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Sham-controlled trials demonstrated safety and efficacy of renal denervation (RDN) to lower blood pressure (BP). Association of baseline heart rate with BP reduction after RDN is incompletely understood.The purpose of this analysis was to evaluate the impact of baseline heart rate on BP reduction without antihypertensive medications in the SPYRAL HTN-OFF MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications) Pivotal trial.Patients removed from any antihypertensive medications were enrolled with office systolic blood pressure (SBP) ≥150 and 180 mm Hg and randomized 1:1 to RDN or sham control. Patients were separated according to baseline office heart rate 70 or ≥70 beats/min. BP changes from baseline to 3 months between treatment arms were adjusted for baseline SBP using analysis of covariance.Scatter plots of 3-month changes in 24-hour and office SBP illustrate a wide range of changes in SBP for different baseline heart rates. Treatment difference at 3 months between RDN and sham control with baseline office heart rate ≥70 beats/min for 24-hour SBP was -6.2 mm Hg (95% CI: -9.0 to -3.5 mm Hg) (P 0.001) and for baseline office heart rate 70 beats/min it was -0.1 mm Hg (-3.8 to 3.6 mm Hg) (P = 0.97) with an interaction P value of 0.008. Results were similar for changes in office, daytime, and nighttime SBP at 3 months, with a greater reduction in SBP with baseline office heart rate ≥70 beats/min.Reduction in mean office, 24-hour, daytime, and nighttime SBP for RDN at 3 months was greater with baseline office heart rate ≥70 than 70 beats/min, suggesting an association between baseline heart rate and BP reduction after RDN. (SPYRAL PIVOTAL-SPYRAL HTN-OFF MED Study; NCT02439749).

OBJECTIVE Time to return to work (RTW) after elective lumbar spine surgery is variable and dependent on many factors including patient, work-related, and surgical factors. The primary objective of this study was to describe the time and rate of RTW after elective lumbar spine surgery. Secondary objectives were to determine predictors of early RTW (< 90 days) and no RTW in this population. METHODS A retrospective analysis of prospectively collected data from the multicenter Canadian Spine Outcomes and Research Network (CSORN) surgical registry was performed to identify patients who were employed and underwent elective 1- or 2-level discectomy, laminectomy, and/or fusion procedures between January 2015 and December 2019. The percentage of patients who returned to work and the time to RTW postoperatively were calculated. Predictors of early RTW and not returning to work were determined using a multivariable Cox regression model and a multivariable logistic regression model, respectively. RESULTS Of the 1805 employed patients included in this analysis, 71% returned to work at a median of 61 days. The median RTW after a discectomy, laminectomy, or fusion procedure was 51, 46, and 90 days, respectively. Predictors of early RTW included male gender, higher education level (high school or above), higher preoperative Physical Component Summary score, working preoperatively, a nonfusion procedure, and surgery in a western Canadian province (p < 0.05). Patients who were working preoperatively were twice as likely to RTW within 90 days (HR 1.984, 95% CI 1.680–2.344, p < 0.001) than those who were employed but not working. Predictors of not returning to work included symptoms lasting more than 2 years, an increased number of comorbidities, an education level below high school, and an active workers’ compensation claim (p < 0.05). There were fourfold odds of not returning to work for patients who had not been working preoperatively (OR 4.076, 95% CI 3.087–5.383, p < 0.001). CONCLUSIONS In the Canadian population, 71% of a preoperatively employed segment returned to work after 1- or 2-level lumbar spine surgery. Most patients who undergo a nonfusion procedure RTW after 6 to 8 weeks, whereas patients undergoing a fusion procedure RTW at 12 weeks. Working preoperatively significantly increased the likelihood of early RTW.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH. ispartof: JOURNAL OF HYPERTENSION vol:39 issue:9 pages:1742-1767 ispartof: location:Netherlands status: published

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

Background Exercise is a common approach for the management of patients with chronic non-specific low back pain (LBP). However, there is no clear mechanistic evidence or consensus on what type of exercise is more effective than others. While considerable evidence suggests a link between lumbar muscle health (e.g., atrophy and fatty infiltration) with functional deficits, it is unknown whether exercises targeting the lumbar spine can lead to noticeable improvements in muscle health and functional outcomes. The primary aim of this study is to compare the effect of combined motor control and isolated strengthening lumbar exercises (MC + ILEX) versus a general exercise group (GE) on multifidus muscle morphology (size and composition). Secondary aims include assessing the effect of the interventions on overall paraspinal muscle health, pain and disability, as well as psychological factors as possible effect modifiers. Methods A total of 50 participants with chronic non-specific LBP and moderate to severe disability, aged between 18 and 60, will be recruited from the local orthopaedic clinics and university community. Participants will be randomised (1:1) to either the MC + ILEX or GE group. Participants will undergo 24 individually supervised exercise sessions over a 12-week period. The primary outcome will be multifidus morphology (atrophy) and composition (fatty infiltration). Secondary outcomes will be muscle function (e.g., % thickness change during contraction), morphology, lumbar extension strength, pain intensity and disability. Potential treatment effect modifiers including maladaptive cognitions (fear of movement, catastrophizing), anxiety, depression, physical activity, and sleep quality will also be assessed. All measurements will be obtained at baseline, 6-week and 12-week; self-reported outcomes will also be collected at 24-week. Between-subjects repeated measure analysis of variance will be used to examine the changes in paraspinal muscle morphology over the different time points. Linear mixed models will be used to assess whether baseline scores can modify the response to the exercise therapy treatment. Discussion The results of this study will help clarify which of these two common interventions promote better results in terms of overall paraspinal muscle heath, back pain, disability and psychological factors in adults with chronic LBP. Trial registration NTCT04257253, registered prospectively on February 5, 2020.

