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STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is defined by pauses in breathing during sleep, but daytime breathing dysregulation may also be present. Sleep may unmask breathing instability in OSA that is usually masked by behavioral influences during wakefulness. A breath-hold (BH) challenge has been used to demonstrate breathing instability. One measure of breathing stability is breathing rate variability (BRV). We aimed to assess BRV during rest and in response to BH in OSA. METHODS: We studied 62 participants (31 with untreated OSA: respiratory event index [mean ± SD] 20 ± 15 events/h, 12 females, age 51 ± 14 years, body mass index [BMI] 32 ± 8 kg/m(2); 31 controls: 17 females, age 47 ± 13 years; BMI 26 ± 4 kg/m(2)). Breathing movements were collected using a chest belt for 5 minutes of rest and during a BH protocol (60 seconds baseline, 30 seconds BH, 90 seconds recovery, 3 repeats). From the breathing movements, we calculated median breathing rate (BR) and interquartile BRV at rest. We calculated change in BRV during BH recovery from baseline. Group comparisons of OSA vs control were conducted using analysis of covariance with age, sex, and BMI as covariates. RESULTS: We found 10% higher BRV in OSA vs controls (P < .05) during rest. In response to BH, BRV increased 7% in OSA vs 1% in controls (P < .001). Resting BR was not significantly different in OSA and controls, and sex and age did not have any significant interaction effects. BMI was associated with BR at rest (P < .05) and change in BRV with BH (P < .001), but no significant BMI-by-group interaction effect was observed. CONCLUSIONS: The findings suggest breathing instability as reflected by BRV is high in OSA during wakefulness, both at rest and in response to a stimulus. Breathing instability together with high blood pressure variability in OSA may reflect a compromised cardiorespiratory consequence in OSA during wakefulness. CITATION: Pal A, Martinez F, Akey MA, et al. Breathing rate variability in obstructive sleep apnea during wakefulness. J Clin Sleep Med. 2022;18(3):825–833.

Haploinsufficiency in SYNGAP1 is implicated in intellectual disability (ID) and autism spectrum disorder (ASD) and affects the maturation of dendritic spines. The abnormal spine development has been suggested to cause a disbalance of excitatory and inhibitory (E/I) neurotransmission at distinct developmental periods. In addition, E/I imbalances in Syngap1+/− mice might be due to abnormalities in K+–Cl− co-transporter function (NKCC1, KCC2), in a maner similar to the murine models of Fragile-X and Rett syndromes. To study whether an altered intracellular chloride ion concentration represents an underlying mechanism of modified function of GABAergic synapses in Dentate Gyrus Granule Cells of Syngap1+/− recordings were performed at different developmental stages of the mice. We observed depolarised neurons at P14–15 as illustrated by decreased Cl− reversal potential in Syngap1+/− mice. The KCC2 expression was decreased compared to Wild-type (WT) mice at P14–15. The GSK-3β inhibitor, 6-bromoindirubin-3ʹ-oxime (6BIO) that crosses the blood–brain barrier, was tested to restore the function of GABAergic synapses. We discovered that the intraperitoneal administration of 6BIO during the critical period or young adolescents [P30 to P80 (4-week to 10-week)] normalised an altered E/I balance, the deficits of synaptic plasticity, and behavioural performance like social novelty, anxiety, and memory of the Syngap1+/− mice. In summary, altered GABAergic function in Syngap1+/− mice is due to reduced KCC2 expression leading to an increase in the intracellular chloride concentration that can be counteracted by the 6BIO, which restored cognitive, emotional, and social symptoms by pharmacological intervention, particularly in adulthood.

The past two decades have seen a sharp increase in suicide and psychiatric hospitalizations for children and adolescents. While many youth are served well in the inpatient psychiatry setting, a sub...

The novel severe acute respiratory syndrome coronavirus 2, SARS-CoV-2 (coronavirus Disease 19 (COVID-19)) was identified as the causative agent of viral pneumonias in Wuhan, China in December 2019, and has emerged as a pandemic causing acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. Interim guidance by the World Health Organization states that extracorporeal membrane oxygenation (ECMO) should be considered as a rescue therapy in COVID-19-related ARDS. International registries tracking ECMO in COVID-19 patients reveal a 21%–70% incidence of acute renal injury requiring renal replacement therapy (RRT) during ECMO support. The indications for initiating RRT in patients on ECMO are similar to those for patients not requiring ECMO. RRT can be administered during ECMO via a temporary dialysis catheter, placement of a circuit in-line hemofilter, or direct connection of continuous RRT in-line with the ECMO circuit. Here we review methods for RRT during ECMO, RRT initiation and timing during ECMO, anticoagulation strategies, and novel cytokine filtration approaches to minimize COVID-19’s pathophysiological impact.

Severe burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine (p −7 M angiotensin II (p p p

Chondrosarcomas of the skull base are rare intracranial tumors of chondroid origin. The rarity of these lesions has made it difficult to form a consensus on optimal treatment regimens. The aim of this study was to provide a comprehensive analysis of prognostic factors, treatment modalities, and survival outcomes in patients with chondrosarcoma of the skull base.Patients with diagnosis codes for chondrosarcoma of the skull base were queried from the National Cancer Database for the years 2004-2016. Outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization.A total of 718 patients with chondrosarcoma of the skull base were identified. Mean overall survival (OS) in these patients was 10.7 years. Older age and presence of metastases were associated with worsened OS. Of patients, 83.3% received surgical intervention, and both partial resection and radical resection were associated with significantly improved OS (P0.001). Neither radiotherapy nor chemotherapy improved OS; however, patients who received proton-based radiation and patients who received high-dose radiation (≥6000 cGy) had significantly improved OS compared with patients who received traditional radiation.In the largest study to our knowledge of skull base chondrosarcoma to date, both partial resection and radical resection significantly improved OS, thus supporting the goal of maximal safe resection to preserve vital neurovascular structures without sacrificing outcome. In patients who received radiotherapy, proton-based modalities and high-dose radiation were associated with increased OS.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, with an increased incidence among the elderly. However, the optimal treatment strategy in elderly patients remains unclear. This study seeks to investigate the effect of patient selection and treatment strategies on survival trends in these patients.Patients with diagnosis codes specific for GBM were queried from the National Cancer Database during 2004-2016. Univariate and multivariate Cox regression analysis was performed to investigate outcomes. Survival curves and 5-year survival were also generated based on patient-specific factors.Among 104,456 patients with GBM identified, elderly patients were less likely to receive radiotherapy (61.3% vs. 77.8%; P0.001) or chemotherapy (47.2% vs. 62.9%; P0.001) or to undergo surgical resection (68.3% vs. 81.8; P0.001). Mean overall survival was 9.1 months (standard deviation, 10.0) and 5-year survival was 5.3%. Multivariate analysis showed age 75-84 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.12-1.73; P = 0.003) and lower Karnofsky Performance Status (50-70: HR, 1.68, 95% CI, 1.35-2.08, P0.001; ≤40: HR, 1.79, 95% CI 1.18-2.72, P = 0.006) were associated with decreased overall survival, whereas surgical resection (subtotal resection: HR, 0.52, 95% CI, 0.38-0.71, P0.001; gross total resection: HR, 0.29, 95% CI, 0.21-0.41, P0.001), radiotherapy (HR, 0.65; 95% CI, 0.47-0.91; P = 0.012), and chemotherapy (HR, 0.65; 95% CI, 0.48-0.88; P = 0.006) were associated with increased overall survival in elderly patients.In an analysis of 104,456 patients with GBM, all treatment modalities were found to be used less frequently in elderly patients. Increasing age and poor performance status were associated with worsened survival. Gross total resection was associated with the greatest survival benefit, and chemotherapy and radiotherapy also improved survival outcomes. These treatment options improved outcomes regardless of performance status. Although maximal treatment strategies may improve survival in elderly patients with GBM, these treatment strategies must be balanced against patient-specific factors and quality-of-life concerns.

