Citations

AbstractThe liver and kidney are key organs of metabolic homeostasis in the body and display complex interactions. Liver diseases often have direct and immediate effects on renal physiology and function. Conversely, acute kidney injury (AKI) is a common problem in patients with both acute and chronic liver diseases. AKI in patients with acute liver failure is usually multifactorial and involves insults similar to those seen in the general AKI population. Liver cirrhosis affects and is directly affected by aberrations in systemic and renal hemodynamics, inflammatory response, renal handling of sodium and free water excretion, and additional nonvasomotor mechanisms. Subsequent problems, for example, worsening ascites, hyponatremia, and AKI, often complicate management of patients with chronic progressive liver disease and add to their morbidity and mortality. Thus, AKI must be carefully defined and diagnosed in patients with liver disease. The kidney also plays a pivotal role in balancing acid–base disturbances resulting from advanced liver disease, making AKI in the setting of end-stage liver disease very difficult to manage clinically. While renal dysfunction in these patients often resolves following orthotopic liver transplant, dialysis may be required as a bridge to transplantation to mitigate the metabolic disarray found in these critically ill patients.

AbstractBackgroundElevated uptake of the [18F]AV‐1451 tau‐PET ligand has been observed cross‐sectionally in subjects with progressive supranuclear palsy (PSP). However, it is unknown how the ligand performs longitudinally in PSP. We aimed to determine how regional measures of change on [18F]AV‐1451 PET perform as longitudinal biomarkers of PSP compared with the more established biomarker of rate of midbrain atrophy.MethodsSixteen subjects with PSP underwent 2 serial [18F]AV‐1451 tau‐PET scans and 3‐Tesla MRI over 12 months and were age‐ and sex‐matched to 39 healthy controls with longitudinal [18F]AV‐1451 PET. Median [18F]AV‐1451 uptake was calculated for each scan for regions of interest across the brain and divided by uptake in cerebellar crus to create standard uptake value ratios. Midbrain volume on MRI was also calculated for each scan. Sample sizes required to power placebo‐controlled treatment trials were calculated.ResultsRate of midbrain atrophy was significantly increased in PSP compared with controls. [18F]AV‐1451 regional change measures were significantly increased in PSP compared with controls in the pallidum, precentral cortex, dentate nucleus of the cerebellum, and midbrain. Change over time in the PSP Rating Scale correlated with change in midbrain volume but did not correlate with change in the [18F]AV‐1451 measures. Smallest sample‐size estimates were obtained with rate of midbrain atrophy, followed by the PSP Rating Scale, with both outperforming [18F]AV‐1451 measures.Conclusions[18F]AV‐1451 tau‐PET measures increase over time in subjects with PSP, but longitudinal [18F]AV‐1451 measures may not perform as well as rate of midbrain atrophy as biomarkers for PSP clinical trials. © 2018 International Parkinson and Movement Disorder Society

AbstractIncreased activation of the major pro‐inflammatory NF‐κB pathway leads to numerous age‐related diseases, including chronic liver disease (CLD). Rapamycin, an inhibitor of mTOR, extends lifespan and healthspan, potentially via suppression of inflammaging, a process which is partially dependent on NF‐κB signalling. However, it is unknown if rapamycin has beneficial effects in the context of compromised NF‐κB signalling, such as that which occurs in several age‐related chronic diseases. In this study, we investigated whether rapamycin could ameliorate age‐associated phenotypes in a mouse model of genetically enhanced NF‐κB activity (nfκb1−/−) characterized by low‐grade chronic inflammation, accelerated aging and CLD. We found that, despite showing no beneficial effects in lifespan and inflammaging, rapamycin reduced frailty and improved long‐term memory, neuromuscular coordination and tissue architecture. Importantly, markers of cellular senescence, a known driver of age‐related pathology, were alleviated in rapamycin‐fed animals. Our results indicate that, in conditions of genetically enhanced NF‐κB, rapamycin delays aging phenotypes and improves healthspan uncoupled from its role as a suppressor of inflammation.

Study Design. This study retrospectively analyzes prospectively collected data. Objective. Here, we aim to determine the influence of preoperative and 12-month modified Japanese Orthopedic Association (mJOA) on satisfaction and understand the change in mJOA severity classification after surgical management of degenerative cervical myelopathy (DCM). Summary of Background Data. DCM is a progressive degenerative spine disease resulting from cervical cord compression. The natural progression of DCM is variable; some patients experience periods of stability, while others rapidly deteriorate following disease onset. The mJOA is commonly used to grade and categorize myelopathy symptoms, but its association with postoperative satisfaction has not been previously explored. Methods. The quality and outcomes database (QOD) was queried for patients undergoing elective surgery for DCM. Patients were divided into mild (≥14), moderate (9 to 13), or severe (<9) categories on the mJOA scores. A McNemar–Bowker test was used to assess whether a significant proportion of patients changed mJOA category between preoperative and 12 months postoperative. A multivariable proportional odds ordinal logistic regression model was fitted with 12-month satisfaction as the outcome of interest. Results. We identified 1963 patients who underwent elective surgery for DCM and completed 12-months follow-ups. Comparing mJOA severity level preoperatively and at 12 months revealed that 55% remained in the same category, 37% improved, and 7% moved to a worse category. After adjusting for baseline and surgery-specific variables, the 12-month mJOA category had the highest impact on patient satisfaction (P < 0.001). Conclusion. Patient satisfaction is an indispensable tool for measuring quality of care after spine surgery. In this sample, 12-month mJOA category, regardless of preop mJOA, was significantly correlated with satisfaction. Given these findings, it is important to advise patients of the probability that surgery will change their mJOA severity classification and the changes required to achieve postoperative satisfaction. Level of Evidence: 3