Background: To identify, analyze, and report the patient- and procedure-related factors associated with surgical site infection (SSI) after spinal fusion (SF) surgery. Methods: We included any SSI-SF from January 2013 to September 2015. A total of 989 spine surgeries that required instrumentation were performed. Results: Twenty-four out of 989 (2.43%) patients presented with SSI. More than half of the SSI cases (54%) got infected with either exclusively gram-negative bacteria or a combination of gram-negative and gram-positive bacteria; 9.1% of the surgeries involved the sacral spine (90 out of 989 patients). SSI in long constructs (more than 3 levels) was performed in 66.7% compared with 33.3% with short constructs; 87.5 % of the reported SSI (21 patients) were done through a posterior approach. Of patients who had SSI, 87.5% received prophylactic antibiotics, 92% were operated on during the daytime shift, 50% required blood transfusion, and 79% required surgical debridement. Four patients out of 24 patients died (17%) due to unrelated SSI complications. Conclusions: The overall incidence of gram-negative infections after long SFs remains low in our study population. Despite this low overall incidence, our results demonstrate a relative higher incidence of gram-negative SSIs in surgeries involving more than 3 spinal levels and for all those involving the sacral spine. We propose that there may be a potential benefit of gram-negative prophylactic antibiotic coverage in patients falling in either 1 of these categories. Further multivariate analysis and/or randomized studies may be necessary to confirm our results. Level of Evidence: 3.

Study Design: Systematic review. Objectives: Adult spinal deformity (ASD) can be a debilitating condition with a profound impact on patients’ health-related quality of life (HRQoL). Many reports have suggested that the frailty status of a patient can have a significant impact on the outcome of the surgery. The present review aims to identify all pre-operative patient-specific frailty markers that are associated with postoperative outcomes following corrective surgery for ASD of the lumbar and thoracic spine. Methods: A systematic review of the literature was performed to identify findings regarding pre-operative markers of frailty and their association with postoperative outcomes in patients undergoing ASD surgery of the lumbar and thoracic spine. The search was performed in the following databases: PubMed, Embase, Cochrane and CINAHL. Results: An association between poorer performance on frailty scales and worse postoperative outcomes. Comorbidity indices were even more frequently employed with similar patterns of association between increased comorbidity burden and postoperative outcomes. Regarding the assessment of HRQoL, worse pre-operative ODI, SF-36, SRS-22 and NRS were shown to be predictors of post-operative complications, while ODI, SF-36 and SRS-22 were found to improve post-operatively. Conclusions: The findings of this review highlight the true breadth of the concept of “frailty” in ASD surgical correction. These parameters, which include frailty scales and various comorbidity and HRQoL indices, highlight the importance of identifying these factors preoperatively to ensure appropriate patient selection while helping to limit poor postoperative outcomes.

Currently there is no prospective pain and health related quality of life (HRQOL) data of patients with potentially unstable spinal metastases who were treated with surgery ± radiation or radiation alone.An international prospective cohort multicenter study of patients with potentially unstable spinal metastases, defined by a SINS score 7 to 12, treated with surgery ± radiation or radiotherapy alone was conducted. HRQOL was evaluated with the numeric rating scale (NRS) pain score, the SOSGOQ2.0, the SF-36, and the EQ-5D at baseline and 6, 12, 26, and 52 weeks after treatment.A total of 136 patients were treated with surgery ± radiotherapy and 84 with radiotherapy alone. At baseline, surgically treated patients were more likely to have mechanical pain, a lytic lesion, a greater median Spinal Instability Neoplastic score, vertebral compression fracture, lower performance status, HRQOL, and pain scores. From baseline to 12 weeks post-treatment, surgically treated patients experienced a 3.0-point decrease in NRS pain score (95% CI -4.1 to -1.9, p.001), and a 12.7-point increase in SOSGOQ2.0 score (95% CI 6.3-19.1, p.001). Patients treated with radiotherapy alone experienced a 1.4-point decrease in the NRS pain score (95% CI -2.9 to 0.0, p=.046) and a 6.2-point increase in SOSGOQ2.0 score (95% CI -2.0 to 14.5, p=.331). Beyond 12 weeks, significant improvements in pain and HRQOL metrics were maintained up to 52-weeks follow-up in the surgical cohort, as compared with no significant changes in the radiotherapy alone cohort.Patients treated with surgery demonstrated clinically and statistically significant improvements in pain and HRQOL up to 1-year postsurgery. Treatment with radiotherapy alone resulted in improved pain scores, but these were not sustained beyond 3 months and HRQOL outcomes demonstrated nonsignificant changes over time. Within the SINS potentially unstable group, distinct clinical profiles were observed in patients treated with surgery or radiotherapy alone.

Background Diabetes and hypertension are risk factors for renal and cardiovascular outcomes. Data on the association of achieved blood pressure (BP) with renal outcomes in patients with and without diabetes are sparse. We investigated the association of achieved SBP, DBP with renal outcomes and urinary albumin excretion (UAE) in people with vascular disease. Methods In this pooled analysis, we assessed renal outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, randomized to The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial and to Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease trials investigating telmisartan, ramipril and their combination with a median follow-up of 56 months. Standardized office BP was measured every 6 months, estimated glomerular filtration rate (eGFR) and UAE at baseline, 2 years and study end. Associations of mean achieved BP on treatment were investigated on major renal outcomes including end-stage renal disease (ESRD), decline of eGFR by at least 40%, doubling of creatinine and the composites thereof and on UAE. Analyses were by Cox regression analysis, analysis of variance and Chi2-test. Of 30 937 patients with complete data, 19 450 patients without and 11 487 with diabetes were enrolled between 1 December 2001 and 31 July 2003 and followed until 31 July 2008. Data were pooled as the outcomes for telmisartan 80 mg/day (n = 2903) or placebo (n = 2907) for Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease and ramipril 10 mg/day (n = 8407), telmisartan 80 mg/day (n = 8386) or the combination of both (n = 8334) were similar. Results For both those with and without diabetes, the hazard ratios for the composites ESRD or doubling of serum creatinine (707 events overall) and ESRD or 40% eGFR loss (2371 events overall) reached a nadir at achieved SBP of 120 to less than 140 mmHg, and increased with higher and lower SBP with similar relative risk with or without diabetes. For example, risk for the former composite reached a hazard ratios 3.06 (confidence interval 1.90-4.92) with a mean achieved SBP more than 160 mmHg compared with 120 to less than 130 mmHg with diabetes and hazard ratios 2.14 (1.09-4.26) without diabetes. In contrast, the development of new microalbuminuria and macroalbuminuria (3002 and 846 events overall) associated linearly over the whole range of achieved SBP (apart from a slight increase in risk at SBP less than 120 mmHg only in those without diabetes). Absolute risks for the composite and albuminuria outcomes were consistently greater in those with diabetes as compared with without diabetes with high event rates over the whole SBP spectrum. The increased renal risk at low SBP was not related to a meaningful reduction of mandated study drugs or open label renin-angiotensin-aldosterone system inhibition. Conclusion In patients at high cardiovascular risk, SBP levels more than 140 mmHg and less than 120 are associated with increased risk for renal outcomes. Renal risk was greater in diabetes across the whole range of achieved SBP and DBP. These data suggest similar target BP range in patients with and without diabetes to prevent renal outcomes, a frequent complication in high-risk vascular patients. Clinical trial registration Clinical Trial registration: http://clinicaltrials.gov.Unique identifier: NCT00153101.

