bluuebunny/crossref_metadata_2025 huggingface dataset:
The diagnostic work-up of cancer-associated myositis
Authors: Selva-O’Callaghan Albert , Martinez-Gómez Xavier , Trallero-Araguás Ernesto , Pinal-Fernández Iago
Published: June 2018

Purpose of review

Despite the well-recognized association between malignancy and myositis, definite data indicating the best strategy for diagnosing cancer in myositis patients is lacking. In this article, we review the data on cancer screening in patients with myositis, and propose an algorithm for this purpose based on recently published data.

Recent findings

Evidence has recently emerged supporting blind screening in patients with certain myositis phenotypes. In addition to the clinical examination, imaging techniques such as PET/computed tomography scanning and whole-body MRI, and determination of the autoantibody profile beyond anti-TIF1γ antibody, the well known cancer biomarker in dermatomyositis, will help the clinician face this complex clinical situation. Molecules related to the checkpoint inhibitor pathway, specifically soluble programmed death 1, may also have a role in the diagnostic work-up of cancer in myositis. In the future, blood tests analysing circulating DNA will certainly help in detecting patients with cancer-associated myositis (CAM).

A step forward has been achieved in the pathway to establish optimal cancer screening for myositis patients. International consensus guidelines for an effective diagnostic work-up of CAM are in progress and will be of paramount importance to improving the outcome in these patients.
Quantitative Risk Factor Analysis of Postoperative Dysphagia After Anterior Cervical Discectomy and Fusion (ACDF) Using the Eating Assessment Tool-10 (EAT-10)
Authors: Yew Andrew Y. , Nguyen Matthew T. , Hsu Wellington K. , Patel Alpesh A.
Published: June 2018

Study Design.

A retrospective case series.

Objective.

The aim of this study was to utilize the Eating Assessment Tool-10 (EAT-10) to quantitatively analyze risk factors contributing to dysphagia after anterior cervical discectomy and fusion (ACDF).

Summary of Background Data.

ACDF is one of the most common procedures performed in the United States, with postoperative dysphagia rates ranging from 2% to 60%. The EAT-10 is a self-administered, symptom-specific 10-item clinical instrument to document dysphagia symptom severity and has demonstrated excellent internal consistency, test-retest reliability, and criterion-based validity.

Methods.

This study utilized a retrospective chart review of 163 patients from July 2013 to October 2017 who underwent ACDF at a single institution and prospectively completed EAT-10 surveys pre- and postoperatively. EAT-10 scores were collected preoperatively and at postoperative day 1, day 14, 1 month, 3 months, 6 months, and 12 months. Preselected risk factors were abstracted from the patients’ chart. Univariate analyses were performed to identify candidate variables that correlated with abnormal EAT-10 scores at each time point. Multivariate logistic regression was then utilized to identify risk factors that were independently correlated with abnormal EAT-10 scores at each time point.

Results.

Female gender, younger patients, and increased operating room (OR) time was associated with increased rates of dysphagia in the early postoperative period. History of obstructive sleep apnea, history of asthma, increased American Society of Anesthesiologists (ASA) score, and a larger number of spinal levels included in the surgery were correlated with increased dysphagia in the later postoperative periods.

Conclusion.

Dysphagia is common following ACDF. Factors associated with longer-term dysphagia seem to be more associated with pre-existing medical comorbidities. Understanding risk factors that correlate with increased rates of dysphagia has the potential to improve preoperative patient counseling and changes in operative management.

Level of Evidence: 4
Preferences of Spine Surgeons With Regard to Management of Intraoperative Durotomy
Authors: Pendi Arif , Wang Jeffrey C. , Bederman Stacey Samuel , Farhan Saifal-Deen , Bhatia Nitin N. , Lee Yu-Po , Ashraf Jahanzeb , Acosta Frank L.
Published: June 2018

Study Design:

This was a cross-sectional study.

Objective:

The objective of this study was to determine spine surgeons’ preferences for the intraoperative and postoperative management of intraoperative durotomy (IDT) in decompression and spinal fusion surgeries.

Summary of Background Data:

Management guidelines for IDT remain elusive. Traditionally, management consists of intraoperative suturing and postoperative bed rest. However, preferences of North American spine surgeons may vary, particularly according to type of surgery.

Materials and Methods:

Spine surgeons of AO Spine North America (AOSNA) were surveyed online anonymously to determine which techniques they preferred to manage IDT in decompression and fusion. Differences in preferences according to surgery type were compared using the Fisher exact test. A series of linear regressions were conducted to identify demographic predictors of spine surgeons’ preferences.

Results:

Of 217 respondents, most were male (95%), orthopedic surgeons (70%), practiced at an academic center (50%), were in practice 0–19 years (71%) and operated on 100–300 patients per year (70%). The majority of surgeons applied sutures (93%–96%) and sealant (82%–84%). Surgeons also used grafts (26%–27%), drains (18%), other techniques (4%–5%), blood patch (2%–3%), or no intraoperative management (1%–2%). Postoperatively, most surgeons recommended bed rest (74%–75%). Antibiotics (22%), immediate mobilization (18%–20%), reoperation (14%–16%), other techniques (6%), or no postoperative management (5%) were also preferred. Management preferences did not vary significantly between decompression and fusion surgeries (all P-values>0.05). Specialty, practice facility, years in practice, and patients per year were identified as independent predictors of IDT management preferences (P<0.05).

