Functional Outcomes of Congenital Scoliosis at a Mean 35-Year Follow-up Post In Situ Fusion. Revisiting Patients From the 2002 Goldberg et al Study.

BACKGROUND: The management of congenital scoliosis poses a significant challenge for treating surgeons. The aim of our study was to provide insight into the long-term clinical results of spinal fusion in congenital scoliosis. METHODS: We performed a retrospective review of the scoliosis database in our institution for the period 1976 until 2002 identifying 43 patients with congenital scoliosis who underwent spinal fusion. Patient demographics, diagnosis, levels fused, and radiographs were evaluated. Patients were evaluated for unplanned return to the operating room (UPROR) via SRS 22, EQ5D-5L, and Oswestry Disability Index (ODI). RESULTS: Of the 43 patients who fulfilled the inclusion criteria, 22 patients agreed to participate, 3 patients were known to be deceased and 18 patients were lost to follow-up or declined to participate and were excluded. The mean age of the respondents was 40.7 years (range, 30 to 47 y) with a mean follow-up from index surgery of 35 years (range, 20 to 44 y). At most recent follow-up, 12 patients (54%) underwent UPROR. The mean age at diagnosis was 3.4 years (range, birth to 11.5 y), and the mean age for first surgery was 5.8 years (range, 1 to 13 y). As regards radiologic follow-up; the mean number of levels fused was 5.2 (range, 2 to 12). Thoracic fusion was performed in 17 patients (77%). The mean T1 to T12 height at index surgery and maturity was 166 mm (range, 130 to 240 mm) and 202 mm (range, 125 to 270 mm), respectively. The mean functional scores at follow-up were SRS 22: 4.5 (range, 2.4 to 5), cumulative EQ5D-5L score 7.2 (range, 5 to 15), and ODI: 8% (range, 2 to 30%). All respondents completed high school, 10 patients (45%) completed university, and 2 patients were awarded doctorates. Currently, 17 patients (77%) are in paid employment. CONCLUSIONS: This report constitutes the largest series of patients treated by spinal arthrodesis for congenital scoliosis followed into maturity. We demonstrate the thorax continues to grow after index fusion, patient-reported outcomes were satisfactory with superior educational and employment rates and unplanned return to theatre is rare in adult life. LEVEL OF EVIDENCE: Therapeutic Level IV.

Applying atomistic neural networks to bias conformer ensembles towards bioactive-like conformations.

Identifying bioactive conformations of small molecules is an essential process for virtual screening applications relying on three-dimensional structure such as molecular docking. For most small molecules, conformer generators retrieve at least one bioactive-like conformation, with an atomic root-mean-square deviation (ARMSD) lower than 1 Å, among the set of low-energy conformers generated. However, there is currently no general method to prioritise these likely target-bound conformations in the ensemble. In this work, we trained atomistic neural networks (AtNNs) on 3D information of generated conformers of a curated subset of PDBbind ligands to predict the ARMSD to their closest bioactive conformation, and evaluated the early enrichment of bioactive-like conformations when ranking conformers by AtNN prediction. AtNN ranking was compared with bioactivity-unaware baselines such as ascending Sage force field energy ranking, and a slower bioactivity-based baseline ranking by ascending Torsion Fingerprint Deviation to the Maximum Common Substructure to the most similar molecule in the training set (TFD2SimRefMCS). On test sets from random ligand splits of PDBbind, ranking conformers using ComENet, the AtNN encoding the most 3D information, leads to early enrichment of bioactive-like conformations with a median BEDROC of 0.29 ± 0.02, outperforming the best bioactivity-unaware Sage energy ranking baseline (median BEDROC of 0.18 ± 0.02), and performing on a par with the bioactivity-based TFD2SimRefMCS baseline (median BEDROC of 0.31 ± 0.02). The improved performance of the AtNN and TFD2SimRefMCS baseline is mostly observed on test set ligands that bind proteins similar to proteins observed in the training set. On a more challenging subset of flexible molecules, the bioactivity-unaware baselines showed median BEDROCs up to 0.02, while AtNNs and TFD2SimRefMCS showed median BEDROCs between 0.09 and 0.13. When performing rigid ligand re-docking of PDBbind ligands with GOLD using the 1% top-ranked conformers, ComENet ranked conformers showed a higher successful docking rate than bioactivity-unaware baselines, with a rate of 0.48 ± 0.02 compared to CSD probability baseline with a rate of 0.39 ± 0.02. Similarly, on a pharmacophore searching experiment, selecting the 20% top-ranked conformers ranked by ComENet showed higher hit rate compared to baselines. Hence, the approach presented here uses AtNNs successfully to focus conformer ensembles towards bioactive-like conformations, representing an opportunity to reduce computational expense in virtual screening applications on known targets that require input conformations.

