Publications by authors named "Paul Park"

415 Publications

Exogenous extracellular matrix proteins decrease cardiac fibroblast activation in stiffening microenvironment through CAPG.

J Mol Cell Cardiol 2021 Jun 9. Epub 2021 Jun 9.

Department of Biomedical Engineering, Case School of Engineering, Case Western Reserve University, Cleveland, OH, USA. Electronic address:

Controlling fibrosis is an essential part of regenerating the post-ischemic heart. In the post-ischemic heart, fibroblasts differentiate to myofibroblasts that produce collagen-rich matrix to physically stabilize the infarct area. Infarct models in adult mice result in permanent scarring unlike newborn animals which fully regenerate. Decellularized extracellular matrix (dECM) hydrogels derived from early-aged hearts have been shown to be a transplantable therapy that preserves heart function and stimulates cardiomyocyte proliferation and vascularization. In this study, we investigate the anti-fibrotic effects of injectable dECM hydrogels in a cardiac explant model in the context of age-associated tissue compliance. Treatments with adult and fetal dECM hydrogels were tested for molecular effects on cardiac fibroblast activation and fibrosis. Altered sensitivity of fibroblasts to the mechanosignaling of the remodeling microenvironment was evaluated by manipulating the native extracellular matrix in explants and also with elastomeric substrates in the presence of dECM hydrogels. The injectable fetal dECM hydrogel treatment decreases fibroblast activation and contractility and lowers the stiffness-mediated increases in fibroblast activation observed in stiffened explants. The anti-fibrotic effect of dECM hydrogel is most observable at highest stiffness. Experiments with primary cells on elastomeric substrates with dECM treatment support this phenomenon. Transcriptome analysis indicated that dECM hydrogels affect cytoskeleton related signaling including Macrophage capping protein (CAPG) and Leupaxin (LPXN). CAPG was down-regulated by the fetal dECM hydrogel. LPXN expression was decreased by stiffening the explants; however, this effect was reversed by dECM hydrogel treatment. Pharmacological disruption of cytoskeleton polymerization lowered fibroblast activation and CAPG levels. Knocking down CAPG expression with siRNA inhibited fibroblast activation and collagen deposition. Collectively, fibroblast activation is dependent on cooperative action of extracellular molecular signals and mechanosignaling by cytoskeletal integrity.
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http://dx.doi.org/10.1016/j.yjmcc.2021.06.001DOI Listing
June 2021

What is the Comparison in Robot Time per Screw, Radiation Exposure, Robot Abandonment, Screw Accuracy, and Clinical Outcomes Between Percutaneous and Open Robot-Assisted Short Lumbar Fusion? A Multicenter, Propensity-Matched Analysis of 310 Patients.

Spine (Phila Pa 1976) 2021 Jun 4. Epub 2021 Jun 4.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA New York Institute of Technology College of Osteopathic Medicine, Old Westbury, NY, USA Department of Neurosurgery, University of Virginia Health System, Charlottesville, VA, USA Department of Neurosurgery, State University of New York, Buffalo, NY, USA Department of Orthopaedics, Virginia Spine Institute, Reston, VA, USA.

Study Design: Multicenter cohort.

Objective: To compare the robot time/screw, radiation exposure, robot abandonment, screw accuracy, and 90-day outcomes between robot-assisted percutaneous and robot-assisted open approach for short lumbar fusion (1-and 2-level).

Summary Of Background Data: There is conflicting literature on the superiority of robot-assisted minimally invasive spine surgery to open techniques. A large, multicenter study is needed to further elucidate the outcomes and complications between these two approaches.

Methods: We included adult patients (≥18 years old) who underwent robot-assisted short lumbar fusion surgery from 2015-2019 at four independent institutions. A propensity score matching (PSM) algorithm was employed to control for the potential selection bias between percutaneous and open surgery. The minimum follow-up was 90 days after the index surgery.

Results: After PSM, 310 patients remained. The mean (standard deviation) charlson comorbidity index was 1.6 (1.5) and 53% of patients were female. The most common diagnoses included high grade spondylolisthesis (grade >2)(48%), degenerative disc disease (22%), and spinal stenosis (25%), and the mean number of instrumented levels was 1.5(0.5). The operative time was longer in the open (198 minutes) vs. the percutaneous group (167 minutes, P-value=0.007). However, the robot time/screw was similar between cohorts (P-value>0.05). The fluoroscopy time/screw for percutaneous (14.4 seconds) was longer than the open group (10.1 seconds, P-value=0.021). The rates for screw exchange and robot abandonment, were similar between groups (P-value>0.05). The estimated blood loss (open:146 mL vs. percutaneous:61.3 mL, P-value < 0.001) and transfusion rate (open:3.9% vs. percutaneous:0%, P-value=0.013) were greater for the open group. The 90-day complication rate and mean length of stay were not different between cohorts(P-value>0.05).

Conclusion: Percutaneous robot-assisted spine surgery may increase radiation exposure, but can achieve a shorter operative time and lower risk for intraoperative blood loss for short-lumbar fusion. Percutaneous approaches do not appear to have an advantage for other short-term postoperative outcomes. Future multicenter studies on longer fusion surgeries and the inclusion of patient-reported outcomes are needed.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000004132DOI Listing
June 2021

Navigation and Robotic-Assisted Single-Position Prone Lateral: Technique, Feasibility, Safety, and Case Series.

World Neurosurg 2021 May 28. Epub 2021 May 28.

Department of Neurosurgery, University of Michigan, 3552 Taubman, 1500 E. Medical Center Dr., Ann Arbor, Michigan, USA. Electronic address:

Background: Single-position prone lateral interbody fusion is a recently introduced technical modification of the minimally invasive retroperitoneal transpsoas approach for lateral lumbar interbody fusion (LLIF). Several technical descriptions of single-position prone LLIF have been published with traditional fluoroscopy for guidance. However, there has been no investigation of either 3-D CT-based navigation for prone LLIF or integration with robotic assistance platforms with the prone lateral technique. This study evaluated the feasibility and safety of spinal navigation and robotic assistance for single-position prone LLIF.

Methods: Retrospective review of medical records and a prospectively acquired database for a single center was performed to examine immediate and 30-day clinical and radiographic outcomes for consecutive patients undergoing single-position prone LLIF with spinal navigation and/or robotic assistance.

Results: Nine patients were treated, 4 female and 5 male. Mean age was 65.4 years (range: 46-75 years), and body-mass index was 30.2 kg/m (range: 24-38 kg/m). The most common surgical indication was adjacent segment disease (44.4%), followed by pseudoarthrosis (22.2%), spondylolisthesis (11.1%), degenerative disc disease (11.1%), and recurrent stenosis (11.1%). Postoperative approach-related complications included one patient (11.1%) with pain-limited bilateral hip flexor weakness (4/5) and pain-limited left knee extension weakness (4/5) and one patient (11.1%) with right lateral thigh numbness and dysesthesia. All cages were placed within quarters 2-3, signifying the middle portion of the disc space. There were no instances of misguidance by navigation.

Conclusion: Integration of spinal navigation and robotic assistance appears feasible, accurate, and safe as an alternative to fluoroscopic guidance for single-position LLIF.
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http://dx.doi.org/10.1016/j.wneu.2021.05.097DOI Listing
May 2021

Pathophysiological mechanisms underlying gastrointestinal symptoms in patients with COVID-19.

World J Gastroenterol 2021 May;27(19):2341-2352

Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, United States.

