Bacterial community profiles of select tributaries of Laguna Lake in the Philippines.

Laguna Lake is known for its ecological, economic, and cultural importance. Effects of urbanization and accumulation of emerging pollutants have been associated with its water quality; however, the microbial ecology of its tributaries remains to be explored. We report bacterial community profiles from shotgun metagenomes of its select tributary waters.

Antecubital Burn Resulting From Antenna Coupling: A Case Report.

CASE: We present the case of a 54-year-old man who underwent elective hip disarticulation complicated by third-degree burn of the left antecubital fossa requiring skin graft. After careful review, it was determined that "antenna coupling" as a result of electrosurgery was the likely cause. We present an experiment demonstrating this phenomenon. CONCLUSION: Antenna coupling is a real but rare cause of intraoperative burns not previously described in the orthopaedic literature. Care should be taken to avoid coiling or running bovie or other electrosurgical device cords with other metallic cords or corded devices.

Predicting major complications and discharge disposition after adult spinal deformity surgery.

BACKGROUND CONTEXT: Several spine-specific comorbidity indices are available to help risk-stratify patients before they undergo invasive spine procedures. Studies of patients with adult spinal deformity (ASD) typically use the Charlson Comorbidity Index (CCI), which is not specific to spine patients. PURPOSE: To compare the CCI with the Seattle Spine Score (SSS), the Adult Spinal Deformity-Comorbidity Score (ASD-CS), and the Modified 5-Item Frailty Index (mFI-5) and identify which tool more accurately predicted major perioperative complications and discharge disposition after ASD surgery. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: Patients with ASD who underwent spinal arthrodesis of at least four levels at a single institution. OUTCOME MEASURES: Self-reported measures include SSS, ASD-CS, and mFI-5. Functional measures include the CCI. METHODS: We retrospectively reviewed records of 164 patients with ASD who underwent spinal arthrodesis of ≥ four levels from January 2008 to February 2018 at our U.S. academic tertiary care center and who had available Oswestry Disability Index values. To assess the predictive ability of the comorbidity indices, we created five multivariable logistic regression models, with the presence of major complications and discharge disposition (home or inpatient rehabilitation) as the primary outcome variables. The base model used validated demographic and surgical factors that were predictors of complications and outcomes in those with ASD and within the broader spinal literature. The other four models used the base model along with one of the four indices. The predictive ability of each model was compared using goodness-of-fit testing, with higher pseudo-R2 values and lower Akaike information criteria (AIC) values indicating better model fit. RESULTS: Thirty-one patients (19%) experienced major perioperative complications, and 68 (42%) were discharged to inpatient rehabilitation facilities (vs home). The model using the SSS had the highest pseudo-R2 value and lowest AIC value for both major complications and discharge disposition. The mFI-5 had a similar predictive ability. The models using the CCI and ASD-CS were weaker predictors. CONCLUSIONS: Compared with the CCI and the ASD-CS, the SSS and the mFI-5 were strong predictors of major complications and discharge disposition after ASD surgery. These results suggest that the SSS and the mFI-5 are preferable to the CCI for clinical risk stratification and outcomes research in patients undergoing ASD surgery.

Risk factors for proximal junctional kyphosis in a multicenter study of Lenke type 5 and 6 adolescent idiopathic scoliosis patients.

PURPOSE: In Lenke type 5 and 6 curves, a major thoracolumbar or lumbar curve, the rates of PJK are reported as high as 50%. The purpose of this study was to confirm the rate of PJK, investigate possible risk factors, and evaluate surgical complications and the long-term effects of PJK on patient outcomes. METHODS: A retrospective review of multicenter data identified 192 with patients with 2 year and 94 with 5-year follow-up. Included patients had a Lenke type 5 or 6 curve and underwent a selective thoracolumbar or lumbar curve fusion. All radiographs preoperatively and postoperatively (1 year, 2 years, and 5 years) were evaluated. Demographic and radiographic data was analyzed as risk factors for PJK using a multi-variate regression. Outcomes scores and complications were compared between groups. RESULTS: 17 patients (8.9%) developed radiographic PJK; 1 at 1 year, 7 at 2 years, and another 9 at 5 years. All 17 patients had an upper instrumented vertebra (UIV) within 3 levels or less caudal of the thoracic kyphosis apex (the most horizontal vertebra on the sagittal); no patient with a UIV 4 or more levels from the thoracic apex (n = 96) developed PJK (X2 = 13.03, p < 0.001). In addition, PJA > 8° was found to significantly increase the risk of PJK (p = 0.039). SRS scores were significantly worse for PJK patients at 5 years in the self-image and function (p < 0.01). CONCLUSION: In Lenke 5/6 curves, no patient with a UIV 4 or more levels caudal to the thoracic kyphosis apex had PJK up to 5 years postoperatively. PJA greater than 8° was identified as a risk factor for PJK. Patients with radiographic PJK had worse SRS scores 5 years postoperatively.

A comparison of pin site complications between large and small pin diameters in robotic-assisted total knee arthroplasty.