Deep generative models for 3D molecular structure.

Deep generative models have gained recent popularity for chemical design. Many of these models have historically operated in 2D space; however, more recently explicit 3D molecular generative models have become of interest, which are the topic of this article. Dozens of published models have been developed in the last few years to generate molecules directly in 3D, outputting both the atom types and coordinates, either in one-shot or adding atoms or fragments step-by-step. These 3D generative models can also be guided by structural information such as a binding pocket representation to successfully generate molecules with docking score ranges similar to known actives, but still showing lower computational efficiency and generation throughput than 1D/2D generative models and sometimes producing unrealistic conformations. We advocate for a unified benchmark of metrics to evaluate generation and propose perspectives to be addressed in next implementations.

Perioperative Mobile Telehealth Program for Post-Prostatectomy Incontinence: A Randomized Clinical Trial.

PURPOSE: Perioperative pelvic floor muscle training can hasten recovery of bladder control and reduce severity of urinary incontinence following radical prostatectomy. Nevertheless, most men undergoing prostatectomy do not receive this training. The purpose of this trial was to test the effectiveness of interactive mobile telehealth (mHealth) to deliver an evidence-based perioperative behavioral training program for post-prostatectomy incontinence. MATERIALS AND METHODS: This was a 3-site, 2-arm, randomized trial (2014-2019). Men with prostate cancer scheduled to undergo radical prostatectomy were randomized to a perioperative behavioral program (education, pelvic floor muscle training, progressive exercises, bladder control techniques) or a general prostate cancer education control condition, both delivered by mHealth for 1-4 weeks preoperatively and 8 weeks postoperatively. The primary outcome was time to continence following surgery measured by the ICIQ (International Consultation on Incontinence Questionnaire) Short-Form. Secondary outcomes measured at 6, 9 and 12 months included Urinary Incontinence Subscale of Expanded Prostate Cancer Index Composite; pad use; International Prostate Symptom Score QoL Question and Global Perception of Improvement. RESULTS: A total of 245 men (ages 42-78 years; mean=61.7) were randomized. Survival analysis using the Kaplan-Meier estimate showed no statistically significant between-group differences in time to continence. Analyses at 6 months indicated no statistically significant between-group differences in ICIQ scores (mean=7.1 vs 7.0, p=0.7) or other secondary outcomes. CONCLUSIONS: mHealth delivery of a perioperative program to reduce post-prostatectomy incontinence was not more effective than an mHealth education program. More research is needed to assess whether perioperative mHealth programs can be a helpful addition to standard prostate cancer care.

Use of Messaging Principles to Design a Facebook Ad Promoting Public Engagement in Serious Illness Care for National Healthcare Decisions Day.

Public hesitation to engage in advance care planning, consultation with palliative care, and admission to hospice is a significant barrier to improving patient outcomes. In previous study, we derived five empirically supported messaging principles, and in this project we used these messaging principles to design, place, and analyze a 60-second video for the Oregon Coalition for Living Well with Serious Illness. The video was scripted to emphasize a single message that had emerged from the empirical research: that "you should have a say in your care." We deliberately did not use the term "advance care planning" because our prior focus groups showed that most consumers did not use this term. The marketing plan for the resulting video on Facebook included a paid sponsorship of the full-length video through a Facebook boosted post, and three 10-second ads featuring key lines from the video that tested different elaborations of the central message. Facebook Analytics indicated that the 60-second video was viewed 67,650 times in the week it was promoted. The three 10-second ads, which showed selected moments from the full-length video, were viewed a total of 253,087 times. Of the three 10-second ads, the one emphasizing "What matters to me is being near my family" (65% of clicks) strongly outperformed "I don't want to go out on a machine" and "I've heard so many medical horror stories" (35% for both messages combined) as messages that persuaded viewers to click through the ad to the website. Use of the messaging principles to guide the design and marketing of this Facebook ad shows that (1) the public is interested in serious illness care, (2) that targeted social media can be used to reach a defined public audience, and that (3) this public messaging strategy can be implemented at relatively low cost.