Conclusions:

Although North American spine surgeons preferred to manage IDT with sutures augmented by sealant followed by bed rest after surgery, less common techniques were also preferred during the intraoperative and postoperative periods. Notably, intraoperative and postoperative IDT management preferences did not change in accordance to the type of surgery being conducted.

Level of Evidence

Level V.
Minimally Invasive Cervical Laminectomy for Cervical Spondylotic Myelopathy
Authors: Ross Miner N. , Ross Donald A.
Published: June 2018

Objective:

Cervical spondylotic myelopathy is a common cause of neurological disability, especially in aging populations. There are several approaches to decompress the cervical spinal cord, including anterior cervical discectomy and fusion, corpectomy and fusion, arthroplasty, posterior cervical laminectomy with or without fusion, and laminoplasty. Less well described is minimally invasive cervical laminectomy. The authors report their technique and results for minimally invasive cervical laminectomy.

Materials and Methods:

The authors describe in detail their surgical technique and results of 30 consecutive cases. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) myelopathy scores were recorded.

Results:

In total, 30 cases were included. Mean age was 69 years (range, 57–89 y). Twelve procedures were at C3–4, 4 at C4–5, 5 at C5–6, 4 at C7–T1, 3 at C3–4 and C4–5, 1 at C4–5 and C5–6, and 1 at C5–6 and C6–7. Mean preoperative mJOA score was 12.1 (range, 4–15). Average length of surgery was 142 minutes. Mean follow-up was 27 months (range, 3–64 mo). At 3 months, mean postoperative mJOA score was 14.0 (range, 5–17). Mean mJOA improvement of 1.9 was statistically significant (P<0.001). Seventeen patients had magnetic resonance imaging (MRI) available at 3 months postoperatively (5 patients had no MRI, 3 patients had MRI contraindications, and 5 are pending). No MRI findings led to further surgery. There were no durotomies and no wound infections. A single patient had an unexplained new neurological deficit that resolved over 6 months.

Conclusions:

Minimally invasive laminectomy for cervical myelopathy is safe and effective and may be an underutilized procedure.
Complete and Prolonged Response of Renal Cell Carcinoma With Rhabdoid Features to Checkpoint Inhibitor Therapy
Authors: Wynja Emily , Solomon Benjamin , Bleeker Jonathan
Published: June 2018

Checkpoint inhibitor immunotherapy has recently been proven to be an attractive treatment option for a wide variety of malignancies. Nivolumab, an anti-programmed cell death protein-1 antibody, has been proven effective and safe in treating metastatic renal cell carcinoma (RCC) with a clear cell component. We report the case of a patient with high-grade clear cell RCC with rhabdoid features who has achieved a durable complete response with nivolumab therapy after multiple surgical interventions and progression on pazopanib. Genomic evaluation in this case was characterized in part by a PBRM1 variant, similar to the only other described case of RCC with rhabdoid features obtaining a complete response to nivolumab. This case supports the potential utility of checkpoint inhibitors in aggressive, rare subtypes of RCC where there are limited options for therapy.
Nivolumab induced inflammation of seborrheic keratoses: a novel cutaneous manifestation in a metastatic melanoma patient
Authors: Rambhia Pooja H. , Honda Kord , Arbesman Joshua
Published: June 2018

Immune checkpoint inhibitors targeting the programmed cell death (PD)-1 receptor have dramatically changed the landscape of metastatic melanoma treatment. Nevertheless, these immuno-modulatory agents have associated side effects, including dermatologic manifestations. To this end, we report a patient with metastatic melanoma that was treated with a PD-1 inhibitor, and subsequently developed inflammation of existing seborrheic keratosis lesions and new verrucous keratoses, a cutaneous side effect that has not been previously reported to our knowledge. The etiology of seborrheic and verrucous keratoses is not well understood, although their physical and histopathologic similarities to chronic viral-derived lesions, such as human papilloma virus, suggest a potential viral association. Chronic viral infections are known to result in T-cell tolerance because of persistent antigen stimulation. PD-1 inhibition is able to reinvigorate exhausted T cells, which are accordingly able to decrease viral load. Thus, the inflammatory reaction, seen in our patient, may be the result of PD-1 inhibition reactivating virally driven T lymphocytes.
Influence of Sex, Age, and Weight on Levetiracetam Pharmacokinetics
Authors: Alzueta Natalia , Ortega Ana , Aldaz Azucena
Published: June 2018

Background:

Levetiracetam (LEV) is a second-generation antiepileptic drug extensively used in therapeutics. The aim of this study was to evaluate the influence that sex, age, and weight exert on LEV pharmacokinetics in clinical practice.

Methods:

We conducted a 6-year retrospective observational study. Patients were classified in subgroups according to sex, weight (normal range, overweight, and obese), and age (young adult: 16–30 years old, middle-aged adult: 31–50 years old, advanced adult: 51–64 years old, and elderly adult: ≥65 years old). We compared LEV apparent oral clearance (LEV CL/F) between the subgroups.

