Search

Childhood socioeconomic position (SEP) is inversely associated with cardiovascular disease and all-cause mortality. Obesity in adulthood may be a biologic mechanism. Objectives were to systematically review literature published between 1998 and 2008 that examined associations of childhood SEP with adulthood obesity. Five databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, Web of Science) were searched for studies from any country, in any language. Forty-eight publications based on 30 studies were identified. In age-adjusted analyses, inverse associations were found between childhood SEP and adulthood obesity in 70% (14 of 20) of studies in females and 27% (4 of 15) in males. In studies of females showing inverse associations between childhood SEP and adulthood obesity, typical effect sizes in age-adjusted analyses for the difference in body mass index between the highest and lowest SEP were 1.0-2.0 kg/m(2); for males, effect sizes were typically 0.2-0.5 kg/m(2). Analyses adjusted for age and adult SEP showed inverse associations in 47% (8 of 17) of studies in females and 14% (2 of 14) of studies in males. When other covariates were additionally adjusted for, inverse associations were found in 4 of 12 studies in females and 2 of 8 studies in males; effect sizes were typically reduced compared with analyses adjusted for age only. In summary, the findings suggest that childhood SEP is inversely related to adulthood obesity in females and not associated in males after adjustment for age. Adulthood SEP and other obesity risk factors may be the mechanisms responsible for the observed associations between childhood SEP and adulthood obesity. [ABSTRACT FROM AUTHOR]

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount., Competing Interests: Disclosure The author Chirag Shah reported Consultant Impedimed, PreludeDX, and Videra Surgical as conflicts of interest. The remaining authors have stated that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The objective of the present study was to evaluate the carbon fiber obtained from textile PAN fiber, in its different forms, as a potential scaffolds synthetic bone. Thirty-four adult rats were used (Rattus norvegicus, albinus variation), two critical sized bone defects were made that were 5 mm in diameter. Twenty-four animals were randomly divided into four groups: control (C)-bone defect + blood clot, non-activated carbon fiber felt (NACFF)-bone defect + NACFF, activated carbon fiber felt (ACFF)-bone defect + ACFF, and silver activated carbon fiber felt (Ag-ACFF)-bone defect + Ag-ACFF, and was observed by 15 and 60 days for histomorphometric, three-dimensional computerized microtomography (microCT) and mineral apposition analysis. On histomorphometric and microCT analyses, NACFF were associated with higher proportion of neoformed bone and maintenance of bone structure. On fluorochrome bone label, there was no differences between the groups. NACFF has shown to be a promising synthetic material as a scaffold for bone regeneration., (© 2024 Wiley Periodicals LLC.)

The periodontal tissue is made up of supporting tissues and among its functions, it promotes viscoelastic properties, proprioceptive sensors, and dental anchorage. Its progressive destruction by disease leads to the loss of bone and periodontal ligaments. For this reason, biomaterials are constantly being developed to restore tissue function. Various techniques are being used to promote regenerative dentistry, including 3D bioprinting with bioink formulations. This paper aims to review the different types of bioink formulations and 3D bioprinting techniques used in periodontal tissue regeneration. Different techniques have been formulated, and the addition of different materials into bioinks has been conducted, with the intention of improving the process and creating a bioink that supports cell viability, proliferation, differentiation, and stability for periodontal tissue regeneration.

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Advanced diagnostic bronchoscopy targeting the lung periphery has developed at an accelerated pace over the last two decades, whereas evidence to support introduction of innovative technologies has been variable and deficient. A major gap relates to variable reporting of diagnostic yield, in addition to limited comparative studies. Objectives: To develop a research framework to standardize the evaluation of advanced diagnostic bronchoscopy techniques for peripheral lung lesions. Specifically, we aimed for consensus on a robust definition of diagnostic yield, and we propose potential study designs at various stages of technology development. Methods: Panel members were selected for their diverse expertise. Workgroup meetings were conducted in virtual or hybrid format. The cochairs subsequently developed summary statements, with voting proceeding according to a modified Delphi process. The statement was cosponsored by the American Thoracic Society and the American College of Chest Physicians. Results: Consensus was reached on 15 statements on the definition of diagnostic outcomes and study designs. A strict definition of diagnostic yield should be used, and studies should be reported according to the STARD (Standards for Reporting Diagnostic Accuracy Studies) guidelines. Clinical or radiographic follow-up may be incorporated into the reference standard definition but should not be used to calculate diagnostic yield from the procedural encounter. Methodologically robust comparative studies, with incorporation of patient-reported outcomes, are needed to adequately assess and validate minimally invasive diagnostic technologies targeting the lung periphery. Conclusions: This American Thoracic Society/American College of Chest Physicians statement aims to provide a research framework that allows greater standardization of device validation efforts through clearly defined diagnostic outcomes and robust study designs. High-quality studies, both industry and publicly funded, can support subsequent health economic analyses and guide implementation decisions in various healthcare settings.

Objective: Treatment for Chiari malformation type I (CM-I) often includes surgical intervention in both pediatric and adult patients. The authors sought to investigate fundamental differences between these populations by analyzing data from pediatric and adult patients who required CM-I decompression., Methods: To better understand the presentation and surgical outcomes of both groups of patients, retrospective data from 170 adults and 153 pediatric patients (2000-2019) at six institutions were analyzed., Results: The adult CM-I patient population requiring surgical intervention had a greater proportion of female patients than the pediatric population (p < 0.0001). Radiographic findings at initial clinical presentation showed a significantly greater incidence of syringomyelia (p < 0.0001) and scoliosis (p < 0.0001) in pediatric patients compared with adult patients with CM-I. However, presenting signs and symptoms such as headaches (p < 0.0001), ocular findings (p = 0.0147), and bulbar symptoms (p = 0.0057) were more common in the adult group. After suboccipital decompression procedures, 94.4% of pediatric patients reported symptomatic relief compared with 75% of adults with CM-I (p < 0.0001)., Conclusions: Here, the authors present the first retrospective evaluation comparing adult and pediatric patients who underwent CM-I decompression. Their analysis reveals that pediatric and adult patients significantly differ in terms of demographics, radiographic findings, presentation of symptoms, surgical indications, and outcomes. These findings may indicate different clinical conditions or a distinct progression of the natural history of this complex disease process within each population, which will require prospective studies to better elucidate.

Background: Vaccination against COVID-19 is highly effective in preventing severe disease and hospitalization, but primary COVID mRNA vaccination schedules often differed from those recommended by the manufacturers due to supply chain issues. We investigated the impact of delaying the second dose on antibody responses to COVID mRNA-vaccines in a prospective cohort of health-care workers in Quebec., Methods: We recruited participants from the McGill University Health Centre who provided serum or participant-collected dried blood samples (DBS) at 28-days, 3 months, and 6 months post-second dose and at 28-days after a third dose. IgG antibodies to SARS-CoV2 spike (S), the receptor-binding domain (RBD), nucleocapsid (N) and neutralizing antibodies to the ancestral strain were assessed by enzyme-linked immunosorbent assay (ELISA). We examined associations between long (≤89 days) versus short (<89 days) between-dose intervals and antibody response through multivariable mixed-effects models adjusted for age, sex, prior covid infection status, time since vaccine dose, and assay batch., Findings: The cohort included 328 participants who received up to three vaccine doses (>80% Pfizer-BioNTech). Weighted averages of the serum (n=744) and DBS (n=216) cohort results from the multivariable models showed that IgG anti-S was 31% higher (95% CI: 12% to 53%) and IgG anti-RBD was 37% higher (95% CI: 14% to 65%) in the long vs . short interval participants, across all time points., Interpretation: Our study indicates that extending the covid primary series between-dose interval beyond 89 days (approximately 3 months) provides stronger antibody responses than intervals less than 89 days. Our demonstration of a more robust antibody response with a longer between dose interval is reassuring as logistical and supply challenges are navigated in low-resource settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Almeida, Schiller, Ke, Sakr, Plesa, Vanamala, Moneger, Bazan, Lucchesi, Wozniak, Fritz, Piccirillo, Pelchat, Arnold, Galipeau, McCluskie, Langlois, Dasgupta and Mazer.)