PURPOSE: Robotic-assisted total knee arthroplasty typically necessitates use of tracking pins, which can vary in diameter. Complications such as infections and fractures at the pin-site have been observed, but clarification of the effect of pin diameter on complication is needed. The aim of this study is to compare the pin-related complication rates following robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm diameter pins. METHODS: In this retrospective cohort study, 90-day pin-site complication rates after robotic-assisted total knee arthroplasty were compared between 4.5 mm diameter and 3.2 mm diameter groups. In total, 367 patients were included: 177 with large pin diameter and 190 with small pin diameter. All four pin sites were evaluated using postoperative radiographs. Cases without orthogonal views or visualization of all four pin tracts were noted. Multivariate logistic regression was used to control for age, which differed between the two cohorts. RESULTS: The rate of pin-site complications was 5.6% in the large pin diameter cohort and 2.6% in the small pin diameter cohort, with no statistically significant difference between the groups. The adjusted odds ratio for complications in small compared to large diameter group was 0.48, with a p-value of 0.18. The most common pin-site complication was infection/persistent drainage, found in 1.9% of patients, followed by intraoperative fracture of the second cortex in 1.4%. Intraoperative fracture could not be ruled out in 96 cases due to inadequate radiographic visualization of all pin sites. There was one postoperative pin-site fracture in the large diameter cohort, which required operative fixation. CONCLUSION: This study demonstrates no statistically significant difference in pin-site complication rates after robotic-assisted total knee arthroplasty between 4.5 mm and 3.2 mm pin diameter cohorts, although there was a trend towards increased intraoperative and postoperative pin-site fractures in the 4.5 mm group.

Patellar Tendon Injury: A Bibliometric Analysis of the Most-Cited Articles Demonstrates Relatively High Overall Level of Evidence.

Purpose: To identify and analyze the 50 most-cited articles in patellar tendon injury research. Methods: The ISI Web of Science and SCOPUS databases were used to conduct a search for articles pertaining to patellar tendon injury. For the top 50 most-cited articles, bibliometric data (title, first and senior author, citation count, journal, publication year, citation density, country of origin, Level of Evidence [LOE]) and topic of article were recorded. Results: The mean number of citations was 172.0 ± 88.2 (range 101-546). There was a statistically significant correlation between publication year and citation density (r = 0.61, P < .01). The earliest article was the third most-cited article (362 citations), published by Blazina et al. in 1973, which discussed the epidemiology of patellar tendinopathy. The first and second most-cited articles (546 and 466 citations, respectively) covered surgical outcomes of patellar tendinopathy and prevalence of patellar tendinopathy among elite athletes. A total of 14 articles (28%) discussed nonoperative management, whereas only 5 articles discussed surgical management (10%). The most frequent LOE category was a LOE of IV (n = 18, 36%), but 19 studies (38%) were LOE I or LOE II. Conclusions: Among the top 50 most-cited studies regarding patellar tendon injury, a relatively high number were of a high LOE (19 Level I or II, 38%), affirming that these articles in patellar tendon injury research are not only influential, but also of high-quality evidence. Clinical Relevance: This bibliometric analysis provides an efficient tool for educators, researchers, and evidence-based practitioners to identify and evaluate the most influential articles in patellar tendon injury research.

Preoperative duration of pain is associated with chronic opioid use after adult spinal deformity surgery.

PURPOSE: Few studies have explored the association between preoperative patient-reported measures and chronic opioid use following adult spinal deformity (ASD) surgery. We sought to explore the association between preoperative duration of pain, as well as other patient-reported factors, and chronic opioid use after ASD surgery. METHODS: We retrospectively reviewed our U.S. academic tertiary care hospital's database of ASD patients. We included patients 18 years or older who underwent arthrodesis of four or more spinal levels from January 2008 to February 2018, with 2-year follow-up. The primary outcome variable was chronic opioid use, defined as opioid use at both 1 and 2 years postoperatively. We analyzed patient characteristics; duration of preoperative pain (<4 years or ≥4 years); radiculopathy; preoperative Scoliosis Research Society-22r (SRS-22r) score; Oswestry Disability Index (ODI) value; and surgical characteristics. RESULTS: Of 119 patients who met the inclusion criteria, 93 (78%) were women, and mean ± standard deviation age was 59 ± 13. Sixty patients (50%) reported preoperative opioid use, and 35 (29%) reported chronic opioid use. Preoperative opioid use was associated with higher odds of chronic use (adjusted odds ratio, 5.9; 95% confidence interval 1.6-21), as was preoperative pain duration of ≥4 years (adjusted odds ratio, 3.3; 95% confidence interval 1.1-9.8). Patient characteristics, surgical variables, ODI value, and SRS-22r score were not significantly associated with chronic postoperative opioid use. CONCLUSION: Preoperative opioid use and duration of pain of ≥4 years were associated with higher odds of chronic opioid use after ASD surgery. LEVEL OF EVIDENCE: III.