Background The Surgical Council on Resident Education (SCORE) curriculum is aligned with the American Board of Surgery (ABS) objectives. Our program adopted the SCORE curriculum in 2015 after poor ABS In-Training Examination (ABSITE) performance and lowest quartile ABS Certifying Exam (CE) and Qualifying Exam (QE) first-time pass rates. We examined the association of SCORE use with ABSITE performance and ABS board exam first-time pass rate. Study design At a single institution, a retrospective review of surgery residents’ SCORE metrics and ABSITE percentile was conducted for academic years 2015 to 2019. Metrics analyzed on the SCORE web portal were mean total minutes and total visits per resident for all residents using SCORE that year. First-time pass rates of the ABS QE and CE were examined from 2013 to 2019. Chi-square and linear regression analysis were performed, and a 95% level of confidence was assumed (alpha = 0.05). Results Yearly data from categorical general surgery residents showed a significant increase in total minutes, total visits, and ABSITE percentile. Combined first time pass rates for the ABS QE and CE significant increased from 70.8% in 2013 to 2015 to 93.9% in 2016 to 2019 (p = 0.018). Conclusions Increased longitudinal use of the SCORE curriculum was associated with programmatic improvements in ABSITE performance and ABS board exam first-time pass rate.

Due to its complicated legal status, the effects of cannabis on elective spine surgery patients have not been well studied. In this nationwide analysis, we find that cannabis abuse is associated with higher perioperative thromboembolism and neurologic complications, respiratory complications, sepsis, length of stay, hospital charges, and rates of unfavorable discharge disposition.Retrospective cohort analysis of a nationwide administrative database. The aim of this study was to analyze the association between cannabis abuse and serious adverse events following elective spine surgery. Cannabis is the most popular illicit drug in the United States, and its use has been increasing in light of state efforts to decriminalize and legalize its use for both medical and recreational purposes. Its legal status has long precluded extensive research into its adverse effects, and to date, little research has been done on the sequelae of cannabis on surgical patients, particularly in spine surgery. The 2012–2015 Nationwide Inpatient Sample was queried for all patients undergoing common elective spine surgery procedures. These patients were then grouped by the presence of concurrent diagnosis of cannabis use disorder and compared with respect to various peri- and postoperative complications, all-cause mortality, discharge disposition, length of stay, and hospitalization costs. Propensity score matching was utilized to control for potential baseline confounders. A total of 423,978 patients met inclusion/exclusion criteria, 2393 (0.56%) of whom had cannabis use disorder. After controlling for baseline characteristics and comorbid tobacco use, these patients similar inpatient mortality, but higher rates of perioperative thromboembolism (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2–4.0; P = 0.005), respiratory complications (OR 2.0; 95% CI 1.4–2.9; P 0.001), neurologic complications such as stroke and anoxic brain injury (OR 2.9; 95% CI 1.2–7.5; P = 0.007), septicemia/sepsis (OR 1.5; 95% CI 1.0 to 2.5; P = 0.031), and nonroutine discharge (P 0.001), as well as increased lengths of stay (7.1 vs. 5.2 days, P 0.001) and hospitalization charges ($137,631.30 vs. $116,112.60, P 0.001). Cannabis abuse appears to be associated with increased perioperative morbidity among spine surgery patients. Physicians should ensure that a thorough preoperative drug use history is taken, and that affected patients be adequately informed of associated risks. Level of Evidence: 3.

STUDY OBJECTIVES: Cardiovascular comorbidities in obstructive sleep apnea (OSA) are difficult to treat, perhaps due to autonomic dysfunction. We assessed beat-to-beat blood pressure (BP) variability (BPV) in OSA while considering other markers derived from electrocardiogram and continuous BP signals. METHODS: We studied 66 participants (33 participants with OSA: respiratory event index [mean ± SEM]: 21.1 ± 2.7 events/h; 12 females, aged 51.5 ± 2.4 years; body mass index: 32.8 ± 1.4 kg/m(2); 33 healthy controls: 20 females; aged 45.3 ± 2.4 years; body mass index: 26.3 ± 0.7 kg/m(2)). We collected 5-minute resting noninvasive beat-to-beat BP and electrocardiogram values. From BP, we derived systolic, diastolic, and mean BP values, and calculated variability as standard deviations (systolic BPV, diastolic BPV, BPV). We also calculated diastole-to-systole time (time to peak). From the electrocardiogram, we derived QRS markers and calculated heart rate and heart rate variability. We performed a multivariate analysis of variance based on sex and group (OSA vs control), with Bonferroni-corrected post hoc comparisons (P ≤ .05) between groups. We calculated correlations of BPV with biological variables. RESULTS: Multivariate analysis of variance showed effects of diastolic BPV and BPV in OSA; post hoc comparisons revealed high diastolic BPV and BPV only in female participants with OSA vs controls. QRS duration was higher in OSA, with post hoc comparisons showing the effect only in males. BPV correlated positively with heart rate variability in controls but not in participants with OSA. BPV correlated positively with time to peak in females with OSA and OSA combined, whereas there was no BPV–time-to-peak correlation in healthy participants. CONCLUSIONS: The findings show sex-specific autonomic dysfunction reflected in beat-to-beat BP in OSA. The higher BPV may reflect poor baroreflex control or vascular damage in OSA, which are potential precursors to cardiovascular complications. CITATION: Pal A, Martinez F, Aguila AP, et al. Beat-to-beat blood pressure variability in patients with obstructive sleep apnea. J Clin Sleep Med. 2021;17(3):381–392.

Study Design: Retrospective cohort study. Objective: Spinal chordomas are rare primary malignant neoplasms of the primitive notochord. They are slow growing but locally aggressive lesions that have high rates of recurrence and metastasis after treatment. Gold standard treatment remains en-bloc surgical resection with questionable efficacy of adjuvant therapies such as radiation and chemotherapy. Here we provide a comprehensive analysis of prognostic factors, treatment modalities, and survival outcomes in patients with spinal chordoma. Methods: Patients with diagnosis codes specific for chordoma of spine, sacrum, and coccyx were queried from the National Cancer Database (NCDB) during the years 2004-2016. Outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. Results: 1,548 individuals were identified with a diagnosis of chordoma, 60.9% of which were at the sacrum or coccyx and 39.1% at the spine. The mean overall survival of patients in our cohort was 8.2 years. Increased age, larger tumor size, and presence of metastases were associated with worsened overall survival. 71.2% of patients received surgical intervention and both partial and radical resection were associated with significantly improved overall survival ( P < 0.001). Neither radiotherapy nor chemotherapy administration improved overall survival; however, amongst patients who received radiation, those who received proton-based radiation had significantly improved overall survival compared to traditional radiation. Conclusion: Surgical resection significantly improves overall survival in patients with spinal chordoma. In those patients receiving radiation, those who receive proton-based modalities have improved overall survival. Further studies into proton radiotherapy doses are required.