We investigated the survival and patterns of failure in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) in early stage non-small cell lung cancer (NSCLC) treated with single-fraction stereotactic body radiation therapy (SF-SBRT) of 27-34 Gray. A single-institution retrospective review of patients with biopsy-proven early stage ADC or SCC undergoing definitive SF-SBRT between September 2008 and February 2023 was performed. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes included local failure (LF), nodal failure (NF), and distant failure (DF). Of 292 eligible patients 174 had adenocarcinoma and 118 had squamous cell carcinoma. There was no significant change in any outcome except distant failure. Patients with ADC were significantly more likely to experience distant failure than patients with SCC ( p = 0.0081). In conclusion, while SF-SBRT produced similar LF, NF, DFS, and OS, the higher rate of distant failure in ADC patients suggests that ongoing trials of SBRT and systemic therapy combinations should report their outcomes by histology.

Objective: During the COVID-19 pandemic, the American Association of Neurological Surgeons (AANS) Young Neurosurgeons Committee (YNC) and Neurosurgery Research & Education Foundation (NREF) launched the YNC-NREF Webinar Series to provide young and aspiring neurosurgeons with timely information, education, and inspiration in the absence of in-person programming., Design: Five 90-minute Zoom webinars were evaluated, each including 1-2 keynote speakers, a panel discussion, and an audience question-and-answer section. Topics included overviews of neurosurgery, the match, subspecialties, and inspirational career stories. Optional pre- and post-webinar surveys with 11-point Likert-type scores were distributed to attendees. We compared groups using chi-squared and Kruskal-Willis tests, and perceptions pre- and post-webinar using Mann-Whitney tests., Setting: The webinars were live using Zoom, and the recordings were published on NREF's YouTube channel., Participants: The webinar series targeted young neurosurgeons. The first five episodes had a particular focus on medical students and undergraduates., Results: A total of 673 unique participants attended the webinar series; 257 (38%) and 78 (11%) attendees completed the pre- and post-webinar survey, respectively. Respondents had high baseline interest in neurosurgery and were motivated to learn about the match and training in the US, understand neurosurgeons' day-to-day lives, and ask questions. There were significant differences in perceptions between USMSs, IMSs, and undergraduate students. The webinar improved attendees' knowledge about neurosurgical specialties, the match, and US neurosurgery training., Conclusions: The YNC and NREF effectively engaged a large, diverse audience through an online webinar series, building a foundation for future virtual programming by organized neurosurgery. ACGME competencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Importance: There is no decision-making framework in the early-adoption stage of novel surgical technologies, putting the quality of health care and resource allocation of the health care system at risk., Objective: To investigate relevant weighted criteria that decision-makers may use to make an informed decision for the early adoption of innovative surgical technologies., Design, Setting, and Participants: This multi-institutional decision analytical modeling study used a mixed-methods multicriteria decision analysis (MCDA) and had 2 phases. First, a panel of 12 experts validated decision criteria in the literature and identified additional criteria. Second, 33 Canadian experts prioritized the main criteria (domains) using the composition pairwise-comparison weight-elicitation method (analytical hierarchy process model) and ranked their subcriteria using the direct-ranking elicitation method (Likert scale). Data were analyzed, and response consistency was estimated using the consistency ratio. Analysis of variance was used to assess for significant differences between expert responses. The MCDA was conducted at McGill University between 2021 and 2023. Data were collected nationally by inviting experts in Canada., Main Outcome and Measure: Criteria domain weights and subcriteria rankings. Priority vectors, which are priority scores analyzed and prioritized from expert responses, were used to rank criteria domains and subcriteria for decision-making on adopting new innovative surgical technologies., Results: A total of 45 experts (33 male [73.3%] and 12 female [26.7%]) were invited with different levels of education (22 experts with MD or equivalent, 13 experts with master's degree, and 12 experts with PhD degree) and years of experience (4 experts with <10, 12 experts with 11-20, 18 experts with 21-30, and 11 experts with >30 years). Surgeon experts (23 individuals) were from all surgical disciplines, and nonsurgeon experts (22 individuals) were administrative officers in surgical device procurement, health technology assessment experts, and hospital directors. A total of 7 domains and 44 subcriteria were identified. The MCDA model found that clinical outcomes had the highest priority vector, at 0.429, followed by patients and public relevance (0.135). Hospital-specific criteria (priority vector, 0.099), technology-specific criteria (priority vector, 0.092), and physician-specific criteria (priority vector, 0.087) were the next most highly ranked. The lowest priority vectors were for economic criteria, at 0.083, and finally policies and procedures, at 0.075. There was consensus in the responses (consistency ratio = 0.006), and there were no statistically significant differences between expert responses., Conclusions and Relevance: This study weighted priority criteria domains in importance and established ranked subcriteria for decision-making of early adoption of surgical technologies. Putting these criteria into a framework may help surgeons and decision-makers make informed decisions for the early adoption of new surgical technologies.

Study Design: Retrospective Multi-Institutional Database Study., Objective: Investigate the effect of metabolic syndrome (MetS) on the outcomes of Transforaminal Lumbar Interbody Fusion (TLIF)., Summary of Background Data: TLIF procedures in lumbar spine pathology are common. MetS is a combination of conditions, including medication required hypertension, diabetes mellitus (DM), and body mass index (BMI) of 30 kg/m 2 s or more. The prevalence of MetS has increased drastically over the past two decades. Our study aimed to understand the effect of MetS on morbidity and mortality of TLIF postoperatively., Methods: Our study used American College of Surgeons National Surgical Quality Improvement (ACS-NSQIP) data from 2006 to 2019 to find all patients who underwent TLIF. Patients with MetS were compared to those without MetS. Fisher's test identified univariate relationships between MetS and preoperative/postoperative variables. Multivariable logistic regression models were utilized to analyze the association between MetS and postoperative morbidity and mortality., Results: 54,980 patients were identified who received TLIF. 10.7 % had MetS preoperatively. Patients with and without MetS showed statistically significant univariate differences in most preoperative and postoperative variables. After adjusting for preoperative comorbidities, patients with MetS had greater multivariate-adjusted odds of wound infections (aOR = 1.5889, CI 1.1952-2.112, p = 0.00144), pulmonary events (aOR = 1.5517, CI 1.1207-2.1485, p = 0.00813), renal events (aOR = 2.8685, CI 1.5511-5.3045, p = 0.00078), sepsis (aOR = 1.6773, CI 1.1647-2.4155, p = 5.44E-03), and return to OR (aOR = 1.4764, CI 1.2201-1.7866, p = 6.19E-05)., Conclusions: Patients with MetS are at elevated risk for various morbidity and mortality markers after TLIF. Surgeons performing TLIFs on these patients should be aware of the increased potential for postoperative events that may complicate the patient's recovery., Level of Evidence: Level III., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