Impact of the COVID-19 Pandemic on Pelvic and Acetabular Trauma: Experiences From a National Tertiary Referral Centre.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on daily life. Restrictions imposed to help minimise virus transmission have limited both population movement and employment, as well as altering the potential mechanisms of high-energy trauma. The objective of this study was to assess the impact of the COVID-19 pandemic on pelvic and acetabular trauma. Materials and methods A retrospective observational study of the incidence, causality, patient profile, fracture morphology, and treatment strategy of pelvic and acetabular trauma managed in a national tertiary referral specialist pelvic and acetabular centre between the 1st of March and 1st of August 2020 was undertaken and compared to corresponding time periods in the two preceding years. Results A total of 78 patients were referred for management following pelvic and acetabular trauma during the study period with a mean age of 52 years (SD +/- 24.2). Overall, 45% and 42% of patients were referred following isolated pelvic or acetabular fractures respectively. The most frequent mechanism of injury was a fall from height (>1m) (42%), with 53% of patients suffering from concomitant injuries and 32% requiring surgical management. While there was a statistically significant difference in mechanism of injury (P=0.026), there was no significant difference in overall incidence, fracture types, incidence of concomitant injuries, or overall proportion requiring surgical intervention during the study period when compared to previous years. Conclusion While some variation in the mechanisms of injury have been observed, the overall incidence, patient, fracture, and injury profiles associated with pelvic and acetabular trauma appear to have remained consistent during the COVID-19 pandemic. Additionally, the number and proportion of those requiring surgical treatment of these fractures have remained stable. Understanding the continued burden of these potentially severe injuries may help guide injury prevention, treatment, and resource allocation as the pandemic continues.

Bereavement is different: A multinational bereavement symptom model validation.

Clinicians need to rule out an appropriate grief reaction when diagnosing major depression. This study identifies symptom differences by bereavement status and validates a symptom model of bereavement. Symptom features from six national cross-sectional epidemiological samples were analyzed and estimates pooled. Crying often, thinking of death, appetite loss, waking up early, trouble sleeping, and depending on others were significantly more likely in the bereaved. Symptoms of thinking of or attempting suicide, feeling one would be better off dead or wanting to die, worthlessness, social conflict, worthlessness with difficulty making decisions, being discouraged, feeling less than others, being troubled, not coping, feeling hopeless, sleeping more, being upset and history of an anxiety disorder were all significantly less likely among the bereaved. Moderate to good model discrimination effect sizes were found. Good model performance was found when narrowly defined complicated bereavement cases were excluded. On the whole the bereaved are more likely to report symptoms consistent with a normal grief reaction. As depression screening becomes the norm in primary care, normal grief that meets Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) symptom criteria for a MDE likely has a high risk of being diagnosed inappropriately as pathological depression.

Public Messaging for Serious Illness Care in the Age of Coronavirus Disease: Cutting through Misconceptions, Mixed Feelings, and Distrust.

A year ago, we began a project designed to align public messages from 10 organizations involved in advance care planning (ACP), palliative care (PC), and hospice to increase public engagement. By public messaging, we are referring to a well-established evidence-driven method of disseminating information at scale that enables the public to take action to protect their health. Our project plan was upended by the coronavirus disease 2019 (COVID-19) pandemic-but we used the opportunity to conduct focus groups during the pandemic that, compared with focus groups conducted before the pandemic, provide an important portrait of public perceptions of serious illness care that can be used to design for greater public engagement. Our findings can be summarized in three observations. First, misunderstanding of ACP, PC, and hospice is wide ranging and deep. Second, COVID-19 evokes its own brand of confusion and ambivalence that is distinct from other serious illnesses. And third, distrust of the health care system has become the new normal. Despite these findings, our focus group participants strongly endorsed five messaging principles (1) talk up the benefits, (2) present choices for every step, (3) use stories that are positive and aspirational, (4) invite dialogue-more than once, and (5) invoke a new team-of people who matter, clinicians, medical institutions, and community organizations who are ready to help. After listening to 100-word stories describing real patient experiences with ACP, PC, and hospice, our focus group participants expressed interest and appreciation. But to improve public engagement broadly, we need to explain our work to the general public in a way that makes them want to know more.

Functional Status at Liver Transplant Waitlisting Correlates With Greater Odds of Encephalopathy, Ascites, and Spontaneous Bacterial Peritonitis.