Retrospective review of hospital charts. (1) To determine the microbiological profile of patients with surgical site infections following posterior spinal fusion surgery (PSF) for Adolescent Idiopathic scoliosis (AIS). (2) To study the treatment outcome of patients with surgical site infections (SSI) following surgery for AIS. (3) To identify the key differences in presentation and management of acute and delayed SSI following AIS surgery. There has been increasing evidence of the role of P. acnes in deep surgical site infections. Literature related to this is abundant in relation to shoulder arthroplasty; however, it is sparse in relation to spine surgery. We conducted a retrospective review of all patients treated for AIS during a 5-year period (2010–2014) at our institution, with a minimum of 2-year follow-up after the index surgery. Patients with a postoperative infection following their index surgery were included. Charts of AIS patients with post-op infections were reviewed for details of the index surgery, time to presentation of the infection, presenting signs/symptoms, microbiology details, details of surgical and antibiotic treatment, and outcomes. Nine (2.8%) post-op infections were identified out of 315 cases for AIS during this period. Seven (2.2%) involved P. acnes. Two (0.6%) involved MSSA. The average time for cultures to show growth was 6.1 days (range 5–8 days) in P. acnes group and 2–3 days in MSSA group. Patients with P. acnes infections were treated with implant removal, debridement and antibiotics. All patients achieved solid fusion except two patients from the P. acnes group had pseudoarthrosis and had to undergo revision fusion. Propionibacterium acnes was the single most common bacteria isolated from delayed surgical site infection following PSF in AIS patients. Optimal treatment consists of debridement, implant removal and antibiotics. These patients have high incidence of pseudoarthrosis. Level IV.

Background: The use of spinal stabilization with decompression has been shown to improve survival, spinal stability, and ambulatory status in patients with metastatic spinal tumors. However, the poor bone quality typically seen in these patients can prevent adequate stabilization. Fenestrated pedicle screws permit augmented fixation via injection of bone cement into the vertebral body upon screw placement, potentially mitigating the difficulties in achieving adequate stabilization in these patients. Objective: To compare surgical outcomes of posterior spinal fusion in patients with cancerous spinal lesions between polymethyl methacrylate cement–augmented fenestrated screws and standard pedicle screws. Methods: A total of 19 consecutive patients with cancerous spinal lesions receiving posterior spinal fusion (PSF) with pedicle screws from a single surgeon were retrospectively reviewed for demographic information, comorbidities, surgical parameters, and outcomes. Results: Ten patients underwent PSF with cement augmentation, whereas 9 underwent standard PSF. There was no significant difference in demographics, comorbidities, or surgical characteristics. Operative time was significantly greater in the cement-augmented group (302 ± 100 minutes vs 203 ± 55 minutes; P = .015). There was no significant difference in rates of operation or readmission between the cohorts nor was there any significant difference in discharge disposition. There was 1 case of surgical site infection (in a patient with a fenestrated screw) and no cases of cement extravasation. No instances of mechanical hardware failure were recorded. Conclusions: Fenestrated screws confer similar risk profiles as nonfenestrated screws for posterior spinal fusion in patients with spinal cancer. However, fenestrated screws may affect operative time, radiation exposure, and impose risk of cement extravasation. Cement-augmented fenestrated pedicle screws may be a viable option for patients with poor bone quality associated with metastatic disease without significantly increased rates of surgical complications. Level of Evidence: 3.

Objective Relative value units (RVUs) form the backbone of health care service reimbursement calculation in the United States. However, it remains unclear how well RVUs align with objective measures of procedural complexity within neurosurgery. Methods The 2018 American College of Surgeons National Surgical Quality Improvement Program database was queried for neurosurgical procedures with >50 patients, using Current Procedural Terminology (CPT) codes. Length of stay (LOS), operative time, mortality, and readmission and reoperation rates were collected for each code and a univariate correlation analysis was performed, with significant predictors entered into a multivariate logistic regression model, which generated predicted work RVUs, which were compared with actual RVUs to identify undervalued and overvalued procedures. Results Among 64 CPT codes, LOS, operative time, mortality, readmission, and reoperation were significant independent predictors of work RVUs and together explained 76% of RVU variance in a multivariate model (R2 = 0.76). Using a difference of >1.5 standard deviations from the mean, procedures associated with greater than predicted RVU included surgery for intracranial carotid circulation aneurysms (CPTs 61697 and 61700; residual RVU = 12.94 and 15.07, respectively), and infratemporal preauricular approaches to middle cranial fossa (CPT 61590; residual RVU = 15.39). Conversely, laminectomy/foraminotomy for decompression of additional spinal cord, cauda equina, and/or nerve root segments (CPT 63048; residual RVU = –21.30), transtemporal craniotomy for cerebellopontine angle tumor resection (CPT 61526; residual RVU = –9.95), and brachial plexus neuroplasty (CPT 64713; residual RVU = –11.29) were associated with lower than predicted RVU. Conclusions Work RVUs for neurosurgical procedures are largely predictive of objective measures of surgical complexity, with few notable exceptions.

The central giant cell granuloma (CGCG) presents as a benign, painless, slow-growing swelling of the jaw. These lesions are reported more frequently in females and most often occur in the mandible. Radiographically, it presents as a distinct delineated bony pathology with a loss of lamina dura around teeth. There can be frequent signs of displacement of teeth and tooth germs. Currently, the usually followed surgical treatment of the CGCG ranges from simple curettage to en -bloc resection. The extensive resection of aggressive and larger lesions inevitably results in the loss of teeth and tooth germs, especially in younger patients. Since, calcitonin has a direct inhibiting effect on osteoclasts and is efficient in controlling diseases with increased osteoclast activity, such as Paget’s disease, and osteoclastic bone metastases, hence serve as a promising alternative. This paper presents the effectiveness and safety of Calcitonin nasal spray, in the management of a CGCG of the jaw, in an 8-year-old patient who was given calcitonin as first-line therapy. Keywords: Bony pathology, Calcitonin nasal spray, Central giant cell granuloma (CGCG), Enbloc resection, Management, Swellings of jaws.

Background. The use of physical activity tracker devices has increased within the general population. However, there is limited medical literature studying the efficacy of such devices in adolescents with obesity. In this study, we explored the feasibility of using wearable activity tracking devices as an adjunct intervention on adolescents with obesity. Methods. Randomized controlled pilot trial evaluated the feasibility (attrition ≤50%) of an activity tracking intervention (ATI) and its effects on weight loss in adolescents with obesity enrolled in an adolescent weight management clinic (AWMC). Outcomes included feasibility (attrition rate) and absolute change in BMI. Differences between groups at 6, 12, and 18 weeks were examined. Results. Forty-eight participants were enrolled in the study. Eighteen subjects were randomly assigned to the ATI group and 30 to control. The average age was 14.5 years. Overall, the majority of participants were Hispanic (56%). Sexes were equally distributed. The average baseline BMI was 37.5 kg/m2. At the study conclusion, the overall attrition rate was 52.1%, 44.4% in the ATI group versus 56.6% in the control group, with a differential attrition of 12.2%. The ATI and control groups each showed an absolute decrease in BMI of −0.25 and −2.77, respectively, with no significant differences between the groups. Conclusion. The attrition rate in our study was >50%. Participation in the AWMC by the ATI and control groups resulted in maintenance of BMI and body weight for the study duration. However, the use of an activity tracking device was not associated with greater weight loss. This trial is registered with NCT03004378.