Gastrointestinal (GI) symptoms, such as diarrhea, abdominal pain, vomiting, and anorexia, are frequently observed in patients with coronavirus disease 2019 (COVID-19). However, the pathophysiological mechanisms connecting these GI symptoms to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain elusive. Previous studies indicate that the entry of SARS-CoV-2 into intestinal cells leads to downregulation of angiotensin converting enzyme 2 (ACE2) receptors resulting in impaired barrier function. While intestinal ACE2 functions as a chaperone for the amino acid transporter B0AT1, the B0AT1/ACE2 complex within the intestinal epithelium acts as a regulator of gut microbiota composition and function. Alternations to the B0AT1/ACE2 complex lead to microbial dysbiosis through increased local and systemic immune responses. Previous studies have also suggested that altered serotonin metabolism may be the underlying cause of GI disorders involving diarrhea. The findings of elevated plasma serotonin levels and high fecal calprotectin in COVID-19 patients with diarrhea indicate that the viral infection evokes a systemic inflammatory response that specifically involves the GI. Interestingly, the elevated proinflammatory cytokines correlate with elevated serotonin and fecal calprotectin levels further supporting the evidence of GI inflammation, a hallmark of functional GI disorders. Moreover, the finding that rectal swabs of COVID-19 patients remain positive for SARS-CoV-2 even after the nasopharynx clears the virus, suggests that viral replication and shedding from the GI tract may be more robust than that of the respiratory tract, further indicating fecal-oral transmission as another important route of viral spread. This review summarized the evidence for pathophysiological mechanisms (impaired barrier function, gut inflammation, altered serotonin metabolism and gut microbiota dysbiosis) underlying the GI symptoms in patients with COVID-19.
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http://dx.doi.org/10.3748/wjg.v27.i19.2341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130047PMC
May 2021

Is There a Difference Between Navigated and Non-Navigated Robot Cohorts in Robot-Assisted Spine Surgery? A Multicenter, Propensity-Matched Analysis of 2,800 Screws and 372 Patients.

Spine J 2021 May 19. Epub 2021 May 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Background Context: Robot-assisted spine surgery continues to rapidly develop as evidenced by the growing literature in recent years. In addition to demonstrating excellent pedicle screw accuracy, early studies have explored the impact of robot-assisted spine surgery on reducing radiation time, length of hospital stay, operative time, and perioperative complications in comparison to conventional freehand technique. Recently, the Mazor X Stealth Edition was introduced in 2018. This robotic system integrates Medtronic's Stealth navigation technology into the Mazor X platform, which was introduced in 2016. It is unclear what the impact of these advancements have made on clinical outcomes.

Purpose: To compare the outcomes and complications between the most recent iterations of the Mazor Robot systems: Mazor X and Mazor X Stealth Edition.

Study Design: Multicenter cohort PATIENT SAMPLE: Among four different institutions, we included adult (≥18 years old) patients who underwent robot-assisted spine surgery with either the Mazor X (non-navigated robot) or Stealth (navigated robot) platforms.

Outcome Measures: Primary outcomes included robot time per screw, fluoroscopic radiation time, screw accuracy, robot abandonment, and clinical outcomes with a minimum 90 day follow up.

Methods: A one-to-one propensity-score matching algorithm based on perioperative factors (e.g. demographics, comorbidities, primary diagnosis, open vs. percutaneous instrumentation, prior spine surgery, instrumented levels, pelvic fixation, interbody fusion, number of planned robot screws) was employed to control for the potential selection bias between the two robotic systems. Chi-square/fisher exact test and t-test/ANOVA were used for categorical and continuous variables, respectively.

Results: From a total of 646 patients, a total of 372 adult patients were included in this study (X: 186, Stealth: 186) after propensity score matching. The mean number of instrumented levels was 4.3. The mean number of planned robot screws was 7.8. Similar total operative time and robot time per screw occurred between cohorts (p>0.05). However, Stealth achieved significantly shorter fluoroscopic radiation time per screw (Stealth: 7.2 seconds vs. X: 10.4 seconds, p<0.001) than X. The screw accuracy for both robots was excellent (Stealth: 99.6% vs. X: 99.1%, p=0.120). In addition, Stealth achieved a significantly lower robot abandonment rate (Stealth: 0% vs. X: 2.2%, p=0.044). Furthermore, a lower blood transfusion rate was observed for Stealth than X (Stealth: 4.3% vs. X: 10.8%, p=0.018). Non-robot related complications such as dura tear, motor/sensory deficits, return to the operating room during same admission, and length of stay was similar between robots (p>0.05). The 90-day complication rates were low and similar between robot cohorts (Stealth: 5.4% vs. X: 3.8%, p=0.456).

Conclusion: In this multicenter study, both robot systems achieved excellent screw accuracy and low robot time per screw. However, using Stealth led to significantly less fluoroscopic radiation time, lower robot abandonment rates, and reduced blood transfusion rates than Mazor X. Other factors including length of stay, and 90-day complications were similar.
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http://dx.doi.org/10.1016/j.spinee.2021.05.015DOI Listing
May 2021

Do robot-related complications influence 1 year reoperations and other clinical outcomes after robot-assisted lumbar arthrodesis? A multicenter assessment of 320 patients.

J Orthop Surg Res 2021 May 12;16(1):308. Epub 2021 May 12.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, 161 Fort Washington Avenue, New York, NY, 10032, USA.

Background: Robot-assisted platforms in spine surgery have rapidly developed into an attractive technology for both the surgeon and patient. Although current literature is promising, more clinical data is needed. The purpose of this paper is to determine the effect of robot-related complications on clinical outcomes METHODS: This multicenter study included adult (≥18 years old) patients who underwent robot-assisted lumbar fusion surgery from 2012-2019. The minimum follow-up was 1 year after surgery. Both bivariate and multivariate analyses were performed to determine if robot-related factors were associated with reoperation within 1 year after primary surgery.

Results: A total of 320 patients were included in this study. The mean (standard deviation) Charlson Comorbidity Index was 1.2 (1.2) and 52.5% of patients were female. Intraoperative robot complications occurred in 3.4% of patients and included intraoperative exchange of screw (0.9%), robot abandonment (2.5%), and return to the operating room for screw exchange (1.3%). The 1-year reoperation rate was 4.4%. Robot factors, including robot time per screw, open vs. percutaneous, and robot system, were not statistically different between those who required revision surgery and those who did not (P>0.05). Patients with robot complications were more likely to have prolonged length of hospital stay and blood transfusion, but were not at higher risk for 1-year reoperations. The most common reasons for reoperation were wound complications (2.2%) and persistent symptoms due to inadequate decompression (1.5%). In the multivariate analysis, robot related factors and complications were not independent risk factors for 1-year reoperations.

Conclusion: This is the largest multicenter study to focus on robot-assisted lumbar fusion outcomes. Our findings demonstrate that 1-year reoperation rates are low and do not appear to be influenced by robot-related factors and complications; however, robot-related complications may increase the risk for greater blood loss requiring a blood transfusion and longer length of stay.
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http://dx.doi.org/10.1186/s13018-021-02452-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114480PMC
May 2021

Identifying patients at risk for nonroutine discharge after surgery for cervical myelopathy: an analysis from the Quality Outcomes Database.

J Neurosurg Spine 2021 May 7:1-9. Epub 2021 May 7.

15Department of Neurological Surgery, University of Utah, Salt Lake City, Utah.

Objective: Optimizing patient discharge after surgery has been shown to impact patient recovery and hospital/physician workflow and to reduce healthcare costs. In the current study, the authors sought to identify risk factors for nonroutine discharge after surgery for cervical myelopathy by using a national spine registry.