BACKGROUND & AIMS: Whether higher liver transplant (LT) waitlist mortality in patients with poor functional status (FS) is mediated by higher prevalence of cirrhosis complications is not clear. We aim to evaluate the impact of FS on risk of hepatic encephalopathy (HE), ascites, and spontaneous bacterial peritonitis (SBP) among adults listed for LT. METHODS: Using 2005-2018 United Network for Organ Sharing LT data, we retrospectively evaluated the impact of FS on prevalence of ascites, HE, and SBP among adults listed for LT using Karnofsky Performance Status Score categories (KPSS-1: FS 80-100%, KPSS-2: 60-70%, KPSS-3: 40-50%, KPSS-4: 10-30%), stratified by underlying liver disease etiology. Between-group comparisons used chi-squared methods and adjusted multivariate logistic regression. RESULTS: Among 100,618 adults listed for LT (68.8% male, 72.4% non-Hispanic white) 35.2% were KPSS-1, 36.6% KPSS-2, 15.7% KPSS-3, and 12.6% KPSS-4 at time of LT waitlist registration. Patients with worse FS were significantly more likely to have ascites, HE, and SBP at time of waitlist registration (KPSS-1 vs. KPSS-4: ascites, 66% vs. 93%; HE, 81% vs. 49%; SBP, 4% vs. 16%, p < 0.001 for all). On multivariate regression, compared with patients with KPSS-1, those with KPSS-4 had significantly higher odds of ascites (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.37-1.62, p < 0.01), HE (OR: 1.69, 95% CI: 1.59-1.80, p < 0.01), and SBP (OR: 2.17, 95% CI: 1.98-2.38, p < 0.01), which was observed across all liver disease etiologies. CONCLUSION: Worse FS is associated with higher odds of cirrhosis complications including ascites, HE, and SBP, which was observed across all liver disease etiologies.

Skin Puckering in a Tibial Fracture.

Skin puckering is a feature observed in fractures that undergo large displacements at the time of initial injury and occur as a result of adherence of the dermal tissues to the underlying fracture fragment. Herein, we discuss the interesting case of a 47-year-old male who suffered a comminuted tibial shaft fracture which resulted in marked pretibial skin puckering prior to fracture reduction with striking corresponding images noted on computerised tomography (CT) scanning.

Mercury 4.0: from visualization to analysis, design and prediction.

The program Mercury, developed at the Cambridge Crystallographic Data Centre, was originally designed primarily as a crystal structure visualization tool. Over the years the fields and scientific communities of chemical crystallography and crystal engineering have developed to require more advanced structural analysis software. Mercury has evolved alongside these scientific communities and is now a powerful analysis, design and prediction platform which goes a lot further than simple structure visualization.

Correction to: Patients with Alcoholic Liver Disease Have Worse Functional Status at Time of Liver Transplant Registration and Greater Waitlist and Post-transplant Mortality Which Is Compounded by Older Age.

The original version of the article unfortunately contained an error in Figure 3. X-axis of Figures 3(a-d) should be 'Time in months'. Corrected version of Figure 3 is given.

Patients with Alcoholic Liver Disease Have Worse Functional Status at Time of Liver Transplant Registration and Greater Waitlist and Post-transplant Mortality Which Is Compounded by Older Age.

BACKGROUND: Worse functional status correlates with increased mortality on the liver transplant (LT) waitlist. Whether functional status affects LT outcomes equally across cirrhosis etiologies is unclear. AIMS: We evaluate the impact of functional status on waitlist and post-LT mortality stratified by etiology and age. METHODS: Functional status among US adults from 2005 to 2017 United Network for Organ Sharing LT registry data was retrospectively evaluated using Karnofsky Performance Status Score (KPS-1 = functional status 80-100%, KPS-2 = 60-70%, KPS-3 = 40-50%, KPS-4 = 10-30%). Waitlist and post-LT survival were stratified by KPS and cirrhosis etiology, including alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis C (HCV), and HCV/ALD, and evaluated using Kaplan-Meier and multivariate Cox proportional hazard models. RESULTS: Among 94,201 waitlist registrants (69.4% men, 39.5% HCV, 26.7% ALD, 23.2% NASH), ALD patients had worse functional status compared to HCV (KPS-4: 17.2% vs. 8.3%, p < 0.001). Worse functional status at time of waitlist registration was associated with higher 90-day waitlist mortality with the greatest effect in ALD (KPS-4 vs. KPS-1: ALD HR 2.16, 95% CI 1.83-2.55; HCV HR 2.17, 95% CI 1.87-2.51). Similar trends occurred in 5-year post-LT survival with ALD patients the most harmed. Compared to patients < 50 years, patients ≥ 65 years had increased waitlist mortality at 90-days if they had HCV or HCV/ALD, and 5-year post-LT mortality regardless of cirrhosis etiology with ALD patients most severely affected. CONCLUSIONS: In a retrospective cohort study of patients, US ALD patients had disparately worse functional status at time of LT waitlist registration. Worse functional status correlated with higher risk of waitlist and post-LT mortality, affecting ALD and HCV patients the most.

Pretibial Panniculitis Ossificans-A Rare but Significant Diagnosis.