BACKGROUND/PURPOSE: Surgical indications and techniques have changed over the last fifteen years. The number of Pediatric Surgery training programs has also increased. We sought to examine the effect of these changes on resident education by examining case log data. METHODS: Accreditation Council for Graduate Medical Education (ACGME) case logs for graduating Pediatric Surgery residents were examined from 2004-2018. Using the summary statistics provided, linear regression analysis was conducted on each case log code and category. RESULTS: In 2004, there were 24 Pediatric Surgery training programs and 24 Pediatric Surgery residents graduating with an average of 979.8 total cases logged. In 2018, there were 36 programs with 38 residents graduating with an average of 1260.2 total cases logged. Total case volume of graduating residents significantly increased over the last 15 years (p

Since the publication of the hybrid algorithm there has been rapid development of new specialty wires, microcatheters, guide extensions, and low-profile balloons to facilitate successful coronary chronic total occlusion percutaneous coronary intervention. With development of new devices, it is best to categorize them by design and intended task. This enables a safe and systematic approach to coronary chronic total occlusion percutaneous coronary intervention and avoid overlap and waste. This article serves as a guide for tool selection for the interventional cardiologist performing coronary chronic total occlusion percutaneous coronary intervention.

Background: Nomophobia is defined as “the fear of being without a mobile phone or unable to use it.” Nowadays, it is considered a modern age phobia. It is to be considered as a form of behavioral addiction. Aim: This study aims to determine the level of nomophobia in the Indian population aged between 15 and 35 years. Materials and Methods: A personalized questionnaire was designed in the Google Forms and distributed among the targeted audience. The questionnaire contained three parts: consent letter, sociodemographic details, and nomophobia questionnaire. A total of 2061 valid responses were analyzed in SPSS software. Results: Out of 2061, 52.9% of the respondents were male and 47.1% were female. 92.2% of the respondents were between 18 and 24 years of age group. Moreover, 79.1% of the respondents are undergraduate or pursuing their graduation. 35.5% of the respondents were from metropolitan city, 38.8% were from an urban city, and 12.15% were from a semiurban city, while the rest 13.6% were from rural areas. 74.8% of the respondents were moderate nomophobic, 18.9% were severe nomophobic, and 6.3% were mild nomophobic. Conclusion: In this study, we observed that nomophobia is moderate to severe and that our “physical, mental, and social health” has a major concern.

Objective Giant cell tumors (GCTs) constitute 5% of all primary bone tumors with spinal GCTs (SGCTs) accounting for 2%–15% of all GCTs. The standard of care for SGCT has been maximal surgical resection. However, many adjuvant therapies have been used owing to the difficulty in achieving gross total resection combined with the high local recurrence rate. The purpose of the present study was to analyze the incidence, management, and outcomes of SGCT. Methods Patients with diagnosis codes specific for SGCT were queried from the National Cancer Database from 2004 to 2016. The outcomes were investigated using Cox univariate and multivariate regression analyses, and survival curves were generated for comparative visualization. Results The search criteria identified 92 patients in the NCDB dataset from 2004 to 2016 with a diagnosis of SGCT. Of the 92 patients, 64.1% had undergone surgical intervention, 24.8% had received radiotherapy, and 15.2% had received immunotherapy. Univariate analysis revealed that age ≥55 years and tumor location in the sacrum/coccyx were associated with worsened overall survival (OS) and that surgical resection was associated with improved OS. On multivariate analysis, age 55–64 years was associated with worsened OS, and radical surgical resection was associated with improved OS. The survival analysis revealed improved OS with surgery but not with radiotherapy, chemotherapy, or immunotherapy. Conclusion SGCT is a rare primary bone tumor of the vertebral column. The standard of care has been surgical resection with the goal of gross total resection; however, adjuvant therapies have often been used. Our study found that surgical resection significantly improved OS and that immunotherapy neared significance in improving OS.

Objective Under-recognition of alpha-1 antitrypsin deficiency (AATD) is well documented in AATD-lung disease but is rarely reported in patients with liver cirrhosis requiring liver transplantation. This report examines the frequency of newly diagnosed AATD based on pathologic examination of explanted livers following liver transplantation, trends in diagnosis over time, and prognostic correlates of under-recognition outcomes following liver transplantation. Methods This study retrospectively reviewed 1473 pathology reports from adult patients (>18 years) undergoing liver transplantation at Cleveland Clinic between 2004 and 2017. Pathology reports of explanted livers exhibiting periodic acid-Schiff, diastase-resistant inclusion bodies (PAS+G) suggestive of AATD were included and medical records were reviewed regarding demographics, AATD genotype, alternative etiologies for cirrhosis, presence of emphysema, and survival outcomes. Kaplan-Meier estimates of survival outcomes were compared between patients diagnosed pre-liver transplantation and that newly diagnosed post-liver transplantation. Results Of 1473 explanted liver pathology reports examined, 117 (7.9%) showed PAS+G suggestive of AATD. The diagnosis of AATD in these 117 patients was established pre-liver transplantation in 36 (30.8%, group 1) and in 46 (39.3%) post-liver transplantation (group 2a). Testing for AATD was not undertaken in 35 (29.9%) of patients despite having PAS+G on explanted livers (group 2b). Post-liver transplantation survival analysis showed a trend (P = 0.098) towards enhanced survival in group 1 vs. group 2 at 10 years. Conclusions This study shows that diagnosis of AATD is overlooked and frequently delayed in patients with cirrhosis undergoing liver transplantation. The observed trend towards higher survival in patients diagnosed with AATD pre-liver transplantation suggests the opportunity to enhance outcomes by earlier recognition of AATD.

Background Responsive neuromodulation (RNS) is a treatment option for patients with medically refractory bilateral mesial temporal lobe epilepsy (MTLE). A paucity of data exists on the feasibility and clinical outcome of hippocampal-sparing bilateral RNS depth lead placements within the parahippocampal white matter or temporal stem. Objective To evaluate seizure reduction outcomes with at least a 1-yr follow-up in individuals with bilateral MTLE undergoing hippocampus-sparing implantation of RNS depth leads. Methods A retrospective analysis of prospectively collected data was performed on patients at our institution with bilateral MTLE who were implanted with RNS depth leads along the longitudinal extent of bitemporal parahippocampal white matter or temporal stem. Baseline and postoperative seizure frequency, previous surgical interventions, and postimplantation electrocorticography and stimulation data were analyzed. Results Ten patients were included in the study (7 male, 3 female). Overall seizure frequency declined by a median 44.25% at 3.13 yr (standard deviation 3.31) postimplantation. Four patients (40%) achieved 50% responder rate at latest follow-up. Two of four patients with focal onset bilateral tonic-clonic seizures became completely seizure-free. Forty percent of patients were previously implanted with a vagus nerve stimulator, and 20% underwent a prior temporal lobectomy. All depth lead placements were confirmed as radiographically located in the parahippocampal white matter or temporal stem without hippocampus violation. There were no cases of lead malposition. Conclusion Extrahippocampal or temporal stem white matter targeting during RNS surgery for bitemporal MTLE is feasible and allows for electrographic seizure detection. Larger controlled studies with longer follow-up are needed to validate these preliminary findings.

