Neurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in ...psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data.
We retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs).
Mean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (β = −0.22, 95 % CI −0.86, 0.39, p = 0.516) nor UHR group (β = −0.37, 95 % CI −0.90, 0.19, p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group.
Our study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.
In recent years, attention has turned to examining the biodistribution of EVs in recipient animals to bridge between knowledge of EV function in vitro and in vivo. We undertook a systematic review of ...the literature to summarize the biodistribution of EVs following administration into animals. There were time‐dependent changes in the biodistribution of small‐EVs which were most abundant in the liver. Detection peaked in the liver and kidney in the first hour after administration, while distribution to the lungs and spleen peaked between 2–12 h. Large‐EVs were most abundant in the lungs with localization peaking in the first hour following administration and decreased between 2–12 h. In contrast, large‐EV localization to the liver increased as the levels in the lungs decreased. There was moderate to low localization of large‐EVs to the kidneys while localization to the spleen was typically low. Regardless of the origin or size of the EVs or the recipient species into which the EVs were administered, the biodistribution of the EVs was largely to the liver, lungs, kidneys, and spleen. There was extreme variability in the methodology between studies and we recommend that guidelines should be developed to promote standardization where possible of future EV biodistribution studies.
Retrospective cohort comparative study.
To determine the prevalence of major complications, identify risk factors, and assess long-term clinical benefit after revision adult spinal deformity surgery.
...No study has analyzed risk factors for major complications in long revision fusion surgery and whether or not occurrence of a major complication affects ultimate clinical outcome.
Analysis of consecutive adult patients who underwent multilevel revision surgery for spinal deformity with a minimum 2-year follow-up was performed. All complications were classified as either major or minor. Outcome analysis was conducted with the Scoliosis Research Society and Oswestry Disability Index scores.
A total of 166 patients (mean age = 53.8 years) were identified with a mean follow-up of 3.5 years (range: 2-7). Primary diagnoses included idiopathic/de novo scoliosis (107), degenerative (35), trauma (7), neuromuscular scoliosis (6), congenital deformity (5), ankylosing spondylitis (2), tumor (2), Scheuermann kyphosis (1), and rheumatoid arthritis (1). Most common secondary diagnoses that necessitated revision surgery were adjacent segment disease, fixed sagittal imbalance, and pseudarthrosis. Overall, 34.3% of patients developed major complications (19.3% perioperative; 18.7% follow-up). Associated risk factors for perioperative complications were patient- (age > 60 years, medical comorbidities, obesity) and surgery-related (pedicle subtraction osteotomy). Performance of a 3-column osteotomy and postoperative radiographic changes that suggested progressive loss of sagittal correction were recognized as risk factors for follow-up complications. Equivalent outcome scores were reported by patients preoperatively, but those experiencing follow-up complications reported lower scores at the final follow-up.
Overall, 34.4% of patients experienced major complications after long revision fusion surgery. Different risk factors were identified for perioperative versus follow-up complications. The occurrence of a follow-up, not but perioperative, major complication seemed to have a negative impact on ultimate clinical outcome.
Lateral ankle sprains (LAS) have been reported as one of the most common musculoskeletal injuries observed in sports and in individuals who are recreationally active. Approximately 40% of individuals ...who sustain a LAS develop a condition known as chronic ankle instability (CAI). Years of research has identified numerous impairments associated with CAI such as decreases in range of motion (ROM), strength, postural control, and altered movement patterns during functional activities when compared to individuals with no LAS history. As a result, an impairment-based rehabilitation model was developed to treat the common impairments associated with CAI. The impairment-based rehabilitation model has been shown to be an effective rehabilitation strategy at improving both clinical and patient-oriented outcomes in patients with CAI. To date, the efficacy of an impairment-based rehabilitation model has not been evaluated in patients with an acute LAS. Prior to implementing an impairment-based model for the treatment of an acute LAS, similarities between impairments associated with acute LAS and CAI across the spectrum of the healing process is warranted. Therefore, the purpose of this review paper is to compare and contrast impairments and treatment techniques in individuals with an acute LAS, sub-acute LAS, and CAI. A secondary purpose of this review is to provide clinical commentary on the management of acute LAS and speculate how the implementation of an impairment-based rehabilitation strategy for the treatment of acute LAS could minimize the development of CAI. The main findings of this review were that similar impairments (decreased ROM, strength, postural control, and functional activities) are observed in patients with acute LAS, sub-acute LAS, and CAI, suggesting that the impairments associated with CAI are a continuation from the original impairments developed during the initial LAS. Therefore, the use of an impairment-based model may be advantageous when treating patients with an acute LAS.