Results:

A total of 238 LEV basal serum concentrations (LEV C0) corresponding to 156 patients were identified. Significant differences were observed in LEV CL/F between males and females when LEV CL/F was expressed as L/h [mean (SD): 4.79 (1.84) L/h in males versus 4.13 (1.64) L/h in females;P< 0.001]. These differences were not significant when LEV CL/F was normalized by weight [mean (SD): 60.64 (24.90) mL/h/kg in males versus 64.10 (28.87) mL/h/kg in females; n.s.]. Weight in females was 17% lower compared with males. A progressive reduction in LEV CL/F was observed with increasing age, in a proportion that was similar to the decline in renal function. The elderly patients presented 30% lower LEV CL/F (mL/h/kg) and 43% lower creatinine clearance (CCr) in comparison with adults. No statistically significant differences were observed in LEV CL/F calculated in L/h between weight subgroups. However, when LEV CL/F was expressed in mL/h/kg, a progressive reduction was observed [normal weight: 72.21 (28.97); overweight: 57.84 (25.38); obese: 49.45 (14.50);P< 0.001]. A significant and positive correlation between CCr and LEV CL/F was observed, confirming the important role of the renal function in LEV CL/F. The CCr increased in each sex group when weight increased; however, LEV CL/F (L/h) remained constant.

Conclusions:

Sex, age, and weight affect LEV pharmacokinetics, having an impact on the individual dosage regimen needed to achieve the therapeutic objective. Sex is a conditioning factor of LEV CL/F, although its influence is principally due to the weight. LEV CL/F decreases with advancing age, proportionally to the decline in renal function. It is confirmed that LEV dosage per body weight is not required, and prescribing higher doses of LEV in obese patients is not justified. These data suggest that routine LEV therapeutic drug monitoring in the elderly patients, patients with renal dysfunction, and obese patients is indicated.
Outcome of Human Donor Corneas Stored for More Than 4 Weeks
Authors: Madzak Aida , Hjortdal Jesper
Published: June 2018

Purpose:

Organ culture is the most common method for preservation of human donor corneas within Europe, and the maximum accepted storage period is typically set to 4 weeks. However, little is known about the fate of prolonged (4+ wks) organ culture storage of donor corneas. The aim of this study was to evaluate the clinical outcomes of corneal grafts preserved from 4 to 7 weeks compared with corneal grafts preserved up to 4 weeks in organ culture medium.

Methods:

A registry study was performed, identifying 1252 corneal transplantations [Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PKP)] between February 2008 and November 2015 at Aarhus University Hospital, Denmark. Data were extracted from The Danish Cornea Bank Registry and The Swedish Cornea Registry, which also includes Danish patients. The outcomes evaluated, 2 years after transplantation, were graft function, rebubbling rates in DSAEK surgeries, rejection rates, and endothelial cell density (ECD).

Results:

A total of 808 donor corneas were stored for ≤29 days, with a mean preservation time being 20 ± 6 days (mean ± SD, range: 6–29 days). A total of 444 donor corneas were stored for >29 days, with a mean preservation time being 38 ± 7 days (mean ± SD, range: 30–72 days). In both DSAEK (n = 835) and PKP (n = 417), no statistically significant difference was observed in the frequency of graft failure (DSAEK, P = 0.9 and PKP, P = 0.74), rebubbling rates (DSAEK P = 0.07), rejection rates (DSAEK, P = 0.08 and PKP, P = 0.95), or ECD (DSAEK, P = 0.56 and PKP, P = 0.44) between donor corneas cultured for ≤29 days and donor corneas cultured for >29 days.

Conclusions:

Corneas stored in organ culture for more than 4 weeks are equally suitable for DSAEK and PKP transplantation as corneas stored in organ culture for up to 4 weeks.
LOXL1 Polymorphisms: Genetic Biomarkers that Presage Environmental Determinants of Exfoliation Syndrome
Authors: Pasquale Louis R. , Kang Jae Hee , Fan BaoJian , Levkovitch-Verbin Hani , Wiggs Janey L.
Published: June 2018

An agnostic high throughput search of the genome revealed a robust association betweenLOXL1genetic polymorphisms and exfoliation syndrome (XFS), a discovery that likely would not have been possible with candidate or family-based gene search strategies. While questions remain regarding howLOXL1gene variants contribute to XFS pathogenesis, it is clear that the frequencies of disease-related alleles do not track with the varying disease burden throughout the world, prompting a search for environmental risk factors. A geo-medicine approach revealed that disease load seemed to increase as a function of the distance from the equator. The exact reason for this extraequatorial disease distribution pattern remains unclear, but a greater amount of time spent outdoors is a robust risk factor for XFS, suggesting climatic factors such as ocular solar exposure and colder ambient temperature may be involved in disease pathogenesis. Prospective studies have also implicated higher coffee consumption and lower dietary folate intake in association with incident XFS. The discovery of environmental risk factors for XFS suggests that preventive measures may help to reduce ocular morbidity from XFS.
A Role for Clusterin in Exfoliation Syndrome and Exfoliation Glaucoma?
Authors: Wiggs Janey L. , Kang Jae Hee , Fan BaoJian , Levkovitch-Verbin Hani , Pasquale Louis R.
Published: June 2018