Methods: The Quality Outcomes Database cervical module was queried for patients who had undergone surgery for cervical myelopathy between 2016 and 2018. Nonroutine discharge was defined as discharge to postacute care (rehabilitation), nonacute care, or another acute care hospital. A multivariable logistic regression predictive model was created using an array of demographic, clinical, operative, and patient-reported outcome characteristics.

Results: Of the 1114 patients identified, 11.2% (n = 125) had a nonroutine discharge. On univariate analysis, patients with a nonroutine discharge were more likely to be older (age ≥ 65 years, 70.4% vs 35.8%, p < 0.001), African American (24.8% vs 13.9%, p = 0.007), and on Medicare (75.2% vs 35.1%, p < 0.001). Among the patients younger than 65 years of age, those who had a nonroutine discharge were more likely to be unemployed (70.3% vs 36.9%, p < 0.001). Overall, patients with a nonroutine discharge were more likely to present with a motor deficit (73.6% vs 58.7%, p = 0.001) and more likely to have nonindependent ambulation (50.4% vs 14.0%, p < 0.001) at presentation. On multivariable logistic regression, factors associated with higher odds of a nonroutine discharge included African American race (vs White, OR 2.76, 95% CI 1.38-5.51, p = 0.004), Medicare coverage (vs private insurance, OR 2.14, 95% CI 1.00-4.65, p = 0.04), nonindependent ambulation at presentation (OR 2.17, 95% CI 1.17-4.02, p = 0.01), baseline modified Japanese Orthopaedic Association severe myelopathy score (0-11 vs moderate 12-14, OR 2, 95% CI 1.07-3.73, p = 0.01), and posterior surgical approach (OR 11.6, 95% CI 2.12-48, p = 0.004). Factors associated with lower odds of a nonroutine discharge included fewer operated levels (1 vs 2-3 levels, OR 0.3, 95% CI 0.1-0.96, p = 0.009) and a higher quality of life at baseline (EQ-5D score, OR 0.43, 95% CI 0.25-0.73, p = 0.001). On predictor importance analysis, baseline quality of life (EQ-5D score) was identified as the most important predictor (Wald χ2 = 9.8, p = 0.001) of a nonroutine discharge; however, after grouping variables into distinct categories, socioeconomic and demographic characteristics (age, race, gender, insurance status, employment status) were identified as the most significant drivers of nonroutine discharge (28.4% of total predictor importance).

Conclusions: The study results indicate that socioeconomic and demographic characteristics including age, race, gender, insurance, and employment may be the most significant drivers of a nonroutine discharge after surgery for cervical myelopathy.
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http://dx.doi.org/10.3171/2020.11.SPINE201442DOI Listing
May 2021

Disparities in outcomes after spine surgery: a Michigan Spine Surgery Improvement Collaborative study.

J Neurosurg Spine 2021 May 7:1-9. Epub 2021 May 7.

1Department of Neurosurgery, Henry Ford Hospital, Detroit.

Objective: Most studies on racial disparities in spine surgery lack data granularity to control for both comorbidities and self-assessment metrics. Analyses from large, multicenter surgical registries can provide an enhanced platform for understanding different factors that influence outcome. In this study, the authors aimed to determine the effects of race on outcomes after lumbar surgery, using patient-reported outcomes (PROs) in 3 areas: the North American Spine Society patient satisfaction index, the minimal clinically important difference (MCID) on the Oswestry Disability Index (ODI) for low-back pain, and return to work.

Methods: The Michigan Spine Surgery Improvement Collaborative was queried for all elective lumbar operations. Patient race/ethnicity was categorized as Caucasian, African American, and "other." Measures of association between race and PROs were calculated with generalized estimating equations (GEEs) to report adjusted risk ratios.

Results: The African American cohort consisted of a greater proportion of women with the highest comorbidity burden. Among the 7980 and 4222 patients followed up at 1 and 2 years postoperatively, respectively, African American patients experienced the lowest rates of satisfaction, MCID on ODI, and return to work. Following a GEE, African American race decreased the probability of satisfaction at both 1 and 2 years postoperatively. Race did not affect return to work or achieving MCID on the ODI. The variable of greatest association with all 3 PROs at both follow-up times was postoperative depression.

Conclusions: While a complex myriad of socioeconomic factors interplay between race and surgical success, the authors identified modifiable risk factors, specifically depression, that may improve PROs among African American patients after elective lumbar spine surgery.
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http://dx.doi.org/10.3171/2020.10.SPINE20914DOI Listing
May 2021

Complications in ambulatory pediatric patients with nonidiopathic spinal deformity undergoing fusion to the pelvis using the sacral-alar-iliac technique within 2 years of surgery.

J Neurosurg Pediatr 2021 Apr 30:1-8. Epub 2021 Apr 30.

Objective: Significant investigation in the adult population has generated a body of research regarding proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) following long fusions to the sacrum and pelvis. However, much less is known regarding early complications, including PJK and PJF, in the ambulatory pediatric patient. As such, the objective of this study was to address the minimal literature on early complications after ambulatory pediatric patients underwent fusion to the sacrum with instrumentation to the pelvis in the era of sacral-alar-iliac (S2AI) instrumentation.

Methods: The authors performed a retrospective review of pediatric patients with nonidiopathic spinal deformity < 18 years of age with ambulatory capacity who underwent fusion to the pelvis at a multisurgeon pediatric academic spine practice from 2016 to 2018. All surgeries were posterior-only approaches with S2AI screws as the primary technique for sacropelvic fixation. Descriptive, outcome, and radiographic data were obtained. The definition of PJF included symptomatic PJK presenting as fracture, screw pullout, or disruption of the posterior osseoligamentous complex.

Results: Twenty-five patients were included in this study. Nine patients (36.0%) had 15 complications for an overall complication rate of 60.0%. Unplanned return to the operating room occurred 8 times in 6 patients (24.0%). Four patients (16.0%) had wound issues (3 with deep wound infection and 1 with wound breakdown) requiring reoperation. Three patients (12.0%) had PJF, all requiring reoperation. A 16-year-old female patient with syndromic scoliosis underwent extension of fusion due to posterior tension band failure at 6 months. A 17-year-old male patient with neuromuscular scoliosis underwent extension of fusion due to proximal screw pullout at 5 months. A 10-year-old female patient with congenital scoliosis underwent extension for PJF at 5 months following posterior tension band failure. One patient had pseudarthrosis requiring reoperation 20 months postoperatively.

Conclusions: Fixation to the pelvis enables significant deformity correction, but with rather high rates of complications and unexpected returns to the operating room. Considerations of sagittal plane dynamics for PJK and PJF should be strongly analyzed when performing fixation to the pelvis in ambulatory pediatric patients.
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http://dx.doi.org/10.3171/2020.11.PEDS19641DOI Listing
April 2021

Implementation outcomes of national decentralization of integrated outpatient services for severe non-communicable diseases to district hospitals in Rwanda.

Trop Med Int Health 2021 Apr 23. Epub 2021 Apr 23.

Rwanda Biomedical Center, Rwanda Ministry of Health, Kigali, Rwanda.

Objectives: Effective coverage of non-communicable disease (NCD) care in sub-Saharan Africa remains low, with the majority of services still largely restricted to central referral centres. Between 2015 and 2017, the Rwandan Ministry of Health implemented a strategy to decentralise outpatient care for severe chronic NCDs, including type 1 diabetes, heart failure and severe hypertension, to rural first-level hospitals. This study describes the facility-level implementation outcomes of this strategy.

Methods: In 2014, the Ministry of Health trained two nurses in each of the country's 42 first-level hospitals to implement and deliver nurse-led, integrated, outpatient NCD clinics, which focused on severe NCDs. Post-intervention evaluation occurred via repeated cross-sectional surveys, informal interviews and routinely collected clinical data over two rounds of visits in 2015 and 2017. Implementation outcomes included fidelity, feasibility and penetration.

