PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.

BACKGROUND: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID. OBJECTIVE: We sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships. METHODS: Clinical data from patients with PLCG2 variants were obtained via standardized questionnaire. PLCG2 variants were generated by mutagenesis of enhanced green fluorescent protein (EGFP)-PLCG2 plasmid, which was overexpressed in Plcg2-deficient DT-40 B cells. B-cell receptor-induced calcium flux and extracellular signal-regulated kinase phosphorylation were assayed by flow cytometry. In some cases, stimulation-induced calcium flux was also measured in primary patient cells. RESULTS: Three-fourths of PLCG2 variants produced functional alteration of B-cell activation, in vitro. Thirteen variants led to gain of function (GOF); however, most functional variants defined a new class of PLCG2 mutation, monoallelic loss of function (LOF). Susceptibility to infection and autoinflammation were common with both GOF and LOF variants, whereas a new phenotypic cluster consisting of humoral immune deficiency, autoinflammation, susceptibility to herpesvirus infection, and natural killer cell dysfunction was observed in association with multiple heterozygous LOF variants detected in both familial and sporadic cases. In some cases, PLCG2 variants produced greater effects in natural killer cells than in B cells. CONCLUSIONS: This work expands the genotypic and phenotypic associations with functional variation in PLCG2, including a novel form of ID in carriers of heterozygous loss of PLCG2 function. It also demonstrates the need for more diverse assays for assessing the impact of PLCG2 variants on human disease.

Long-term effectiveness and feasibility of CT-guided cryoablation as a novel treatment option for symptomatic lumbar synovial cysts.

OBJECTIVE: To present a case series with a long-term follow-up of CT-guided cryoablation procedure for the minimally invasive treatment of symptomatic lumbar facet synovial cyst with a mean follow-up of 38 months (range, 15-55). MATERIALS AND METHODS: We present a retrospective, uncontrolled clinical case series in a single institution on patients treated with CT-guided cryoablation for symptomatic lumbar facet joint synovial cyst refractory to or not suitable for imaging-guided rupture procedure. In two cases, patients underwent cryoablation and cyst rupture within a 2-week period. Outcome measures were post-procedural radiologic studies and clinical examinations up to the end of the follow-up. Selected patients underwent post-procedural clinical and CT and MRI imaging which were reviewed up to the conclusion of the follow-up. All patients were clinically assessed and evaluated by spine surgery team. Technical success was complete resolution of patient's symptoms. RESULTS: We treated 3 females and 3 males (mean age 64 years). Four patients had cysts located at L4-L5, and the remaining two at L5-S1. We used two cryoprobes in five patients, and three in one. Clinical and/or technical success was documented in all cases (mean follow-up, 38 months [range, 15-55]). We found no major complications related to the cryoablation itself. CONCLUSION: Our initial experience with CT-guided cryoablation for symptomatic lumbar facet synovial cysts describes a less invasive alternative treatment option to surgery for the management of such lesions. Our long-term outcome experience showed low recurrence and complication rates. CT-guided cryoablation may be a reasonable alternative approach to treat lumbar synovial cysts that are refractory or contraindicated to the rupture procedure and where surgical management is unfeasible.

5-years patency results of Zilver PTX on the femoro-popliteal arterial segment: A Northern Sydney experience.

BACKGROUND: The burden of peripheral arterial disease is increasing. Treatment of femoro-popliteal lesions remains challenging despite novel endovascular devices. Drug-eluting stents suppress post-treatment inflammation and reducing neo-intimal hyperplasia to reduce in-stent restenosis. METHODS: A multi-centre retrospective 5-years longitudinal study was undertaken to evaluate freedom from clinically driven target limb revascularisation (FF CD-TLR) and patency of Zilver PTX stents in treating symptomatic femoro-popliteal stenotic lesions. Kaplan-Meier survival curves were used to demonstrate FF CD-TLR, primary, primary assisted and secondary patency. RESULTS: There were 148 patients and 183 lesions treated with a mean age of 80.3 years and 52% males. The all-cause 5-years mortality was 25%. FF CD-TLR yearly patencies to 5 years were 81%, 67%, 62%, 57% and 52%, respectively, with significantly poorer outcomes for in-stent restenosis, longer stent lengths and lesions at the femoro-popliteal junction. Primary patencies were 63%, 47%, 40%, 34% and 24%, assisted primary patencies were 90%, 75%, 68%, 59% and 48% and secondary patencies were 96%, 94%, 94%, 92% and 92%. Major adverse limb events were 5% at 1-year and cumulative at 5-years was 16%. DISCUSSION: The clinical outcomes in this study population are comparable to recent publications with smaller cohorts. Our study confirms Zilver PTX has very good primary patency over 5 years with no discernible effect on all-cause mortality in an elderly cohort with particularly long treated lesions. Our results are similar to those seen in younger patients with shorter lesions. Nonetheless, longer lesions required more reinterventions to maintain patency. CONCLUSION: Zilver PTX is a safe and durable drug-eluting stent when utilised in the management of femoro-popliteal stenotic lesions with good long-term patency and limited need for re-intervention.