The multifunctional protein clusterin (CLU) is a secreted glycoprotein ubiquitously expressed throughout the body, including in the eye. Its primary function is to act as an extracellular molecular chaperone, preventing the precipitation and aggregation of misfolded extracellular proteins. Clusterin is commonly identified at fluid-tissue interfaces, and has been identified in most body fluids. It is a component of exfoliation material, and CLU mRNA is reduced in eyes with exfoliation syndrome compared with controls. SNPs located in the CLU genomic region have been associated with Alzheimer disease (AD) at the genome-wide level and several CLU SNPs located in an apparent regulatory region have been nominally associated with XFS/XFG in Caucasians with European ancestry and in south Indians. Interestingly, clusterin associates with altered elastic fibers in human photoaged skin and prevents UV-induced elastin aggregation in vitro. In light of the known geographic risk factors for XFS/XFG, which could include UV light, investigations of CLU-geographic interactions could be of interest. Future studies investigating rare CLU variation and other complex interactions including gene-gene interactions in XFS/XFG cases and controls may also be fruitful. Although CLU has been considered as a therapeutic target in AD, cancer and dry eye, a role for clusterin in XFS/XFG needs to be better defined before therapeutic approaches involving CLU can be entertained.
Recent Advances in the Surgical Management of Glaucoma in Exfoliation Syndrome
Authors: Sayed Mohamed S. , Lee Richard K.
Published: June 2018

Surgical and laser procedures traditionally used in the management of exfoliation glaucoma (XFG) include laser trabeculoplasty, trabeculectomy, and glaucoma drainage implant surgery. Having demonstrated similar safety and efficacy in XFG compared with primary open-angle glaucoma, trabeculectomy remains the most commonly performed surgery in XFG. Recent trends in practice patterns in developed nations demonstrate a shift towards glaucoma drainage implant surgery, which is currently the procedure of choice in XFG for many, particularly in developed nations. In addition, cataract surgery alone may significantly decrease intraocular pressure in patients with XFG, may prevent glaucoma development in patients with exfoliation syndrome, and is recommended to be performed early in the course of the disease. With the relatively recent introduction of nonpenetrating glaucoma surgery and the ongoing evolution of minimally invasive glaucoma surgery, several other surgical procedures have now become part of the glaucoma surgeon’s armamentarium when treating XFG, including the Ex-PRESS shunt, deep sclerectomy, viscocanalostomy, Trabectome, as well as angle procedures. These techniques have demonstrated promising results in various types of glaucoma. More research is, however, needed to establish the safety and efficacy of these procedures in XFG.
Exfoliation Syndrome and Cataract Surgery
Authors: Crandall Alan S.
Published: June 2018

Cataract extraction in exfoliation syndrome requires careful preoperative assessment and planning. Knowledge of the degree of pupil dilation and zonular integrity are essential for safely perform cataract surgery in these eyes. Capsule rhexis should be 5.5 mm and all intraoperative maneuvers should be designed to minimize zonular stress. The surgeon should be versatile in various nuclear disassembly techniques and consider use of capsular support devices when warranted. Cortical cleanup should proceed via a tangential approach and attempts should be made to removal residual lens epithelial cells so as to minimize postoperative capsular contraction syndrome.
Genetics of Exfoliation Syndrome
Authors: Aung Tin , Chan Anita S. , Khor Chiea-Chuen
Published: June 2018

Exfoliation syndrome (XFS) is an age-related systemic disorder of the extracellular matrix with important ocular manifestations. In this disorder, exfoliation material (XFM) is deposited in the anterior chamber of the eye on the lens, iris, ciliary body, as well as other intraocular structures. This accumulation of XFM can obstruct the trabecular meshwork, resulting in elevated intraocular pressure and eventually causing glaucomatous optic neuropathy. In itself a highly hereditable condition, XFS is also the commonest recognizable cause of open-angle glaucoma worldwide, accounting for a majority of cases in some countries. Outside the eye, XFM deposits around blood vessels, particularly in association with elastic connective tissue, are found in numerous organs, including the skin, heart, and lungs. Long suspected to be a genetic disorder on the basis of familial aggregation studies, recent genome-wide association studies uncovered strong association between 7 genetic loci (LOXL1, CACNA1A, FLT1-POMP, TMEM136-ARHGEF12, AGPAT1, RBMS3, and SEMA6A) and increased risk of XFS. At the same time, a lower than usual sibling relative risk for XFS compared with other inherited conditions suggests XFS to be a complex disorder. The evidence to date suggests that additional genetic loci and biological insights for XFS remain to be identified through larger studies.
Catheter-assisted 360-Degree Trabeculotomy for Congenital Glaucoma
Authors: Toshev Anani P. , Much Martin M. , Klink Thomas , Pfeiffer Norbert , Hoffmann Esther M. , Grehn Franz
Published: June 2018

Purpose:

To determine feasibility, efficacy, and safety of ab externo 360-degree trabeculotomy with illuminated microcatheter for congenital glaucoma.

Patients and Methods:

The postoperative results of 36 eyes in 23 consecutive patients who underwent 360-degree trabeculotomy for primary congenital glaucoma (PCG) or secondary congenital glaucoma using an illuminated microcatheter were retrospectively analyzed. Success criteria were defined as intraocular pressure (IOP) ≤18 mm Hg without (complete success) and with medication (qualified success).