Results: By 2017, all NCD clinics were staffed by at least one NCD-trained nurse. Among the approximately 27 000 nationally enrolled patients, hypertension was the most common diagnosis (70%), followed by type 2 diabetes (19%), chronic respiratory disease (5%), type 1 diabetes (4%) and heart failure (2%). With the exception of warfarin and beta-blockers, national essential medicines were available at more than 70% of facilities. Clinicians adhered to clinical protocols at approximately 70% agreement with evaluators.

Conclusion: The government of Rwanda was able to scale a nurse-led outpatient NCD programme to all first-level hospitals with good fidelity, feasibility and penetration as to expand access to care for severe NCDs.
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http://dx.doi.org/10.1111/tmi.13593DOI Listing
April 2021

Patient-reported outcome improvements at 24-month follow-up after fusion added to decompression for grade I degenerative lumbar spondylolisthesis: a multicenter study using the Quality Outcomes Database.

J Neurosurg Spine 2021 Apr 16:1-10. Epub 2021 Apr 16.

16Department of Neurological Surgery, University of California, San Francisco, California.

Objective: The ideal surgical management of grade I lumbar spondylolisthesis has not been determined despite extensive prior investigations. In this cohort study, the authors used data from the large, multicenter, prospectively collected Quality Outcomes Database to bridge the gap between the findings in previous randomized trials and those in a more heterogeneous population treated in a typical practice. The objective was to assess the difference in patient-reported outcomes among patients undergoing decompression alone or decompression plus fusion.

Methods: The primary outcome measure was change in 24-month Oswestry Disability Index (ODI) scores. The minimal clinically important difference (MCID) in ODI score change and 30% change in ODI score at 24 months were also evaluated. After adjusting for patient-specific and clinical factors, multivariable linear and logistic regressions were employed to evaluate the impact of fusion on outcomes. To account for differences in age, sex, body mass index, and baseline listhesis, a sensitivity analysis was performed using propensity score analysis to match patients undergoing decompression only with those undergoing decompression and fusion.

Results: In total, 608 patients who had grade I lumbar spondylolisthesis were identified (85.5% with at least 24 months of follow-up); 140 (23.0%) underwent decompression alone and 468 (77.0%) underwent decompression and fusion. The 24-month change in ODI score was significantly greater in the fusion plus decompression group than in the decompression-only group (-25.8 ± 20.0 vs -15.2 ± 19.8, p < 0.001). Fusion remained independently associated with 24-month ODI score change (B = -7.05, 95% CI -10.70 to -3.39, p ≤ 0.001) in multivariable regression analysis, as well as with achieving the MCID for the ODI score (OR 1.767, 95% CI 1.058-2.944, p = 0.029) and 30% change in ODI score (OR 2.371, 95% CI 1.286-4.371, p = 0.005). Propensity score analysis resulted in 94 patients in the decompression-only group matched 1 to 1 with 94 patients in the fusion group. The addition of fusion to decompression remained a significant predictor of 24-month change in the ODI score (B = 2.796, 95% CI 2.228-13.275, p = 0.006) and of achieving the 24-month MCID ODI score (OR 2.898, 95% CI 1.214-6.914, p = 0.016) and 24-month 30% change in ODI score (OR 2.300, 95% CI 1.014-5.216, p = 0.046).

Conclusions: These results suggest that decompression plus fusion in patients with grade I lumbar spondylolisthesis may be associated with superior outcomes at 24 months compared with decompression alone, both in reduction of disability and in achieving clinically meaningful improvement. Longer-term follow-up is warranted to assess whether this effect is sustained.
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http://dx.doi.org/10.3171/2020.9.SPINE201082DOI Listing
April 2021

The role of ketamine in opioid-free spinal deformity surgery: is it possible and beneficial?

J Spine Surg 2021 Mar;7(1):55-61

The Och Spine Hospital, NewYork-Presbyterian/Columbia University Medical Center, New York, NY, USA.

Background: As the opioid epidemic in the United States has continued to gain momentum in recent years, the current study aims to explore the efficacy of ketamine in a traditionally challenging setting regarding pain control, and contribute toward developing an opioid-free intraoperative pain protocol in spinal deformity surgery.

Methods: Fifty-four patients who underwent spinal deformity surgery between January 1, 2017 and December 31, 2017 by one senior surgeon were included. Demographic data and preoperative opioid use was collected. Surgical details including number of levels fused, estimated blood loss, and operative time was also collected. All patients received a hydromorphone patient-controlled anesthesia (PCA) device postoperatively. 36/54 patients received perioperative ketamine during their procedure, both intraoperatively and postoperatively. The consumption of postoperative hydromorphone and the ratio of doses given by doses attempted postoperatively were recorded. Patient charts were also reviewed for documented ileus during their inpatient stay.

Results: Mean age was 49 years, and 31% were male. Average BMI was 24.3 kg/m. The average number of levels fused was 11.6. Mean operative time was 10.7 hrs, and average EBL was 1,522 mL. The mean length of stay was 8 days. Average postoperative PCA use of hydromorphone in the no ketamine group (NK) (n=18) was 5.99 mg compared to 6.91 mg for those who received perioperative ketamine (K) (n=36); there was no significant difference between populations (P=0.57), although the variances was significant (P=0.044). There was no correlation between intraoperative ketamine and postoperative PCA use (r=-0.05; P=0.72). Additionally, there was no correlation between postoperative PCA use and dose of postoperative ketamine received (r=-0.15; P=0.27). The ratio of doses given: attempted was 0.61 in the NK group and 0.59 in those in the K group (P=0.79). Average postoperative hydromorphone use was 5.48 mg in patients that did not use opioids preoperatively (n=39) compared to 12.77 mg in those who used opioids preoperatively (n=9; P=0.0003). 9/54 patients had a documented ileus during their admission, while 4/9 (11%) had received ketamine (P=0.095).

Conclusions: Though our study showed no significant change in postoperative opioid requirement in our population, our results show that integration of ketamine in these extensive operations fare similarly to traditional opioid-based regimens. There was also no significant association seen between ketamine use and adverse side effects such as ileus. At our institution we are currently establishing opioid-free intraoperative pain protocols that use ketamine as an adjunct, and further study will explore the effect this may have on postoperative opioid consumption for spinal surgery patients as well as postoperative patients in general.
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http://dx.doi.org/10.21037/jss-19-475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024753PMC
March 2021

Flexion-extension standing radiographs underestimate instability in patients with single-level lumbar spondylolisthesis: comparing flexion-supine imaging may be more appropriate.

J Spine Surg 2021 Mar;7(1):48-54

Department of Orthopaedics, Columbia University Medical Center, The Spine Hospital at New York-Presbyterian, New York, NY, USA.

Background: Generally, most spine surgeons agree that increased segmental motion viewed on flexion-extension radiographs is a reliable predictor of instability; however, these views can be limited in several ways and may underestimate the instability at a given lumbar segment.

Methods: Consecutively collected adult (≥18 years old) patients with symptomatic single-level lumbar spondylolisthesis were reviewed from a two-surgeon database from 2015 to 2019. Routine standing lumbar X-rays (neutral, flexion, extension) and supine lumbar MRI (sagittal T2-weighted imaging sequence) were performed. Patients were excluded if they had prior lumbar surgery, missing radiographic data, or if the time between X-rays and MRI was >6 months.