Capacity of deep-sea corals to obtain nutrition from cold seeps aligned with microbiome reorganization.

Cold seeps in the deep sea harbor various animals that have adapted to utilize seepage chemicals with the aid of chemosynthetic microbes that serve as primary producers. Corals are among the animals that live near seep habitats and yet, there is a lack of evidence that corals gain benefits and/or incur costs from cold seeps. Here, we focused on Callogorgia delta and Paramuricea sp. type B3 that live near and far from visual signs of currently active seepage at five sites in the deep Gulf of Mexico. We tested whether these corals rely on chemosynthetically-derived food in seep habitats and how the proximity to cold seeps may influence; (i) coral colony traits (i.e., health status, growth rate, regrowth after sampling, and branch loss) and associated epifauna, (ii) associated microbiome, and (iii) host transcriptomes. Stable isotope data showed that many coral colonies utilized chemosynthetically derived food, but the feeding strategy differed by coral species. The microbiome composition of C. delta, unlike Paramuricea sp., varied significantly between seep and non-seep colonies and both coral species were associated with various sulfur-oxidizing bacteria (SUP05). Interestingly, the relative abundances of SUP05 varied among seep and non-seep colonies and were strongly correlated with carbon and nitrogen stable isotope values. In contrast, the proximity to cold seeps did not have a measurable effect on gene expression, colony traits, or associated epifauna in coral species. Our work provides the first evidence that some corals may gain benefits from living near cold seeps with apparently limited costs to the colonies. Cold seeps provide not only hard substrate but also food to cold-water corals. Furthermore, restructuring of the microbiome communities (particularly SUP05) is likely the key adaptive process to aid corals in utilizing seepage-derived carbon. This highlights that those deep-sea corals may upregulate particular microbial symbiont communities to cope with environmental gradients.

Patient Expectations About Palliative Treatment for Symptomatic Spinal Metastases: A Qualitative Study.

OBJECTIVES: Patients with spinal metastases often receive palliative surgery or radiation therapy to maintain or improve health-related quality of life. Patients with unrealistic expectations regarding treatment outcomes have been shown to be less satisfied with their post-treatment health status. This study evaluated expectations of patients with spinal metastases scheduled for surgery and/or radiation therapy. METHODS: Individual semistructured interviews were conducted with patients with symptomatic spinal metastases before and 6 weeks after surgery and/or radiation therapy. Expectations regarding treatment outcomes were discussed before treatment, and level of fulfillment of these pretreatment expectations was discussed after treatment. Interviews were recorded, transcribed and analyzed according to the thematic analysis method to identify themes. RESULTS: Before treatment, patients thought they were not, or minimally, informed about (expected) treatment outcomes, but they felt well informed about treatment procedures and possible complications. Although patients expected pain relief and improvement in daily functioning, they found it difficult to describe any recovery timeline or the impact of these expected improvements on their daily life. Patients generally understood that treatment was not curative, but lacked insight into the impact of treatment on life expectancy given that this was hardly discussed by their surgeon and/or radiation oncologist. Pretreatment expectations regarding pain and daily functioning were only partially met in most patients post-treatment. CONCLUSIONS: Patients thought they were not, or only minimally, informed about expected outcomes after surgery and/or radiation therapy for symptomatic spinal metastases. Improvements in patient-physician communication and counseling could help guide patients toward realistic pretreatment expectations.

Practice Variation between Salaried and Fee-for-Service Surgeons for Lumbar Surgery.