About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke).There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring.Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated.Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks.Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care.Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular).Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión.La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado.La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades.La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria.Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

Cerca de una cuarta parte de los adultos tienen hipertensión, el principal factor de riesgo de muerte (inclusive la causada por cardiopatía y accidente cerebrovascular). Existen políticas eficaces que podrían ayudar a las personas a elegir opciones saludables para prevenir el aumento de la presión arterial; si se las aplicara plenamente, se podría evitar en gran medida el desarrollo de hipertensión. La hipertensión es fácil de detectar y tratar, PERO solo alrededor de 50% de los adultos que presentan dicha afección son conscientes de su situación y solamente 1 de cada 7 de ellos recibe el tratamiento adecuado. La prevención y el control de la hipertensión es el mecanismo principal para prevenir y controlar las enfermedades no transmisibles y un modelo para evitar otros riesgos de presentar dichas enfermedades. La adopción de un modo de vida saludable y el tratamiento farmacológico efectivo podrían prevenir y controlar la hipertensión en la mayoría de las personas si se implementaran de manera sistemática en la población; en todos los entornos es posible aplicar intervenciones sencillas, que pueden usarse para mejorar la atención primaria. Es urgente adoptar medidas sostenidas para introducir cambios eficaces en las políticas públicas y los sistemas de salud pública con miras a prevenir y controlar la hipertensión.

Purpose Event-based clinical outcome trials have shown limited evidence to support guidelines recommendations to lower blood pressure (BP) to

This article discusses the difficulties Kutztown University’s Rohrbach Library- and many libraries- face when evaluating eBook collections, and the process used to overcome some of the obstacles to...

Catheter-based renal denervation (RDN) reduces blood pressure (BP) throughout the 24-h period, as reported in several randomized sham-controlled trials. Reduction of BP in the early morning hours is especially important due to increased cardiovascular risks during that time. In this report, we examine the impact of RDN on systolic BP (SBP) and diastolic BP (DBP) during the critical morning surge period in a post-hoc analysis of patients in the SPYRAL HTN-ON MED trial. Ambulatory BP measurements were collected at baseline and 6 months for treatment and control patient groups over 24-h periods. Average morning BP surge is the difference between average morning BP and average nighttime BP, and the morning surge slope reflects the rate of change of BP from nighttime to morning. Mean morning DBP surge slopes were significantly lower for RDN vs. control groups at 6 months (1.1 vs. 3.6 mmHg/h; p = 0.029). In the RDN group, morning DBP surge slopes were significantly lower at 6 months compared to baseline (1.1 vs. 4.1 mmHg/h; p = 0.006). Similar patterns were observed for mean morning SBP surge slope but did not reach statistical significance. This decrease in the morning DBP surge slope, an index of the sympathetically-mediated morning BP surge, thus indicates a drop in late morning BP relative to early morning/nocturnal BP in the RDN group. Thus, RDN appears effective in attenuating the slope of morning surge in DBP that might indicate possible benefits in a high-risk hypertensive population. https://www.clinicaltrials.gov (NCT02439775), registered May 12, 2015.

Blood pressure–lowering drugs have different blood pressure–lowering profiles. We studied if differences in blood pressure mean and variability can explain the differences in risks of cardiovascular events and death among 15 245 high-risk hypertensive patients randomized to valsartan or amlodipine and followed for 4.2 years in the VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation). We selected patients with ≥3 visits and performed Cox regression analyses, defining mean blood pressure as a time-dependent covariate and visit-to-visit and within-visit blood pressure variability as the SD. Of 14 996 eligible patients, participants in the valsartan group had higher systolic mean blood pressure by 2.2 mm Hg, higher visit-to-visit systolic variability by 1.4 mm Hg, and higher within-visit systolic variability by 0.2 mm Hg ( P values

Background The SPYRAL HTN clinical trial program was initiated with two 80-patient pilot studies, SPYRAL HTN-OFF MED and SPYRAL HTN-ON MED, which provided biological proof of principle that renal denervation has a blood pressure-lowering effect versus sham controls for subjects with uncontrolled hypertension in the absence or presence of antihypertensive medications, respectively. Trial design Two multicenter, prospective, randomized, sham-controlled trials have been designed to evaluate the safety and efficacy of catheter-based renal denervation for the reduction of blood pressure in subjects with hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) or presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications. The primary efficacy endpoint is baseline-adjusted change from baseline in 24-h ambulatory systolic blood pressure. The primary safety endpoint is incidence of major adverse events at 1 month after randomization (or 6 months in cases of new renal artery stenosis). Both trials utilize a Bayesian design to allow for prespecified interim analyses to take place, and thus, the final sample sizes are dependent on whether enrollment is stopped at the first or second interim analysis. SPYRAL HTN-OFF MED Pivotal will enroll up to 300 subjects and SPYRAL HTN-ON MED Expansion will enroll up to 221 subjects. A novel Bayesian power prior approach will leverage historical information from the pilot studies, with a degree of discounting determined by the level of agreement with data from the prospectively powered studies. Conclusions The Bayesian paradigm represents a novel and promising approach in device-based hypertension trials. Clinical trial registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02439749 (SPYRAL HTN-OFF MED Pivotal) and NCT02439775 (SPYRAL HTN-ON MED Expansion).