COVID-19, caused by the novel coronavirus strain SARS-CoV-2 that emerged in late 2019, has resulted in a global pandemic. COVID-19 was initially believed to occur less frequently in children with relatively mild disease. However, severe disease and varied presentations have been reported in infected children, one of such being intussusception. There have only been three reported cases of intussusception in the pediatric population infected with COVID-19. In this paper, we will discuss the management and treatment of a novel fourth case of COVID-19-associated intussusception. This case is the first reported in the USA and suggests that COVID-19 may be implicated in the development of intussusception. Pediatricians should consider the possibility of intussusception when a child with COVID-19 presents with abdominal pain.

Background Endovascular therapy is often the preferred first treatment option for chronic limb threatening ischemia (CLTI) patients. Drug coated balloons (DCB) reduce restenosis rates compared to percutaneous transluminal angioplasty (PTA), however DCB use has not been studied systematically in patients with CLTI. Thus, the optimal treatment option for these complex lesions remains controversial. Methods We report on 327 patients with CLTI treated either with DCB (n = 105) or non-DCB (n = 222) for femoropopliteal disease. Data were retrieved from the Excellence in Peripheral Artery Disease (XLPAD) registry ( NCT01904851 ). Two DCB types were used at the discretion of the operator: Lutonix® (BARD Peripheral Vascular, Inc., Tempe, AZ, USA) and IN.PACT AdmiralTM (Medtronic, Santa Rosa, CA, USA). Odds ratios and the respective 95% confidence interval were synthesized to examine the association between the two groups in terms of all-cause mortality, target limb repeat endovascular or surgical revascularization, target vessel revascularization (TVR), major and minor amputation at 12 months of follow up. Results The mean lesion length was 150.0 mm (SD:123.2) and 151.2 mm (SD:108.3) for the DCB and non-DCB group respectively. No difference between the two groups was detected in terms of all-cause mortality (2.86%vs2.7%,p = .94), target limb repeat endovascular or surgical revascularization (16.19%vs12.61%,p = .25), TVR (16.19%vs.11.71%,p = .26) or minor amputation (15.24%vs10.81%,p = .25) at 12 months of follow up. Although a higher incidence of 12 months major amputation was observed in the DCB group (11%vs.4%,p = .01), after adjusting for several risk factors the odds of major amputation were not statistically different between the DCB and non-DCB groups (OR:1.54;95%CI:0.53–4.51;p = .43). Conclusions Both DCB and non-DCB strategies are effective modalities for revascularization of patients with CLTI. No differences were identified between the DCB and non-DCB group in terms of late outcomes during 12 months of follow up.

Background Endoscopic postoperative recurrence (POR) of Crohn’s Disease (CD) following ileocolonic resection (ICR) is common; however, optimal treatment strategies of identified POR are unknown. We assessed the role of biologic therapy to treat endoscopic POR in a real-world cohort. Methods Retrospective cohort study of adult CD patients who underwent ICR from 2009–2020 at a tertiary center. Patients with endoscopic POR detected on postoperative colonoscopy and a subsequent follow-up colonoscopy were included. Patients were categorized by biologic therapy at time of POR and further sub-grouped by therapy modification after POR detection (no change, therapy optimization, or change in biologic class). Therapy optimization included: starting or modifying immunomodulator therapy, corticosteroids, or budesonide. POR was defined by Rutgeerts’ ≥ i2b. Results 203 CD patients (49.8% female, 15.4% > 1 prior ICR, 49.0% pre-operative biologic exposure) were included. Of these, 137 (67%) patients were not on biologic therapy at POR detection: 43% subsequently started a biologic, 23% optimized therapy, and 34% had no change. 66 (33%) patients were on anti-TNF at POR identification: 24% subsequently changed biologic class, 48% optimized anti-TNF, and 27% had no change (Figure 1). There was no difference in median time from ICR to POR detection (483 days, p=0.08) or inter-colonoscopy interval (483 days, p=0.25) between groups. In patients not on biologics at POR detection, those who started a biologic saw a 21% increase in subsequent endoscopic remission compared to those who optimized therapy (49.2% vs 28.1%, p=0.09) and a 12% increase compared to those who received no change (49.2% vs 37%). In patients not on biologics with severe POR (i3/i4, n=62), there was significantly higher remission rate by starting biologic therapy compared to optimizing existing therapy (53.3% vs 16.7%) or no change (53.3% vs 35.7%), p=0.04. In individuals receiving anti-TNF at time of POR, there was a 25% increase in endoscopic remission in patients who switched biologic class compared to those who optimized therapy (56.2% vs 31.2%) and a 34% increase compared to those with no change (56.2% vs 22.2%), p=0.1. Furthermore, significantly higher rates of improved Rutgeerts’ score were observed in switching biologic class compared to therapy optimization (68.8% vs 43.8%) or no change (68.8% vs 27.8%), p=0.04. Conclusion After endoscopic POR detection following ICR, initiating biologic therapy in individuals not previously receiving it, and changing mechanism of action in those already receiving anti-TNF, may improve clinical outcomes compared to alternative management strategies. If confirmed, these findings may inform optimal management strategies for endoscopic POR.

Background SEGA is a rare, slow-growing CNS neoplasm that has historically been treated by surgical resection. However, the advent of a mammalian target of rapamycin complex-1 inhibitor, everolimus, has shown promising results in recent clinical trials. We sought to provide an analysis of epidemiological and survival risk factors in this rare tumor entity, while comparing trends in surgical management before and after introduction of everolimus in SEGAs. Methods Patients with SEGA were queried from the National Cancer Database between 2004 and 2015. Standard statistical analysis was conducted to assess variables associated with the odds of performing surgery and survival, while controlling for confounding variables. Results A total of 460 patients were diagnosed with SEGA. Multivariable analysis of survival demonstrated that increased age was associated with decreased survival (HR, 1.05; P Conclusion Our analysis of SEGAs demonstrated that age was the only variable affecting overall survival. Surgical resection was performed in older patients with larger tumors (> 20 mm) as a primary mode of treatment, without chemoradiotherapy. Expectedly, rates of surgical resection were found to have decreased since 2011, after FDA approval of everolimus for SEGA treatment.

Low-dose rivaroxaban reduced major adverse cardiac and limb events among patients with stable atherosclerotic vascular disease (ASCVD) in the COMPASS trial. The objective of our study was to evaluate the eligibility and budgetary impact of the COMPASS trial in a real-world population. The VA administrative and clinical databases were utilized to conduct a cross-sectional study to identify patients eligible for low-dose rivaroxaban receiving care at all 141 facilities between October 1, 2014 and September 30, 2015. Proportion of patients with stable ASCVD eligible for low-dose rivaroxaban and prevalence of multiple risk enrichment criteria among eligible patients. Pharmaceutical budgetary impact using VA pharmacy pricing. Chi-squared and Student’s t tests were used to compare patients eligible versus ineligible patients. From an initial cohort of 1,248,214 patients with ASCVD, 488,495 patients (39.1%) met trial eligibility criteria. Eligible patients were older (74.2 vs 64.5 years) with higher proportion of hypertension (84.1% vs 82.1%) and diabetes (46.2% vs 32.9) compared with ineligible patients (p

BACKGROUND/PURPOSE: The U.S. has an alarming rate of firearm injuries. Racial disparities among victims and predictors of outcomes are not well established. Our objective was to assess costs, length of stay (LOS), and inpatient mortality among nonfatal and fatal pediatric firearm injuries that required hospitalization. METHODS: Pediatric (≤ 18 years of age) hospitalizations with a firearm injury discharge diagnosis were identified from the national Kids’ Inpatient Databases (KID) for 2006 through 2012. Firearm injury intent, weapon type, and hospitalization rates by racial groups were examined. Inpatient mortality, costs, and length of stay were examined using regression models. RESULTS: Of 15,211 hospitalizations, the majority of injuries were due to assault (60%) and the intentions of firearm injury differed by race (p < 0.001). The median cost per hospitalization was $10,159 (interquartile range: $5,071 to $20,565), totaling more than a quarter of a billion dollars. On regression analysis, Black (OR: 0.41; CI: 0.30–0.55) and Hispanic (OR: 0.47; CI: 0.34–0.66) patients were less likely to die than White patients. CONCLUSION: Pediatric firearm injury circumstances and survival vary by race with Whites being more likely to experience unintentional injury and suicide, while Blacks and Hispanics are more likely to experience inflicted injury.