OBJECTIVE: To examine differences in surgical practices between salaried and fee-for-service (FFS) surgeons for two common degenerative spine conditions. Surgeons may offer different treatments for similar conditions on the basis of their compensation mechanism. METHODS: The study assessed the practices of 63 spine surgeons across eight Canadian provinces (39 FFS surgeons and 24 salaried) who performed surgery for two lumbar conditions: stable spinal stenosis and degenerative spondylolisthesis. The study included a multicenter, ambispective review of consecutive spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network registry between October 2012 and July 2018. The primary outcome was the difference in type of procedures performed between the two groups. Secondary study variables included surgical characteristics, baseline patient factors, and patient-reported outcome. RESULTS: For stable spinal stenosis (n = 2234), salaried surgeons performed statistically fewer uninstrumented fusion (p < 0.05) than FFS surgeons. For degenerative spondylolisthesis (n = 1292), salaried surgeons performed significantly more instrumentation plus interbody fusions (p < 0.05). There were no statistical differences in patient-reported outcomes between the two groups. CONCLUSIONS: Surgeon compensation was associated with different approaches to stable lumbar spinal stenosis and degenerative lumbar spondylolisthesis. Salaried surgeons chose a more conservative approach to spinal stenosis and a more aggressive approach to degenerative spondylolisthesis, which highlights that remuneration is likely a minor determinant in the differences in practice of spinal surgery in Canada. Further research is needed to further elucidate which variables, other than patient demographics and financial incentives, influence surgical decision-making.

Proteomic Portraits Reveal Evolutionarily Conserved and Divergent Responses to Spinal Cord Injury.

Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of cerebrospinal fluid and serum samples from 111 patients with acute SCI and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at 6 months with an area under the receiver operating characteristic curve of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response and establish the cerebrospinal fluid abundance of glial fibrillary acidic protein as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.

Factors contributing to a longer length of stay in adults admitted to a quaternary spinal care center.

BACKGROUND: Longer hospital length of stay (LOS) has been associated with worse outcomes and increased resource utilization. However, diagnostic and patient-level factors associated with LOS have not been well studied on a large scale. The goal was to identify patient, surgical and organizational factors associated with longer patient LOS for adult patients at a high-volume quaternary spinal care center. METHODS: We performed a retrospective analysis of 13,493 admissions from January 2006 to December 2019. Factors analyzed included age, sex, admission status (emergent vs scheduled), ASIA grade, operative vs non-operative management, mean blood loss, operative time, and adverse events. Specific adverse events included surgical site infection (SSI), other infection (systemic or UTI), neuropathic pain, delirium, dural tear, pneumonia, and dysphagia. Diagnostic categories included trauma, oncology, deformity, degenerative, and "other". A multivariable linear regression model was fit to log-transformed LOS to determine independent factors associated with patient LOS, with effects expressed as multipliers on mean LOS. RESULTS: Mean LOS for the population (SD) was 15.8 (34.0) days. Factors significantly (p < 0.05) associated with longer LOS were advanced patient age [multiplier on mean LOS 1.011/year (95% CI: 1.007-1.015)], emergency admission [multiplier on mean LOS 1.615 (95% CI: 1.337-1.951)], ASIA grade [multiplier on mean LOS 1.125/grade (95% CI: 1.051-1.205)], operative management [multiplier on mean LOS 1.211 (95% CI: 1.006-1.459)], and the occurrence of one or more AEs [multiplier on mean LOS 2.613 (95% CI: 2.188-3.121)]. Significant AEs included postoperative SSI [multiplier on mean LOS 1.749 (95% CI: 1.250-2.449)], other infections (systemic infections and UTI combined) [multiplier on mean LOS 1.650 (95% CI: 1.359-2.004)], delirium [multiplier on mean LOS 1.404 (95% CI: 1.103-1.787)], and pneumonia [multiplier on mean LOS 1.883 (95% CI: 1.447-2.451)]. Among the diagnostic categories explored, degenerative patients experienced significantly shorter LOS [multiplier on mean LOS 0.672 (95%CI: 0.535-0.844), p < 0.001] compared to non-degenerative categories. CONCLUSION: This large-scale study taking into account diagnostic categories identified several factors associated with patient LOS. Future interventions should target modifiable factors to minimize LOS and guide hospital resource allocation thereby improving patient outcomes and quality of care and decreasing healthcare-associated costs.

Temporal analysis of complication rates of cervical spine surgery for degenerative spine disease between younger and older cohorts using the CSORN registry: Is age just a number?