Topical pharmacologic interventions versus placebo for epidemic keratoconjunctivitis.

BACKGROUND: Viruses cause about 80% of all cases of acute conjunctivitis. Human adenoviruses are believed to account for 65% to 90% of cases of viral conjunctivitis, or 20% to 75% of all causes of infectious keratoconjunctivitis worldwide. Epidemic keratoconjunctivitis (EKC) is a highly contagious subset of adenoviral conjunctivitis that has been associated with large outbreaks at military installations and at medical facilities. It is accompanied by severe conjunctival inflammation, watery discharge, and light sensitivity, and can lead to chronic complications such as corneal and conjunctival scarring with discomfort and poor quality of vision. Due to a lack of consensus on the efficacy of any pharmacotherapy to alter the clinical course of EKC, no standard of care exists, therefore many clinicians offer only supportive care. OBJECTIVES: To assess the efficacy and safety of topical pharmacological therapies versus placebo, an active control, or no treatment for adults with EKC. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, which contains the Cochrane Eyes and Vision Trials Register; 2021, Issue 4); Ovid MEDLINE; Ovid Embase; Latin American and Caribbean Health Sciences database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), with no restrictions on language or year of publication. The date of the last search was 27 April 2021. SELECTION CRITERIA: We included randomized controlled trials in which antiseptic agents, virustatic agents, or topical immune-modulating therapy was compared with placebo, an active control, or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We identified 10 studies conducted in Asia, Europe, the Middle East, and North Africa with a total of 892 participants who were treated for 7 days to 6 months and followed for 7 days up to 1.5 years. Study characteristics and risk of bias In most studies participants were predominantly men (range: 44% to 90%), with an age range from 9 to 82 years. Three studies reported information on trial registration, but we found no published study protocol. The majority of trials had small sample sizes, ranging from 18 to 90 participants enrolled per study; the only exception was a trial that enrolled 350 participants. We judged most studies to be at high or unclear risk of bias across risk of bias domains. Findings We included 10 studies of 892 EKC participants and estimated combined intervention effects in analyses stratified by steroid-containing control treatment or artificial tears. Six trials contributed to the comparisons of topical interventions (povidone-iodine [PVP-I], trifluridine, ganciclovir, dexamethasone plus neomycin) with artificial tears (or saline). Very low certainty evidence from two trials comparing trifluridine or ganciclovir with artificial tears showed inconsistent effects on shortening the mean duration of cardinal symptoms or signs of EKC. Low certainty evidence based on two studies (409 participants) indicated that participants treated with PVP-I alone more often experienced resolution of symptoms (risk ratio (RR) 1.15, 95% confidence interval (CI) 1.07 to 1.24) and signs (RR 3.19, 95% CI 2.29 to 4.45) during the first week of treatment compared with those treated with artificial tears. Very low certainty evidence from two studies (77 participants) suggested that PVP-I or ganciclovir prevented the development of subepithelial infiltrates (SEI) when compared with artificial tears within 30 days of treatment (RR 0.24, 95% CI 0.10 to 0.56). Four studies compared topical interventions (tacrolimus, cyclosporin A [CsA], trifluridine, PVP-I + dexamethasone) with topical steroids, and one trial compared fluorometholone (FML) plus polyvinyl alcohol iodine (PVA-I) with FML plus levofloxacin. Evidence from one trial showed that more eyes receiving PVP-I 1.0% plus dexamethasone 0.1% had symptoms resolved by day seven compared with those receiving dexamethasone alone (RR 9.00, 95% CI 1.23 to 66.05; 52 eyes). In two trials, fewer eyes treated with PVP-I or PVA-I plus steroid developed SEI within 15 days of treatment compared with steroid alone or steroid plus levofloxacin (RR 0.08, 95% CI 0.01 to 0.55; 69 eyes). One study found that CsA was no more effective than steroid for resolving SEI within four weeks of treatment (RR 0.84, 95% CI 0.67 to 1.06; N = 88). The evidence from trials comparing topical interventions with steroids was overall of very low level certainty. Adverse effects Antiviral or antimicrobial agents plus steroid did not differ from artificial tears in terms of ocular discomfort upon instillation (RR 9.23, 95% CI 0.61 to 140.67; N = 19). CsA and tacrolimus eye drops were associated with more cases of severe ocular discomfort, and sometimes intolerance, when compared with steroids (RR 4.64, 95% CI 1.15 to 18.71; 2 studies; N = 141). Compared with steroids, tacrolimus did not increase the risk of elevated intraocular pressure (RR 0.07, 95% CI 0 to 1.13; 1 study; N = 80), while trifluridine conferred no additional risk compared to tear substitute (RR 5.50, 95% CI 0.31 to 96.49; 1 study; N = 97). Overall, bacterial superinfection was rare (one in 23 CsA users) and not associated with use of the intervention steroid (RR 3.63, 95% CI 0.15 to 84.98; N = 51). The evidence for all estimates was of low or very low certainty. AUTHORS' CONCLUSIONS: The evidence for the seven specified outcomes was of low or very low certainty due to imprecision and high risk of bias. The evidence that antiviral agents shorten the duration of symptoms or signs when compared with artificial tears was inconclusive. Low certainty evidence suggests that PVP-I alone resolves signs and symptoms by seven days relative to artificial tears. PVP-I or PVA-I, alone or with steroid, is associated with lower risks of SEI development than artificial tears or steroid (very low certainty evidence). The currently available evidence is insufficient to determine whether any of the evaluated interventions confers an advantage over steroids or artificial tears with respect to virus eradication or its spread to initially uninvolved fellow eyes. Future updates of this review should provide evidence of high-level certainty from trials with larger sample sizes, enrollment of participants with similar durations of signs and symptoms, and validated methods to assess short- and long-term outcomes.