Objectives The aim of this study was to investigate bipolar radiofrequency renal denervation in patients with hypertension not receiving medications at baseline. Background A blood pressure–reducing effect of renal denervation has been difficult to isolate in clinical investigations. Methods REDUCE HTN: REINFORCE (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension) was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150 to 180 mm Hg and average 24-h ambulatory SBP of 135 to 170 mm Hg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-h ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled. Safety assessments included all-cause death, renal failure, severe hypotension or syncope, hypertensive crisis, and renal artery stenosis. Results Baseline 24-h blood pressure was 148.3 ± 10.9/85.7 ± 9.1 mm Hg for the denervation group (n = 34, mean age 58.5 ± 10.1 years, 47% women) and 149.1 ± 7.2/86.4 ± 9.8 mm Hg for the control group (n = 17, mean age 58.2 ± 9.8 years, 24% women). At 8 weeks, mean 24-h SBP reductions for the renal denervation and control groups were −5.3 mm Hg (95% confidence interval [CI]: −8.8 to −1.8 mm Hg) and −8.5 mm Hg (95% CI: −13.3 to −3.8 mm Hg), respectively (difference 3.3 mm Hg; 95% CI: −2.8 to 9.3 mm Hg; p = 0.30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of −7.2 mm Hg (95% CI: −15.2 to 0.8 mm Hg; p = 0.08), −9.7 mm Hg (95% CI: −17.7 to −1.7 mm Hg; p = 0.02), and −11.4 mm Hg (95% CI: −19.2 to −3.7 mm Hg; p Conclusions Future studies of radiofrequency renal denervation must anticipate delayed treatment effects. (Renal Denervation Using the Vessix Renal Denervation System for the Treatment of Hypertension [REDUCE HTN: REINFORCE]; NCT02392351)

Background An intranasal formulation of esketamine, combined with an oral antidepressant, is approved in the USA and the European Union for adults with treatment-resistant depression (TRD). Transient cardiovascular stimulatory effects have been reported with ketamine. Methods Cardiovascular effects of esketamine nasal spray, combined with an oral antidepressant, were evaluated in 1708 esketamine-treated adults with TRD in six trials (five double-blind, placebo-controlled (486 placebo-treated patients); one open-label) of 4–52 weeks’ duration. Patients with established cardiovascular disease, including uncontrolled hypertension (> 140/> 90 mmHg), history of hypertensive crisis, or clinically significant electrocardiogram (ECG) abnormalities, were excluded from enrollment. Effects on cardiac repolarization were assessed in a phase I randomized, positive- and active-controlled thorough corrected QT (QTc) interval study. For adverse events, odds ratio (OR) [95% confidence interval] for esketamine/antidepressant versus antidepressant/placebo was calculated. Results Adverse events related to increased BP were reported in 12.8% of all esketamine-treated patients (in double-blind trials: esketamine/antidepressant 11.6% vs. antidepressant/placebo 3.9%; OR 3.2 [1.9–5.8]). Among the patients without a history of hypertension, new antihypertensive medication was initiated by 2.1% (6/280) of patients in the esketamine/antidepressant group versus 1.2% (2/171) of patients in the antidepressant/placebo group, in the double-blinded studies. Adverse events related to abnormal heart rate were reported in 3.0% of all esketamine-treated patients (in double-blind trials: 1.6% vs. 0.8%; OR 1.9 [0.5–8.6]). Overall, three cardiovascular adverse events related to BP increase were reported as serious and severe, and there was one fatal event considered unrelated (acute cardiac failure). BP increases reached the maximum postdose value within ~ 40 min of esketamine dosing and returned to the predose range by ~ 1.5 h postdose. In two studies (4-week duration, age 18–64 years), the largest mean maximum systolic/diastolic postdose BP increases were 13.3/8.7 mmHg for esketamine/antidepressant and 6.1/4.9 mmHg for antidepressant/placebo, and in a short-term elderly study (age ≥ 65 years) were 16.0/9.5 and 11.1/6.8 mmHg, respectively. Across studies/study phases

Study Design:Broad narrative review.Objective:To review and summarize the current literature on guidelines, outcomes, techniques and indications surrounding multiple modalities of minimizing blood loss in spine surgery.Methods:A thorough review of peer-reviewed literature was performed on the guidelines, outcomes, techniques, and indications for multiple modalities of minimizing blood loss in spine surgery.Results:There is a large body of literature that provides a consensus on guidelines regarding the appropriate timing of discontinuation of anticoagulation, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and herbal supplements prior to surgery. Additionally, there is a more heterogenous discussion the utility of preoperative autologous blood donation facilitated by erythropoietin and iron supplementation for healthy patients slated for procedures with high anticipated blood loss and for whom allogeneic transfusion is likely. Intraoperative maneuvers available to minimize blood loss include positioning and maintaining normothermia. Tranexamic acid (TXA), bipolar sealer electrocautery, and topical hemostatic agents, and hypotensive anesthesia (mean arterial pressure (MAP) Conclusion:As the volume and complexity of spinal procedures rise, intraoperative blood loss management has become a pivotal topic of research within the field. There are many tools for minimizing blood loss in patients undergoing spine surgery. The current literature supports combining techniques to use a cost- effective multimodal approach to minimize blood loss in the perioperative period.

Hypertension (HTN) is an important risk factor for cardiovascular disease (CVD) but the association between HTN and CVD cannot be explained by average blood pressure (BP) alone. BP variability (BPV) is another important factor, along with the effects of HTN on the vasculature. The concept of systemic hemodynamic atherothrombotic syndrome (SHATS) has been proposed, describing an age-related and synergistic vicious cycle of hemodynamic stress and vascular disease. The importance of SHATS is based on the assumption that the assessment of BPV and arterial disease is likely to provide an effective opportunity to intervene early to reduce progression to HTN in younger patients or to CVD events and organ damage in older patients. In addition to providing an overview of current evidence for the mechanisms and clinical data related to SHATS, this article proposes a new SHATS score for use to diagnose and assess the severity of SHATS. The score includes two components - a BP score and a vascular score - which are multiplied to generate the SHATS score. This reflects the synergistic, rather than additive, effects of BP and vascular disease on target organ damage and CVD events. Although it requires refinement and validation in future studies, early detection of SHATS using tools such as the proposed score, combined with population-based stratification and technology-based anticipation medicine incorporating real-time individual data, has the potential to contribute to meaningful reductions in rates of CVD events and target organ damage.