Results: All 39 patients with symptomatic, single-level lumbar spondylolisthesis were identified. The mean age was 57.3±16.7 years and 66% were female. There was good intra- and inter-rater reliability agreement between measured values on the presence of instability. The slip percentage (SP) difference was significantly highest in the flexion-supine (FS) (5.7 mm, 12.3%) and neutral standing-supine (NS) (4.3 mm, 8.7%) groups, both of which were significantly higher compared with the flexion-extension (FE) group (1.8 mm, 4.5%, P<0.001). Ventral instability based on SP >8% was observed more frequently in FS (79.5%) and NS (52.6%) groups compared with FE group (16.7%, P<0.001). No statistically significant correlation was found between SP and disc angle for all radiographic views.

Conclusions: Comparing standing lateral and flexion X-rays with supine MRIs provides higher sensitivity to assess instability than standard flexion-extension radiographs. The FS and NS comparisons also show greater slip percentage differences at higher slip grades, but not at different lumbar levels. These changes are not dependent on age or gender.
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http://dx.doi.org/10.21037/jss-20-631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024755PMC
March 2021

Risk factors and morbidity associated with surgical site infection subtypes following adult neurosurgical procedures.

Br J Neurosurg 2021 Mar 29:1-7. Epub 2021 Mar 29.

Department of Neurosurgery, Michigan Medicine, Ann Arbor, MI, USA.

Objective: Studies on surgical site infection (SSI) in adult neurosurgery have presented all subtypes of SSIs as the general 'SSI'. Given that SSIs constitute a broad range of infections, we hypothesized that clinical outcomes and management vary based on SSI subtype.

Methods: A retrospective analysis of all neurosurgical SSI from 2012-2019 was conducted at a tertiary care institution. SSI subtypes were categorized as deep and superficial incisional SSI, brain, dural or spinal abscesses, meningitis or ventriculitis, and osteomyelitis.

Results: 9620 craniotomy, shunt, and fusion procedures were studied. 147 procedures (1.5%) resulted in postoperative SSI. 87 (59.2%) of these were associated with craniotomy, 36 (24.5%) with spinal fusion, and 24 (16.3%) with ventricular shunting. Compared with superficial incisional primary SSI, rates of reoperation to treat SSI were highest for deep incisional primary SSI (91.2% vs 38.9% for superficial,  < 0.001) and second-highest for intracranial SSI (90.9% vs 38.9%,  = 0.0001). Postoperative meningitis was associated with the highest mortality rate (14.9%). Compared with superficial incisional SSI, the rate of readmission for intracranial SSI was highest (57.6% vs 16.7%,  = 0.022).

Conclusion: Deep incisional and organ space SSI demonstrate a greater association with morbidity relative to superficial incisional SSI. Future studies should assess subtypes of SSI given these differences.
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http://dx.doi.org/10.1080/02688697.2021.1905773DOI Listing
March 2021

Timing of conversion to cervical malalignment and proximal junctional kyphosis following surgical correction of adult spinal deformity: a 3-year radiographic analysis.

J Neurosurg Spine 2021 Mar 19:1-9. Epub 2021 Mar 19.

2Department of Orthopedic Surgery, Hospital for Special Surgery, New York, New York.

Objective: The goal of this study was to assess the conversion rate from baseline cervical alignment to postoperative cervical deformity (CD) and the corresponding proximal junctional kyphosis (PJK) rate in patients undergoing thoracolumbar adult spinal deformity (ASD) surgery.

Methods: The operative records of patients with ASD with complete radiographic data beginning at baseline up to 3 years were included. Patients with no baseline CD were postoperatively stratified by Ames CD criteria (T1 slope-cervical lordosis mismatch [TS-CL] > 20°, cervical sagittal vertical axis [cSVA] > 40 mm), where CD was defined as fulfilling one or more of the Ames criteria. Severe CD was defined as TS-CL > 30° or cSVA > 60 mm. Follow-up intervals were established after ASD surgery, with 6 weeks postoperatively defined as early; 6 weeks-1 year as intermediate; 1-2 years as late; and 2-3 years as long-term. Descriptive analyses and McNemar tests identified the CD conversion rate, PJK rate (< -10° change in uppermost instrumented vertebra and the superior endplate of the vertebra 2 levels superior to the uppermost instrumented vertebra), and specific alignment parameters that converted.

Results: Two hundred sixty-six patients who underwent ASD surgery (mean age 59.7 years, 77.4% female) met the inclusion criteria; 103 of these converted postoperatively, and the remaining 163 did not meet conversion criteria. Thirty-eight patients converted to CD early, 26 converted at the intermediate time point, 29 converted late, and 10 converted in the long-term. At conversion, the early group had the highest mean TS-CL at 25.4° ± 8.5° and the highest mean cSVA at 33.6 mm-both higher than any other conversion group. The long-term group had the highest mean C2-7 angle at 19.7° and the highest rate of PJK compared to other groups (p = 0.180). The early group had the highest rate of conversion to severe CD, with 9 of 38 patients having severe TS-CL and only 1 patient per group converting to severe cSVA. Seven patients progressed from having only malaligned TS-CL at baseline (with normal cSVA) to CD with both malaligned TS-CL and cSVA by 6 weeks. Conversely, only 2 patients progressed from malaligned cSVA to both malaligned cSVA and TS-CL. By 1 year, the former number increased from 7 to 26 patients, and the latter increased from 2 to 20 patients. The revision rate was highest in the intermediate group at 48.0%, versus the early group at 19.2%, late group at 27.3%, and long-term group at 20% (p = 0.128). A higher pelvic incidence-lumbar lordosis mismatch, lower thoracic kyphosis, and a higher thoracic kyphosis apex immediately postoperatively significantly predicted earlier rather than later conversion (all p < 0.05). Baseline lumbar lordosis, pelvic tilt, and sacral slope were not significant predictors.

Conclusions: Patients with ASD with normative cervical alignment who converted to CD after thoracolumbar surgery had varying radiographic findings based on timing of conversion. Although the highest number of patients converted within 6 weeks postoperatively, patients who converted in the late or long-term follow-up intervals had higher rates of concurrent PJK and greater radiographic progression.
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http://dx.doi.org/10.3171/2020.8.SPINE20320DOI Listing
March 2021

Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma.

Cell Rep 2021 Mar;34(11):108870

Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address:

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR.
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http://dx.doi.org/10.1016/j.celrep.2021.108870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057695PMC
March 2021

The minimally invasive interbody selection algorithm for spinal deformity.

J Neurosurg Spine 2021 Mar 12:1-8. Epub 2021 Mar 12.

13Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.

Objective: Minimally invasive surgery (MIS) for spinal deformity uses interbody techniques for correction, indirect decompression, and arthrodesis. Selection criteria for choosing a particular interbody approach are lacking. The authors created the minimally invasive interbody selection algorithm (MIISA) to provide a framework for rational decision-making in MIS for deformity.

Methods: A retrospective data set of circumferential MIS (cMIS) for adult spinal deformity (ASD) collected over a 5-year period was analyzed by level in the lumbar spine to identify surgeon preferences and evaluate segmental lordosis outcomes. These data were used to inform a Delphi session of minimally invasive deformity surgeons from which the algorithm was created. The algorithm leads to 1 of 4 interbody approaches: anterior lumbar interbody fusion (ALIF), anterior column release (ACR), lateral lumbar interbody fusion (LLIF), and transforaminal lumbar interbody fusion (TLIF). Preoperative and 2-year postoperative radiographic parameters and clinical outcomes were compared.