STUDY DESIGN: An ambispective review of consecutive cervical spine surgery patients enrolled in the Canadian Spine Outcomes and Research Network (CSORN) between January 2015 and September 2019. PURPOSE: To compare complication rates of degenerative cervical spine surgery over time between older (> 65) and younger age groups (< 65). More elderly people are having spinal surgery. Few studies have examined the temporal nature of complications of cervical spine surgery by patient age groups. METHODS: Adverse events were collected prospectively using adverse event forms. Binary logistic regression analysis was utilized to assess associations between risk modifiers and adverse events at the intra-, peri-operative and 3 months post-surgery. RESULTS: Of the 761 patients studied (age < 65, n = 581 (76.3%) and 65 + n = 180 (23.7%), the intra-op adverse events were not significantly different; < 65 = 19 (3.3%) vs 65 + = 11 (6.1%), p < 0.087. Peri-operatively, the < 65 group had significantly lower percentage of adverse events (65yrs (11.2%) vs. 65 + = (26.1%), p < 0.001). There were no differences in rates of adverse events at 3 months post-surgery (< 65 = 39 (6.7%) vs. 65 + = 12 (6.7%), p < 0.983). Less blood loss (OR = 0.99, p < 0.010) and shorter length of hospital stay (OR = 0.97, p < 0.025) were associated with not having intra-op adverse events. Peri-operatively, > 1 operated level (OR = 1.77, p < 0.041), shorter length of hospital stay (OR = 0.86, p < 0.001) and being younger than 65 years (OR = 2.11, p < 0.006) were associated with not having adverse events. CONCLUSION: Following degenerative cervical spine surgery, the older and younger age groups had significantly different complication rates at peri-operative time points, and the intra-operative and 3-month post-operative complication rates were similar in the groups.

AFX unibody stent graft: Effective and safe for the treatment of severe aorto-iliac occlusive disease.

OBJECTIVES: The primary objective of this study was to determine the primary, assisted primary and secondary patency rates of the Endologix AFX stent-graft in patients considered high risk for open surgery with complex aorto-iliac occlusive disease. The secondary objective was to determine 30-day major adverse cardiovascular and cerebrovascular events. METHODS: A retrospective review was undertaken of clinical records of 38 patients who underwent AFX stent-graft placement for aorto-iliac occlusive disease from 2016 to 2019. Patient data was de-identified and entered into a REDcap secure database. Descriptive statistical analysis (means and standard deviations) and Kaplan-Meier survival curves were created to determine the duration of patency of the AFX stent-graft system. RESULTS: Primary patency rates at 6, 12 and 24 months were 92%, 92% and 84%, respectively. Assisted primary patency rates at these times were 100%, 100% and 93% with secondary patency of 100% maintained throughout. The incidence of 30-day major adverse cardiovascular and cerebrovascular events was 8% and major adverse limb events was 3%. One death unrelated to the AFX device occurred during the study period though outside of the 30-day peri-operative period. CONCLUSIONS: Primary, assisted primary and secondary patency rates of AFX stent-grafts, when used to treat aorto-iliac occlusive disease, are high. This study supports the use of the AFX stent-graft for the endovascular treatment of complex aorto-iliac occlusive disease as an alternative to other endovascular options as well as a safe alternative to open aorto-iliac or aorto-femoral bypass in patients who are at high risk for open procedures.

The Risk Assessment and Prediction Tool (RAPT) Score Predicts Discharge Destination, Length of Stay, and Postoperative Mobility After Total Joint Arthroplasty.