Objectives To characterize the blood pressure (BP) profile of the new β3-adrenergic receptor agonist, vibegron, in patients with overactive bladder. Methods Patients were randomized to once-daily vibegron 75 mg or placebo for 28 days and underwent ambulatory BP monitoring. The primary endpoint was change from baseline (CFB) to day 28 in mean daytime ambulatory systolic BP (SBP). Secondary endpoints were CFB in mean 24-h SBP and in mean daytime and mean 24-h ambulatory diastolic BP (DBP) and heart rate (HR). Safety was assessed through adverse event reporting. Results Of 214 patients randomized, 96 receiving vibegron and 101 receiving placebo had evaluable baseline and day 28 measurements. Overall, 39.6 and 30.7% of patients receiving vibegron and placebo, respectively, had preexisting hypertension. The least squares mean difference (LSMD; 90% confidence interval) between vibegron and placebo in CFB in mean daytime SBP was 0.8 (-0.9, 2.5) mmHg. LSMD in CFB in mean daytime DBP and HR was 0.0 mmHg and 0.9 bpm, respectively. No significant differences between treatments were seen in CFB in mean 24-h SBP (LSMD, 0.6 mmHg), DBP (-0.2 mmHg) or HR (1.0 bpm). The most common treatment-emergent adverse event was hypertension, with rates comparable between groups [vibegron: n = 5 (4.7%); placebo: n = 4 (3.7%)]. One patient receiving vibegron took a prohibited medication (phentermine) known to increase BP. Conclusions Once-daily vibegron had no statistically significant or clinically relevant effects on BP or HR.

Summary Background Increased blood pressure is the biggest contributor to the global burden of disease and mortality. Data suggest that less than half of the population with hypertension is aware of it. May Measurement Month was initiated to raise awareness of the importance of blood pressure and as a pragmatic interim solution to the shortfall in screening programmes. Methods This cross-sectional survey included volunteer adults (≥18 years) who ideally had not had their blood pressures measured in the past year. Each participant had their blood pressure measured three times and received a a questionnaire about demographic, lifestyle, and environmental factors. The primary objective was to raise awareness of blood pressure, measured by number of countries involved, number of people screened, and number of people who have untreated or inadequately treated hypertension (defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, or on the basis of receiving antihypertensive medication). Multiple imputation was used to estimate the mean of the second and third blood pressure readings if these were not recorded. Measures of association were analysed using linear mixed models. Findings Data were collected from 1 201 570 individuals in 80 countries. After imputation, of the 1 128 635 individuals for whom a mean of the second and third readings was available, 393 924 (34·9%) individuals had hypertension. 153 905 (17·3%) of 888 616 individuals who were not receiving antihypertensive treatment were hypertensive, and 105 456 (46·3%) of the 227 721 individuals receiving treatment did not have controlled blood pressure. Significant differences in adjusted blood pressures and hypertension prevalence were apparent between regions. Adjusted blood pressure was higher in association with antihypertensive medication, diabetes, cerebrovascular disease, smoking, and alcohol consumption. Blood pressure was higher when measured on the right arm than on the left arm, and blood pressure was highest on Saturdays. Interpretation Inexpensive global screening of blood pressure is achievable using volunteers and convenience sampling. Pending the set-up of systematic surveillance systems worldwide, MMM will be repeated annually to raise awareness of blood pressure. Funding International Society of Hypertension, Centers for Disease Control and Prevention, Servier Pharmaceutical Co.

Objective: The win ratio is a statistical methodology to evaluate clinical trial outcomes using multiple hierarchical endpoints. We applied the win ratio to patients in SPYRAL HTN-ON MED pilot study to quantify potential differences in renal denervation (RDN) efficacy utilizing different blood pressure (BP) reduction thresholds. Methods: In the SPYRAL HTN-ON MED pilot study, patients were enrolled with office systolic BP (OSBP) ≥150 mmHg and Results: The calculated win ratio favored RDN: 2.78 (95% CI: 1.58, 5.48, p Conclusions: Win ratio methodology applied to the SPYRAL HTN-ON MED pilot study demonstrated that RDN was associated with a 2.6-2.8 times greater likelihood of BP or drug reduction compared with sham patients when evaluated across different BP reduction thresholds at 6 months.

Study Design: International multicenter prospective observational cohort study on patients undergoing radiation +/− surgical intervention for the treatment of symptomatic spinal metastases. Objectives: To investigate the association between the total Spinal Instability Neoplastic Score (SINS), individual SINS components and PROs. Methods: Data regarding patient demographics, diagnostics, treatment, and PROs (SF-36, SOSGOQ, EQ-5D) was collected at baseline, 6 weeks, and 12 weeks post-treatment. The SINS was assessed using routine diagnostic imaging. The association between SINS, PRO at baseline and change in PROs was examined with the Spearmans rank test. Results: A total of 307 patients, including 174 patients who underwent surgery+/− radiotherapy and 133 patients who underwent radiotherapy were eligible for analyses. In the surgery+/− radiotherapy group, 18 (10.3%) patients with SINS score between 0-6, 118 (67.8%) with a SINS between 7-12 and 38 (21.8%) with a SINS between 13-18, as compared to 55 (41.4%) SINS 0-6, 71(53.4%) SINS 7-12 and 7 (5.2%) SINS 13-18 in the radiotherapy alone group. At baseline, the total SINS and the presence of mechanical pain was significantly associated with the SOSGOQ pain domain (r = −0.519, P < 0.001) and the NRS pain score (r = 0.445, P < 0.001) for all patients. The presence of mechanical pain demonstrated to be moderately associated with a positive change in PROs at 12 weeks post-treatment. Conclusion: Spinal instability, as defined by the SINS, was significantly correlated with PROs at baseline and change in PROs post-treatment. Mechanical pain, as a single SINS component, showed the highest correlations with PROs.