Results: Eleven surgeons completed 100 cMISs for ASD with 338 interbody devices, with a minimum 2-year follow-up. The type of interbody approach used at each level from L1 to S1 was recorded. The MIISA was then created with substantial agreement. The surgeons generally preferred LLIF for L1-2 (91.7%), L2-3 (85.2%), and L3-4 (80.7%). ACR was most commonly performed at L3-4 (8.4%) and L2-3 (6.2%). At L4-5, LLIF (69.5%), TLIF (15.9%), and ALIF (9.8%) were most commonly utilized. TLIF and ALIF were the most selected approaches at L5-S1 (61.4% and 38.6%, respectively). Segmental lordosis at each level varied based on the approach, with greater increases reported using ALIF, especially at L4-5 (9.2°) and L5-S1 (5.3°). A substantial increase in lordosis was achieved with ACR at L2-3 (10.9°) and L3-4 (10.4°). Lateral interbody arthrodesis without the use of an ACR did not generally result in significant lordosis restoration. There were statistically significant improvements in lumbar lordosis (LL), pelvic incidence-LL mismatch, coronal Cobb angle, and Oswestry Disability Index at the 2-year follow-up.

Conclusions: The use of the MIISA provides consistent guidance for surgeons who plan to perform MIS for deformity. For L1-4, the surgeons preferred lateral approaches to TLIF and reserved ACR for patients who needed the greatest increase in segmental lordosis. For L4-5, the surgeons' order of preference was LLIF, TLIF, and ALIF, but TLIF failed to demonstrate any significant lordosis restoration. At L5-S1, the surgical team typically preferred an ALIF when segmental lordosis was desired and preferred a TLIF if preoperative segmental lordosis was adequate.
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http://dx.doi.org/10.3171/2020.9.SPINE20230DOI Listing
March 2021

Age as a Predictor for Complications and Patient-reported Outcomes in Multilevel Transforaminal Lumbar Interbody Fusions: Analyses From the Michigan Spine Surgery Improvement Collaborative (MSSIC).

Spine (Phila Pa 1976) 2021 Mar;46(6):356-365

Division of Neurosurgery, Ascension Providence Hospital, Michigan State University, College of Human Medicine, Southfield, MI.

Study Design: Retrospective review of a multi-institutional data registry.

Objective: The authors sought to determine the association between age and complications & patient-reported outcomes (PRO) in patients undergoing multilevel transforaminal interbody lumbar fusion (MTLIF).

Summary Of Background Data: Elderly patients undergoing MTLIF are considered high risk. However, data on complications and PRO are lacking. Additionally, safety of multilevel lumbar fusion in the elderly remains uncertain.

Methods: Patients ≥50-year-old who underwent MTLIF for degenerative lumbar spine conditions were analyzed. Ninety-day complications and PROs (baseline, 90-d, 1-y, 2-y) were queried using the MSSIC database. PROs were measured by back & leg visual analog scale (VAS), Patient-reported Outcomes Measurement Information System (PROMIS), EuroQol-5D (EQ-5D), and North American Spine Society (NASS) Patient Satisfaction Index. Univariate analyses were used to compare among elderly and complication cohorts. Generalized estimating equation (GEE) was used to identify predictors of complications and PROs.

Results: A total of 3120 patients analyzed with 961 (31%) ≥ 70-y-o and 2159 (69%) between 50-69. A higher proportion of elderly experienced postoperative complications (P = .003) including urinary retention (P = <.001) and urinary tract infection (P = .002). Multivariate analysis demonstrated that age was not independently associated with complications. Number of operative levels was associated with any (P = .001) and minor (P = .002) complication. Incurring a complication was independently associated with worse leg VAS and PROMIS scores (P = <.001). Preoperative independent ambulation was independently associated with improved PROMIS, and EQ5D (P = <.001). Within the elderly, preoperative independent ambulation and lower BMI were associated with improved PROMIS (P = <.001). Complications had no significant effect on PROs in the elderly.

Conclusions: Age was not associated with complications nor predictive of functional outcomes in patients who underwent MTLIF. Age alone, therefore, may not be an appropriate surrogate for risk. Furthermore, baseline preoperative independent ambulation was associated with better clinical outcomes and should be considered during preoperative surgical counseling.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003792DOI Listing
March 2021

Impact of surgeon and hospital factors on surgical decision-making for grade 1 degenerative lumbar spondylolisthesis: a Quality Outcomes Database analysis.

J Neurosurg Spine 2021 Feb 19:1-11. Epub 2021 Feb 19.

1Department of Neurological Surgery, University of Miami, Florida.

Objective: Surgical treatment for degenerative spondylolisthesis has been proven to be clinically challenging and cost-effective. However, there is a range of thresholds that surgeons utilize for incorporating fusion in addition to decompressive laminectomy in these cases. This study investigates these surgeon- and site-specific factors by using the Quality Outcomes Database (QOD).

Methods: The QOD was queried for all cases that had undergone surgery for grade 1 spondylolisthesis from database inception to February 2019. In addition to patient-specific covariates, surgeon-specific covariates included age, sex, race, years in practice (0-10, 11-20, 21-30, > 30 years), and fellowship training. Site-specific variables included hospital location (rural, suburban, urban), teaching versus nonteaching status, and hospital type (government, nonfederal; private, nonprofit; private, investor owned). Multivariable regression and predictor importance analyses were performed to identify predictors of the treatment performed (decompression alone vs decompression and fusion). The model was clustered by site to account for site-specific heterogeneity in treatment selection.

Results: A total of 12,322 cases were included with 1988 (16.1%) that had undergone decompression alone. On multivariable regression analysis clustered by site, adjusting for patient-level clinical covariates, no surgeon-specific factors were found to be significantly associated with the odds of selecting decompression alone as the surgery performed. However, sites located in suburban areas (OR 2.32, 95% CI 1.09-4.84, p = 0.03) were more likely to perform decompression alone (reference = urban). Sites located in rural areas had higher odds of performing decompression alone than hospitals located in urban areas, although the results were not statistically significant (OR 1.33, 95% CI 0.59-2.61, p = 0.49). Nonteaching status was independently associated with lower odds of performing decompression alone (OR 0.40, 95% CI 0.19-0.97, p = 0.04). Predictor importance analysis revealed that the most important determinants of treatment selection were dominant symptom (Wald χ2 = 34.7, accounting for 13.6% of total χ2) and concurrent diagnosis of disc herniation (Wald χ2 = 31.7, accounting for 12.4% of total χ2). Hospital teaching status was also found to be relatively important (Wald χ2 = 4.2, accounting for 1.6% of total χ2) but less important than other patient-level predictors.

Conclusions: Nonteaching centers were more likely to perform decompressive laminectomy with supplemental fusion for spondylolisthesis. Suburban hospitals were more likely to perform decompression only. Surgeon characteristics were not found to influence treatment selection after adjustment for clinical covariates. Further large database registry experience from surgeons at high-volume academic centers at which surgically and medically complex patients are treated may provide additional insight into factors associated with treatment preference for degenerative spondylolisthesis.
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http://dx.doi.org/10.3171/2020.8.SPINE201015DOI Listing
February 2021

Postoperative COVID-19 Pneumonia following Resection of a Large Thoracic Chondrosarcoma.

Case Rep Orthop 2021 23;2021:8866848. Epub 2021 Jan 23.

Department of Orthopedic Surgery, Columbia University Medical Center, 622 W. 168th St, PH-11, New York, NY 10032, USA.

Case: A 57-year-old man presenting with two months of insidious shoulder pain was found to have a large thoracic chondrosarcoma invading the spinal canal. The patient's orthopedic oncologist organized an interdisciplinary team including interventional radiology, thoracic surgery, neurosurgery, and plastic surgery. This allowed safe, en bloc tumor resection. The patient's postoperative course was complicated by COVID-19 pneumonia, which was rapidly identified and medically managed with full recovery.