BACKGROUND: Predicting an arthroplasty patient's discharge disposition, length of stay (LOS), and physical function is helpful because it allows for preoperative patient optimization, expectation management, and discharge planning. The goal of this study was to evaluate the ability of the Risk Assessment and Prediction Tool (RAPT) score to predict discharge destination, LOS, and postoperative mobility in patients undergoing primary total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Primary unilateral TKAs (n = 9,064) and THAs (n = 8,649) performed for primary osteoarthritis at our institution from 2018 to 2021 (excluding March to June 2020) were identified using a prospectively maintained institutional registry. We evaluated the associations between preoperative RAPT score and (1) discharge destination, (2) LOS, and postoperative mobility as measured by (3) successful ambulation on the day of surgery and (4) Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" score. RESULTS: On multivariable analyses adjusting for multiple covariates, every one-point increase in RAPT score among TKA patients was associated with a 1.82-fold increased odds of home discharge (P < .001), 0.22 days shorter LOS (P < .001), 1.13-fold increased odds of ambulating on postoperative day 0 (P < .001), and 0.25-point higher Activity Measure for Post-Acute Care score (P < .001). Similar findings were seen among THAs. A RAPT score of 8 or higher was the most sensitive and specific cutoff to predict home discharge. CONCLUSION: Among nearly 18,000 TKA and THA patients, RAPT score was predictive of discharge disposition, LOS, and postoperative mobility. A RAPT score of 8 or higher was the most sensitive and specific cutoff to predict discharge to home. In contrast to prior studies of the RAPT score which have grouped TKAs and THAs together, this study ran separate analyses for TKAs and THAs and found that THA patients seemed to perform better than TKA patients with equal RAPT scores, suggesting that RAPT may behave differently between TKAs and THAs, particularly in the intermediate risk RAPT range.

Degenerative spinal conditions requiring emergency surgery: an evolving crisis in a publicly funded health care system.

BACKGROUND: Surgery for degenerative spine pathologies is typically performed on a scheduled basis; however, worsening symptoms may warrant emergency surgery. An increasing number of patients requiring emergency surgery has been observed (22.6% in 2006 to 34.8% in 2019). We sought to compare the outcomes of patients who received scheduled surgery and those who required emergency surgery. METHODS: All patients treated between Jan. 1, 2006, and Dec. 31, 2019, were included. Retrospective comparisons were made between patients who were scheduled (elective) for surgery and those requiring emergency surgery, patients who were scheduled for surgery and those who decompensated while on the surgical waitlist and patients who presented as de novo emergencies and those who decompensated while on the surgical waitlist. RESULTS: Among the 6217 patients with degenerative pathologies, 4654 (74.9%) patients were scheduled (elective) for surgery and 1563 (25.1%) were patients requiring emergency surgery. Compared with patients who were scheduled, patients requiring emergency surgery had a longer length of stay (LOS) in hospital (5.1 d, interquartile range [IQR] 2.7-11.2 v. 3.6 d, IQR 1.3-6.4, p < 0.001) and lower rate of home discharge (78.6% v. 94.2%, p < 0.001). Patients requiring emergency surgery were 1.34 times more likely to have any adverse events (95% confidence interval [CI] 1.06-1.68, p = 0.01). When compared with patients who were scheduled for surgery, those who decompensated while on the surgical waitlist had longer LOS (7.0 d, IQR 3.3-15.0 v. 3.6 d, IQR 1.3-6.4, p < 0.001), less home discharge (77.6% v. 94.2%, p < 0.001) and were 2.5 times more likely to have any adverse events (95% CI 1.5-4.1, p < 0.001). Patients who decompensated had a 2.1 times higher risk of having any adverse events than patients who presented as de novo emergencies (95% CI 1.2-3.6, p < 0.001). CONCLUSION: We observed worse perioperative outcomes for patients requiring emergency surgery for degenerative spinal conditions than for patients who were scheduled for surgery. Patients who decompensated while on the surgical waitlist had the worst outcomes.

Effectiveness of prophylactic intranasal photodynamic disinfection therapy and chlorhexidine gluconate body wipes for surgical site infection prophylaxis in adult spine surgery.