Topical Pharmacologic Interventions Versus Active Control, Placebo, or No Treatment for Epidemic Keratoconjunctivitis: Findings From a Cochrane Systematic Review.

PURPOSE: To summarize key findings from a Cochrane systematic review of the effectiveness and safety of topical pharmacologic interventions compared with active control or placebo for epidemic keratoconjunctivitis (EKC). DESIGN: Systematic review. METHODS: We included randomized controlled trials that compared antiseptic agents, virustatic agents, or immune-modulating topical therapies with placebo or an active control. We adhered to Cochrane methods for trial selection, data extraction, risk of bias evaluation, and data synthesis. RESULTS: Ten randomized controlled trials with 892 participants with acute or chronic EKC were included. Eight trials compared interventions with artificial tears or saline (n = 4) or with steroids (n = 4); two 3-arm trials contributed data to both comparisons. Estimates suggested that compared with tears, after povidone-iodine (PVP-I) alone (2 studies, 409 participants) more participants with acute EKC had resolution of symptoms (risk ratio [RR] 1.15 [95% confidence interval {CI} 1.07-1.24]) and signs (RR 3.19 [95% CI 2.29-4.45]) within 10 days. In 2 trials comparing treatments with steroid alone or steroid with levofloxacin, fewer eyes treated with PVP-I or polyvinyl alcohol iodine (PVA-I) plus steroid developed subepithelial infiltrates within 21 days (RR 0.08 [95% CI 0.01-0.55]; 69 eyes). No treatment was shown to improve resolution of infiltrates. CONCLUSIONS: Low- to very low-level certainty of evidence suggested that PVP-I or PVA-I with steroid may confer some benefit in acute EKC, but imprecision from small sample sizes, the potential risk of bias from inadequate reporting or trial design, and variability in participant selection, outcome measurement, and reporting limit the amount and quality of evidence.

Deep learning detection of subtle fractures using staged algorithms to mimic radiologist search pattern.

OBJECTIVE: To develop and evaluate a two-stage deep convolutional neural network system that mimics a radiologist's search pattern for detecting two small fractures: triquetral avulsion fractures and Segond fractures. MATERIALS AND METHODS: We obtained 231 lateral wrist radiographs and 173 anteroposterior knee radiographs from the Stanford MURA and LERA datasets and the public domain to train and validate a two-stage deep convolutional neural network system: (1) object detectors that crop the dorsal triquetrum or lateral tibial condyle, trained on control images, followed by (2) classifiers for triquetral and Segond fractures, trained on a 1:1 case:control split. A second set of classifiers was trained on uncropped images for comparison. External test sets of 50 lateral wrist radiographs and 24 anteroposterior knee radiographs were used to evaluate generalizability. Gradient-class activation mapping was used to inspect image regions of greater importance in deciding the final classification. RESULTS: The object detectors accurately cropped the regions of interest in all validation and test images. The two-stage system achieved cross-validated area under the receiver operating characteristic curve values of 0.959 and 0.989 on triquetral and Segond fractures, compared with 0.860 (p = 0.0086) and 0.909 (p = 0.0074), respectively, for a one-stage classifier. Two-stage cross-validation accuracies were 90.8% and 92.5% for triquetral and Segond fractures, respectively. CONCLUSION: A two-stage pipeline increases accuracy in the detection of subtle fractures on radiographs compared with a one-stage classifier and generalized well to external test data. Focusing attention on specific image regions appears to improve detection of subtle findings that may otherwise be missed.

Artificial intelligence in orthopedic implant model classification: a systematic review.

Although artificial intelligence models have demonstrated high accuracy in identifying specific orthopedic implant models from imaging, which is an important and time-consuming task, the scope of prior works and performance of prior models have not been evaluated. We performed a systematic review to summarize the scope, methodology, and performance of artificial intelligence algorithms in classifying orthopedic implant models. We performed a literature search in PubMed, EMBASE, and the Cochrane Library for studies published up to March 10, 2021, using search terms related to "artificial intelligence", "orthopedic", "implant", and "arthroplasty". Studies were assessed using a modified version of the methodologic index for non-randomized studies. Reported outcomes included area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. The search identified 2689 records, of which 11 were included in the final review. The number of implant models evaluated ranged from 2 to 27. Five studies reported overall AUC across all included models which ranged from 0.94 to 1.0. Overall accuracy values ranged from 0.804 to 1.0. One study compared AI model performance with that of three surgeons, reporting similar performance. There was a large degree of variation in methodology and reporting quality. Artificial intelligence algorithms have demonstrated strong performance in classifying orthopedic implant models from radiographs. Further research is needed to compare artificial intelligence alone and as an adjunct with human experts in implant identification. Future studies should aim to adhere to rigorous artificial intelligence development methods and thorough, transparent reporting of methods and results.