OBJECTIVE Back pain and neck pain are two of the most common causes of work loss due to disability, which poses an economic burden on society. Due to recent changes in healthcare policies, patient-centered outcomes including return to work have been increasingly prioritized by physicians and hospitals to optimize healthcare delivery. In this study, the authors used a national spine registry to identify clinical factors associated with return to work at 3 months among patients undergoing a cervical spine surgery. METHODS The authors queried the Quality Outcomes Database registry for information collected from April 2013 through March 2017 for preoperatively employed patients undergoing cervical spine surgery for degenerative spine disease. Covariates included demographic, clinical, and operative variables, and baseline patient-reported outcomes. Multiple imputations were used for missing values and multivariable logistic regression analysis was used to identify factors associated with higher odds of returning to work. Bootstrap resampling (200 iterations) was used to assess the validity of the model. A nomogram was constructed using the results of the multivariable model. RESULTS A total of 4689 patients were analyzed, of whom 82.2% (n = 3854) returned to work at 3 months postoperatively. Among previously employed and working patients, 89.3% (n = 3443) returned to work compared to 52.3% (n = 411) among those who were employed but not working (e.g., were on a leave) at the time of surgery (p < 0.001). On multivariable logistic regression the authors found that patients who were less likely to return to work were older (age > 56–65 years: OR 0.69, 95% CI 0.57–0.85, p < 0.001; age > 65 years: OR 0.65, 95% CI 0.43–0.97, p = 0.02); were employed but not working (OR 0.24, 95% CI 0.20–0.29, p < 0.001); were employed part time (OR 0.56, 95% CI 0.42–0.76, p < 0.001); had a heavy-intensity (OR 0.42, 95% CI 0.32–0.54, p < 0.001) or medium-intensity (OR 0.59, 95% CI 0.46–0.76, p < 0.001) occupation compared to a sedentary occupation type; had workers’ compensation (OR 0.38, 95% CI 0.28–0.53, p < 0.001); had a higher Neck Disability Index score at baseline (OR 0.60, 95% CI 0.51–0.70, p = 0.017); were more likely to present with myelopathy (OR 0.52, 95% CI 0.42–0.63, p < 0.001); and had more levels fused (3–5 levels: OR 0.46, 95% CI 0.35–0.61, p < 0.001). Using the multivariable analysis, the authors then constructed a nomogram to predict return to work, which was found to have an area under the curve of 0.812 and good validity. CONCLUSIONS Return to work is a crucial outcome that is being increasingly prioritized for employed patients undergoing spine surgery. The results from this study could help surgeons identify at-risk patients so that preoperative expectations could be discussed more comprehensively.

Abstract BACKGROUND Given recent differing findings following 2 randomized clinical trials on degenerative lumbar spondylolisthesis (DLS) surgery, there is a need to better define how subsets of patients fare following surgery. OBJECTIVE To investigate the impact of obesity on patient-reported outcomes (PROs) following DLS surgery. METHODS A total of 12 high-enrolling sites were queried, and we found 797 patients undergoing surgery for grade 1 DLS. For univariate comparisons, patients were stratified by BMI ≥ 30 kg/m 2 (obese) and < 30 kg/m 2 (nonobese). Baseline, 3-mo, and 12-mo follow-up parameters were collected. PROs included the North American Spine Society satisfaction questionnaire, numeric rating scale (NRS) back pain, NRS leg pain, Oswestry Disability Index (ODI), and EuroQoL-5D (EQ-5D) Questionnaire. RESULTS We identified 382 obese (47.9%) and 415 nonobese patients (52.1%). At baseline, obese patients had worse NRS back pain, NRS leg pain, ODI, and EQ-5D scores ( P < .001, P = .01, P < .001, and P = .02, respectively). Both cohorts improved significantly for back and leg pain, ODI, and EQ-5D at 12 mo ( P < .001). At 12 mo, similar proportions of obese and nonobese patients responded that surgery met their expectations (62.6% vs 67.4%, P = .24). In multivariate analyses, BMI was independently associated with worse NRS leg pain and EQ-5D at 12 mo ( P = .01 and P < .01, respectively) despite adjusting for baseline differences. CONCLUSION Obesity is associated with inferior leg pain and quality of life—but similar back pain, disability, and satisfaction—12 mo postoperatively. However, obese patients achieve significant improvements in all PRO metrics at 12 mo.

Objective: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. Method: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. Results: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge ‘impairment’ (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. Conclusion: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.

Despite their benevolent care of others, today, more than ever, the cancer care professional who experiences overwhelming feelings of exhaustion, cynicism, and inefficacy is in grave jeopardy of developing burnout. Clinicians are repeatedly physically and emotionally exposed to exceedingly long hours in direct care with seriously ill patients/families, limited autonomy over daily responsibilities, endless electronic documentation, and a shifting medical landscape. The physical and emotional well-being of the cancer care clinician is critical to the impact on quality care, patient satisfaction, and overall success of their organizations. The prevention of burnout as well as targeting established burnout need to be proactively addressed at the individual level and organizational level. In fact, confronting burnout and promoting wellness are the shared responsibility of both oncology clinicians and their organizations. From an individual perspective, oncology clinicians must be empowered to play a crucial role in enhancing their own wellness by identification of burnout symptoms in both themselves and their colleagues, learning resilience strategies (e.g., mindful self-compassion), and cultivating positive relationships with fellow clinician colleagues. At the organizational level, leadership must recognize the importance of oncology clinician well-being; engage leaders and physicians in collaborative action planning, improve overall practice environment, and provide institutional wellness resources to physicians. These effective individual and organizational interventions are crucial for the prevention and improvement of overall clinician wellness and must be widely and systematically integrated into oncology care.