Background: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) can be catastrophic complications associated with adult spinal deformity (ASD) surgery. These complications are markedly influenced by osteoporosis, leading to additional vertebral fracture and pedicle screw loosening. The MRI-based vertebral bone quality score (VBQ) is a newly developed tool that can be used to assess bone quality., Objective: To investigate the utility of the VBQ score in predicting PJK and/or PJF (PJF/PJK) after ASD correction., Methods: We conducted a retrospective chart review to identify patients age ≥50 years who had received ASD surgery of 5 or more thoracolumbar levels. Demographic, spinopelvic parameters, and procedure-related variables were collected. Each patient's VBQ score was calculated using preoperative T1-weighted MRI. Univariate analysis and multivariate logistic regression were performed to determine potential risk factors of PJK/PJF. Receiver operating characteristic analysis and area-under-the-curve values were generated for prediction of PJK/PJF., Results: A total of 116 patients were included (mean age, 64.1 ± 6.8 years). Among them, 34 patients (29.3%) developed PJK/PJF. Mean VBQ scores were 3.13 ± 0.46 for patients with PJK/PJF and 2.46 ± 0.49 for patients without, which was significantly different between the 2 groups ( P < .001). On multivariate analysis, VBQ score was the only significant predictor of PJK/PJF (odds ratio = 1.745, 95% CI = 1.558-1.953, P < .001), with a predictive accuracy of 94.3%., Conclusion: In patients undergoing ASD correction, higher VBQ was independently associated with PJK/PJF occurrence. Measurement of VBQ score on preoperative MRI may be a useful adjunct to ASD surgery planning., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: Perioperative steroids have traditionally been administered during lumbar spine surgery in order to decrease local inflammation and prevent scar tissue formation, which can otherwise contribute to significant, long-lasting postoperative pain due to the formation of epidural fibrosis around lumbar nerve roots. However, the use of steroids in lumbar spine patients has raised concerns of postoperative wound complications caused by corticosteroid-induced immunomodulatory effects and changes in collagen synthesis. Patients with chronic kidney disease (CKD) undergoing spine surgery are at a particularly elevated risk of various complications due to chronic CKD-related systemic inflammation and endothelial dysfunction. It is currently uncertain whether chronic steroid use in CKD patients exerts a protective effect postoperatively due to decreased systemic inflammation or instead is correlated with increased rates of wound complications., Results: Using adjusted odds ratios to control for CKD-related comorbidities, our study of lumbar spine fusion patients who were chronic steroid users vs nonusers found no significant differences in rates of postoperative wound infections in later stage CKD patients. However, we also did not observe statistically significant reductions in hospital length of stay or rates of 30-day mortality, sepsis, or cardiac, pulmonary, and renal events., Conclusions: Our results indicate chronic steroid use neither contributes significantly to rates of wound infections nor exerts a protective effect against postoperative inflammatory complications in lumbar spine patients with CKD., Clinical Relevance: Our findings do not support the practice of holding steroids in chronic users prior to lumbar spine surgery. Perioperative steroids do not appear to increase the risk of postoperative complications, but neither do they improve lumbar spine patient outcomes., Competing Interests: Declaration of Conflicting Interests : The authors report no conflicts of interest or relevant disclosures related to this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

The objective of the present study is to perform a systematic review with meta-analysis of the literature on treatment of developmental dysplasia of the hip (DDH) in patients over eight years of age to provide better understanding of therapeutic strategies and results. Authors carried out a systematic review and metanalysis of the literature on DDH treated in patients aged eight years of age or older. A literature search was carefully performed from June 2019 to June 2020. The articles had to report one stage reconstructive surgical treatment of DDH for patients eight years or older, presenting clinical and radiographic evaluation according to the Tonnis and Severin, and McKay systems. Meta-analysis was carried out using the software metanalyst to perform the pooled effect size Nine studies met the inclusion criteria. They assessed a total of 234 patients and 266 hips. Female patients accounted for 75.7% (eight unknown) and the follow-up ranged from 1 to 17.4 years. The majority of the procedures included an acetabular surgery (93.9%) while femoral shortening was performed in 78%. Acceptable outcomes were found in between 67% (Mckay system) and 91% (Severin system) of the cases. Femoral varus and derrotation shortening associated with redirectional osteotomy of the acetabulum (for those with closed triradiate cartilage) or acetabular redirection/reshaping were the most prevalent combined procedures; this strategy can lead to 60% of acceptable clinical results and 90% of radiographically acceptable results. Therefore, our findings give credence to the recommendation for the treatment of DDH in patients over eight years old.

Aim: To investigate the impact of obesity on postoperative morbidity and mortality in patients who underwent anterior cervical discectomy and fusion (ACDF)., Material and Methods: The American College of Surgeons' National Surgical Quality Improvement Project (NSQIP) files from 2006 to 2019 were queried for all patients who underwent an ACDF. Fisher exact tests were used in analyzing univariate differences in preoperative comorbidities and postoperative morbidity and mortality between patients with and without obesity (BMI ?30 kg/ m < sup > 2 < /sup > ). Results with a p value < 0.05 were considered statistically significant. Multivariable logistic regression models were used in determining the independent impact of obesity on ACDF postoperative morbidity and mortality. A p value < 0.017 was required for multivariate statistical significance., Results: There were 96,882 patients who underwent an ACDF from 2006 to 2019 found. 53.77% had non-obese BMI. Patients had statistically significant differences in most perioperative comorbidities and postoperative outcomes on univariate analysis. On multivariate analysis, patients with obesity has decreased adjusted odds of wound infections (aOR=0.7208, CI 0.574-0.9075, p=0.0053), pulmonary events (aOR=0.7939, CI 0.6903-0.9129, p=0.0012), sepsis (aOR=0.5670, CI 0.4359-0.7374, p=2.32E-05), transfusion requirements (aOR=0.5396, CI 0.4498-0.6473, p=3.04E-11), return to operating room (aOR=0.7537, CI 0.6727-0.8447, p=1.17E-06), and length of stay > 10 days (aOR=0.7061, CI 0.6438-0.7744, p=1.49E-13)., Conclusion: Obesity is a protective factor toward ACDF postoperative complications. Obesity as a marker of patient selection criteria for ACDF procedures should not be used by spine surgeons.