Bacteriological and histopathological findings in cetaceans that stranded in the Philippines from 2017 to 2018.

The relatively high frequency of marine mammal stranding events in the Philippines provide many research opportunities. A select set of stranders (n = 21) from 2017 to 2018 were sampled for bacteriology and histopathology. Pertinent tissues and bacteria were collected from individuals representing eight cetacean species (i.e. Feresa attenuata, Kogia breviceps, Globicephala macrorhynchus, Grampus griseus, Lagenodelphis hosei, Peponocephala electra, Stenella attenuata and Stenella longirostris) and were subjected to histopathological examination and antibiotic resistance screening, respectively. The antibiotic resistance profiles of 24 bacteria (belonging to genera Escherichia, Enterobacter, Klebsiella, Proteus, and Shigella) that were isolated from four cetaceans were determined using 18 antibiotics. All 24 isolates were resistant to at least one antibiotic class, and 79.17% were classified as multiple antibiotic resistant (MAR). The MAR index values of isolates ranged from 0.06 to 0.39 with all the isolates resistant to erythromycin (100%; n = 24) and susceptible to imipenem, doripenem, ciprofloxacin, chloramphenicol, and gentamicin (100%; n = 24). The resistance profiles of these bacteria show the extent of antimicrobial resistance in the marine environment, and may inform medical management decisions during rehabilitation of stranded cetaceans. Due to inadequate gross descriptions and limited data gathered by the responders during the stranding events, the significance of histopathological lesions in association with disease diagnosis in each cetacean stranding or mortality remained inconclusive; however, these histopathological findings may be indicative or contributory to the resulting debility and stress during their strandings. The findings of the study demonstrate the challenges faced by cetacean species in the wild, such as but not limited to, biological pollution through land-sea movement of effluents, fisheries interactions, and anthropogenic activities.

Neurology trial registrations on ClinicalTrials.gov between 2007 and 2018: A cross-sectional analysis of characteristics, early discontinuation, and results reporting.

BACKGROUND: Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting. METHODS: We compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion. RESULTS: Most neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p < 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p < 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p < 0.0001). CONCLUSIONS: Funding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

Transepithelial versus epithelium-off corneal crosslinking for progressive keratoconus.