Management of WHO grade II gliomas (LGG) can include a combination of observation, surgery, radiotherapy (RT), and chemotherapy; however, optimal management remains unclear in regards to RT. The current study seeks to investigate the usage of RT in LGG and its effect on survival outcomes. Patients with diagnosis codes specific for LGG were queried from the National Cancer Database (NCDB) during the years 2004–2016. Kaplan–Meier curves with log-rank testing, univariate and multivariate Cox regression analysis, and comparisons of estimated 3- and 7-year survival were performed to investigate the effect of RT on overall survival. 19,382 patients with LGG were identified with histologically confirmed disease. Kaplan–Meier testing demonstrated RT impacted survival in patients undergoing biopsy or no surgery (p

Pediatric primary high-grade spinal glioma (p-HGSG) is an extremely rare disease process, with little data within the current literature. Akin to primary high-grade gliomas, this cancer has been exemplified by dismal prognosis and poor response to modern treatment paradigms. This study seeks to investigate the current trends affecting overall survival using the National Cancer Database (NCDB). The NCDB was queried for p-HGSG between 2004 and 2016, by utilizing the designated diagnosis codes. Kaplan-Meier curves were generated, and log-rank testing was performed to analyze factors affecting overall survival. In addition, a Cox proportional-hazards model was used to perform multivariate regression analysis of survival outcomes. A cohort of 97 patients was identified with a histologically confirmed p-HGSG. The overall incidence of p-HGSG in all pediatric spinal cord tumors is 7.5%, with a mean survival time of 25.3 months (SD, 21.0) and 5-year overall survival of 17.0%. The majority of patients underwent surgery (n = 87, 89.7%), radiotherapy (n = 73, 75.3%), and chemotherapy (n = 60, 61.9%). Univariate, multivariate, and Kaplan-Meier log-rank testing failed to demonstrate an association between performing surgery, extent of resection, radiotherapy, or chemotherapy with improved survival outcomes. The current study constitutes the largest retrospective analysis of p-HGSGs to date, finding that current treatment options of surgery, radiotherapy, and chemotherapy have unclear benefit. This disease process has a poor prognosis without a current modality of treatment that conclusively alters survival. The risks and side effects of these treatment modalities must be carefully considered in such a highly aggressive disease process, especially given potentially limited survival benefits.

Background: Achieving glycemic control in critical care patients is of paramount importance, and has been linked to reductions in mortality, intensive care unit (ICU) length of stay, and morbiditie...

Objectives The aim of this study was to investigate the impact of spontaneous coronary artery dissection (SCAD) on 30-day readmission rates following hospitalization with acute myocardial infarction (AMI) using a national database. Background AMI in the setting of SCAD represents an uncommon type of myocardial infarction with limited data on short-term outcomes. Methods All hospitalizations with primary or index diagnoses of AMI from 2010 to 2015 in the Nationwide Readmissions Database were queried. The primary outcome was overall 30-day readmission rates in both SCAD and non-SCAD cohorts. Propensity score matching (1:2) was conducted. Results A total of 2,654,087 patients with AMI were included in the final analysis, of whom 1,386 (0.052%) were diagnosed with SCAD. SCAD was associated with a higher readmission rate in the SCAD cohort (12.3% vs. 9.9%; p = 0.022). The main causes of readmissions in the SCAD cohort were cardiac causes (80.6%), and AMI was the most common cardiac cause (44.8%), followed by chest pain (20.1%) and arrhythmia (12.7%). Among the SCAD readmissions, 50.6% patients were readmitted in the first week post-discharge, with 54.5% of AMI readmissions occurring in the first 2 days post-discharge. Conclusions The incidence of 30-day readmission following AMI and SCAD is nontrivial and occurs early post-discharge. Most readmissions are due to cardiac causes, especially AMI. Targeted management approaches are needed to diminish the high rates of readmission and early recurrent AMI.

Introduction: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare tumor of the central nervous system, especially when involving the spinal column or spinal cord. Case Presentation: We present a case of a 5-year-old girl with progressive bilateral lower extremity pain found to have a discrete nodular lesion of the conus with mild heterogeneous enhancement. Surgical decompression and resection demonstrated a pathologic tumor consistent with AT/RT with loss of INI1 protein on immunohistochemistry. Discussion and Conclusion: AT/RT lesions of the conus medullaris are exceedingly rare and associated with extensive disease. We report a rare case of AT/RT with selective involvement of the conus medullaris, as well as describe the surgical, radiographic, and pathologic findings of this tumor.

The use of prasugrel and ticagrelor as part of dual antiplatelet therapy is increasing in patients after percutaneous coronary intervention (PCI). Accordingly, we aimed to evaluate their prescription patterns in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry. We analyzed patients enrolled in NCDR PINNACLE registry from January 2013 to March 2015 who underwent PCI with drug-eluting stent and were prescribed dual antiplatelet therapy. All patients received aspirin. The primary study outcome was a 3-level variable denoting the second antiplatelet agent prescribed: (1) clopidogrel, (2) prasugrel, or (3) ticagrelor. Baseline characteristics were compared among the 3 groups. Odds ratios and 95% credible intervals were calculated from a nested hierarchical Bayesian logistic regression models to identify independent predictors of prescription of antiplatelet medications, incorporating practice and provider as random effects. Our study cohort consisted of 26,710 patients during our study period January 2013 to March 2015. Seventy nine percent of patients were prescribed clopidogrel, 12% prasugrel, and 11% ticagrelor. Patients aged ≥75 years, women, history of tobacco use, Peripheral Arterial Disease (PAD), hypertension, diabetes, previous vascular complication, heart failure, and stroke/transient ischemic attack were more likely to be on clopidogrel than prasugrel or ticagrelor. The relative percentages of ticagrelor and prasugrel were higher in patients with history of myocardial infarction, compared with those without myocardial infarction. In summary, our study highlights the prescription patterns associated with prescription of antiplatelet agents after PCI. We found that both ticagrelor and prasugrel were mostly prescribed per the current practice guidelines, thus reflecting appropriate guideline adherence by practices in NCDR PINNACLE registry.