Background Context: Cage subsidence following transforaminal lumbar interbody fusion (TLIF) has been associated with poor bone quality. Current evidence suggests that the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score correlates with poor bone quality., Purpose: To our knowledge, this is the first study to assess whether the VBQ score can predict the occurrence of postoperative cage subsidence after TLIF surgery., Design/setting: Retrospective single-center cohort., Patient Sample: Patients undergoing single-level TLIF for degenerative spine disease between February 2014 and October 2021., Outcome Measures: Extent of subsidence., Methods: Demographic, procedure-related, and radiographic data were collected for study patients. VBQ scores were determined from preoperative T1-weighted MRI. Subsidence was defined as ≥2 mm of migration of the cage into the superior or inferior end plate or both. Univariate and multivariate logistic regression were used to determine the correlation between potential risk factors for subsidence and actual subsidence rates., Results: Subsidence was observed among 42 of the 74 study patients. The mean VBQ scores were 2.9±0.5 for patients with subsidence and 2.5±0.5 for patients without subsidence. The difference among groups was significant (p=.003). On multivariate logistic regression, a higher VBQ score was significantly associated with an increased risk of subsidence (OR=1.5, 95% CI=1.160-1.973, p=.004) and was the only significant independent predictor of subsidence after TLIF., Conclusion: We found that a higher VBQ score was significantly associated with cage subsidence following TLIF. The MRI-VBQ score may be a valuable tool for assisting in identifying patients at risk of cage subsidence following TLIF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Intrameningeal cysts are rare lesions without definitive etiologies that can involve the dura or arachnoid mater. Spinal arachnoid cysts have been described, and several different etiologies have been hypothesized. This includes one-way valve mechanisms, traumatic herniation of arachnoid through the dura, and abnormal arachnoid membrane proliferation. To the authors' knowledge, no such descriptions exist regarding purely dural-based cystic lesions; however, the authors hypothesize similar mechanisms may be involved. Most notably, a traumatic injury to the dura leading to a one-way valve mechanism may allow for egress of cerebrospinal fluid between the dural layers, splitting them open. This progressive enlargement can lead to displacement of neural elements and subsequent neurological compromise., Methods: We describe a 17-year-old girl who presented with progressive neck and back pain, left upper-extremity numbness, bilateral lower-extremity weakness, paresthesias, and numbness without obvious etiology despite an extensive neurologic investigation. She had undergone conservative management options including multiple medications, physical and chiropractic therapy, and epidural steroid injections. Computed tomography myelography revealed a cerebrospinal fluid leak into the lumbar epidural space for which surgical exploration was performed. Despite utilizing fluoroscopy and intrathecal fluorescein, no leak source was identified. Fluid collection was found contained within the dural layers rather than the epidural space., Results: An intracystic blood patch was performed with near-complete resolution of the lesion by 6-week follow-up and near-complete return of neurologic function., Conclusions: Ventral panspinal cysts are an exceedingly rare cause of radiculopathy and myelopathy that can be resolved by an intracystic blood patch., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease., Data Source: The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles' quality., Data Synthesis: Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4-54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies., Conclusions: The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.

Aim: To compare the perioperative outcomes between single-day combined or separate-day staged surgeries for cervical spinal stenosis., Material and Methods: A retrospective cohort analysis was conducted on consecutive patients admitted at a single institution between July 2015 and April 2019, who underwent either single-day combined or separate-day staged surgeries during the same hospitalization period. Demographics, comorbidities, hospital length of stay, and perioperative complications were compared between the patient groups., Results: Eighty patients (combined surgery: n=68, staged surgery: n=12) were included. Dysphagia was the most commonly reported postoperative complication in 44/80 patients (55%). There were no significant differences in the baseline demographics between the two groups. The staged surgery group had significantly longer total time in the operating room (7.2 vs. 8.5 hours, p=0.002), longer duration of general anesthesia (6.7 vs. 7.6 hours, p=0.006), and higher incidence of postoperative delirium (12.1% vs. 50% p=0.005) than the combined surgery group. The mean hospital length of stay was similar in the two groups (combined surgery: 7.5 days vs. staged surgery: 15.1 days, p=0.09)., Conclusion: Staged anterior and posterior cervical decompressions, stabilizations, and fusions are associated with longer total time in the operating room, longer duration of general anesthesia, and higher incidence of postoperative delirium than combined surgeries.

Objective: To investigate racial disparities in 30-day postoperative outcomes of craniotomy for glioma resection., Methods: 2006-2019 American College of Surgeons' National Surgical Quality Improvement Program files were queried for all patients who underwent a craniotomy for a supratentorial glioma resection. Racial disparities in preoperative variables were studied between the demographic cohorts of Asian, African Americans, Hispanics, and Caucasian. Fisher exact tests were used to examine association of preoperative variables with race. Multivariable logistic regression models, adjusted for all preoperative variables associated with race, were used to determine the odds ratios of postoperative outcomes for each demographic cohort in comparison with Caucasian patients., Results: A total of 12,544 patients were identified: 4% Asian, 5% African American, 7% Hispanic, and 85% Caucasian. African American patients had significantly higher adjusted odds than Caucasian patients of major adverse cardiovascular events (adjusted odds ratio [aOR]: 1.827, 95% confidence interval [CI]: 1.155-2.891, P = 0.01), pulmonary events (aOR: 1.683, 95% CI: 1.145-2.473, P = 0.008), and urinary tract infection (aOR: 2.016, 95% CI: 1.221-3.327, P = 0.006). Asian patients had significantly higher odds than Caucasian patients of requiring a transfusion (aOR: 2.094, 95% CI: 1.343-3.266, P = 0.001). All demographic cohorts had higher odds of having an extended length of stay than Caucasian patients., Conclusions: African American patients who undergo a craniotomy for glioma resection have almost twice the odds of Caucasian patients of having a postoperative major cardiovascular complication, pulmonary complication, or urinary tract infection. All minority groups have higher odds of an extended length of stay as compared with Caucasian patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Although foreign medical graduates (FMGs) have been essential to the US physician workforce, the increasing competitiveness has made it progressively challenging for FMGs to match in US neurosurgery programs. We describe geographic origins and characteristics associated with successful match into US neurosurgery training programs., Methods: Retrospective review of AANS membership data (2007-2017). Scopus was used to collect bibliometrics., Results: From 2009 neurosurgical residents, 165 (8.2%) were FMGs. Most were male (n = 148; 89.6%) with a median age of 34.0 years. Top six feeder countries (TFC) included India (13.9%; n = 23), Lebanon and Pakistan (9.1%; n = 15), Caribbean Region (7.2%; n = 12), Mexico (6.67%; n = 11), and Greece (3.6%; n = 6). Compared to FMGs from non-top feeder countries (NTFC), TFC FMGs had higher H-indices (2 vs 4, p = 0.049), greater number of publications (2 vs 5, p = 0.04), were more likely to have an MBBS/MBBCh (n = 38 vs n = 17, p = 0.03), and had twice as many candidates from major feeder medical schools that successfully matched into a US neurosurgery program (n = 43 vs NTFC = 20, p < 0.001). NTFC FMGs were almost 3-times more likely to match at an affiliated neurosurgery program (8 vs TFC = 3, p = 0.03), while TFC FMGs were 1.5-times more likely to match at an NIH Top-40 program (33 vs NTFC = 21, p = 0.03)., Conclusions: TFC graduates have higher bibliometrics, frequently come from major feeder schools, and have greater match success at a broader selection of programs and NIH top-40 programs. Future studies characterizing FMG country and medical school origins may enable foreign students to geographically target institutions of interest and could allow US programs to better evaluate foreign training environments., (Copyright © 2021. Published by Elsevier B.V.)