Conclusion: Postoperative COVID-19 pneumonia can present insidiously and mimic other postoperative complications. Early identification and testing can promote rapid isolation, proper personal protective equipment use, and guide outcome-improving treatments.
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http://dx.doi.org/10.1155/2021/8866848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868161PMC
January 2021

Supramolecular organization of rhodopsin in rod photoreceptor cell membranes.

Authors:
Paul S-H Park

Pflugers Arch 2021 Feb 16. Epub 2021 Feb 16.

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.

Rhodopsin is the light receptor in rod photoreceptor cells that initiates scotopic vision. Studies on the light receptor span well over a century, yet questions about the organization of rhodopsin within the photoreceptor cell membrane still persist and a consensus view on the topic is still elusive. Rhodopsin has been intensely studied for quite some time, and there is a wealth of information to draw from to formulate an organizational picture of the receptor in native membranes. Early experimental evidence in apparent support for a monomeric arrangement of rhodopsin in rod photoreceptor cell membranes is contrasted and reconciled with more recent visual evidence in support of a supramolecular organization of rhodopsin. What is known so far about the determinants of forming a supramolecular structure and possible functional roles for such an organization are also discussed. Many details are still missing on the structural and functional properties of the supramolecular organization of rhodopsin in rod photoreceptor cell membranes. The emerging picture presented here can serve as a springboard towards a more in-depth understanding of the topic.
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http://dx.doi.org/10.1007/s00424-021-02522-5DOI Listing
February 2021

Survival, fusion, and hardware failure after surgery for spinal metastatic disease.

J Neurosurg Spine 2021 Jan 29:1-8. Epub 2021 Jan 29.

Departments of1Neurosurgery and.

Objective: Decompression with instrumented fusion is commonly employed for spinal metastatic disease. Arthrodesis is typically sought despite limited knowledge of fusion outcomes, high procedural morbidity, and poor prognosis. This study aimed to describe survival, fusion, and hardware failure after decompression and fusion for spinal metastatic disease.

Methods: The authors retrospectively examined a prospectively collected, single-institution database of adult patients undergoing decompression and instrumented fusion for spinal metastases. Patients were followed clinically until death or loss to follow-up. Fusion was assessed using CT when performed for oncological surveillance at 6-month intervals through 24 months postoperatively. Estimated cumulative incidences for fusion and hardware failure accounted for the competing risk of death. Potential risk factors were analyzed with univariate Fine and Gray proportional subdistribution hazard models.

Results: One hundred sixty-four patients were identified. The mean age ± SD was 62.2 ± 10.8 years, 61.6% of patients were male, 98.8% received allograft and/or autograft, and 89.6% received postoperative radiotherapy. The Kaplan-Meier estimate of median survival was 11.0 months (IQR 3.5-37.8 months). The estimated cumulative incidences of any fusion and of complete fusion were 28.8% (95% CI 21.3%-36.7%) and 8.2% (95% CI 4.1%-13.9%). Of patients surviving 6 and 12 months, complete fusion was observed in 12.5% and 16.1%, respectively. The estimated cumulative incidence of hardware failure was 4.2% (95% CI 1.5-9.3%). Increasing age predicted hardware failure (HR 1.2, p = 0.003).

Conclusions: Low rates of complete fusion and hardware failure were observed due to the high competing risk of death. Further prospective, case-control studies incorporating nonfusion instrumentation techniques may be warranted.
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January 2021

Revision Anterior Cervical Disc Arthroplasty: A National Analysis of the Associated Indications, Procedures, and Postoperative Outcomes.

Global Spine J 2021 Jan 19:2192568220979140. Epub 2021 Jan 19.

Department of Orthopaedics, Columbia University Medical Center, The Och Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Retrospective study.

Objective: To examine the associated indications, procedures, and postoperative outcomes after revision ACDA.

Methods: We utilized a national database to identify adult(≥18 years) patients who underwent either a primary ACDA or removal of ACDA over a 10-year period(2008-2017). An in-depth assessment of the reasons for revision surgery and the subsequent procedures performed after the removal of ACDA was done by using both Current Procedural Terminology(CPT) and International Statistical Classification of Diseases (ICD-9,10) coding.

Results: From 2008 to 2017, a total of 3,350 elective, primary ACDA cases were performed. During this time, 69 patients had a revision surgery requiring the removal of ACDA. The most common reasons for revision surgery included cervical spondylosis(59.4%) and mechanical complications(27.5%). After removal of ACDA, common procedures performed included anterior cervical fusion with or without decompression(69.6%), combined anterior/posterior fusion/decompression (11.6%), and replacement of ACDA (7.2%). The indications for surgery did not vary significantly among the different procedures performed (p = 0.318). Patients requiring revision surgery for mechanical complications or those who underwent a combined surgical approach were at significantly higher risk for subsequent short-term complications (p<0.05).

Conclusion: Over a 10-year period, the rate of revision surgery for ACDA was low (2.1%). Nearly 90% of revision cases were due to either cervical spondylosis or mechanical complications. These indications for surgery did not vary significantly among the different procedures performed. These findings will be important during the shared-decision making process for patients undergoing primary or revision ACDA.
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January 2021

Revision Surgery Rates After Minimally Invasive Adult Spinal Deformity Surgery: Correlation with Roussouly Spine Type at 2-Year Follow-Up?

World Neurosurg 2021 Apr 11;148:e482-e487. Epub 2021 Jan 11.

Department of Neurosurgery University of California, San Francisco, San Francisco, California, USA.

Background: Spinopelvic parameters have hitherto dictated much of adult spinal deformity (ASD) correction. The Roussouly classification is used for the normal adult spine. We evaluated whether a correlation would be found between the Roussouly type and the rate of revision surgery in patients with ASD undergoing circumferential minimally invasive spinal (cMIS) correction.

Methods: A multicenter retrospective review of patients who had undergone cMIS surgery for ASD was performed. The inclusion criteria were age ≥18 years and 1 of the following: coronal Cobb angle >20°, sagittal vertical axis >5 cm, pelvic tilt >20°, pelvic incidence (PI) to lumbar lordosis (LL) mismatch >10°, cMIS surgery, and a minimum of 2 years of follow-up data available. The patients were classified by Roussouly type, and the clinical and radiographic outcomes were evaluated.

Results: A total of 104 patients were included in the present analysis. Of the 104 patients, 41 had Roussouly type 1, 32 had type 2, 23 had type 3, and 8 had type 4. Preoperatively, the patients with type 4 had the highest PI (P = 0.002) and LL (P < 0.001). Postoperatively, the PI-LL mismatch, Cobb angle, and sagittal vertical axis were not different among the 4 groups. However, the patients with type 2 had had the highest rate of complications (type 1, 29.3%; type 2, 61.3%; type 3, 34.8%; type 4, 25.0%; P = 0.031). The reoperation rates were comparable (type 1, 19.5%; type 2, 38.7%; type 3, 13.0%; type 4, 12.5%; P = 0.097). The reoperation rates for adjacent segment degeneration or proximal junctional kyphosis were also comparable (P = 0.204 and P = 0.060, respectively).

Conclusions: We did not find a clear correlation between Roussouly type and the rate of revision surgery for adjacent segment disease or proximal junctional kyphosis in patients who had undergone cMIS surgery for ASD.
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http://dx.doi.org/10.1016/j.wneu.2021.01.011DOI Listing
April 2021

Serotonin is elevated in COVID-19-associated diarrhoea.

Gut 2021 Jan 5. Epub 2021 Jan 5.

Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA

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http://dx.doi.org/10.1136/gutjnl-2020-323542DOI Listing
January 2021

"July Effect" Revisited: July Surgeries at Residency Training Programs are Associated with Equivalent Long-term Clinical Outcomes Following Lumbar Spondylolisthesis Surgery.