Pretibial panniculitis ossificans is a rare condition. In this report, we describe a 67-year-old male localized to his right pretibial tissue, approximately 20 years after contusion to the same area.

Autonomic neurophysiologic implications of disorders comorbid with bladder pain syndrome vs myofascial pelvic pain.

AIMS: The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences. METHODS: We compared the presence and relative time of onset of 27 other medical conditions in women with BPS, MPP, both syndromes, and healthy subjects. Analysis included an adjustment for multiple comparisons. RESULTS: Among 107 female subjects (BPS alone = 32; BPS with MPP = 36; MPP alone = 9; healthy controls = 30), comorbidities differentially associated with BPS included irritable bowel syndrome (IBS), dyspepsia, and chronic nausea, whereas those associated with MPP included migraine headache and dyspepsia, consistent with the distinct autonomic neurophysiologic signatures of the two disorders. PTSD (earliest), anxiety, depression, migraine headache, fibromyalgia, chronic fatigue, and IBS usually preceded BPS or MPP. PTSD and the presence of both pelvic pain disorders in the same subject correlated with significantly increased comorbid burden. CONCLUSIONS: Our study suggests a distinct pattern of comorbid conditions in women with BPS. These findings further support our hypothesis of primary vagal defect in BPS as compared with primary sympathetic defect in MPP, suggesting a new model for chronic these pelvic pain syndromes. Chronologically, PTSD, migraine, dysmenorrhea, and IBS occurred early, supporting a role for PTSD or its trigger in the pathophysiology of chronic pelvic pain.

More Severe Deficits in Performance Status at Time of Liver Transplant is Associated With Significantly Higher Risk of Death Following Liver Transplantation.

GOAL: To evaluate the impact of Karnofsky Performance Status score (KPSS) at the time of liver transplantation (LT) on post-LT survival. BACKGROUND: While the Model for End-Stage Liver Disease (MELD) score is used to prioritize individuals for LT, it does not specifically incorporate functional status into patient assessment for LT. METHODS: Using 2005 to 2016 United Network for Organ Sharing data, all adults (age 18 y and above) undergoing LT were identified. The association of KPSS at the time of LT (KPSS 1: functional status 80% to 100%, KPSS 2: 60% to 70%, KPSS 3: 40% to 50%, KPSS 4: 10% to 30%) with post-LT survival was evaluated using Kaplan-Meier methods and adjusted multivariate logistic regression models. RESULTS: Among 66,397 LT recipients (68% male, 72% non-Hispanic white, 22% hepatocellular carcinoma, median age: 55 to 57), women were more likely to be KPSS 4 at the time of LT compared with men (27.95% vs. 22.79%; P<0.001) and African Americans (25.43% vs. 23.03%; P<0.001) and Hispanics (31.69% vs. 23.03%; P<0.001) were more likely to be KPSS 4 than non-Hispanic whites. Worse KPSS at LT correlated with higher post-LT mortality [compared with KPSS 1: Hazard Ratio (HR) for KPSS 2: 1.16, 95% confidence interval (CI): 1.10-1.22; HR for KPSS 3: 1.40; 95% CI: 1.32-1.49; HR for KPSS 4: 1.67; 95% CI: 1.55-1.79]. This increased mortality seen with worse KPSS was observed among all liver disease etiologies and in patients with and without hepatocellular carcinoma. CONCLUSIONS: Worse functional status at the time of LT is strongly associated with higher risk of mortality following LT, emphasizing the importance of optimizing performance status in the preoperative period.

More severe deficits in functional status associated with higher mortality among adults awaiting liver transplantation.

The impact of functional status on liver transplant (LT) waitlist outcomes is not well studied. Early evidence suggests frailty portends increased mortality. We aim to evaluate the association of functional status with LT waitlist survival and the probability of receiving LT among adults with cirrhosis. Using 2005-2016 United Network for Organ Sharing (UNOS) data, we retrospectively assessed the association of functional status, as determined by Karnofsky Performance Status Score (KPSS) with LT waitlist survival and the probability of receiving LT using Kaplan-Meier and multivariate Cox proportional hazard models. Among 118 954 patients listed for LT, patients with worse Karnofsky scores, indicating poor functional status, were progressively more likely to receive liver transplantation compared to patients with better scores, with the most functionally disabled group having 68% higher probability of receiving LT (HR 1.68; 95% CI 1.61-1.75, P < 0.001). Worse functional status was associated with increased waitlist mortality, with the most functionally disabled group 97% more likely to die on the waitlist (HR 1.97; 95% CI 1.81-2.16, P < 0.001). In conclusion, among patients awaiting LT, worse functional status was associated with significantly higher waitlist mortality.