BACKGROUND: Keratoconus is the most common corneal dystrophy. It can cause loss of uncorrected and best-corrected visual acuity through ectasia (thinning) of the central or paracentral cornea, irregular corneal scarring, or corneal perforation. Disease onset usually occurs in the second to fourth decade of life, periods of peak educational attainment or career development. The condition is lifelong and sight-threatening. Corneal collagen crosslinking (CXL) using ultraviolet A (UVA) light applied to the cornea is the only treatment that has been shown to slow progression of disease. The original, more widely known technique involves application of UVA light to de-epithelialized cornea, to which a photosensitizer (riboflavin) is added topically throughout the irradiation process. Transepithelial CXL is a recently advocated alternative to the standard CXL procedure, in that the epithelium is kept intact during CXL. Retention of the epithelium offers the putative advantages of faster healing, less patient discomfort, faster visual rehabilitation, and less risk of corneal haze. OBJECTIVES: To assess the short- and long-term effectiveness and safety of transepithelial CXL compared with epithelium-off CXL for progressive keratoconus. SEARCH METHODS: To identify potentially eligible studies, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature database (LILACS); ClinicalTrials.gov; and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not impose any date or language restrictions. We last searched the electronic databases on 15 January 2020. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which transepithelial CXL had been compared with epithelium-off CXL in participants with progressive keratoconus. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. MAIN RESULTS: We included 13 studies with 723 eyes of 578 participants enrolled; 13 to 119 participants were enrolled per study. Seven studies were conducted in Europe, three in the Middle East, and one each in India, Russia, and Turkey. Seven studies were parallel-group RCTs, one study was an RCT with a paired-eyes design, and five studies were RCTs in which both eyes of some or all participants were assigned to the same intervention. Eleven studies compared transepithelial CXL with epithelium-off CXL in participants with progressive keratoconus. There was no evidence of an important difference between intervention groups in maximum keratometry (denoted 'maximum K' or 'Kmax'; also known as steepest keratometry measurement) at 12 months or later (mean difference (MD) 0.99 diopters (D), 95% CI -0.11 to 2.09; 5 studies; 177 eyes; I2 = 41%; very low certainty evidence). Few studies described other outcomes of interest. The evidence is very uncertain that epithelium-off CXL may have a small (data from two studies were not pooled due to considerable heterogeneity (I2 = 92%)) or no effect on stabilization of progressive keratoconus compared with transepithelial CXL; comparison of the estimated proportions of eyes with decreases or increases of 2 or more diopters in maximum K at 12 months from one study with 61 eyes was RR 0.32 (95% CI 0.09 to 1.12) and RR (non-event) 0.86 (95% CI 0.74 to 1.00), respectively (very low certainty). We did not estimate an overall effect on corrected-distance visual acuity (CDVA) because substantial heterogeneity was detected (I2 = 70%). No study evaluated CDVA gain or loss of 10 or more letters on a logarithm of the minimum angle of resolution (logMAR) chart. Transepithelial CXL may result in little to no difference in CDVA at 12 months or beyond. Four studies reported that either no adverse events or no serious adverse events had been observed. Another study noted no change in endothelial cell count after either procedure. Moderate certainty evidence from 4 studies (221 eyes) found that epithelium-off CXL resulted in a slight increase in corneal haze or scarring when compared to transepithelial CXL (RR (non-event) 1.07, 95% CI 1.01 to 1.14). Three studies, one of which had three arms, compared outcomes among participants assigned to transepithelial CXL using iontophoresis versus those assigned to epithelium-off CXL. No conclusive evidence was found for either keratometry or visual acuity outcomes at 12 months or later after surgery. Low certainty evidence suggests that transepithelial CXL using iontophoresis results in no difference in logMAR CDVA (MD 0.00 letter, 95% CI -0.04 to 0.04; 2 studies; 51 eyes). Only one study examined gain or loss of 10 or more logMAR letters. In terms of adverse events, one case of subepithelial infiltrate was reported after transepithelial CXL with iontophoresis, whereas two cases of faint corneal scars and four cases of permanent haze were observed after epithelium-off CXL. Vogt's striae were found in one eye after each intervention. The certainty of the evidence was low or very low for the outcomes in this comparison due to imprecision of estimates for all outcomes and risk of bias in the studies from which data have been reported. AUTHORS' CONCLUSIONS: Because of lack of precision, frequent indeterminate risk of bias due to inadequate reporting, and inconsistency in outcomes measured and reported among studies in this systematic review, it remains unknown whether transepithelial CXL, or any other approach, may confer an advantage over epithelium-off CXL for patients with progressive keratoconus with respect to further progression of keratoconus, visual acuity outcomes, and patient-reported outcomes (PROs). Arrest of the progression of keratoconus should be the primary outcome of interest in future trials of CXL, particularly when comparing the effectiveness of different approaches to CXL. Furthermore, methods of assessing and defining progressive keratoconus should be standardized. Trials with longer follow-up are required in order to assure that outcomes are measured after corneal wound-healing and stabilization of keratoconus. In addition, perioperative, intraoperative, and postoperative care should be standardized to permit meaningful comparisons of CXL methods. Methods to increase penetration of riboflavin through intact epithelium as well as delivery of increased dose of UVA may be needed to improve outcomes. PROs should be measured and reported. The visual significance of adverse outcomes, such as corneal haze, should be assessed and correlated with other outcomes, including PROs.

How is staging of ALIF following posterior spinal arthrodesis to the pelvis related to functional improvement in patients with adult spinal deformity?

STUDY DESIGN: Retrospective cohort. OBJECTIVES: To compare postoperative functional improvement in patients who underwent staged versus non-staged anterior-posterior spinal arthrodesis for adult spinal deformity (ASD). In patients with ASD, spinal arthrodesis can be performed in 2 stages to avoid the physiologic insult of a lengthy surgery. The association between staged surgery and postoperative functional improvement has not been well studied. METHODS: We included 87 patients (59 women) with ASD who underwent anterior-posterior spinal arthrodesis of > 5 levels with fixation to the pelvis from 2010-2014. Primary outcomes were the frequency of achieving at least a minimal clinically important difference (MCID) in the Scoliosis Research Society-22r (SRS-22r) Activity domain and the timeframe in which it was achieved. The secondary outcome was patient satisfaction (SRS-22r Patient Satisfaction domain). A Cox proportional hazard model was used to compare functional improvement over time between staged and non-staged groups. Our study was powered to detect a relative hazard ratio of 0.53, ß = 0.20. α = 0.05. RESULTS: The frequency of achieving an MCID in SRS-22r Activity score did not differ significantly between the staged group (33/41 patients) and the non-staged group (34/46 patients) (hazard ratio 0.74; 95% confidence interval 0.41-1.36). Median times to achieving an MCID in SRS-22r Activity score were 191 days (interquartile range: 86-674) in the staged group and 181 days (interquartile range: 72-474) in the non-staged group (p = .75). The staged and non-staged groups had similar SRS-22r Patient Satisfaction scores at 3-9 months postoperatively and at final follow-up (both, p > .05). CONCLUSION: Patients with ASD who underwent staged anterior-posterior spinal arthrodesis within 3 months after index surgery were similarly likely to experience functional improvement in the same timeframe as patients who underwent non-staged surgery. Patient satisfaction did not differ significantly between staged and non-staged groups. LEVEL OF EVIDENCE: III.