Results:

In all previously nonoperated eyes with PCG (group 1), the Schlemm’s canal was identified and circumferentially cannulated for 360-degree trabeculotomy. In group 2 comprising of operated eyes with PCG and eyes with secondary congenital glaucoma, the performance of 360-degree trabeculotomy failed in 4 eyes because of the Schlemm’s canal occlusion or high tissue resistance of the trabecular meshwork. Mean preoperative IOP was 28.6±5 and 29.6±9 mm Hg with 7 of 20 eyes and 7 of 9 eyes receiving IOP-lowering medication in group 1 and group 2, respectively. Mean postoperative IOP was reduced to 13±2.7 and 20.2±7.1 mm Hg after a mean follow-up of 15.3 and 12.7 months with 4 of 20 eyes and 5 of 9 eyes receiving medication in group 1 and group 2, respectively. Four eyes underwent further surgery. Complete success was achieved in 16 and 3 eyes, whereas qualified success was achieved in 20 and 4 eyes from group 1 and group 2, respectively. In all eyes, a mild to moderate postoperative hyphema was observed.

Conclusions:

Ab externo catheter-assisted 360-degree trabeculotomy controls IOP in a majority of patients with congenital glaucoma after a single operation. Moderate blood reflux in the anterior chamber is considered as a common postoperative finding. We did not observe hypotony or other severe complications in our series. In 1 patient, we experienced catheter misdirection in an eye that had previously undergone trabeculotomy.
West Indies Glaucoma Laser Study (WIGLS)—2: Predictors of Selective Laser Trabeculoplasty Efficacy in Afro-Caribbeans With Glaucoma
Authors: Realini Tony , Shillingford-Ricketts Hazel , Burt Darra , Balasubramani Goundappa K.
Published: June 2018

Purpose:

To identify factors associated with intraocular pressure (IOP) reduction following selective laser trabeculoplasty (SLT) in Afro-Caribbean people with primary open-angle glaucoma (POAG).

Design:

This was a prospective stepped-wedge study.

Methods:

Data were drawn from 72 Afro-Caribbean subjects with POAG participating in the ongoing West Indies Glaucoma Laser Study. Multivariable mixed-model analysis was utilized to develop a predictive model for percent IOP reduction 12 months following SLT. Putative factors (age, sex, site, baseline IOP, prior use of prostaglandin therapy, number of prewashout IOP-lowering medications, central corneal thickness, severity of glaucoma, duration of follow-up, and signs of acute postoperative inflammation) were evaluated in bivariate analysis. Factors significant at P≤0.2 were included in the final model. Right and left eye data were modeled separately.

Results:

At month 12 following SLT, mean IOP reductions in the West Indies Glaucoma Laser Study were 6.2 to 6.5 mm Hg (29.7% to 31.0%) in right and left eyes. The only factor significant in both eyes (P=0.0005 in right eyes and P<0.0001 in left eyes) was time, with IOP reductions being greatest at month 3 and declining slightly over time through month 12. Vertical cup-disc ratio (P=0.006) and prior prostaglandin therapy (P=0.004) were significant only in right eyes, and central corneal thickness (P=0.014) was significant only in left eyes. Factors significant only unilaterally did not approach significance in fellow eyes, suggesting the possibility that these represent type 1 errors. Site (St. Lucia vs. Dominica) was not a significant factor, establishing generalizability of these treatment outcomes to a broader population of African-derived people.

Conclusions:

This analysis did not identify any subject-specific factors consistently predictive of therapeutic response to SLT. Of note, no factors predicted a suboptimal response. These findings favorably position SLT for broad application as primary therapy in African-derived people with POAG.
Estimating relative efficacy in acute postoperative pain: network meta-analysis is consistent with indirect comparison to placebo alone
Authors: Moore R. Andrew , Derry Sheena , Wiffen Philip J. , Banerjee Samik , Karan Rajesh , Glimm Ekkehard , Wiksten Anna , Aldington Dominic , Eccleston Christopher
Published: June 2018

Network meta-analysis uses direct comparisons of interventions within randomized controlled trials and indirect comparisons across them. Network meta-analysis uses more data than a series of direct comparisons with placebo, and theoretically should produce more reliable results. We used a Cochrane overview review of acute postoperative pain trials and other systematic reviews to provide data to test this hypothesis. Some 261 trials published between 1966 and 2016 included 39,753 patients examining 52 active drug and dose combinations (27,726 given active drug and 12,027 placebo), in any type of surgery (72% dental). Most trials were small; 42% of patients were in trials with arms <50 patients, and 27% in trials with arms ≥100 patients. Response to placebo in third molar extraction fell by half in studies over 30 to 40 years (171 trials, 7882 patients given placebo). Network meta-analysis and Cochrane analyses provided very similar results (average difference 0.04 number needed to treat units), with no significant difference for almost all comparisons apart from some with small patient numbers or small effect size, or both. Network meta-analysis did not detect significant differences between effective analgesics. The similarity between network meta-analysis and Cochrane indirect analyses probably arose from stringent quality criteria in trials accepted in Cochrane reviews (with consequent low risk of bias) and consistency in methods and outcomes. Network meta-analysis is a useful analytical tool that increases our confidence in estimates of efficacy of analgesics in acute postoperative pain, in this case by providing similar results.
Lionfish venom elicits pain predominantly through the activation of nonpeptidergic nociceptors
Authors: Mouchbahani-Constance Stephanie , Lesperance L. Stephen , Petitjean Hugues , Davidova Albena , Macpherson Amanda , Prescott Steven A. , Sharif-Naeini Reza
Published: June 2018