Abstract Background context Recent studies have shown that prophylactic use of intrawound vancomycin in posterior instrumented spine surgery substantially decreases the incidence of wound infections ...requiring repeat surgery. Significant cost savings are thought to be associated with the use of vancomycin in this setting. Purpose To elucidate cost savings associated with the use of intrawound vancomycin in posterior spinal surgeries using a budget-impact model. Study design Retrospective cohort study. Patient sample Data from a cohort of 303 patients who underwent spinal surgery (instrumented and noninstrumented) over 2 years were analyzed; 96 of these patients received prophylactic intrawound vancomycin powder in addition to normal intravenous (IV) antibiotic prophylaxis, and 207 received just routine IV antibiotic prophylaxis. Patients requiring repeat surgical procedures for infection were identified, and the costs of these additional procedures were elucidated. Outcome measure Cost associated with the additional procedure to remediate infection in the absence of vancomycin prophylaxis. Methods We retrospectively reviewed the cost of return procedures for treatment of surgical site infection (SSI). The total reimbursement received by the health care facility was used to model the costs associated with repeat surgery, and this cost was compared with the cost of a single local application of vancomycin costing about $12. Results Of the 96 patients in the treatment group, the return-to-surgery rate for SSI was 0. In the group without vancomycin, seven patients required a total of 14 procedures. The mean cost per episode of surgery, based on the reimbursement, the health care facility received was $40,992 (range, $14,459–$114,763). A total of $573,897 was spent on 3% of the 207-patient cohort that did not receive intrawound vancomycin, whereas a total of $1,152 ($12×96 patients) was spent on the cohort treated with vancomycin. Conclusions This study shows a reduction in SSIs requiring a return-to-surgery—with large cost savings—with use of intrawound vancomycin powder. In our study population, the cost savings totaled more than half a million dollars.
Abstract
BACKGROUND:
Multiple studies have reported on the prevalence of proximal junctional kyphosis (PJK) following spinal deformity surgery; however, none have demonstrated its significance with ...respect to functional outcome scores or revision surgery.
OBJECTIVE:
To evaluate if 20° is a possible critical PJK angle in primary adult scoliosis surgery patients as a threshold for worse patient-reported outcomes.
METHODS:
Clinical and radiographic data of 90 consecutive primary surgical patients at a single institution (2002-2007) with adult idiopathic/degenerative scoliosis and 2-year minimum follow-up were analyzed. Assessment included radiographic measurements, but most notably sagittal Cobb angle of the proximal junctional angle at preoperation, between 1 and 2 months, 2 years, and ultimate follow-up.
RESULTS:
Prevalence of PJK ≥20° at 3.5 years was 27.8% (n = 25). Those with PJK ≥20° at ultimate follow-up were older (mean 56 vs 46 years), had lower number of levels fused (median 8 vs 11), and were proximally fused to the lower thoracic spine more often than upper thoracic spine (all P < .001). PJK ≥20° was associated with significantly higher body mass index and fusion to the sacrum with iliac screws (P < .016, P < .029, respectively). Scoliosis Research Society outcome score changes were lower for PJK patients, but not significantly different from those in the non-PJK group.
CONCLUSION:
PJK ≥20° in primary adult idiopathic/degenerative scoliosis does not lead to revision surgery for PJK, but is univariately associated with older age, shorter constructs starting in the lower thoracic spine, obesity, and fusion to the sacrum. The negative results, supported by Scoliosis Research Society outcome data, provide important guidance on the postoperative management of such PJK patients.
Background
Surgical site infections can complicate posterior spine surgery. Multiple hospital admissions may be required to adequately treat a surgical site infection, which is associated with ...increased costs and lower patient satisfaction. The objective of this study was to evaluate the efficacy of prophylactic intra-wound vancomycin powder in reducing the incidence of repeat surgery for infections after posterior instrumented and noninstrumented spine surgery.
Methods
A series of consecutive patients who underwent instrumented or noninstrumented posterior spine surgery for any indication by two surgeons from July 2010 to July 2012 were reviewed. The preoperative antibiotic regimens of both surgeons were identical, except that one surgeon applied 1 g vancomycin powder directly to the surgical bed before wound closure, while the other did not. Patient demographics, operative details, and rates of reoperation for wound infection in the control and the treatment groups were compared.