Background: Cervical degenerative disc disease is the most common indication for anterior cervical discectomy and fusion. Given the possible complications, patients are stratified before anterior cervical discectomy and fusion by preoperative risk factors to optimize treatment. One preoperative factor is a patient's coagulation profile., Methods: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patient preoperative coagulation profile and postoperative complications. By generating binary logistic regression models, each of the 4 abnormal coagulation categories (bleeding disorder, low platelet count, high partial thromboplastin time, and high international normalized ratio [INR]) were analyzed for their independent impact on increased risk for complications compared with the control cohort., Results: A total of 61,977 patients were assessed. The most common abnormal coagulation was abnormal platelet count (n = 2149). The most common postoperative outcome was an extended length of hospital stay among patients with an abnormal coagulation profile relative to the control cohort. After multivariate analysis, patients with an abnormal INR (odds ratio, 2.2 [1.3-3.8]; P = 0.003) or abnormal platelet count (odds ratio, 1.5 [1.2-2.1]; P = 0.003) had a higher chance of having an extended length of hospital stay relative to patients having a normal coagulation profile. Having an abnormal INR was found to be associated with an increased risk for having "Any complication.", Conclusions: Our results show significant differences in the incidence rates of a multitude of complications among the 5 groups based on univariate analysis. Patients with any abnormal coagulation disorder had increased rates of developing any complication or having an extended length of hospital stay., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The purpose is to identify the impact of operation time length on complications for patients undergoing operative treatment of distal radius fracture., Methods: Patients who underwent operative treatments for distal radius fractures were identified in a national database. Data collected include patient demographic information, comorbidities, and complications., Results: Operation time was found to be an independent predictor for return to the operating room. Operation time was not found to be a predictor of other postoperative complications., Conclusion: Surgeons should work to shorten procedure duration whenever possible to minimize the risks that longer operative times can have on patient outcomes., Competing Interests: Funding- No funds, grants, or other support was received., (© 2021 Professor P K Surendran Memorial Education Foundation. Published by Elsevier B.V. All rights reserved.)

BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG). Vaccine was administered in combination with polyinosinic-polycytidylic acid-poly-I-lysine carboxymethylcellulose (poly-ICLC) every 3 weeks for 8 cycles, followed by once every 6 weeks. Immunomonitoring and imaging were performed every 3 months. Imaging was centrally reviewed. Immunological responses were assessed in PBMCs using mass cytometry.RESULTSA total of 19 patients were enrolled in stratum A (median age,11 years) and 10 in stratum B (median age, 13 years). There were no grade-4 treatment-related adverse events (TRAEs). Injection site reaction was the most commonly reported TRAE. Overall survival (OS) at 12 months was 40% (95% CI, 22%-73%) for patients in stratum A and 39% (95% CI, 16%-93%) for patients in stratum B. The median OS was 16.1 months for patients who had an expansion of H3.3K27M-reactive CD8+ T cells compared with 9.8 months for their counterparts (P = 0.05). Patients with DIPG with below-median baseline levels of myeloid-derived suppressor cells had prolonged OS compared with their counterparts (P < 0.01). Immediate pretreatment dexamethasone administration was inversely associated with H3.3K27M-reactive CD8+ T cell responses.CONCLUSIONAdministration of the H3.3K27M-specific vaccine was well tolerated. Patients with H3.3K27M-specific CD8+ immunological responses demonstrated prolonged OS compared with nonresponders.TRIAL REGISTRATIONClinicalTrials.gov NCT02960230.FUNDINGThe V Foundation, the Pacific Pediatric Neuro-Oncology Consortium Foundation, the Pediatric Brain Tumor Foundation, the Mithil Prasad Foundation, the MCJ Amelior Foundation, the Anne and Jason Farber Foundation, Will Power Research Fund Inc., the Isabella Kerr Molina Foundation, the Parker Institute for Cancer Immunotherapy, and the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R35NS105068).