The lionfish (Pterois volitans) is a venomous invasive species found in the Caribbean and Northwestern Atlantic. It poses a growing health problem because of the increase in frequency of painful stings, for which no treatment or antidote exists, and the long-term disability caused by the pain. Understanding the venom's algogenic properties can help identify better treatment for these envenomations. In this study, we provide the first characterization of the pain and inflammation caused by lionfish venom and examine the mechanisms through which it causes pain using a combination of in vivo and in vitro approaches including behavioral, physiological, calcium imaging, and electrophysiological testing. Intraplantar injections of the venom produce a significant increase in pain behavior, as well as a marked increase in mechanical sensitivity for up to 24 hours after injection. The algogenic substance(s) are heat-labile peptides that cause neurogenic inflammation at the site of injection and induction of Fos and microglia activation in the superficial layers of the dorsal horn. Finally, calcium imaging and electrophysiology experiments show that the venom acts predominantly on nonpeptidergic, TRPV1-negative, nociceptors, a subset of neurons implicated in sensing mechanical pain. These data provide the first characterization of the pain and inflammation caused by lionfish venom, as well as the first insight into its possible cellular mechanism of action.
Azithromycin and Sensorineural Hearing Loss in Adults: A Retrospective Cohort Study
Authors: Alrwisan Adel , Antonelli Patrick J. , Brumback Babette A. , Wei Yu-Jung , Winterstein Almut G.
Published: June 2018

Objective:

To examine whether short-term use of azithromycin increases the risk of sensorineural hearing loss (SNHL) in adults with uncomplicated infections.

Study Design:

A retrospective cohort study using Medicaid claims data, 1999 to 2010.

Patients:

Adults (18–64 years old) who had continuous enrollment in Medicaid for the 12 months (baseline) before the date of first dispensation (index date) of oral azithromycin or amoxicillin ± clavulanate for uncomplicated infections.

Main Outcome Definition:

We operationalized sensorineural hearing loss (SNHL) by a charge for audiometry and followed by a diagnosis of SNHL within 30 days.

Analysis:

We adjusted for the baseline covariates through propensity score matching. Adults were followed for up to 120 days after the index date. The hazard of SNHL in azithromycin-exposed adults was compared with those who had amoxicillin ± clavulanate using a Cox proportional hazard model. We performed several sensitivity analyses by varying the follow-up time, SNHL definition, adjusting for cumulative antibiotic use, and switching exposure status during the follow-up period.

Results:

A total of 493,774 patients entered the study cohort. The unadjusted incidence rates of SNHL were 38 and 41 cases per 10,000 patient-years following exposure to azithromycin and amoxicillin ± clavulanate, respectively. The adjusted (matched) hazard ratio (HR) of SNHL for azithromycin versus amoxicillin ± clavulanate was 0.91 (95% confidence interval [CI], 0.77–1.07). The sensitivity analyses findings were consistent with the primary analysis.

Conclusion:

Azithromycin short-term use was not associated with an increased risk of SNHL in comparison to amoxicillin ± clavulanate.
Pregnancy as a risk factor for thyroid cancer progression
Authors: Rakhlin Luba , Fish Stephanie
Published: June 2018

Purpose of review

The current review evaluates the impact of pregnancy on women with thyroid cancer in three different clinical situations: those with newly diagnosed differentiated thyroid cancer (DTC), those under active surveillance for papillary thyroid microcarcinomas (PMCs), and those with previously treated DTC.

Recent findings

Recent pregnancy is not associated with high-risk pathological features of DTC. In women with known PMCs under active surveillance, pregnancy does not increase the risk of disease progression. Thus, deferring surgery for newly diagnosed DTC or known PMCs until after delivery is safe for both mother and the unborn child. If a woman with previously treated DTC is planning pregnancy, response-to-therapy status is an excellent guide for predicting pregnancy-associated disease progression or recurrence.

Clinical studies consistently show that pregnancy is not associated with significant disease progression in newly diagnosed thyroid cancer, PMCs under active surveillance, or previously treated DTC.
Rural-Urban Differences in Human Immunodeficiency Virus Testing Among US Adults: Findings From the Behavioral Risk Factor Surveillance System
Authors: Henderson Emmett R. , Subramaniam Divya S. , Chen Jiajing
Published: June 2018

Background

Individuals in rural areas of the United States face barriers to human immunodeficiency virus (HIV)-related health care. We aim to assess differences in frequency of lifetime and past-year HIV testing, and differences in testing site location between rural and urban residents of the United States.

Methods

Data from the Behavioral Risk Factor Surveillance System 2015 were analyzed on 250,579 respondents 18 years or older. Weighted multinomial logistic regression analyses compared urban/rural differences in lifetime and past-year HIV testing. Weighted multinomial logistic regression compared urban/rural differences in HIV testing site.

Results

Overall, 26.9% of urban residents and 21.5% of rural residents reported testing for HIV in their lifetime. Of urban residents, 24.5% reported receiving an HIV test in the past year compared with 20.2% of rural residents. Living in a rural area was associated with lower odds of lifetime (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.81–0.90) and past-year HIV testing (OR, 0.84; 95% CI, 0.74–0.95) compared with not testing. Rural residents had higher odds of receiving an HIV test at the hospital or emergency room (adjusted OR, 1.41; 95% CI, 1.23–1.62) or clinic (adjusted OR, 1.21; 95% CI, 1.02–1.24) than a doctor's office.