Purpose: To report a propensity score analysis comparing outcomes of the Supera interwoven nitinol stent to bare nitinol stents (BNS) in the femoropopliteal segment. Materials and Methods: A retrospective study was conducted utilizing data extracted from the Excellence in Peripheral Artery Disease (XLPAD) registry ( ClinicalTrials.gov identifier NCT01904851) on 871 patients (mean age 65.1 years; 713 men) who underwent femoropopliteal balloon angioplasty with either Supera stent implantation in 118 limbs or other contemporary BNS in 753 limbs between January 2006 and December 2016. All patients in both groups were matched for baseline demographic and clinical characteristics in a 1:1 propensity score matching using the nearest neighbor method to create the 118-patient matched BNS cohort. One-year outcomes included all-cause mortality, target vessel revascularization (TVR), and target limb revascularization (TLR). An additional core laboratory analysis was conducted to measure the deployed length of Supera stents. Results: In unmatched data, the Supera stent group had a numerically lower rate of TVR (7.6% vs 13.4%, p=0.08) and a significantly lower 1-year TLR rate (7.6% vs 16.2%, p=0.02) compared to the BNS group. Both groups had similar 1-year mortality (2.5% vs 2.7%, p=0.9). Kaplan-Meier analysis demonstrated that the Supera group had a significantly lower risk of TVR (p=0.02) and TLR (p=0.002) than the BNS group. After propensity matching, the 1-year TVR estimate was lower for Supera stents (7.6% vs 12.7%, p=0.08) and significantly lower for TLR (7.6% vs 13.6%, p=0.04) than the BNS group. There was no statistically significant association between Supera stent elongation (>10% of the labeled stent length) and 1-year risk of TLR (p=0.6). Conclusion: Supera stent usage in femoropopliteal intervention was associated with reduced risk of 1-year repeat target limb revascularization compared with BNS treatment in both unmatched and matched cohorts.

BACKGROUND: Factor XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism may be more effective and result in less bleeding than conventional anticoagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor. METHODS: In this parallel-group, phase 2 trial, we randomly assigned 1242 patients undergoing knee arthroplasty to receive one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or enoxaparin (40 mg once daily). The primary efficacy outcome was venous thromboembolism (which was a composite of asymptomatic deep-vein thrombosis, confirmed symptomatic venous thromboembolism, or death from any cause). The principal safety outcome was bleeding. RESULTS: Among the patients receiving milvexian twice daily, venous thromboembolism developed in 27 of 129 (21%) taking 25 mg, in 14 of 124 (11%) taking 50 mg, in 12 of 134 (9%) taking 100 mg, and in 10 of 131 (8%) taking 200 mg. Among those receiving milvexian once daily, venous thromboembolism developed in 7 of 28 (25%) taking 25 mg, in 30 of 127 (24%) taking 50 mg, and in 8 of 123 (7%) taking 200 mg, as compared with 54 of 252 patients (21%) taking enoxaparin. The dose–response relationship with twice-daily milvexian was significant (one-sided P

Background Discovery of the novel severe acute respiratory syndrome coronavirus 2 (n-SARS-CoV-2) in late 2019 has brought with it a renewed interest in methods of inflammatory mitigation, particularly due to reports of a cytokine release syndrome playing a pathogenic role [1]. One method of decreasing inflammation is through hemofiltration in combination with a dialysis membrane that has a large cutoff for protein permeability (high-cutoff/HCO), thereby capturing inflammatory cytokines and attenuating their harmful side effects. The authors report a patient with severe acute respiratory distress syndrome (ARDS) secondary to COVID-19 infection, requiring Veno-Venous Extracorporeal Life Support (VV-ECLS) who was treated with cytokine hemofiltration and showed clinical improvement. Case Summary Our patient is a 53 year-old female who presented with coronavirus infection and respiratory failure culminating in hypoxemia refractory to conventional mechanical ventilation. She was cannulated onto veno-venous extra-corporeal life support and treated with cytokine hemofiltration using a high-cutoff filter. Following treatment, inflammatory markers improved along with compliance and oxygenation. She was decannulated from ECLS shortly thereafter. IRB approval was waived due to the single case report nature. Consent was obtained for use of images and case data. Discussion Inflammatory modulation has been theorized to be beneficial in the management of organ failure secondary to coronavirus infection. A cytokine release syndrome (CRS) has been implicated in this disease’s pathogenesis. Cytokine hemofiltration is one modality to mitigate harmful inflammation. Our patient demonstrated remarkable improvement with treatment and to our knowledge represents the first report of cytokine hemofiltration as management of COVID-19 respiratory failure in conjunction with VV-ECLS. This therapy warrants further evaluation as a treatment option.

Study Design Systemic review and meta-analysis. Objective To review and establish the effect of tobacco smoking on risk of nonunion following spinal fusion. Methods A systematic search of Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception to December 31, 2020, was conducted. Cohort studies directly comparing smokers with nonsmokers that provided the number of nonunions and fused segments were included. Following data extraction, the risk of bias was assessed using the Quality in Prognosis Studies Tool, and the strength of evidence for nonunion was evaluated using the GRADE working group criteria. All data analysis was performed in Review Manager 5, and a random effects model was used. Results Twenty studies assessing 3009 participants, which included 1117 (37%) smokers, met inclusion criteria. Pooled analysis found that smoking was associated with increased risk of nonunion compared to not smoking ≥1 year following spine surgery (RR 1.91, 95% CI 1.56 to 2.35). Smoking was significantly associated with increased nonunion in those receiving either allograft (RR 1.39, 95% CI 1.12 to 1.73) or autograft (RR 2.04, 95% CI 1.54 to 2.72). Both multilevel and single level fusions carried increased risk of nonunion in smokers (RR 2.30, 95% CI 1.64 to 3.23; RR 1.79, 95% CI 1.12 to 2.86, respectively). Conclusion Smoking status carried a global risk of nonunion for spinal fusion procedures regardless of follow-up time, location, number of segments fused, or grafting material. Further comparative studies with robust methodology are necessary to establish treatment guidelines tailored to smokers.

Background Patients undergoing spine surgery may experience substantial postoperative pain. Objective The aim of this Systematic Review is to examine the clinical efficacy of a newly introduced regional Anesthetic block titled ‘Erector Spinae Plane Block’ (ESPB) for adults undergoing posterior spine surgeries. Methods A formal systematic database search was conducted in PubMed, Ovid Medline, Embase, Cochrane library, and Google Scholar for randomized controlled trials (RCTs) comparing ESPB with control or placebo. Results Our Systematic Review demonstrated a reduction of postoperative pain and opioid consumption in patients who had ESPB compared to control groups for lumbar spine surgery. However, the effect obtained revealed only a short-term benefit. Conclusion Current evidence is insufficient to support the widespread use of ESPB for spine surgery. More studies are warranted to confirm or refute its role in clinical practice.

Burn injury results in adverse myocardial remodeling and heart failure through circulatingcatecholamines and androgen and cytokine cascades. The DNA binding protein PARP1(poly ADP ribose polymerase 1) catalyzes a post translational modification to generatePARylation proteins,which changes the normal function of the modified proteins. Bothof PARP-1 and SIRT1 (sirtuin1) are NAD + dependent. In this study, we propose that PJ34 (PARP-1 inhibitor) would protect the function of burn-remodeled cardiomyocytes.Commercial rats were obtained and were subject to 60% total surface body area (TSBA)scald burns by immersing the abdomen and back in boiling water. They were immediatelytreated with the PJ34 post injury. Separately, the cardiomyocytes (Ac16) were exposedto burn-serum replaced culture medium with or without treatment of lentivirus-PARP1 KOand/or SIRT-PGC-1α agonists in vitro . The in vivo experiments showed that burn-ratsexhibited cardiac hypertrophy, fibrosis and an increase in the inflammatory markers IL-1β, IFN-γ and TNFα. Burned rats had an increased oxidative stress, concomitant withelevated PARP-1 activity and reduced Sirtuin-1 (SIRT1) expression. PJ34 treatment ledto increased SIRT1 and Peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) levels and attenuated oxidative stress, inflammation, and fibrosis. In vitro tests demonstrated that the treatments of PJ34 and SIRT1-PGC-1α axis agonists incardiomyocytes exposed to burn-serum replaced culture medium led to a significantreduction in mit ROS and mitochondrial dysfunction. In Conclusion, PARP1 depletion byPJ34 in vivo and Letivirus-PARP1 KO Ac16 in vitro attenuated cardiomyopathic featuresin burn-rats through the activation of SIRT1 and its downstream antioxidant defensemechanisms. The results of this study suggest a pivotal role of PARP-1 inhibition intreating burn-induced cardiomyopathy. Keywords: Burn injury; PJ34; PARP1; Cardiomyocyte; Lentivirus.