Objective: The increasing competitiveness of the neurosurgical residency match has made it progressively difficult for foreign medical graduates (FMGs) to match in neurosurgery. We compared FMG to U.S. medical graduate (USMG) match rates in neurosurgery and identified factors associated with match outcomes for FMGs in neurosurgery., Methods: Retrospective review of American Association of Neurological Surgeons membership data and Association of American Medical Colleges Charting the Outcomes match reports (2007-2017)., Results: Across 1857 neurosurgical residents (USMG: 91.1%, FMG: 8.9%), average FMG match rates were 24% (range, 15%-35%) versus 83% (range, 75%-94%; P < 0.001) for USMG. FMGs were more male (89.5% vs. 82.0%, P = 0.016), older (33.9 vs. 31.8 years, P = 0.008), and more likely to take research year(s) before matching (95.8% vs. 78.5%, P < 0.001). FMGs had greater publications (5 vs. 2, P < 0.001) and H-indices (3 vs. 1, P < 0.001). The number of matched USMGs increased by 3.3 annually, whereas that of matched FMGs remained unchanged (β = 0.07). Compared with USMGs, FMGs were less likely to match to National Institutes of Health (NIH) Top 40 (32.7% vs. 47.5%, P < 0.001) and Doximity Top 20 (20.0% vs. 29.0%, P = 0.014) programs. FMGs with prior U.S. neurosurgery program affiliation were more likely to match at NIH and Doximity Top 20 programs (P < 0.05). For NIH programs, FMGs were older (35.3 vs. 32.0, P = 0.011), had higher H-indices (5 vs. 2, P < 0.001), publications (7 vs. 2, P < 0.001), and were more likely to take research year(s) (94.4% vs. 76.0%, P = 0.002) than USMGs. FMGs had similar patterns for matching into Doximity Top 20 programs., Conclusions: Although FMGs have lower match rates into U.S. neurosurgery residencies than USMGs, several demographic, professional, and academic factors could increase the chances of successful FMG neurosurgical match., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To investigate preoperative baseline anemia, stratified by severity as a function of hematocrit level, as a risk factor for perioperative complications in geriatric patients undergoing spinal procedures., Background: Previous literature has examined the impact of anemia on risk for complications and adverse outcomes in patients undergoing elective spinal procedures. However, there is a paucity of literature analyzing the impact of anemia in the geriatric population, specifically., Methods: The American College of Surgeons-National Surgical Quality Improvement Database was used to identify patients older than 65 years who had undergone elective spinal procedures and were subsequently stratified into 3 separate cohorts based on hematocrit levels: severe/moderate (hematocrit level <30%), mild (30%-37%), and no anemia (>38%). These patient samples were then analyzed using multivariate analyses to assess severity of anemia as a risk factor for complications in elderly patients undergoing spinal procedures., Results: When anemia classes were analyzed as separate independent risk factors for complications, mild anemia (class II) was a significant risk factor for the same complications as moderate/severe anemia (class III/IV), with the exception of 2 complications, compared with nonanemic patients. Mild anemia was independently associated with wound dehiscence (odds ratio, 1.521; 95% confidence interval, 1.126-2.054; P = 0.006), whereas moderate/severe anemia did not show an increased risk for wound dehiscence. However, moderate/severe anemia independently increased the risk for deep venous thromboembolism (odds ratio, 1.437; 95% confidence interval, 1.028-2.011; P = 0.034), compared with mild anemia. Both categories of anemia independently increased the risk for additional complications such as deep incisional surgical site infection, organ/space surgical site infection, pneumonia, unplanned intubation, ventilator dependence, progressive renal insufficiency, acute renal failure, urinary tract infections, cardiac arrest, myocardial infarctions, blood transfusions, systemic sepsis, reoperation, extended length of stay of ≥5 days, unplanned readmission, and mortality., Conclusions: This study indicated that patients with preoperative baseline anemia were at risk for requiring transfusions, renal failure, and infectious complications. Physicians should be cognizant of anemia as a risk factor affecting numerous perioperative complications and adverse outcomes to work toward improving health-related quality of life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Immunotherapy applications to glioblastoma represent a new treatment frontier. Antigen-targeted immunotherapy approaches hold enormous potential to elicit antigen-specific anti-tumor effects in central nervous system tumors. Still, the paucity of effective antigen targets remains a significant obstacle in safely and effectively treating glioblastoma and other malignant gliomas with relatively low mutation loads. In this review, we highlight the current understanding of and development of immunotherapy to target 1) shared non-mutant antigens 2) shared mutant antigens (neoantigens) derived from cancer-specific mutations 3) personalized neoantigens derived from tumor-specific genetic alterations containing de novo peptide sequences and 4) virus-derived antigens. We also discuss strategies to enhance tumor immunogenicity and neoantigen prediction. Spatial heterogeneity remains a formidable challenge for immunotherapy of glioma; recent advances in targeting multiple antigens and refining the antigen selection pipeline hold great promise to turn the tide against glioma., Competing Interests: Declaration of Competing Interest Hideho Okada is an inventor of the following US utility patent applications; “H3.3 CTL peptides and uses thereof” (Case Number, SF2015-163), which has been exclusively licensed to Tmunity, Inc., “Anti-EGFRvIII chimeric antigen receptor (Case Number, U Penn 02,980), which has been exclusively licensed to Novartis Pharma, Inc. and “Identification of an IL-13 Receptor Alpha2 Peptide Analogue Capable of Enhancing Stimulation of Glioma-Specific CTL Response” which has been exclusively licensed to Stemline, Inc., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain cancer in adults. GBM carries a dismal prognosis because of its proliferative, invasive, and angiogenic capabilities and because of its ability to downregulate the immune system. Immune-based therapies under investigation for GBM have been unsuccessful in vivo because of this downregulation. Cold atmospheric plasma (CAP) is a high-energy state of matter that can be applied directly or indirectly to tumor tissue to serve as an adjunct to immunotherapy in the treatment of GBM because it upregulates the immune system by the induction of reactive oxygen species. CAP has the potential to improve the efficacy of existing and investigative immunotherapies for GBM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Sagittal craniosynostosis is managed with a wide variety of operative strategies. The current investigation compares the clinical outcomes of two widely performed techniques: pi craniectomy and minimally invasive endoscopic strip craniectomy (ESC) followed by helmet therapy., Methods: This IRB-approved retrospective study examined patients diagnosed with nonsyndromic, single-suture sagittal craniosynostosis treated with either pi craniectomy or ESC. Included patients had a minimum postoperative follow-up of 5 months., Results: Fifty-one patients met the inclusion criteria (pi 21 patients, ESC 30 patients). Compared to patients who underwent ESC, the pi patients were older at the time of surgery (mean age 5.06 vs 3.11 months). The mean follow-up time was 23.2 months for ESC patients and 31.4 months for pi patients. Initial cranial index (CI) was similar between the groups, but postoperatively the ESC patients experienced a 12.3% mean increase in CI (from 0.685 to 0.767) compared to a 5.34% increase for the pi patients (from 0.684 to 0.719), and this difference was statistically significant (p < 0.001). Median hospital length of stay (1 vs 2 days) and operative duration (69.5 vs 93.3 minutes) were significantly less for ESC (p < 0.001 for both). The ESC patients showed a trend toward better results when surgery was done at younger ages. Craniectomy width in ESC cases was positively associated with CI improvement (slope of linear regression = 0.69, p = 0.026)., Conclusions: While both techniques effectively treated sagittal craniosynostosis, ESC showed superior results compared to pi craniectomy. ESC showed a trend for better outcomes when done at younger ages, although the trend did not reach statistical significance. A wider craniectomy width (up to 2 cm) was associated with better outcomes than smaller craniectomy widths among the ESC patients.

Malignant gliomas carry a dismal prognosis. Conventional treatment using chemo- and radiotherapy has limited efficacy with adverse events. Therapy with genetically engineered T-cells, such as chimeric antigen receptor (CAR) T-cells, may represent a promising approach to improve patient outcomes owing to their potential ability to attack highly infiltrative tumors in a tumor-specific manner and possible persistence of the adaptive immune response. However, the unique anatomical features of the brain and susceptibility of this organ to irreversible tissue damage have made immunotherapy especially challenging in the setting of glioma. With safety concerns in mind, multiple teams have initiated clinical trials using CAR T-cells in glioma patients. The valuable lessons learnt from those trials highlight critical areas for further improvement: tackling the issues of the antigen presentation and T-cell homing in the brain, immunosuppression in the glioma microenvironment, antigen heterogeneity and off-tumor toxicity, and the adaptation of existing clinical therapies to reflect the intricacies of immune response in the brain. This review summarizes the up-to-date clinical outcomes of CAR T-cell clinical trials in glioma patients and examines the most pressing hurdles limiting the efficacy of these therapies. Furthermore, this review uses these hurdles as a framework upon which to evaluate cutting-edge pre-clinical strategies aiming to overcome those barriers.

Objectives: Very few practical frameworks exist to guide the formulation of recommendations at hospital-based health technology assessment (HTA) units. The objectives of our study were: (i) to identify decision criteria specific to the context of hospital-based health technologies and interventions, (ii) to estimate the extent to which the expert community agrees on the importance of the identified criteria, (iii) to incorporate the identified criteria into a decision-aid tool, and (iv) to illustrate the application of a prototype decision-aid tool., Methods: Relevant decision criteria were identified using existing frameworks for HTA recommendations, our past experience, a literature search, and feedback from a survey of diverse stakeholders., Results: Based on the survey results, twenty-three decision criteria were incorporated into the final framework. We defined an approach that eschewed a scoring system, but instead relied on a visual means for arriving at a final recommendation, by juxtaposing the importance rating for each criterion against the results of the health technology assessment. For a technology to be approved, a majority of criteria considered important should also have received favorable findings., Conclusions: We created a simple and practical decision-aid tool that incorporates all decision criteria relevant to a hospital-based HTA unit. With its ease of use and accessibility, our tool renders the subjective decision-making process more structured and transparent.

Purpose: Prognostic factors associated with Manipulation under anesthesia (MUA) failure remain unknown., Methods: A systematic review of the literature was performed to identify studies that reported prognostic factors associated with MUA for postoperative stiffness., Results: 7 studies analyzing prognostic factors associated with MUA outcomes were included. Several studies note pre-MUA ROM to be a significant prognostic factor affecting post-MUA ROM at final follow-up. Knees with <70° of flexion pre-MUA had less final flexion arc than those with >70°., Conclusions: The strongest prognostic factor for decreased ROM after MUA is severe pre-MUA stiffness.