The impact of chronic steroid use on early postoperative complications in shoulder surgery.

OBJECTIVES: Chronic steroid use has been associated with poor healing and worse long-term outcomes in patients undergoing orthopedic surgery, but the specific risk profile and short-term complications related to chronic steroids in patients undergoing outpatient shoulder surgery are inadequately defined. The purpose of this study is to characterize the effects of chronic steroids on 30-day post-operative complications following arthroscopic and open shoulder surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program was used to identify patients who underwent arthroscopic and open rotator cuff repair, shoulder stabilization, and associated procedures from 2011 to 2018. Patients on chronic steroids were compared with patients not on chronic steroids. Demographic data and 30-day postoperative complications were analyzed. Multivariable logistic regression was used to isolate the effects of chronic steroid use on postoperative complications. RESULTS: We identified 99,970 patients who underwent shoulder surgery during this period, of which 1.7% (1,662 patients) were on chronic steroids. Patients on chronic steroids were older (58.3 ± 0.30vs52.1 ± 0.05 years, p < 0.01), had higher average BMI (30.6 vs 30.1, p = 0.02), and were more likely to be female (54.9%vs38.0%, p < 0.01) and white (76.2%vs73.1%, p < 0.01). Patients on steroids had a higher American Society of Anesthesiologists class, and higher rates of diabetes, CHF, COPD, hypertension, bleeding disorders, and functionally dependency (all P < 0.01). Patients on chronic steroids were less likely to smoke (P < 0.01). Multivariable logistic regression revealed that chronic steroid use was an independent risk factor for major (OR 2.20[1.51-3.21], p < 0.001), minor (OR 2.32[1.13-3.2], p < 0.001), and infectious complications (OR 1.90[1.13-3.2], p = 0.01). CONCLUSIONS: Preoperative chronic steroid use is independently associated with increased odds of major, minor, and infectious complications after open and arthroscopic rotator cuff repair, shoulder stabilization, and associated procedures. Patients on chronic steroids should be counseled about their increased risk for these complications, and both preoperative risk stratification and optimization should be employed to minimize perioperative risk.

Opioid use after adult spinal deformity surgery: patterns of cessation and associations with preoperative use.

OBJECTIVE: The objectives of the study were to determine, among patients with adult spinal deformity (ASD), the following: 1) how preoperative opioid use, dose, and duration of use are associated with long-term opioid use and dose; 2) how preoperative opioid use is associated with rates of postoperative use from 6 weeks to 2 years; and 3) how postoperative opioid use at 6 months and 1 year is associated with use at 2 years. METHODS: Using a single-center, longitudinally maintained registry, the authors identified 87 patients who underwent ASD surgery from 2013 to 2017. Fifty-nine patients reported preoperative opioid use (37 high-dose [≥ 90 morphine milligram equivalents daily] and 22 low-dose use). The duration of preoperative use was long-term (≥ 6 months) for 44 patients and short-term for 15. The authors evaluated postoperative opioid use at 6 weeks, 3 months, 6 months, 1 year, and 2 years after surgery. Multivariate logistic regression was used to determine associations of preoperative opioid use, dose, and duration with use at each time point (alpha = 0.05). RESULTS: The following preoperative factors were associated with opioid use 2 years postoperatively: any opioid use (adjusted odds ratio [aOR] 14, 95% CI 2.5-82), high-dose use (aOR 7.3, 95% CI 1.1-48), and long-term use (aOR 17, 95% CI 2.2-123). All patients who reported high-dose opioid use at the 2-year follow-up examination had also reported preoperative opioid use. Preoperative high-dose use (aOR 247, 95% CI 5.8-10,546) but not long-term use (aOR 4.0, 95% CI 0.18-91) was associated with high-dose use at the 2-year follow-up visit. Compared with patients who reported no preoperative use, those who reported preoperative opioid use had higher rates of use at each postoperative time point (from 94% vs 62% at 6 weeks to 54% vs 7.1% at 2 years) (all p < 0.001). Opioid use at 2 years was independently associated with use at 1 year (aOR 33, 95% CI 6.8-261) but not at 6 months (aOR 4.3, 95% CI 0.95-24). CONCLUSIONS: Patients' preoperative opioid use, dose, and duration of use are associated with long-term use after ASD surgery, and a high preoperative dose is also associated with high-dose opioid use at the 2-year follow-up visit. Patients using opioids 1 year after ASD surgery may be at risk for long-term use.

G2019S-LRRK2 mutation enhances MPTP-linked Parkinsonism in mice.