Key Messages About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke). There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring. Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated. Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks. Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care. Urgent sustained action is needed is needed for effective public polcies and health system changes to prevent and control hypertension

Publication rate can indirectly assess the quality of research presented in scientific meetings. Considering presentations at orthopedic surgery and neurosurgery meetings, 10.5-66% of abstracts are published in scientific journals. Publication rate of abstracts presented at CSS Meetings is unknown. The objective of this study was to evaluate the publication rate of abstracts presented at the Canadian Spine Society(CSS) Annual Meetings from 2005to2014.In October2018, a systematic PubMed search was performed using title and authors of all abstracts presented at CSS Meetings from 2005 to 2014. The following information was retrieved from the articles and abstracts: year, type of presentation, publication in PubMed, time from presentation to final publication, journal and its impact factor(IF).A total of 621 abstracts were presented at CSS meetings from 2005 to 2014. Publication rate in PubMed was 54.8%(N=340/621). Oral presentations were more likely to be published than poster presentations(63.8%vs44.0%; OR=1.45; CI95%=1.20-1.75; P0.0001). The mean time from presentation to publication was 1.76 years(±1.93). The 340 identified articles were published in 87 different journals. Most common journals were Spine(N=75; 22.1%), The Spine Journal(N=40;11.8%), and Journal of Neurosurgery:Spine(N=28;8.2%). IF ranged from 0.18 to 47.66(mean=3.73±4.68). IF of articles presented orally were higher than those presented as poster(P=0.038).The CSS scientific meeting maintain along the years a steady high quality research presentations as manifested by its significant publication rate(54.8%) in medical journals with mean IF of 3.73. In comparison with other spine scientific meetings, publication rates of abstracts presented at CSS meeting is amongst the highest.

Study Design: Meta-analysis of randomized controlled trials (RCTs). Objectives: The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of spinal cord compression in patients with spine metastases from advanced cancers, by evaluating all available RCTs on this subject. Methods: A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing ZA with denosumab in prevention of spinal cord compressions in spine metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were spinal cord compression. Results: Three RCTs (5274 patients) were included. Denosumab was not significantly superior to ZA in reducing the likelihood of spinal cord compression, when all tumor types were combined (odds ratio [OR] 0.92, 95% confidence interval [CI; 0.66, 1.28], P = .66). Denosumab was not significantly favored over ZA in endodermal origin (breast and prostate; OR 0.72, 95% CI [0.43, 1.19], P = .20) and mesodermal origin tumors (solid tumors and multiple myeloma; OR 1.10, 95% CI [0.72, 1.69], P = .66). Conclusion: Denosumab does not significantly reduce the likelihood of spinal cord compressions in comparison to ZA in patients with spine metastases. When spinal cord compressions were grouped by tumor origin (endodermal or mesodermal), there remained no significant difference between denosumab and ZA. Further long-term studies are needed to determine the effectiveness of these treatment regimens.

Use of amlodipine for treatment of arterial hypertension and stable coronary artery disease (CAD) is sometimes limited by occurrence of peripheral edema and headache. We aimed to explore the true magnitude of this phenomenon by determining the rate and placebo-adjusted rate of these side effects.We performed a meta-analysis by including all randomized, placebo-controlled trials reporting edema and headache with amlodipine in patients with arterial hypertension and CAD. Placebo-adjusted rate (%) was determined as follows: (SE amlodipine % - SE placebo %)/SE amlodipine %.Data from 7226 patients of 22 trials were analyzed. Rate of edema was higher on amlodipine vs. placebo (16.6 vs. 6.2%, risk ratio: 2.9, 95% CI: 2.50-3.36, P 0.0001). The placebo-adjusted rate was 63%, indicating that 37% of edema cases were unrelated to amlodipine. Treatment with low/medium doses (2.5-5 mg) resulted in lower rates of edema (risk ratio: 2.01, 95% CI: 1.41-2.88, P = 0.0001) vs. high dose (10 mg) (risk ratio: 3.08, 95% CI 2.62-3.60, P 0.0001, Pforinteraction = 0.03). Incidence of headache was reduced using amlodipine vs. placebo (7.9 vs. 10.9%, risk ratio: 0.77, 95% CI: 0.65-0.90, P = 0.002) and was driven by use of low/medium doses (risk ratio: 0.52, 95% CI: 0.40-0.69, P 0.00001 vs. risk ratio: 0.92, 95%-CI: 0.74-1.15, P = 0.45, for high doses, Pforinteraction = 0.002).Although risks of peripheral edema are three-fold higher on amlodipine, up to one-third of edema cases on amlodipine might not be induced by amlodipine. Headache is reduced on amlodipine treatment, mainly driven by use of this drug at low/medium doses.

Background Patient satisfaction is infrequently investigated despite its importance in assessing efficacy and patient comprehension. The purpose of this study was to investigate patient satisfaction with treatment outcomes after surgery and/or radiotherapy for spinal metastases and to evaluate how health‐related quality of life (HRQOL) is related to patient satisfaction. Methods Patients with spinal metastases treated with surgery and/or radiotherapy were enrolled in a prospective, international, observational study. Demographic, histologic, treatment, and HRQOL data were collected. HRQOL was evaluated with the Numeric Rating Scale pain score, the 3‐level version of the EuroQol 5‐Dimension (EQ‐5D‐3L) instrument, and the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0). Patient satisfaction was derived from the SOSGOQ2.0 at 6, 12, and 26 weeks after treatment. Patients were classified as satisfied, neutral, or dissatisfied. Results Twelve weeks after treatment, 183 of the surgically treated patients (84%) were satisfied, and only 11 (5%) were dissatisfied; in contrast, 101 of the patients treated with radiotherapy alone (77%) were satisfied, and only 7 (5%) were dissatisfied. Significant improvements in pain, physical function, mental health, social function, leg function, and EQ‐5D were associated with satisfaction after surgery. Satisfaction after radiotherapy was associated with significant improvements in pain, mental health, and overall SOSGOQ2.0 scores. Dissatisfaction after treatment was associated with lower baseline values for leg strength and lower social functioning scores for surgically treated patients and with lower social functioning scores and being single for patients treated with radiotherapy. Conclusions High levels of satisfaction with treatment outcomes are observed after surgery and/or radiotherapy for spinal metastases. Posttreatment satisfaction is associated with significant improvements in pain and different dimensions of HRQOL., High levels of satisfaction with treatment outcomes are observed after surgery and/or radiotherapy for spinal metastases. Posttreatment satisfaction is associated with significant improvements in pain and different dimensions of health‐related quality of life.

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.