Objective: As back pain is the presenting symptom in 95% of patients with epidural spinal metastases, appropriately identifying and treating the most symptomatic levels can provide significant palliation. The purpose of this study was to analyze the ability of combined positron emission tomography (PET)/computed tomography (CT) to identify spinal metastases with high metabolic activity and guide radiotherapy. We sought to correlate improvement in back pain with reduction in standard uptake value (SUV) after treatment., Methods: Retrospective review was performed of 72 patients with spinal metastases treated with stereotactic ablative radiation therapy at a single center between 2002 and 2014. PET/CT was used to calculate SUVs for spinal metastases, and treatment planning was based on PET/CT results. Preoperative and postoperative pain levels were assessed in all patients., Results: Reduction in pain scores was found in 78% of treated patients. A significant reduction in pain was identified in patients with >5 metastases compared with fewer lesions (P < 0.05). Degree of change in SUV did not correlate significantly with pain relief. However, comparing pretreatment and posttreatment PET/CT, patients with improved pain consistently displayed decreased SUV., Conclusions: PET/CT was shown to be a useful adjunct in radiation treatment planning with change in SUV correlating with symptomatic improvement. This study paves the way for future prospective studies to further assess utility and cost-effectiveness of this imaging modality in radiation treatment planning for spinal metastases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Knee stiffness following primary total knee arthroplasty can lead to unsatisfactory patient outcomes secondary to persistent pain and loss of function. Manipulation under anesthesia (MUA) remains a viable option for treatment of post-operative stiffness. However, the optimal timing and clinical efficacy of manipulation of anesthesia remains unknown., Methods: A systematic review of the literature was performed to identify studies that reported clinical outcomes for patients who underwent MUA for post-operative stiffness treatment. Repeat MUA procedures were included in the study but were analyzed separately., Results: Twenty-two studies (1488 patients) reported on range of motion (ROM) after MUA, and 4 studies (81 patients) reported ROM after repeat MUA. All studies reported pre-MUA motion of less than 90°, while mean ROM at last follow-up exceeded 90° in all studies except 2. For studies reporting ROM improvement following repeat MUA, the mean pre-manipulation ROM was 80° and the mean post-manipulation ROM was 100.6°., Conclusion: MUA remains an efficacious, minimally invasive treatment option for post-operative stiffness following TKA. MUA provides clinically significant improvement in ROM for most patients, with the best outcomes occurring in patients treated within 12 weeks post-operatively., Prospero Registration Number: CRD42016052215., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Earlier studies on the association between antidepressant use and miscarriage have obtained conflicting results after accounting for the role of depression, and none have taken into account the high risk of induced abortions in women using antidepressants., Methods: We identified 41,964 pregnant women delivering between 1998 and 2002 using Quebec's health administration databases. We compared women prescribed antidepressants in the first trimester and with a recorded diagnosis of depression before pregnancy to (1) women with neither antidepressant use nor a depression diagnosis before or during pregnancy; (2) women with a depression diagnosis before pregnancy, but no antidepressants prescribed in the first trimester; and (3) women prescribed hypothyroid medication in the first trimester, but not antidepressants. We used log binomial regression to assess the adjusted relative risk of miscarriage, corrected for induced abortion risk., Results: The miscarriage risk uncorrected for induced abortions was 16%, 10%, and 9% for depressed women exposed to antidepressants; unexposed depressed women; and unexposed, nondepressed women, respectively. These decreased to 11%, 8%, and 7% after correction for induced abortions. In multivariable analysis, the corrected risk of miscarriage relative to unexposed, nondepressed women was 1.3 (1.1-1.5) for antidepressant-exposed women and 1.1 (1.0-1.2) for unexposed depressed women. The miscarriage relative risk for antidepressant users compared with unexposed depressed women was thus 1.2 (1.0-1.4)., Conclusions: Antidepressant use in the first trimester is associated with an increased risk of miscarriage when compared with either nondepressed or depressed unexposed women, even after accounting for induced abortions.

Background: Smoking paradoxically increases the risk of small-for-gestational-age (SGA) birth but protects against preeclampsia. Some studies have reported a "U-shaped" distribution of fetal growth in preeclamptic pregnancies, but reasons for this are unknown. We investigated whether cigarette smoking interacts with preeclampsia to affect fetal growth, and compared levels of soluble fms-like tyrosine kinase-1 (sFlt-1), a circulating anti-angiogenic protein, in preeclamptic smokers and non-smokers., Methods: From a multicenter cohort of 5337 pregnant women, we prospectively identified 113 women who developed preeclampsia (cases) and 443 controls. Smoking exposure was assessed by self-report and maternal hair nicotine levels. Fetal growth was assessed as z-score of birthweight for gestational age (BWGA). sFlt-1 was measured in plasma samples collected at the 24-26-week visit., Results: In linear regression, smoking and preeclampsia were each associated with lower BWGA z-scores (β = -0.29; p = 0.008, and β = -0.67; p < 0.0001), but positive interaction was observed between smoking and preeclampsia (β = +0.86; p = 0.0008) such that smoking decreased z-score by -0.29 in controls but increased it by +0.57 in preeclampsia cases. Results were robust to substituting log hair nicotine for self-reported smoking and after adjustment for confounding variables. Mean sFlt-1 levels were lower in cases with hair nicotine levels above vs. below the median (660.4 pg/ml vs. 903.5 pg/ml; p = 0.0054)., Conclusions: Maternal smoking seems to protect against preeclampsia-associated fetal growth restriction and may account, at least partly, for the U-shaped pattern of fetal growth described in preeclamptic pregnancies. Smoking may exert this effect by reducing levels of the anti-angiogenic protein sFlt-1.

Introduction: Most biomarker studies of the effects of maternal smoking on fetal growth have been based on a single blood or urinary cotinine value, which is inadequate in capturing maternal tobacco exposure over the entire pregnancy. We used hair biomarkers to compare the associations of maternal self-reported smoking, hair nicotine, and hair cotinine with birth weight for gestational age (BW for GA) among active and passive smokers during pregnancy., Methods: We collected maternal hair in the immediate postpartum period and measured nicotine and cotinine concentrations averaged over the pregnancy in 444 term controls drawn from 5,337 participants in a multicenter nested case-control study of preterm birth. BW for GA Z-score and small for gestational age (SGA) were based on Canadian population-based standards., Results: The addition of hair nicotine to multiple linear regression models containing self-reported active smoking, hair cotinine, or both explained significantly more variance in the BW for GA Z-score (p = .01, .03 and .04, respectively). Similarly, women with hair nicotine, but not cotinine, at or above the median value had a significant increase in the risk of SGA birth (odds ratio: 3.07, 95% CI: 1.25-7.52). No significant association was observed between maternal passive smoking and BW for GA based on hair biomarkers., Conclusions: Hair nicotine is a better predictor of reductions in BW for GA than either hair cotinine or self-report. Our negative results for passive smoking suggest that previously reported small but significant effects may be explained by misclassification of active smokers as passive smokers based on self-report.