Concussions are frequent in sports and can contribute to significant and long-lasting neurological disability. Adolescents are particularly susceptible to concussions, with accurate determination of the injury challenging. Our previous study demonstrated that concussion diagnoses could be aided by metabolomics profiling and machine learning, with particular weighting on changes in plasma glycerophospholipids (PCs). Here, our aim was to report directional change of PCs after concussion and develop a diagnostic concussion panel utilizing a minimum number of plasma PCs. To this end, we enrolled 12 concussed male athletes at our academic Sport Medicine Concussion Clinic, as well as 17 sex-, age-, and activity-matched healthy controls. Blood was drawn and 71 plasma PCs were measured for statistically significant changes within 72 h of injury, and individual PCs were further analyzed with receiver operating characteristic (ROC) curves. Our data demonstrated that 26 of 71 PCs measured were significantly decreased after sports-related concussion (p < 0.01). None of the PCs increased in plasma after concussion. ROC curve analyses identified the top four PCs with areas under the curve (AUCs) ‡0.86 for concussion diagnosis: PCaeC36:0 (0.92; p < 0.001); PCaaC42:6 (0.90; p < 0.001); PCaeC36:2 (0.86; p = 0.001), and PCaaC32:0 (0.86; p = 0.001). Cut-off values in lM were £0.31, 0.22, 5.07, and 4.63, respectively. Importantly, combining these four PCs produced an AUC of 0.96 for concussion diagnoses (p < 0.001; 95% confidence interval, 0.89, 1.00). Our data suggest that as few as four circulating PCs may provide excellent diagnostic potential for adolescent concussion. External validation is required in larger cohorts.

Late-onset Alzheimer’s disease (LOAD) is the most common human neurodegenerative disease. Legacy amyloidogenic mouse models have been useful for understanding disease progression, however in the face of failing human trials more focus on disease translation with new mouse strains that better model human Alzheimer’s disease (AD) is required. MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) groups are identifying and integrating disease-relevant, humanized gene sequences from public databases to create more translatable mouse models for therapy development. Mice expressing strong genetic risk factors for LOAD, APOEe4 and Trem2*R47H, were extensively aged and assayed using a multi-disciplined phenotyping approach associated with and relative to human AD pathology. Behavioral, transcriptomic, metabolic, and neuropathological assays identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes in the absence of mouse amyloid plaque formation. These data provide an important, baseline understanding of the individual effects and interaction between two strong genetic risk factors for LOAD. These two alleles together form a sensitized, background strain (B6.APOE4.Trem2*R47H, which we have termed ‘LOAD1’) necessary to examine how important underlying risk factors interact with any subsequent genetic or environmental cues to drive pathology.

Paroxysmal supraventricular tachycardia (PSVT) is a common tachyarrhythmia, and an electrocardiogram is the best tool for making a diagnosis. If Valsalva maneuvers and carotid sinus massage do not give positive results, then the next choice is either adenosine or calcium channel blockers. At this time, adenosine is the drug of choice of treatment. Verapamil and diltiazem are the most commonly used calcium channel blockers (CCBs). This review aimed to compare the efficacy of both drugs in the treatment of PSVT. We utilized the databases PubMed Central and Medline by using keywords: "calcium channel blockers OR adenosine AND supraventricular tachycardia." In the end, we finalized 32 studies, including observational studies, literature reviews, systematic reviews/metanalysis, and randomized control trials. We included articles only in the English language and related to humans. Two authors completed the quality assessment and evaluation of bias according to specific guidelines. Only high-quality studies were included in this systematic review based on the cut-off score of seven or above. Calcium channel blockers have a longer half-life than adenosine and were previously used as the drug of choice in the treatment of PSVT. Calcium channel blockers are safe if given slowly; however, adenosine is safer and useful when an electrocardiogram is uncertain. We compared both drugs in certain aspects and found equal efficacy. Though safer, adenosine was found to have a higher cost and a higher probability of re-initiation arrhythmia compared to calcium channel blockers.

We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads to rotational and linear accelerations far below what has been reported for sports concussion athletes, we found that 5 daily mTBIs triggered two temporally distinct types of pathological changes. First, during the first days and weeks after injury, the rmTBI produced diffuse axonal injury, a transient inflammatory response and changes in diffusion tensor imaging (DTI) that resolved with time. Second, the rmTBI led to pathological changes that were evident months after the injury including: changes in magnetic resonance spectroscopy (MRS), altered levels of synaptic proteins, behavioural deficits in attention and spatial memory, accumulations of pathologically phosphorylated tau, altered blood metabolomic profiles and white matter ultrastructural abnormalities. These results indicate that exceedingly mild rmTBI, in mice, triggers processes with pathological consequences observable months after the initial injury. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01161-2.

Heart failure (HF) is associated with microcirculatory changes secondary to neuro-humoral imbalance, vascular stiffness and increased sympathetic tone. Near Infra-Red Spectroscopy (NIRS) derived Thenar muscle tissue oxygenation levels (StO(2)) can provide an estimate of the functional status of microcirculation. There is a paucity of literature regarding evaluation of microcirculation in pediatric subjects with HF. We hypothesized that microcirculation and oxygen saturation dynamics as assessed by Thenar StO(2) levels using vascular occlusion test (VOT) would be altered in HF subjects and that these changes may correlate with the severity of heart failure. We prospectively enrolled 60 pediatric subjects (29 healthy control, 31 HF). Baseline StO(2) levels were measured using InSpectra™ StO(2) probe placed over the Thenar eminence of right hand, followed by a VOT for 3 min, during which the changes in StO(2) levels during the occlusion phase and post occlusion phase were recorded. Baseline Thenar StO(2) levels (72 ± 8 vs 76 ± 5, p = 0.02) and time to baseline StO(2) in seconds (150 ± 70 vs 200 ± 70, p = 0.007) were significantly lower in HF group compared to healthy control (HC). In addition, HF patients had a significantly lower trough StO(2) (37 ± 9 vs 42 ± 11%, p = 0.04) and peak StO(2) compared to HC (87 ± 8 vs 91 ± 5%, p = 0.01). However, there was no difference in the rate of desaturation, rate of resaturation or time to peak StO(2) levels in between the 2 groups. Significant correlation was present between baseline Thenar StO(2) levels and NYU Pediatric Heart Failure Index Score (NYU-PHFI) (p = 0.003). This study is the first to report an objective assessment of microcirculation and Thenar tissue oxygen dynamics in pediatric subjects with HF in comparison with HC. Our study suggests altered microcirculation and oxygenation patterns in these subjects as well as correlation with a validated pediatric heart failure clinical score. Large-scale prospective studies are needed to further study the utility of this novel technology in HF subjects.