Background Stress is associated with an increased prevalence of anxiety and depression. Repeated social defeat (RSD) stress in mice increases the release of monocytes from the bone marrow that are recruited to the brain by microglia. These monocytes enhance inflammatory signaling and augment anxiety. Moreover, RSD promotes stress sensitization, in which exposure to acute stress 24 days after cessation of RSD causes anxiety recurrence. The purpose of this study was to determine whether microglia were critical to stress sensitization and exhibited increased reactivity to subsequent acute stress or immune challenge. Methods Mice were exposed to RSD, microglia were eliminated by colony-stimulating factor 1 receptor antagonism (PLX5622) and allowed to repopulate, and responses to acute stress or immune challenge (lipopolysaccharide) were determined 24 days after RSD sensitization. Results Microglia maintained a unique messenger RNA signature 24 days after RSD. Moreover, elimination of RSD-sensitized microglia prevented monocyte accumulation in the brain and blocked anxiety recurrence following acute stress (24 days). When microglia were eliminated prior to RSD and repopulated and mice were subjected to acute stress, there was monocyte accumulation in the brain and anxiety in RSD-sensitized mice. These responses were unaffected by microglial elimination/repopulation. This may be related to neuronal sensitization that persisted 24 days after RSD. Following immune challenge, there was robust microglial reactivity in RSD-sensitized mice associated with prolonged sickness behavior. Here, microglial elimination/repopulation prevented the amplified immune reactivity ex vivo and in vivo in RSD-sensitized mice. Conclusions Microglia and neurons remain sensitized weeks after RSD, and only the immune reactivity component of RSD-sensitized microglia was prevented by elimination/repopulation.

Aims Studies have shown a non-linear relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) and outcomes, with increased risk observed at both low and high blood pressure (BP) levels. We hypothesized that the BP-risk association is different in individuals with and without diabetes at high cardiovascular risk. Methods and results We identified patients with (N = 11 487) or without diabetes (N = 19 450), from 30 937 patients, from 133 centres in 44 countries with a median follow-up of 56 months in the ONTARGET/TRANSCEND studies. Patients had a prior history of stroke, myocardial infarction (MI), peripheral artery disease, or were high-risk diabetics. Patients in ONTARGET had been randomized to ramipril 10 mg daily, telmisartan 80 mg daily, or the combination of both. Patients in TRANSCEND were ACE intolerant and randomized to telmisartan 80 mg daily or matching placebo. We analysed the association of mean achieved in-trial SBP and DBP with the composite outcome of cardiovascular death, MI, stroke and hospitalization for congestive heart failure (CHF), the components of the composite, and all-cause death. Data were analysed by Cox regression and restricted cubic splines, adjusting for risk markers including treatment allocation and accompanying cardiovascular treatments. In patients with diabetes, event rates were higher across the whole spectrum of SBP and DBP compared with those without diabetes (P Conclusion High on treatment BP levels (≥160 or ≥90 mmHg) are associated with increased risk of cardiovascular outcomes and death. Also low levels ( Clinical trial registration http://clinicaltrials.gov.Unique identifier: NCT00153101.

Complying with the demands of drinking water supply whilst minimizing environmental impact poses a great challenge in water management. This study investigates the potential of withdrawal management of drinking water reservoirs to alleviate the disruption of the river continuum by a reservoir dam with respect to temperature and discharge. The aim is the identification of an optimal withdrawal strategy to provide a near‐natural discharge temperature and flow for the downstream river without jeopardizing drinking water production. First, we identify the applicability of new withdrawal regimes for raw water security and downstream river demands. Second, we search for an ideal withdrawal regime in scenario simulations using a numerical reservoir model (“General Lake Model”). The scenarios on a drinking water reservoir in Germany demonstrate that we are able to derive an optimized reservoir management. The numerical model is provided for operators as a simple and efficient tool for optimizing the withdrawal strategy within reservoir management.

Study Design: Ambispective cohort study design. Objectives: Cervical spine metastases have distinct clinical considerations. The aim of this study was to determine the impact of surgical intervention (± radiotherapy) or radiotherapy alone on health-related quality of life (HRQOL) outcomes in patients treated for cervical metastatic spine tumours. Methods: Patients treated with surgery and/or radiotherapy for cervical spine metastases were identified from the Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO) international multicentre prospective observational study. Demographic, diagnostic, treatment, and HRQOL (numerical rating scale [NRS] pain, EQ-5D (3L), SF-36v2, and SOSGOQ) measures were prospectively collected at baseline, 6 weeks, 3 months, and 6 months postintervention. Results: Fifty-five patients treated for cervical metastases were identified: 38 underwent surgery ± radiation and 17 received radiation alone. Surgically treated patients had higher mean spinal instability neoplastic scores compared with the radiation-alone group (13.0 vs 8.0, P < .001) and higher NRS pain scores and lower HRQOL scores compared to the radiation alone group ( P < .05). From baseline to 6 months posttreatment, surgically treated patients demonstrated statistically significant improvements in NRS pain, EQ-5D (5L), and SOSGOQ2.0 scores compared with nonsignificant improvements in the radiotherapy alone group. Conclusions: Surgically treated cervical metastases patients presented with higher levels of instability, worse baseline pain and HRQOL scores compared with patients who underwent radiotherapy alone. Significant improvements in pain and HRQOL were noted for those patients who received surgical intervention. Limited or no improvements were found in those treated with radiotherapy alone.

Background Bisphosphonates (BPs) including zoledronate (zol) have become standard care for bone metastases as they effectively inhibit tumor-induced osteolysis and associated pain. Several studies have also suggested that zol has direct anti-tumor activity. Systemic administration at high doses is the current approach to deliver zol, yet it has been associated with debilitating side effects. Local therapeutic delivery offers the ability to administer much lower total dosage, while at the same time maintaining sustained high-local drug concentration directly at the target treatment site. Here, we aimed to assess effects of lower doses of zol on bone metastases over a longer time. Methods Prostate cancer cell line LAPC4 and prostate-induced bone metastasis cells were treated with zol at 1, 3 and 10 µM for 7 days. Following treatment, cell proliferation was assessed using Almarblue®, Vybrant MTT®, and Live/Dead® viability/cytotoxicity assays. Additionally, cell migration and invasion were carried out using Falcon™ cell culture inserts and Cultrex® 3D spheroid cell invasion assays respectively. Results We show that treatment with 3–10 µM zol over 7-days significantly decreased cell proliferation in both the prostate cancer cell line LAPC4 and cells from spine metastases secondary to prostate cancer. Using the same low-dose and longer time course for treatment, we demonstrate that 10 µM zol also significantly inhibits tumor cell migration and 3D-cell growth/invasion. Conclusions This project harnesses the potential of using zol at low doses for longer treatment periods, which may be a viable treatment modality when coupled with biomaterials or biodevices for local delivery. Electronic supplementary material The online version of this article (10.1186/s12935-019-0745-x) contains supplementary material, which is available to authorized users.