BACKGROUND: Current measures to prevent spinal surgical site infection (SSI) lack compliance and lead to antimicrobial resistance. We aimed to examine the effectiveness of bundled preoperative intranasal photodynamic disinfection therapy (nPDT) and chlorhexidine gluconate (CHG) body wipes in the prophylaxis of spine SSIs in adults, as well as determine our institutional savings attributable to the use of this strategy and identify adverse events reported with nPDT-CHG. METHODS: We performed a 14-year prospective observational interrupted time-series study in adult (age > 18 yr) patients undergoing emergent or elective spine surgery with 3 time-specific cohorts: before rollout of our institution's nPDT-CHG program (2006-2010), during rollout (2011-2014) and after rollout (2015-2019). We used unadjusted bivariate analysis to test for temporal changes across patient and surgical variables, and segmented regression to estimate the effect of nPDT-CHG on the annual SSI incidence rates per period. We used 2 models to estimate the cost of nPDT-CHG to prevent 1 additional SSI per year and the annual cumulative cost savings through SSI prevention. RESULTS: Over the study period, 13 493 patients (mean 964 per year) underwent elective or emergent spine surgery. From 2006 to 2019, the mean age, mean Charlson Comorbidity Index (CCI) score and mean Spine Surgical Invasiveness Index (SSII) score increased from 48.4 to 58.1 years, from 1.7 to 2.6, and from 15.4 to 20.5, respectively (p < 0.001). Unadjusted analysis confirmed a significant decrease in the annual number (74.6 to 26.8) and incidence (7.98% to 2.67%) of SSIs with nPDT-CHG (p < 0.001). After adjustment for mean age, mean CCI score and mean SSII score, segmented regression showed an absolute reduction in the annual SSI incidence rate of 3.36% per year (p < 0.001). The estimated annual cost to prevent 1 additional SSI per year was about $1350-$1650, and the estimated annual cumulative cost savings were $2 484 856-$2 495 016. No adverse events were reported with nPDT-CHG. CONCLUSION: Preoperative nPDT-CHG administration is an effective prophylactic strategy for spinal SSIs, with significant cost savings. Given its rapid action, minimal risk of antimicrobial resistance, broad-spectrum activity and high compliance rate, preoperative nPDT-CHG decolonization should be the standard of care for all patients undergoing emergent or elective spine surgery.

Endocytosis and Endocytic Motifs across the Connexin Gene Family.

Proteins fated to be internalized by clathrin-mediated endocytosis require an endocytic motif, where AP-2 or another adaptor protein can bind and recruit clathrin. Tyrosine and di-leucine-based sorting signals are such canonical motifs. Connexin 43 (Cx43) has three canonical tyrosine-based endocytic motifs, two of which have been previously shown to recruit clathrin and mediate its endocytosis. In addition, di-leucine-based motifs have been characterized in the Cx32 C-terminal domain and shown to mediate its endocytosis. Here, we examined the amino acid sequences of all 21 human connexins to identify endocytic motifs across the connexin gene family. We find that although there is limited conservation of endocytic motifs between connexins, 14 of the 21 human connexins contain one or more canonical tyrosine or di-leucine-based endocytic motif in their C-terminal or intracellular loop domain. Three connexins contain non-canonical (modified) di-leucine motifs. However, four connexins (Cx25, Cx26, Cx31, and Cx40.1) do not harbor any recognizable endocytic motif. Interestingly, live cell time-lapse imaging of different GFP-tagged connexins that either contain or do not contain recognizable endocytic motifs readily undergo endocytosis, forming clearly identifiable annular gap junctions when expressed in HeLa cells. How connexins without defined endocytic motifs are endocytosed is currently not known. Our results demonstrate that an array of endocytic motifs exists in the connexin gene family. Further analysis will establish whether the sites we identified in this in silico analysis are legitimate endocytic motifs.

Georg schmorl prize of the German spine society (DWG) 2021: Spinal Instability Spondylodiscitis Score (SISS)-a novel classification system for spinal instability in spontaneous spondylodiscitis.

PURPOSE: Even though spinal infections are associated with high mortality and morbidity, their therapy remains challenging due to a lack of established classification systems and widely accepted guidelines for surgical treatment. This study's aim therefore was to propose a comprehensive classification system for spinal instability based on the Spinal Instability Neoplastic Score (SINS) aiding spine surgeons in choosing optimal treatment for spontaneous spondylodiscitis. METHODS: Patients who were treated for spontaneous spondylodiscitis and received computed tomography (CT) imaging were included retrospectively. The Spinal Instability Spondylodiscitis Score (SISS) was developed by expert consensus. SINS and SISS were scored in CT-images by four readers. Intraclass correlation coefficients (ICCs) and Fleiss' Kappa were calculated to determine interrater reliabilities. Predictive validity was analyzed by cross-tabulation analysis. RESULTS: A total of 127 patients were included, 94 (74.0%) of which were treated surgically. Mean SINS was 8.3 ± 3.2, mean SISS 8.1 ± 2.4. ICCs were 0.961 (95%-CI: 0.949-0.971) for total SINS and 0.960 (95%-CI: 0.946-0.970) for total SISS. SINS yielded false positive and negative rates of 12.5% and 67.6%, SISS of 15.2% and 40.0%, respectively. CONCLUSION: We show high reliability and validity of the newly developed SISS in detecting unstable spinal lesions in spontaneous spondylodiscitis. Therefore, we recommend its use in evaluating treatment choices based on spinal biomechanics. It is, however, important to note that stability is merely one of multiple components in making surgical treatment decisions.

