of injury, and should alert doctors to look for other associated injuries.

Partnered pharmacist charting on admission in the General Medical and Emergency Short-stay Unit - a cluster-randomised controlled trial in patients with complex medication regimens.

WHAT IS KNOWN AND OBJECTIVE: Patients admitted to general medical units and emergency short-stay units are often complex with multiple comorbidities, polypharmacy and at risk for drug-related problems associated with increased morbidity and mortality. The aim of this study was to evaluate the effectiveness of a partnered pharmacist charting model completed at the time of admission to prevent medication errors. METHODS: We conducted an unblinded cluster randomized controlled trial comparing partnered pharmacist charting to standard medical charting among patients admitted to general medical units and emergency short-stay units with complex medication regimens or polypharmacy. This trial was conducted at an adult major referral hospital in metropolitan Melbourne, Australia, with an annual emergency department attendance of approximately 60 000 patients. The evaluation included patients' medication charts written in the period of 16 March 2015 to 27 July 2015. Patients randomized to the intervention were managed using the partnered pharmacist charting model. The primary outcome variable was a medication error identified by an independent assessor within 24 h of admission, who was not part of the patient's admission process. RESULTS: Of the 473 patients who received standard medical staff charting during the study period, 372 (78·7%) had at least one medication error identified compared to 15 patients (3·7%) on the partnered pharmacist charting arm (P < 0·001). The relative risk of an error with standard medical charting was 21·4 (95% CI: 13·0-35·0) with a number needed to treat (NNT) to prevent one error of 1·3 (95% CI: 1·3-1·4), and the relative risk of a high or extreme risk error with standard medical charting was 150·9 (95% CI: 21·2-1072·9) with a NNT to prevent one high or extreme error of 2·7 (95% CI 2·4-3·1). WHAT IS NEW AND CONCLUSION: Partnering between medical staff and pharmacists to jointly chart initial medications on admission significantly reduced inpatient medication errors (including errors of high and extreme risk) among general medical and emergency short-stay patients with complex medication regimens or polypharmacy.

Prophylactic radiotherapy against heterotopic ossification following internal fixation of acetabular fractures: a comparative estimate of risk.

OBJECTIVE: Radiotherapy (RT) is effective in preventing heterotopic ossification (HO) around acetabular fractures requiring surgical reconstruction. We audited outcomes and estimated risks from RT prophylaxis, and alternatives of indometacin or no prophylaxis. METHODS: 34 patients underwent reconstruction of acetabular fractures through a posterior approach, followed by a 8-Gy single fraction. The mean age was 44 years. The mean time from surgery to RT was 1.1 days. The major RT risk is radiation-induced fatal cancer. The International Commission on Radiological Protection (ICRP) method was used to estimate risk, and compared with a method (Trott and Kemprad) specifically for estimating RT risk for benign disease. These were compared with risks associated with indometacin and no prophylaxis. RESULTS: 28 patients (82%) developed no HO; 6 developed Brooker Class I; and none developed Class II-IV HO. The ICRP method suggests a risk of fatal cancer in the range of 1 in 1000 to 1 in 10,000; the Trott and Kemprad method suggests 1 in 3000. For younger patients, this may rise to 1 in 2000; and for elderly patients, it may fall to 1 in 6000. The risk of death from gastric bleeding or perforation from indometacin is 1 in 180 to 1 in 900 in older patients. Without prophylaxis risk of death from reoperation to remove HO is 1 in 4000 to 1 in 30,000. CONCLUSION: These results are encouraging, consistent with much larger series and endorse our multidisciplinary management. Risk estimates can be used in discussion with patients. ADVANCES IN KNOWLEDGE: The risk from RT prophylaxis is small, it is safer than indometacin and substantially overlaps with the range for no prophylaxis.

SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus.

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.

Randomized controlled trial of a new portable calf compression device (Venowave) for prevention of venous thrombosis in high-risk neurosurgical patients.