Conclusions

This study highlights significant rural health disparities in rates of lifetime and past-year HIV testing. Targeted interventions are needed to remove structural barriers in rural communities, such as long distances to clinics and low availability of free HIV testing at clinics serving the uninsured or underinsured. Furthermore, rural providers should be encouraged to routinely offer HIV screening to their patients.
Heterosexual Anal and Oral Sex in Adolescents and Adults in the United States, 2011–2015
Authors: Habel Melissa A. , Leichliter Jami S. , Dittus Patricia J. , Spicknall Ian H. , Aral Sevgi O.
Published: June 2018

Background

Heterosexual anal and oral sex are related to the acquisition and transmission of sexually transmitted diseases (STDs). As common reportable STDs (chlamydia, gonorrhea, and syphilis) in the United States are increasing, it is important to understand recent oral and anal sexual behaviors.

Methods

We examined the prevalence and correlates of heterosexual anal and oral sex, associated condom use, and having multiple partners among men and women aged 15 to 44 years.

Results

Approximately one third of women and men had ever engaged in anal sex, including 11% of adolescents (15–19 years). Most women and men had ever received or given oral sex (at >75%). Six percent and 7% of women and men, respectively, used a condom at last oral sex compared with 20% and 30% who used a condom at last anal sex. Having multiple sex partners in the past year was most common among adolescents, never or formerly married persons, and those who had a nonmonogamous partner. Less than 10% reported multiple anal sex partners in the past year. A substantial minority had multiple oral or anal sex partners; black women and men had the highest reports of oral sex partners by race/ethnicity.

Conclusions

Anal and oral sex are common sexual practices. Given the low rates of condom use during these behaviors, it is important that recommendations for sexual risk assessments are followed. Tailored messaging regarding risk for STD and human immunodeficiency virus acquisition during oral and anal sex may benefit adolescents, singles, and divorced individuals. Future discussions regarding the benefits of extragenital STD testing for heterosexuals may be useful.
Interventions to Increase Point-of-Care Ultrasound Use in a Pediatric Emergency Department
Authors: Musisca Megan A. , Neuman Mark I. , Gravel Cynthia A. , Monuteaux Michael C. , Rempell Rachel G.
Published: June 2018

Objective

We sought to determine which interventions have effectively increased point-of-care ultrasound (US) use in a pediatric emergency department (ED).

Design/Methods

We evaluated the impact of specific interventions conducted over a 5-year period (2010–2015) on point-of-care US performance in a tertiary care pediatric ED. Ultrasound use by attending physicians and fellows was ascertained from a departmental database. Interventions assessed included the following: (1) initiation of an US fellowship, (2) acquisition of a second US machine, (3) performance of an US-related research project in the department, (4) initiation of faculty US curriculum, (5) earlier introduction of US education for pediatric emergency medicine fellows, and (6) administrative mandate dictating faculty requirements for credentialing. Mean monthly US use was trended over time using statistical process control methodology, and the impact of major interventions was analyzed using interrupted time-series analyses.

Results

The mean number of US scans increased from 2.0 to 5.9 per attending per month and from 4.3 to 7.1 per fellow per month over the study period. Using interrupted time-series analyses, we observed the only intervention to significantly increase attending US utilization was an administrative credentialing mandate, with an associated increase of 6% per month (incidence rate ratio, 1.06; 95% confidence interval, 1.01–1.11).

Conclusions

Point-of-care US use has increased over time for both fellows and attending physicians. We observed that an administrative mandate led to a significant increase in US use among attending physicians.
A Novel Innovation for Surgical Flap Markings Using Projected Stencils
Authors: Sayadi Lohrasb R. , Chopan Mustafa , Maguire Kevin , Banyard Derek A. , Ehret Zachary , Evans Gregory R. D. , Widgerow Alan D.
Published: June 2018

Despite the vast amount of technological advancement seen in the operating room, surgical markings are still drawn as “best estimates” the same way Susruta drew them in the sixth century bc. Many of the flaps used in plastic surgery have precise geometries that are hard to replicate by hand. In this article, the authors describe a novel approach in making surgical markings more accurate by using a pico-projector to project a prefabricated flap, designed on Google Sketchup, as a stencil. Projected and hand-drawn rhomboid and bilobed flaps were tested on cadavers, with both quantitative and qualitative outcomes favoring the projected flaps. This unique concept can not only be used in the operating room but also serve as an educational tool for training plastic and reconstructive surgeons.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
The Role of Norepinephrine and α-Adrenergic Receptors in Acute Stress-Induced Changes in Granulocytes and Monocytes
Authors: Beis Daniel , von Känel Roland , Heimgartner Nadja , Zuccarella-Hackl Claudia , Bürkle Alexander , Ehlert Ulrike , Wirtz Petra H.
Published: June 2018

Objective

Acute stress induces redistribution of circulating leucocytes in humans. Although effects on lymphocytes as adaptive immune cells are well understood, the mechanisms underlying stress effects on granulocytes and monocytes as innate immune blood cells are still elusive. We investigated whether the stress hormone norepinephrine (NE) and α-adrenergic receptors (α-ADRs) may play a mediating role.