All over the MAP: describing pressure variability in acute spinal cord injury.

STUDY DESIGN: Observational study. OBJECTIVES: To examine the feasibility of meeting the current clinical guidelines for the hemodynamic management of acute spinal cord injury (SCI) which recommend maintaining mean arterial pressure (MAP) at 85-90 mmHg in the days following injury. METHODS: This study examined data collected minute-by-minute to describe the pressure profile in the first 5 days following SCI in 16 patients admitted to the Intensive Care Unit at Vancouver General Hospital (40 ± 19 years, 13 M/3 F, C4-T11). MAP and intrathecal pressure (ITP) were monitored at 100 Hz by arterial and lumbar intrathecal catheters, respectively, and reported as the average of each minute. Spinal cord perfusion pressure was calculated as the difference between MAP and ITP. The minute-to-minute difference (MMdiff) of each pressure variable was calculated as the absolute difference between consecutive minutes. RESULTS: Only 24 ± 7% of MAP recordings were between 85 and 90 mmHg. Average MAP MMdiff was ~3 mmHg. The percentage of MAP recordings within target range was negatively correlated with the degree of variability (i.e. MMdiff; r = -0.64, p < 0.008) whereas higher mean MAP was correlated with greater variability (r = 0.57, p = 0.021). CONCLUSIONS: Our findings point to the 'real life' challenges in maintaining MAP in acute SCI patients. Given MAP fluctuated ~3 mmHg minute-to-minute, maintaining MAP within a 5 mmHg range with conventional volume replacement and vasopressors presents an almost impossible task for clinicians and warrants reconsideration of current management guidelines.

Telerehabilitation has similar clinical and patient-reported outcomes compared to traditional rehabilitation following total knee arthroplasty.

PURPOSE: Telehealth rehabilitation (telerehab) is an increasingly popular cost-saving alternative to traditional rehabilitation after total joint arthroplasty. We compared the safety and efficacy of an institutional telerehab program to conventional "face-to-face" rehabilitation in a sample of patients undergoing total knee arthroplasty (TKA). METHODS: A retrospective matched cohort study was performed. Medicare patients who utilized telerehab following unilateral TKA were matched in a 1:3 ratio to those utilizing conventional rehabilitation. Patients were matched on sex, body mass index (BMI, ± 5 kg/m2), preoperative extension (± 10 degrees), preoperative flexion (± 10 degrees), and Risk Assessment and Prediction Tool (RAPT) score (± 2 points). Ninety-day unplanned healthcare encounters, 120-day manipulations under anesthesia (MUAs), and 6-week and 3-month changes in the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR), pain visual analog scale (VAS), Veterans RAND 12 (VR-12), and Lower-Extremity Activity Scale (LEAS) were compared between groups. RESULTS: Eighty-two telerehab patients and 244 conventional rehab patients were included. After matching, there were no differences in 90-day unplanned healthcare encounters or 120-day MUA rates between groups. There were no differences in 6-week or 3-month changes in KOOS-JR, VAS pain, or VR-12 mental or physical sub-scores between groups. Telerehab patients had a greater improvement in LEAS score at 3 months compared to the conventional group (mean difference 1.9, P = 0.03). CONCLUSION: In a matched cohort study of 326 TKA patients, telerehab patients had similar rates of unplanned healthcare encounters and MUAs and similar patient-reported outcomes compared to conventional PT patients, suggesting that telerehab can be an equally effective alternative to conventional PT following TKA. LEVEL OF EVIDENCE: III.

Expectations of treatment outcomes in patients with spinal metastases; what do we tell our patients? A qualitative study.