BACKGROUND: Patients undergoing neurosurgical procedures are at risk of venous thromboembolism (VTE), but often have contraindications for anticoagulant prophylaxis. OBJECTIVES: To assess the efficacy and tolerability of a new, lightweight, portable, battery-powered, intermittent calf compression device, Venowave, for the prevention of VTE in neurosurgical inpatients. PATIENTS/METHODS: We performed an open randomized controlled trial comparing Venowave with control for the prevention of VTE in patients undergoing neurosurgery. The primary outcome was the composite of asymptomatic deep vein thrombosis (DVT) detected by screening venography or compression ultrasound performed on day 9 (± 2 days) and symptomatic VTE. RESULTS: We randomized 75 patients to receive Venowave devices and 75 to the control group. All patients were prescribed graduated compression stockings and physiotherapy. VTE occurred in three patients randomized to Venowave and in 14 patients randomized to control (4.0% vs. 18.7%, relative risk 0.21; 95% confidence interval 0.05-0.75, P = 0.008). Similar reductions were seen for proximal DVT (2.7% vs. 8.0%) and symptomatic VTE (0% vs. 2.7%), and the results were consistent in all subgroups examined. CONCLUSIONS: Venowave devices are effective in preventing VTE in high-risk neurosurgical patients.

Effects of rosuvastatin on subclinical atherosclerosis and arterial stiffness in rheumatoid arthritis: a randomized controlled pilot trial.

OBJECTIVE: To ascertain the effect of rosuvastatin on carotid atherosclerosis and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive 10 mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed prospectively every 3 months for 12 months. Intima-media thickness (IMT), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured at baseline, 6 and 12 months. RESULTS: Rosuvastatin resulted in statistically significant reductions of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo. However, rosuvastatin had no significant effect on changes in inflammatory markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1 (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to 4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement in the Disease Activity Score (DAS) and a reduction in fibrinogen level was observed at 6 and 12 months compared with baseline in the rosuvastatin group. The treatment group exhibited a significant increase in SEVR (from 157 ± 28% to 163 ± 33% in the rosuvastatin group compared with from 143 ± 18% to 143 ± 26% in the placebo group, p = 0.023), but no significant effect was observed in the changes in IMT and AIx. CONCLUSION: Our data suggest that rosuvastatin has a modest anti-inflammatory effect in RA patients with low disease activity in terms of reduction in DAS and fibrinogen level. Rosuvastastin may also improve subendocardial perfusion and lower the urate level.

miR-145-dependent targeting of junctional adhesion molecule A and modulation of fascin expression are associated with reduced breast cancer cell motility and invasiveness.

Micro RNAs are small non-coding RNAs, which regulate fundamental cellular and developmental processes at the transcriptional and translational level. In breast cancer, miR-145 expression is downregulated compared with healthy control tissue. As several predicted targets of miR-145 potentially regulate cell motility, we aimed at investigating a potential role for miR-145 in breast cancer cell motility and invasiveness. Assisted by Affymetrix array technology, we demonstrate that overexpression of miR-145 in MDA-MB-231, MCF-7, MDA-MB-468 and SK-BR-3 breast cancer cells and in Ishikawa endometrial carcinoma cells leads to a downregulation of the cell-cell adhesion protein JAM-A and of the actin bundling protein fascin. Moreover, podocalyxin and Serpin E1 mRNA levels were downregulated, and gamma-actin, transgelin and MYL9 were upregulated upon miR-145 overexpression. These miR-145-dependent expression changes drastically decreased cancer cell motility, as revealed by time-lapse video microscopy, scratch wound closure assays and matrigel invasion assays. Immunofluorescence microscopy demonstrated restructuring of the actin cytoskeleton and a change in cell morphology by miR-145 overexpression, resulting in a more cortical actin distribution, and reduced actin stress fiber and filopodia formation. Nuclear rotation was observed in 10% of the pre-miR-145 transfected MDA-MB-231 cells, accompanied by a reduction of perinuclear actin. Luciferase activation assays confirmed direct miR-145-dependent regulation of the 3'UTR of JAM-A, whereas siRNA-mediated knockdown of JAM-A expression resulted in decreased motility and invasiveness of MDA-MB-231 and MCF-7 breast cancer cells. Our data identify JAM-A and fascin as novel targets of miR-145, firmly establishing a role for miR-145 in modulating breast cancer cell motility. Our data provide a rationale for future miR-145-targeted approaches of antimetastatic cancer therapy.

Carbimazole-induced agranulocytosis: does antineutrophil cytoplasmic antibody have a role?

Carbimazole is a drug that is widely used for hyperthyroid disorders, such as Graves' disease. Agranulocytosis is a rare idiosyncratic adverse reaction to the drug which is potentially fatal. This report describes a patient with a history of successfully treated pyoderma gangrenosum, who developed agranulocytosis 3 weeks after commencement of carbimazole for Graves' disease. It may give credence to the theory that implicates antineutrophil cytoplasmic antibodies in the pathogenesis of agranulocytosis induced by antithyroid drugs.