Results
Both the control group and treatment group consisted of 150 patients; mean ages were 58.33 and 54.14 years, respectively. Both groups had low rates of deep infection requiring surgical intervention. The treatment group had a significantly lower rate of infection requiring reoperation or surgical debridement (0 %; 95 % CI: 0 %–2.4 %) compared with the control group (4 %; 95 % CI: 1.5 %–8.5 %) (
P
= 0.0297). The six infections identified in the control group resulted in 12 repeat operative debridement procedures. Gram-positive organisms were identified in 66.7 % of infections. No complications were related to the application of vancomycin powder.
Conclusions
The results of this study demonstrate that adjunctive vancomycin powder applied directly to the surgical bed before closure seems effective in preventing deep infections that require operative debridement following posterior spine surgery.
To decrease surgical site infections, we initiated a protocol of preliminary preparation of the skin and surrounding plastic drapes with alcohol foam, and the placement of a suprafascial drain in ...addition to a subfascial drain in obese patients in 2004. In 2008, we additionally placed 500 mg of vancomycin powder into the wound prior to closure. The purpose of this study was to analyze the infection rates for three groups: Group C (control that received standard perioperative intravenous antibiotics alone), Group AD (alcohol foam and drain), and Group VAD (vancomycin with alcohol foam and drain).
A consecutive series of 1001 all-posterior cervical spine surgical procedures performed at one institution by the senior author from 1995 to 2010 was retrospectively reviewed. These surgical procedures included foraminotomy, laminectomy, laminoplasty, arthrodesis, instrumentation, and/or osteotomies. There were 483 patients in Group C, 323 in Group AD, and 195 in Group VAD.
In Group C, nine (1.86%) of the 483 patients had an acute postoperative deep infection, in which methicillin-resistant Staphylococcus aureus was the most common pathogen. A significantly higher rate of infection was found in patients with an active smoking history (p = 0.008; odds ratio = 2.6 95% confidence interval, 1.0 to 7.1), rheumatoid arthritis (p = 0.005; odds ratio = 4.0 95% confidence interval, 1.4 to 7.9), and a body mass index of ≥30 kg/m2 (p = 0.005; odds ratio = 4.1 95% confidence interval, 1.5 to 7.7). Group AD (n = 323) had one infection, a significant decrease compared with Group C (p = 0.047). In Group VAD, none of the 195 patients had infections, which was also a significant decrease compared with Group C (p = 0.048).
In this study, preliminary preparation with alcohol foam and the placement of suprafascial drains for deep wounds resulted in one postoperative deep infection in 323 surgical procedures. The addition of intrawound vancomycin powder in 195 consecutive posterior cervical spine surgical procedures resulted in no infections and no adverse effects. To our knowledge, this is the first description of a technique for significantly decreasing postoperative cervical spine infections.
Extracellular vesicles (EVs) are lipid-bound vesicles released from cells that play a crucial role in many physiological processes and pathological mechanisms. As such, there is great interest in ...their biodistribution. One currently accessible technology to study their fate in vivo involves fluorescent labelling of exogenous EVs followed by whole-animal imaging. Although this is not a new technology, its translation from studying the fate of whole cells to subcellular EVs requires adaptation of the labelling techniques, excess dye removal and a refined experimental design. In this Review, we detail the methods and considerations for using fluorescence in vivo and ex vivo imaging to study the biodistribution of exogenous EVs and their roles in physiology and disease biology.
From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The prevalence of this population ranges ...between 2 and 22 per 100,000 persons in Canada and varies by region. Until recently, fixed-duration fludarabine-based chemoimmunotherapy (CIT) was the primary treatment option in Canada for this patient population. The ECOG1912 trial has since demonstrated that ibrutinib and rituximab therapy are as effective as fludarabine-cyclophosphamide-rituximab (FCR) in this population. The ALLIANCE trial showed that rituximab added no incremental benefit to ibrutinib. Canadian payors and physicians adopted ibrutinib monotherapy as the CLL standard of care, even in the young, fit population, although frontline ibrutinib therapy is often reimbursed by provincial public drug plans only in patients with high-risk disease or those who are unfit to receive fludarabine. Young, fit patients with CLL and their physicians may now choose between continuous ibrutinib monotherapy and fixed-duration CIT with FCR. Factors affecting this choice include patient preference and the short- and long-term toxicity profiles of both regimens, and a risk-based algorithm is provided. As new continuous-therapy options enter the market, all treatment choices present benefits and risks that must be communicated to the patient.
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