Methods

In a stress study, we cross-sectionally tested 44 healthy men for associations between stress-induced NE increases and simultaneous granulocyte and monocyte cell count increases, as measured immediately before and several times after the Trier Social Stress Test. In a subsequent infusion study, 21 healthy men participated in three different experimental trials with sequential infusions of 1- and 15-minute duration with varying substances (saline as placebo, the nonspecific α-ADR blocker phentolamine [2.5 mg/min], and NE [5 μg/min]): trial 1 = saline+saline, trial 2 = saline+NE, trial 3 = phentolamine+NE. Granulocyte and monocyte cell numbers were assessed before, immediately after, 10 minutes, and 30 minutes after infusion procedures.

Results

In the stress study, higher NE related to higher neutrophil stress changes (β = .31,p =.045,R2change = .09), but not epinephrine stress changes. In the infusion study, saline+NE induced significant increases in neutrophil (F(3/60) = 43.50,p< .001, η2= .69) and monocyte (F(3/60) = 18.56,p< .001, η2= .48) numbers compared with saline+saline. With phentolamine+NE, neutrophil (F(3/60) = 14.41,p< .001, η2= .42) and monocyte counts (F(2.23/44.6) = 4.32,p =.016, η2= .18) remained increased compared with saline+saline but were lower compared with saline+NE (neutrophils:F(3/60) = 19.55,p< .001, η2= .494, monocytes:F(3/60) = 2.54,p= .065, η2= .11) indicating partial mediation by α-ADRs. Trials did not differ in eosinophil and basophil count reactivity.

Conclusions

Our findings suggest that NE-induced immediate increases in neutrophil and monocyte numbers resemble psychosocial stress effects and can be reduced by blockade of α-ADRs.
Psychosocial Stress Over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community
Authors: Gebreab Sirak Zenebe , Vandeleur Caroline L. , Rudaz Dominique , Strippoli Marie-Pierre F. , Gholam-Rezaee Mehdi , Castelao Enrique , Lasserre Aurélie M. , Glaus Jennifer , Pistis Giorgio , Kuehner Christine , von Känel Roland , Marques-Vidal Pedro , Vollenweider Peter , Preisig Martin
Published: June 2018

Objective

The complex relationship between psychosocial stress over the lifetime, psychological factors, and cardiometabolic risk is still poorly understood. Accordingly, our aims were (1) to independently assess the associations between childhood adversity, life-event stress in remote (earlier than the last 5 years), and recent adulthood and cardiometabolic risk, and (2) to determine the role of psychological factors including personality, coping, and depression in these associations.

Methods

The sample included 2674 adults, aged 35 to 66 years, randomly selected from urban area. Participants underwent a physical examination including the assessment of obesity markers, blood pressure, and blood lipid and glucose levels. Stress during adulthood was determined using the severity scores of 52 stressful life events. Information on adverse childhood experiences and major depressive disorders was collected using semistructured interviews, whereas personality traits and coping mechanisms were evaluated through questionnaires.

Results

Both childhood adversity and stress in remote adulthood were associated with elevated body mass index (β [95% confidence interval {CI}] = 0.249 [0.029 to 0.468]; 0.020 [0.006 to 0.034]), waist circumference (β [95% CI] = 0.061 [0.024 to 0.099]; 0.08 [0.04 to 0.11]), and the global cardiometabolic risk score (β [95% CI] = 0.278 [0.017 to 0.540]; 0.017 [0.001 to 0.033]) after adjustment for sociodemographic, lifestyle, and psychological factors. In addition, childhood adversity was associated with low high density lipoprotein levels (β [95% CI] = −0.021 [−0.042 to 0.000]), as well as increased fat mass and systolic blood pressure levels (β [95% CI] = 0.506 [0.165 to 0.846]; 0.952 [0.165 to 1.740]) and stress in remote adulthood with apolipoprotein B levels (β [95% CI] = 0.607 [0.312 to 0.901]). Psychological factors did not account for these associations and were not effect modifiers.

Conclusions

Our data demonstrate that psychosocial stress during childhood and remote adulthood favor adiposity and abnormal lipid metabolism.
Does 2-L Split-Dose Polyethylene Glycol Bowel Preparation Improve the Quality of Screening Colonoscopy?
Authors: Chen Jingtao , Athilingam Ponrathi , Brady Patrick
Published: June 2018

Effectiveness of colonoscopy as a screening tool for colorectal cancer prevention depends on the quality of bowel preparation. The type of bowel preparation agent prescribed is largely dependent on the prescriber's preference, indicating a lack of standard. A retrospective study (N= 84) compared the quality of bowel preparation using 2-L split-dose polyethylene glycol prep (MoviPrep) to other standard bowel preparations. Colonic mucosa visualized using the Boston Bowel Preparation Scale, cecal intubation indicating successful completion of colonoscopy, scope withdrawal time, and procedure duration were measured as outcomes. Gastroenterologists from one academic practice prescribed 2-L split-dose bowel preparation (MoviPrep) (Group A) compared with Group B that did not prescribe MoviPrep. Results of an independentttest between the 2 provider groups demonstrated a statistically significant difference in colon visualization based on Boston Bowel Preparation Score (t[40] = − 2.1,p= .035). Similar statistically significant results were seen within Group A, which received 2-L split-dose polyethylene glycol bowel preparation and other preparations (t[61] = − 2.55,p= .013). All patients had successful completion of colonoscopy, with no statistical difference in procedure duration and scope withdrawal time. Future studies should confirm the benefits of 2-L split-dose polyethylene glycol preparation for improved colon visualization during screening colonoscopy.