Effect of household passive smoking exposure on the risk of ischaemic heart disease in never-smoke female patients in Hong Kong.

OBJECTIVE: To investigate the relation between household passive smoking exposure and risk of ischaemic heart disease (IHD) among never-smoke female patients by a retrospective case-control analysis. METHODS: This study recruited 314 patients with IHD who had never smoked and 319 controls who were admitted for other reasons in the same hospital during the same period. Subjects were interviewed about their exposure to household passive smoking. The dose metrics of passive smoking exposure were evaluated by using "pack years" and "hour years", which indicated the cumulative amount and duration of exposure. The ORs and 95% CIs were computed by unconditional logistic regression, adjusted for other risk factors. RESULTS: Subjects with passive smoking exposure were associated with higher risk of IHD (OR 1.51, 95% CI 1.01 to 2.27, p = 0.043) when compared to non-exposed subjects. Subjects exposed to an average of > or =1 pack of cigarette per day had an OR of 1.69 (95% CI 1.07 to 2.68, p = 0.025). The OR was 1.52 for those exposed for > or =5 years (95% CI 1.01 to 2.29, p = 0.043) and was 1.82 for those exposed > or =4 h per day (95% CI 1.05 to 3.15, p = 0.032). Similarly, the risk of IHD increased with cumulative exposure duration, with an OR of 1.53 (95% CI 1.01 to 2.32, p = 0.043) at the exposure level > or =5 pack years, and an OR of 1.61 (95% CI 1.03 to 2.52, p = 0.037) at the exposure level > or =20 hour years. There was a significant dose-response association between the exposure measures and risk of IHD (p<0.01 for trend). CONCLUSION: Our data suggested an increased risk of IHD from passive household smoking in female never-smoke subjects, and demonstrated a dose-response association.

Tissue Doppler velocity is superior to strain imaging in predicting long-term cardiovascular events after cardiac resynchronisation therapy.

OBJECTIVE: To examine the predictive value of systolic dyssynchrony measured by tissue Doppler velocity versus tissue Doppler strain imaging on long-term outcome after cardiac resynchronisation therapy (CRT). DESIGN: Cohort study. SETTING: Two university hospitals. PATIENTS: Two hundred and thirty-nine patients (65 (SD 12) years, 76% males) who underwent CRT. INTERVENTIONS: Baseline echocardiography with tissue Doppler imaging (TDI) and clinical follow-up for 37 (20) months. MAIN OUTCOME MEASURES: The time to peak systolic velocity during ejection phase (Ts) and the time to peak systolic strain (T(epsilon)) were assessed for dyssynchrony, that is the maximal delay in Ts and the maximal delay in T(epsilon) among the four left ventricular basal segments. Occurrence of cardiovascular endpoints between patients with and without dyssynchrony was compared by Kaplan-Meier curves, followed by Cox regression analysis for potential predictor(s). RESULTS: There were 78 (33%) deaths, with cardiovascular causes in 64 (27%) patients, while 136 (57%) patients were hospitalised for cardiovascular events, including decompensated heart failure in 87 (36%) patients. Patients with the maximal delay in Ts of > or =65 ms showed a lower event rate for cardiovascular mortality (19% vs 38%, logrank chi2 = 7.803, p = 0.005) and other prognostic endpoints. In Cox regression analysis, the maximal delay in Ts (hazard ratio (HR) 0.463, 95% CI 0.270 to 0.792, p = 0.005) and ischaemic aetiology (HR 2.716, 95% CI 1.505 to 4.901, p = 0.001) were independent predictors of cardiovascular mortality. In contrast, the maximal delay in T(epsilon) of > or =80 ms failed to predict any cardiovascular event. CONCLUSIONS: Echocardiographic evidence of prepacing systolic dyssynchrony measured by TDI velocity, but not TDI strain, predicted lower long-term cardiovascular events after CRT.

Disease chronicity and activity predict subclinical left ventricular systolic dysfunction in patients with systemic lupus erythematosus.