Evidence is lacking on whether the duration and timing of low socioeconomic position (SEP) across a person's life course may be associated with incidence of type 2 diabetes mellitus (T2D). The authors' objectives were to investigate associations between cumulative SEP and the incidence of T2D in the Framingham Offspring Study (n = 1,893; 52% women; mean baseline age = 34 years). Pooled logistic regression analyses demonstrated that age-adjusted cumulative SEP was associated with T2D in women (for low vs. high cumulative SEP, odds ratio (OR) = 1.92, 95% confidence interval (CI): 1.08, 3.42). Age-adjusted analyses for young-adulthood SEP (7.85 for ≤12 vs. >16 years of education, OR = 2.84, 95% CI: 1.03), active professional life SEP (for laborer vs. professional/executive/supervisory/technical occupations, OR = 2.40, 95% CI: 1.05, 5.47), and social-mobility frameworks (for declining life-course SEP, OR = 2.99, 95% CI: 1.39, 6.44; for stable low vs. stable high life-course SEP, OR = 1.85, 95% CI: 1.02, 3.35) all demonstrated associations between low SEP and T2D incidence in women. No association was observed between childhood SEP and T2D in women for father's education (some high school or less vs. any postsecondary education, OR = 1.26, 95% CI: 0.72, 2.22). In men, there was little evidence of associations between life-course SEP and T2D incidence. These findings suggest that cumulative SEP is inversely associated with incidence of T2D in women, and that this association may be primarily due to the women's educational levels and occupations.

Cutis laxa is a rare inherited or acquired disorder of elastic tissue characterized by inelastic and loose skin. Congenital cutis laxa may present with internal organ involvement, determining a worse prognosis. The authors present the case of a female patient with clinical manifestations suggestive of the hereditary form of the disease, with consanguineous parents (second-degree cousins) and a brother who died with a similar clinical presentation. The genetic study of the FBLN5 gene was important to confirm the diagnosis, define the prognosis, and provide genetic counseling to the family.

Associations between life course socioeconomic position (SEP) and novel biological risk markers for coronary heart disease such as inflammatory markers are not well understood. Most studies demonstrate inverse associations of life course SEP with C-reactive protein (CRP), interleukin-6 (IL-6) and fibrinogen, however little is known about associations between life course SEP and other inflammatory markers including intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor II (TNFR2), lipoprotein phospholipase A2 (Lp-PLA2) activity, monocyte chemoattractant protein-1 (MCP-1) or P-selectin. The objectives of this analysis were to determine whether three life course SEP frameworks ("accumulation of risk", "social mobility" and "sensitive periods") are associated with the aforementioned inflammatory markers. We examined 1413 Framingham Offspring Study participants (mean age 61.2+/-8.6 years, 54% women), using multivariable regression analyses. In age- and sex-adjusted regression analyses, cumulative SEP ("accumulation of risk" SEP framework), for low vs. high SEP, was inversely associated with CRP, IL-6, ICAM-1, TNFR2, Lp-PLA2 activity, MCP-1 and fibrinogen. We found that there were few consistent trends between social mobility trajectories and most inflammatory markers. Own educational attainment was inversely associated with 7 of 8 studied inflammatory markers, while father's education, father's occupation and own occupation were inversely associated with 4, 5 and 4 inflammatory markers, respectively, in age- and sex-adjusted analyses. The strengths of association between SEP and inflammatory markers were typically substantially accounted for by CHD risk markers (smoking, body mass index, systolic blood pressure, total:HDL cholesterol ratio, fasting glucose, medications, depressive symptomatology) suggesting these may be important mechanisms that explain associations between SEP and the studied inflammatory markers., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Cumulative exposure to socioeconomic disadvantage across the life course may be inversely associated with coronary heart disease (CHD); the mechanisms are not fully clear. An objective of this study was to determine whether cumulative life-course socioeconomic position (SEP) is associated with CHD incidence in a well-characterized US cohort that had directly assessed childhood and adulthood measures of SEP and prospectively measured CHD incidence. Furthermore, analyses aimed to evaluate whether adjustment for CHD risk factors reduces the association between cumulative life-course SEP and CHD. The authors examined 1,835 subjects who participated in the Framingham Heart Study Offspring Cohort from 1971 through 2003 (mean age, 35.0 years; 52.4% women). Childhood SEP was measured as father's education; adulthood SEP was assessed as own education and occupation. CHD incidence included myocardial infarction, coronary insufficiency, and coronary death. Cox proportional hazards analyses indicated that cumulative SEP was associated with incident CHD after adjustment for age and sex (hazard ratio = 1.82, 95% confidence interval: 1.17, 2.85 for low vs. high cumulative SEP score). Adjustment for CHD risk factors reduced that magnitude of association (hazard ratio = 1.29, 95% confidence interval: 0.78, 2.13). These findings underscore the potential importance of CHD prevention and treatment efforts for those whose backgrounds include low SEP throughout life.

Context and Objective: The role of tepid sponging to promote fever control in children is controversial. We did not find any studies reporting on the effectiveness of tepid sponging in addition to dipyrone. The aim of this study was to compare the effects of tepid sponging plus dipyrone with dipyrone alone for reducing fever., Design and Setting: A randomized clinical trial was undertaken at Instituto Materno-Infantil Professor Fernando Figueira, Recife, Pernambuco., Methods: Children from six months to five years old with axillary temperature greater than 38 masculineC in the emergency ward between January and July 2006 were eligible. One hundred and twenty children were randomly assigned to receive oral dipyrone (20 mg/kg) or oral dipyrone and tepid sponging for 15 minutes. The primary outcome was mean temperature reduction after 15, 30, 60, 90 and 120 minutes. Secondary outcomes were crying and irritability., Results: 106 children finished the study. After the first 15 minutes, the fall in axillary temperature was significantly greater in the sponged group than in the control group (p < 0.001). From 30 to 120 minutes, better fever control was observed in the control group. Crying and irritability were observed respectively in 52% and 36% of the sponged children and in none and only two of the controls., Conclusions: Tepid sponging plus dipyrone cooled faster during the first 15 minutes, but dipyrone alone presented better fever control over the two-hour period. Tepid sponging caused mild discomfort, crying and irritability for most of the children., Clinical Trial Registration Number: ACTRN12608000083392.

Context and Objective: Several studies in developed countries have documented that a significant percentage of children are given inappropriate doses of acetaminophen and ibuprofen. The objective of this paper was to investigate parents' accuracy in giving dipyrone and acetaminophen to their children, in a poor region., Design and Setting: Cross-sectional study at the pediatric emergency department of Instituto Materno-Infantil Prof. Fernando Figueira, a teaching hospital in Pernambuco., Methods: The inclusion criteria were age between 3 and 36 months, main complaint of fever and at least one dose of dipyrone or acetaminophen given to the child during the 24 hours preceding their arrival at the emergency department. The mothers were asked for demographic information and about the antipyretic doses given, which were compared with the recommended dosage., Results: Among the 200 patients studied, 117 received dipyrone and 83 received acetaminophen. Overall, 75 % received an incorrect dose of antipyretic. Of the patients who received dipyrone, 105 (89.7%) were given an incorrect dose; 16 (15.2%) received too little dipyrone, and 89 (84.8%) received too much. Of the patients who received acetaminophen, 45 (54.2%) were given an incorrect dose; 38 (84.4%) received too little acetaminophen, and 7 (15.6%) received too much. There were no differences in maternal and child characteristics between the groups receiving correct and incorrect doses of medication, except for the type of medication (dipyrone versus acetaminophen)., Conclusions: Most of the children treated were given inappropriate doses, mainly dipyrone overdosing and acetaminophen underdosing.