BACKGROUND: Realistic pre-treatment expectations are important and have been associated with post-treatment health related quality of life (HRQOL). Patient expectations are greatly influenced by physicians, as they are the primary resource for information. This study aimed to explore the communication practices of physicians regarding treatment outcomes for patients with spinal metastases, and physician experiences with patients' pre-treatment expectations. METHODS: An international qualitative study using semi-structured interviews with physicians routinely involved in treating metastatic spine disease (spine surgeons, radiation and medical oncologists, and rehabilitation specialists) was conducted. Physicians were interviewed about the content and extent of information they provide to patients with spinal metastases regarding treatment options, risks and treatment outcomes. Interviews were transcribed verbatim and analyzed using a thematic coding network. RESULTS: After 22 interviews data saturation occurred. The majority of the physicians indicated that they currently do not establish patients' pre-treatment expectations, despite acknowledging the importance of these expectations. Spine surgeons often believe that patient expectations are disproportionate. Physicians expressed they manage expectations by detailing the most common risks and providing a broad but nonspecific overview of treatment outcomes. While the palliative intent seems clear to the physicians, their perception is that the implications of a palliative treatment remains elusive to most patients. CONCLUSION: This study highlights the current gap in patient-physician communication regarding expectations of treatment outcomes of patients with spinal metastases. These results warrant further research to improve communication practices and determine the effect of patient expectations on patient reported outcomes in this population.

Variation in surgical treatment of degenerative spondylolisthesis in Canada: surgeon assessment of stability and impact on treatment.

INTRODUCTION: Controversy exists regarding the optimal surgical treatment of degenerative lumbar spondylolisthesis (DS). Not all DS patients are the same, and the degree to which inherent stability may dictate treatment is unknown. The purpose of this study was to determine the variability in surgical approach relative to surgeon classified stability. The secondary objective was to compare patient-reported outcomes (PROs) across different surgical techniques and grades of stability. METHODS: Patients prospectively enrolled from eleven tertiary care institutions and followed from 2015 to 2019. The surgical technique was at the surgeon's discretion. Surgeons were asked to grade the degree of instability based on the degenerative spondylolisthesis instability classification system (DSIC). DSIC categorizes three different types (I-stable, II-potentially unstable, and III-unstable). One-year changes in PROs were compared between each group. Multivariable regression was used to identify any characteristics that explained variability in treatment. RESULTS: There were 323 patients enrolled in this study. Surgeons' stability classification versus procedure [decompression alone (D)/decompression and posterolateral fusion (D-PL)/and decompression with posterior/transforaminal lumbar interbody fusion (D-PLIF/TLIF)] were as follows: type I (n = 91): D-41%/D-PL-13%/D-PLIF/TLIF-46%; type II (n = 175): D-23%/D-PL-17%/D-PLIF/TLIF-60%; and type III (n = 57):(D-0%/D-PL-14%/D-PLIF/TLIF-86%). Type I patients undergoing D-PL had some improvements in EQ-5D and NRS versus those undergoing D-PLIF/TLIF but otherwise there were no other significant differences between groups. Regression analysis demonstrated advanced age (OR = 1.06, CI 1.02-10.12) and type I (OR = 2.61, CI 1.17-5.81) were associated with receiving decompression surgery alone. CONCLUSIONS: There exists considerable variation in surgical management of DS in Canada. Given similar PROs in two of the three groups, there is potential to tailor surgical intervention and improve resource utilization.

Patient perspective: diagnosis and prognosis of acute spinal cord injuries.

STUDY DESIGN: Qualitative study. OBJECTIVES: The purpose of this study is to understand the patient perspective after diagnosis of an acute traumatic spinal cord injury (tSCI). Discussing the diagnosis and prognosis of a tSCI with a patient can be a challenging experience for both the patient and the physician. As such, this paper attempts to better understand the patient experience to improve communication when discussing this life-altering injury. SETTING: Vancouver General Hospital, Vancouver, British Columbia, Canada. METHODS: This study is a qualitative study utilizing grounded theory and semi-structured interviews. The interview transcripts were manually coded using manifest and latent content analysis. Major and minor codes were identified and discussed. RESULTS: In total, 17 interviews were conducted, fifteen individuals with tSCI who received acute care at Vancouver General Hospital (VGH) and eleven family members were interviewed. Patient participants were interviewed individually or in a paired interview with a participating family member. Patient participants had varying spinal cord injuries from AIS A-D. Two major themes were identified from the interviews. The first major theme was physician demeanor (general approach and attitude towards patients) and the second major theme was delivery of information (content, timing, and source). CONCLUSIONS: This study summarizes the preferences of patients who sustained a tSCI discussions regarding their diagnosis and prognosis in the acute care setting. The goal of this study is to help guide physician interactions at this difficult and vulnerable time for patients with hopes to improve patient care through effective communication.