OBJECTIVE: This study investigates parameters that could predict subclinical cardiac dysfunction in systemic lupus erythematosus (SLE) in the absence of valvular, clinical coronary artery and pericardial disease. DESIGN: A case-control trial. SETTING: Rheumatology clinic, a university teaching hospital. PATIENTS: Eighty-two female SLE patients (49 (SD 9) years) and 82 female normal subjects (49 (13) years) matched for age, body mass index, blood pressure and heart rate. INTERVENTIONS: All underwent standard echocardiography and tissue Doppler imaging. MAIN OUTCOME MEASURES: Twenty-two (27%) patients had evidence of impaired left ventricular (LV) long-axis function with mean myocardial peak systolic velocity (Sm) of basal six segments <4.4 cm/s and also subnormal stress-corrected midwall fractional shortening. Thirty-four (42%) patients demonstrated impaired right ventricular (RV) long-axis function. These occurred in the presence of comparable normal LV ejection fraction, cardiac index, and RV fractional area change to the control group. Patients with subnormal mean Sm were older (49 (8) vs 44 (9); p = 0.043) and had a higher prevalence of hypertension (46% vs 22%; p = 0.034), longer disease duration >10 years (82% vs 50%, p = 0.01), higher disease activity score (73% vs 48% for Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)> or =1, p = 0.049) and end-organ damage index (64% vs 47% with Systemic Lupus International Collaborating Clinics Damage Index (SLICC)> or =1, p = 0.049) than those with normal values. Disease duration >10 years, disease activity index and increased arterial stiffness provided additional incremental predictive value of LV long-axis function. CONCLUSION: SLE patients have subclinical long and short-axis dysfunctions. Regular monitoring of cardiac function by tissue Doppler echocardiography may be indicated for patients who had SLE for >10 years, frequent flare or when arterial stiffening is demonstrated.

Expression of syndecan-2 in the amoeboid microglial cells and its involvement in inflammation in the hypoxic developing brain.

The present study examined the expression of heparan sulphate proteoglycan, syndecan-2 (Sdc-2) in the corpus callosum and the amoeboid microglial cells (AMC) in the neonatal rat brain in response to hypoxia. In 1-day old Wistar rats subjected to hypoxia the mRNA and protein expression of Sdc-2 in the corpus callosum, heavily populated by AMC, was increased up to 3 days after the hypoxic exposure. Immunoexpression of Sdc-2 was localized in AMC as confirmed by double labeling using microglial marker. Primary cultures of microglial cells subjected to hypoxia showed a significant increase in Sdc-2 expression. Application of Sdc-2 to microglial cultures under hypoxia increased the release of tumor necrosis factor-alpha, interleukin-1beta, chemokine (C-C motif) ligand 2 (CCL2), and chemokine (C-X-C motif) ligand 12 (CXCL12) by the microglial cells. Additionally, Sdc-2 enhanced the production of reactive oxygen species (ROS) by microglia subjected to hypoxia. Edaravone [3-methyl-1phenyl-2-pyrazolin-5-one], an antioxidant drug, suppressed the hypoxia- and Sdc-2-induced increased production of cytokines, chemokines, and ROS. In the light of these findings, we suggest that Sdc-2 plays an important role in microglial production of inflammatory cytokines, chemokines, and ROS in hypoxic conditions. In this connection, edaravone suppressed the hypoxia- and Sdc-2-induced increased cytokine and ROS production suggesting its therapeutic potential in ameliorating neuroinflammation.

Hypertension and heart failure: a dysfunction of systole, diastole or both?

The pathological myocardial hypertrophy associated with hypertension contains the seed for further maladaptive development. Increased myocardial oxygen consumption, impaired epicardial coronary perfusion, ventricular fibrosis and remodelling, abnormalities in long-axis function and torsion, cause, to a varying degree, a mixture of systolic and diastolic abnormalities. In addition, chronotropic incompetence and peripheral factors such as lack of vasodilator reserve and reduced arterial compliance further affect cardiac output particularly on exercise. Many of these factors are common to hypertensive heart failure with a normal ejection fraction as well as systolic heart failure. There is increasing evidence that these apparently separate phenotypes are part of a spectrum of heart failure differing only in the degree of ventricular remodelling and volume changes. Furthermore, dichotomizing heart failure into systolic and diastolic clinical entities has led to a paucity of clinical trials of therapies for heart failure with a normal ejection fraction. Therapies aimed at reversing myocardial fibrosis, and targets outside the heart such as enhancing vasodilator reserve and improving chronotropic incompetence deserve further study and may improve the exercise capacity of hypertensive heart failure patients. Hypertension heart disease with heart failure is simply not a dysfunction of systole and diastole. Other peripheral factors including heart rate and vasodilator response with exercise may deserve equal attention in an attempt to develop more effective treatments for this disorder.