Spine (Phila Pa 1976) 2021 Jun;46(12):836-843

Department of Neurological Surgery, University of California, San Francisco, Ca.

Study Design: Retrospective analysis of a prospective registry.

Objective: We utilized the Quality Outcomes Database (QOD) registry to investigate the "July Effect" at QOD spondylolisthesis module sites with residency trainees.

Summary Of Background Data: There is a paucity of investigation on the long-term outcomes following surgeries involving new trainees utilizing high-quality, prospectively collected data.

Methods: This was an analysis of 608 patients who underwent single-segment surgery for grade 1 degenerative lumbar spondylolisthesis at 12 high-enrolling sites. Surgeries were classified as occurring in July or not in July (non-July). Outcomes collected included estimated blood loss, length of stay, operative time, discharge disposition, complications, reoperation and readmission rates, and patient-reported outcomes (Oswestry Disability Index [ODI], Numeric Rating Scale [NRS] Back Pain, NRS Leg Pain, EuroQol-5D [EQ-5D] and the North American Spine Society [NASS] Satisfaction Questionnaire). Propensity score-matched analyses were utilized to compare postoperative outcomes and complication rates between the July and non-July groups.

Results: Three hundred seventy-one surgeries occurred at centers with a residency training program with 21 (5.7%) taking place in July. In propensity score-matched analyses, July surgeries were associated with longer operative times ( average treatment effect = 22.4 minutes longer, 95% confidence interval 0.9-449.0, P = 0.041). Otherwise, July surgeries were not associated with significantly different outcomes for the remaining perioperative parameters (estimated blood loss, length of stay, discharge disposition, postoperative complications), overall reoperation rates, 3-month readmission rates, and 24-month ODI, NRS back pain, NRS leg pain, EQ-5D, and NASS satisfaction score (P > 0.05, all comparisons).

Conclusion: Although July surgeries were associated with longer operative times, there were no associations with other clinical outcomes compared to non-July surgeries following lumbar spondylolisthesis surgery. These findings may be due to the increased attending supervision and intraoperative education during the beginning of the academic year. There is no evidence that the influx of new trainees in July significantly affects long-term patient-centered outcomes.Level of Evidence: 3.
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June 2021

A Comparison of Various Surgical Treatments for Degenerative Cervical Myelopathy: A Propensity Score Matched Analysis.

Global Spine J 2020 Dec 30:2192568220976092. Epub 2020 Dec 30.

Department of Orthopaedics, Columbia University Medical Center, The Spine Hospital at New York-Presbyterian, New York, NY, USA.

Study Design: Retrospective Cohort.

Objective: To compare the short-term outcomes for Laminoplasty, Laminectomy/fusion, and ACDF.

Methods: We utilized a prospectively-collected, multi-center national database with a propensity score matching algorithm to compare the short-term outcomes for laminoplasty, laminectomy/fusion, and multi-level (3) ACDF (with and without corpectomy). Bivariate analyses involved both chi-square/fisher exact test and t-test/ANOVA on perioperative factors. Multivariate analyses were performed to determined independent risk factors for short term outcomes.

Results: 546 patients remained after propensity score matching, with 182 patients in each cohort. ACDF required the longest operative time 188 ± 79 versus laminectomy/fusion (169 ± 75, p = 0.017), and laminoplasty (167 ± 66, p = 0.004). ACDF required the shortest hospital stay (LOS ≥ 2: ACDF 56.6%, laminoplasty 89.6%, laminectomy/fusion 93.4%, p < 0.05). ACDF had lower overall complications (ACDF 3.9%, laminoplasty 7.7%, laminectomy/fusion 11.5%, p < 0.05), mortality (ACDF 0%, laminoplasty 0.55%, laminectomy/fusion 2.2%, p < 0.05), and unplanned readmissions (ACDF 4.4%, laminoplasty 4.4%, laminectomy/fusion 9.9%, p < 0.05). No significant differences were seen in the other outcomes including DVT/PT, acute renal failure, UTI, stroke, cardiac complications, or sepsis. In the multivariate analysis, laminectomy/fusion (OR 17, reference: ACDF) and laminoplasty (OR10, reference: ACDF) were strong independent risk factors for LOS ≥ 2 days. Laminectomy/fusion (OR 3.2, reference: ACDF) was an independent predictor for any adverse events 30-days after surgery.

Conclusions: Laminectomy/fusion carries the highest risk for morbidity, mortality, and unplanned readmissions in the short-term postoperative period. Laminoplasty and ACDF cases carry similar short-term complications risks. ACDF is significantly associated with the longest operative duration and shortest LOS without an increase in individual or overall complications, readmissions, or reoperations.
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December 2020

Differential Aggregation Properties of Mutant Human and Bovine Rhodopsin.

Biochemistry 2021 01 27;60(1):6-18. Epub 2020 Dec 27.

Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio 44106, United States.

Rhodopsin is the light receptor required for the function and health of photoreceptor cells. Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinal degeneration. Bovine rhodopsin is often used as a model to understand the effect of pathogenic mutations in rhodopsin due to the abundance of structural information on the bovine form of the receptor. It is unclear whether or not the bovine rhodopsin template is adequate in predicting the effect of these mutations occurring in human retinal disease or in predicting the efficacy of therapeutic strategies. To better understand the extent to which bovine rhodopsin can serve as a model, human and bovine P23H rhodopsin mutants expressed heterologously in cells were examined. The aggregation properties and cellular localization of the mutant receptors were determined by Förster resonance energy transfer and confocal microscopy. The potential therapeutic effects of the pharmacological compounds 9- retinal and metformin were also examined. Human and bovine P23H rhodopsin mutants exhibited different aggregation properties and responses to the pharmacological compounds tested. These observations would lead to different predictions on the severity of the phenotype and divergent predictions on the benefit of the therapeutic compounds tested. The bovine rhodopsin template does not appear to adequately model the effects of the P23H mutation in the human form of the receptor.
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http://dx.doi.org/10.1021/acs.biochem.0c00733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863732PMC
January 2021

Decentralized, primary-care delivered epilepsy services in Burera District, Rwanda: Service use, feasibility, and treatment.

eNeurologicalSci 2021 Mar 28;22:100296. Epub 2020 Nov 28.

Partners In Health, Boston, USA.

Background: Integrating epilepsy care into primary care settings could reduce the global burden of illness attributable to epilepsy. Since 2012, the Rwandan Ministry of Health and the international nonprofit Partners In Health have collaboratively used a multi-faceted implementation program- MESH MH-to integrate and scale-up care for epilepsy and mental disorders within rural primary care settings in Burera district, Rwanda. We here describe demographics, service use and treatment patterns for patients with epilepsy seeking care at MESH-MH supported primary care health centers.

Methods And Findings: This was a retrospective cohort study using routinely collected data from fifteen health centers in Burera district, from January 2015 to December 2016. 286 patients with epilepsy completed 3307 visits at MESH-MH participating health centers over a two year period (Jan 1st 2015 to Dec 31st 2016). Men were over twice as likely to be diagnosed with epilepsy than women (OR 2.38, CI [1.77-3.19]), and children under 10 were thirteen times as likely to be diagnosed with epilepsy as those 10 and older (OR 13.27, CI [7.18-24.51]). Carbamazepine monotherapy was prescribed most frequently (34% of patients).

Conclusion: Task-sharing of epilepsy care to primary care via implementation programs such as MESH-MH has the potential to reduce the global burden of illness attributable to epilepsy.
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http://dx.doi.org/10.1016/j.ensci.2020.100296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724371PMC
March 2021