AIMS The randomized sham-controlled SPYRAL HTN-OFF MED trial demonstrated that renal denervation (RDN) using a multi-electrode catheter lowers ambulatory blood pressure (BP) in non-medicated hypertensive patients. The current report describes the effects of RDN on heart rate (HR) in this population. METHODS AND RESULTS Patients were enrolled with an office systolic BP (SBP) of ≥150 mmHg and

Retrospective review of results from a prospectively collected Canadian cohort in comparison to published literature.(1) To investigate whether patients in a universal health care system have different outcomes than those in a multitier health care system in surgical management of degenerative spondylolisthesis (DS). (2) To identify independent factors predictive of outcome in surgical DS patients.Canada has a national health insurance program with unique properties. It is a single-payer system, coverage is universal, and access to specialist care requires referral by the primary care physician. The United States on the other hand is a multitier public/private payer system with more rapid access for insured patients to specialist care.Surgical DS patients treated between 2013 and 2016 in Canada were identified through the Canadian Spine Outcome Research Network (CSORN) database, a national registry that prospectively enrolls consecutive patients with spinal pathology from 16 tertiary care academic hospitals. This population was compared with the surgical DS arm of patients treated in the Spine Patients Outcome Research Trial (SPORT) study. We compared baseline demographics, spine-related, and health-related quality of life (HRQOL) outcomes at 3 months and 1 year. Multivariate analysis was used to identify factors predictive of outcome in surgical DS patients.The CSORN cohort of 213 patients was compared with the SPORT cohort of 248 patients. Patients in the CSORN cohort were younger (mean age 60.1 vs. 65.2; p.001), comprised fewer females (60.1% vs. 67.7%; p=.09), and had a higher proportion of smokers (23.3% vs. 8.9%; p.001). The SPORT cohort had more patients receiving compensation (14.6% vs. 7.7%; p.001). The CSORN cohort consisted of patients with slightly greater baseline disability (Oswestry disability index scores: 47.7 vs. 44.0; p=.008) and had more patients with symptom duration of greater than 6 months (93.7% vs. 62.1%; p.001). The CSORN cohort showed greater satisfaction with surgical results at 3 months (91.1% vs. 66.1% somewhat or very satisfied; p.01) and 1 year (88.2% vs. 71.0%, p.01). Improvements in back and leg pain were similar comparing the two cohorts. On multivariate analysis, duration of symptoms, treatment group (CSORN vs. SPORT) or insurance type (public/Medicare/Medicaid vs. Private/Employer) predicted higher level of postoperative satisfaction. Baseline depression was also associated with worse Oswestry disability index at 1-year postoperative follow-up in both cohorts.Surgical DS patients treated in Canada (CSORN cohort) reported higher levels of satisfaction than those treated in the United States (SPORT cohort) despite similar to slightly worse baseline HRQOL measures. Symptom duration and insurance type appeared to impact satisfaction levels. Improvements in other patient-reported health-related quality of life measures were similar between the cohorts.

Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. Methods: Patients with a daytime ambulatory BP ≥135/85 mm Hg and Results: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group ( P =0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P =0.010 and 1.4±1.5 versus 2.0±1.8, P =0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (−18.1±12.2 versus −15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: −4.3 mm Hg, 95% confidence interval, −7.9 to −0.6, P =0.024). There were no major adverse events in either group through 6 months. Conclusions: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02649426.

Background Traumatic atlanto-axial rotatory subluxation (AARS) in an adult is a rare condition, which if left untreated can be fatal. In addition to this, many symptoms experienced such as neck pain and stiffness are non-specific which often leads to misdiagnosis, thus delaying definitive treatment. AARS can be divided into traumatic and non-traumatic causes with the latter generally encompassing congenital cervical spine abnormalities. Case presentation We present a case of a 66-year-old female with traumatic rotatory AARS, which was initially misdiagnosed in the emergency department. This patient was subsequently recalled to the hospital when the misdiagnosis was spotted the following day from imaging results. The patient was initially managed conservatively as an inpatient using head halter cervical traction which proved to give good clinical reduction allowing discharge with Miami J upon ambulation. Upon follow up the patient was experiencing continuous pain but remained neurovascularly intact. She thus opted for definitive management with C1-C2 stabilization with an open reduction and internal fixation. Conclusion This case demonstrates the importance of having a high index of suspicion to diagnose AARS in cervical spine trauma presenting to the emergency department, until exclusion can be made using imaging and clinical examination.

Summary Background Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. Methods In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18–75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT02649426 . Findings Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (−8·0 mm Hg [IQR –16·4 to 0·0] vs –3·0 mm Hg [–10·3 to 1·8]; median between-group difference –4·5 mm Hg [95% CI –8·5 to –0·3]; adjusted p=0·022); the median between-group difference was –5·8 mm Hg (95% CI –9·7 to –1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Interpretation Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Funding ReCor Medical.

Background: The aim of this review is to investigate current uses of fibrinogen as a tool to reduce operative and postoperative blood loss in different surgical fields especially orthopedic spine surgery. This is a systematic review. Methods: MEDLINE (via Ovid 1946 to June 1, 2020) and Embase (via Ovid 1947 to June 1, 2020) were searched using the keywords “fibrinogen”, “surgery”, and “spine” for relevant studies. The search strategy used text words and relevant indexing to identify articles discussing the use of fibrinogen to control surgical blood loss. Results: The original literature search yielded 407 articles from which 68 duplications were removed. Three hundred thirty-nine abstracts and titles were screened. Results were separated by surgical specialties. Conclusions: Multiple studies have looked at the role of fibrinogen for acute bleeding in the operative setting. The current evidence regarding the use of fibrinogen concentrate in spine surgery is promising but limited, even though this is a field with the potential for severe hemorrhage. Further trials are required to understand the utility of fibrinogen concentrate as a first-line therapy in spine surgery and to understand the importance of target fibrinogen levels and subsequent dosing and administration to allow recommendations to be made in this field.

Background There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. Methods Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). Results An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. Conclusions Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.