Parkinson's disease (PD) is a common neurodegenerative disease with a heterogeneous etiology that involves genetic and environmental factors or exogenous. Current LRRK2 PD animal models only partly reproduce the characteristics of the disease with very subtle dopaminergic neuron degeneration. We developed a new model of PD that combines a sub-toxic MPTP insult to the G2019S-LRRK2 mutation. Our newly generated mice, overexpressing mutant G2019S-LRRK2 protein in the brain, displayed a mild, age-dependent progressive motor impairment, but no reduction of lifespan. Cortical neurons from G2019S-LRRK2 mice showed an increased vulnerability to stress insults, compared with neurons overexpressing wild-type WT-LRRK2, or non-transgenic (nTg) neurons. The exposure of LRRK2 transgenic mice to a sub-toxic dose of MPTP resulted in severe motor impairment, selective loss of dopamine neurons and increased astrocyte activation, whereas nTg mice with MPTP exposure showed no deficits. Interestingly, mice overexpressing WT-LRRK2 showed a significant impairment that was milder than for the mutant G2019S-LRRK2 mice. L-DOPA treatments could partially improve the movement impairments but did not protect the dopamine neuron loss. In contrast, treatments with an LRRK2 kinase inhibitor significantly reduced the dopaminergic neuron degeneration in this interaction model. Our studies provide a novel LRRK2 gene-MPTP interaction PD mouse model, and a useful tool for future studies of PD pathogenesis and therapeutic intervention.

Leptospira spp. and Toxoplasma gondii in stranded representatives of wild cetaceans in the Philippines.

BACKGROUND: The stranding events of cetaceans in the Philippines provide opportunities for gathering biological information and specimens, especially from the pelagic forms. As part of an effort to monitor the health of wild cetaceans, this study detected Leptospira spp. and Toxoplasma gondii, causative agents of the emerging zoonotic diseases leptospirosis and toxoplasmosis respectively, in their stranded representatives. From October 2016-August 2018, 40 cetaceans (representing 14 species) that stranded nationwide were sampled for brain, cardiac muscle, skeletal muscle, kidney, and blood tissues, urine, and sera. These were subjected to molecular, serological, culture, and histopathological analyses to detect the target pathogens. RESULTS: T. gondii was detected in 20 (71%) of the 28 cetaceans with biological samples subjected to either molecular detection through RE gene amplification or IgG antibodies detection through agglutination-based serological assay. On the other hand, Leptospira was detected in 18 (64%) of 28 cetaceans with biological samples subjected to bacterial culture, molecular detection through 16S rDNA amplification, or IgM antibodies detection through ELISA-based serological assay. CONCLUSIONS: There is the plausibility of toxoplasmosis and leptospirosis in cetacean populations found in the Philippines, however, acute or chronic phases of infections in sampled stranded individuals cannot be confirmed in the absence of supporting pathological observations and corroborating detection tests. Further studies should look for more evidences of pathogenicity, and explore the specific mechanisms by which pelagic cetacean species become infected by Leptospira spp. and T. gondii. As there is growing evidence on the role of cetaceans as sentinels of land-sea movement of emerging pathogens and the diseases they cause, any opportunity, such as their stranding events, should be maximized to investigate the health of their populations. Moreover, the role of leptospirosis or toxoplasmosis in these stranding events must be considered.

Cysteamine Protects Neurons from Mutant Huntingtin Toxicity.

BACKGROUND: The potential benefit of cysteamine for Huntington's disease has been demonstrated in HD animal models. Cysteamine and its derivate cystamine were shown to reduce neuropathology and prolong lifespan. Human studies have demonstrated safety, and suggestive results regarding efficacy. Despite all the studies available in vivo, there are only few in vitro studies, and the mechanism of action of cysteamine remains unclear. OBJECTIVE: The objective of this study is to assess the capacity of cysteamine for neuroprotection against mutant Huntingtin in vitro using cellular models of HD, and to provide initial data regarding mechanism of action. METHODS: We tested the neuroprotective properties of cysteamine in vitro in our primary neuron and iPSC models of HD. RESULTS: Cysteamine showed a strong neuroprotective effect (EC50 = 7.1 nM) against mutant Htt-(aa-1-586 82Q) toxicity, in a nuclear condensation cell toxicity assay. Cysteamine also rescued mitochondrial changes induced by mutant Htt. Modulation of the levels of cysteine or glutathione failed to protect neurons, suggesting that cysteamine neuroprotection is not mediated through cysteine metabolism. Taurine and Hypotaurine, which are metabolites of cysteamine can protect neurons against Htt toxicity, but the inhibition of the enzyme converting cysteamine to hypotaurine does not block either protective activity, suggesting independent protective pathways. Cysteamine has been suggested to activate BDNF secretion; however, cysteamine protection was not blocked by BDNF pathway antagonists. CONCLUSIONS: Cysteamine was strongly neuroprotective with relatively high potency. We demonstrated that the main neuroprotective pathways that have been proposed to be the mechanism of protection by cysteamine can all be blocked and still not prevent the neuroprotective effect. The results suggest the involvement of other yet-to-be-determined neuroprotective pathways.