bluuebunny/crossref_metadata_2025 huggingface dataset:
Diminishing Clinical Returns of Multilevel Minimally Invasive Lumbar Interbody Fusion
Authors: Passias Peter G. , Bortz Cole , Horn Samantha R. , Segreto Frank A. , Stekas Nicholas , Ge David H. , Alas Haddy , Varlotta Christopher G. , Frangella Nicholas J. , Lafage Renaud , Lafage Virginie , Steinmetz Leah , Vasquez-Montes Dennis , Diebo Bassel , Janjua Muhammad B. , Moawad Mohamed A. , Deflorimonte Chloe , Protopsaltis Themistocles S. , Buckland Aaron J. , Gerling Michael C.
Published: June 2019

Study Design.

Single institution retrospective clinical review.

Objective.

To investigate the relationship between levels fused and clinical outcomes in patients undergoing open and minimally invasive surgical (MIS) lumbar fusion.

Summary of Background Data.

Minimally invasive spinal fusion aims to reduce the morbidity associated with conventional open surgery. As multilevel arthrodesis procedures are increasingly performed using MIS techniques, it is necessary to weigh the risks and benefits of multilevel MIS lumbar fusion as a function of fusion length.

Methods.

Patients undergoing <4 level lumbar interbody fusion were stratified by surgical technique (MIS or open), and grouped by fusion length: 1-level, 2-levels, 3+ levels. Demographics, Charlson Comorbidity Index (CCI), surgical factors, and perioperative complication rates were compared between technique groups at different fusion lengths using means comparison tests.

Results.

Included: 361 patients undergoing lumbar interbody fusion (88% transforaminal, 14% lateral; 41% MIS). Breakdown by fusion length: 63% 1-level, 22% 2-level, 15% 3+ level. Op-time did not differ between groups at 1-level (MIS: 233 min vs. Open: 227, P = 0.554), though MIS at 2-levels (332 min vs. 281) and 3+ levels (373 min vs. 323) were longer (P = 0.033 and P = 0.231, respectively). While complication rates were lower for MIS at 1-level (15% vs. 30%, P = 0.006) and 2-levels (13% vs. 27%, P = 0.147), at 3+ levels, complication rates were comparable (38% vs. 35%, P = 0.870). 3+ level MIS fusions had higher rates of ileus (13% vs. 0%, P = 0.008) and a trend of increased adverse pulmonary events (25% vs. 7%, P = 0.110). MIS was associated with less EBL at all lengths (all P < 0.01) and lower rates of anemia at 1-level (5% vs. 18%, P < 0.001) and 2-levels (7% vs. 16%, P = 0.193). At 3+ levels, however, anemia rates were similar between groups (13% vs. 15%, P = 0.877).

Conclusion.

MIS lumbar interbody fusions provided diminishing clinical returns for multilevel procedures. While MIS patients had lower rates of perioperative complications for 1- and 2-level fusions, 3+ level MIS fusions had comparable complication rates to open cases, and higher rates of adverse pulmonary and ileus events.

Level of Evidence: 3
The Role of Biologics in the Treatment of Flatfoot
Authors: Shimozono Yoshiharu , Fansa Ashraf M. , Kennedy John G.
Published: June 2019

Symptomatic adult-acquired flatfoot deformity (AAFD) is traditionally treated by realignment osteotomy and a tendon transfer. Despite high success rates for this procedure, prolonged recovery time and associated morbidities may lead many patients to shy away from having this type of surgery performed on them. Over the past decade, the use of biologics such as platelet-rich plasma and concentrated bone marrow aspirate concentrate has been gaining much popularity. The efficacy of these biologics to treat tendon pathologies is currently well supported in the literature. Therefore, when treating early AAFD with a functioning posterior tibial tendon, biological agents have the potential to enhance tendon healing and functional recovery. In this review we will be discussing the treatment algorithm which we currently use in our practice to manage AAFD. This will include the use of biologics with minimally invasive procedures, such as posterior tibial tendon tendoscopy and subtalar arthroereisis screws, which have the potential to address the biological and mechanical aspects of this common pathology.

Level of Evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
The “FraMo” System: A New Mini-Invasive Technique in the Treatment of Proximal Humerus Fractures
Authors: Moro Gian Luigi , Mezzadri Umberto , Mancini Nikj , Naim Rodriguez Nadim , Tartaglia Giuseppe , Gatti Michele , Pedretti Alberto , Fraschini Gianfranco
Published: June 2019

Fractures of the proximal humerus are relatively common injuries in adults accounting for 5% of fractures. Nowadays the most common technique used is open reduction internal fixation with LCP plates. The risks associated with open reduction internal fixation had led us to develop and apply a “hybrid” system, which is based on external fixation and closed surgery principles. This system is capable of stabilize up to 4 fragment fractures on different planes while conferring a strong enough fixation to maintain fracture reduction while allowing the patient to perform passive and active movement since the first day following the surgery. Our study group started on November 2009 until December 2015 and consisted of 118 patients with a mean age of 68.84±10.52 years for females (76) and 65.62±12.56 for males (44). Patients were classified according to the AO/OTA (Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma association) Classification. In a few patients we performed mini lateral accesses to allow reduction of the humeral head and greater tuberosity. Shoulder mobilization was initiated from the first day following surgery. The external fixator was removed at 5 weeks with successive check-ups at 3, 6, and 12 months. The majority of type B and type C1 fractures had almost a complete functional recovery. Patients also, especially in the elderly, reported a good quality of life without pain during any range of motion. Our group of patients, after removal of the apparatus at 5 weeks following the surgery, had a mean articular range of motion with active abduction of 90 degrees and about 100 degrees with passive abduction. Postoperative CS scores at 12 months follow-up was 75,47±8.02. In addition there was also significant (P<0.05) improvement between preoperative and postoperative visual analog scale measurements (in cm), 7.67±2.70 and 1.71±2.08, respectively. This technique has shown good functional results with reduced surgical risks and complications that are typical of open reduction surgical fixation of proximal humerus fractures, is quick in execution and minimally invasive. Given the very good results of the study of this new external fixation technique has shown to be a viable option for the treatment of proximal humerus fractures.
Extra-articular Corrective Osteotomy With Bone Grafting to Achieve Lengthening and Regain Alignment for Distal Radius Fracture Malunion
Authors: Huang Hui-Kuang , Hsu Shiuan-Hau , Hsieh Feng-Chi , Chang Kai-Hui , Chu Heuy-Ling , Wang Jung-Pan
Published: June 2019

Surgical correction of the distal radius fracture malunion is challenging because of the 3-dimensional deformity. We propose a method by using the Kapandji intrafocal pinning in corrective osteotomy for treatment of the distal radius fracture malunion to facilitate the alignment correction while using the bone graft to restore the radial length. The surgery was started with the osteotomy from a volar approach, and the osteotomy gap was expanded gradually. Then, allobone grafting was performed to maintain the corrected radial length. We used the Kapandji intrafocal pinning dorsally to provide dorsal supporting force and radially to correct the radial inclination. Finally, a volar plate was used to buttress and push the distal fragment to fit as to regain the correct volar tilt. We enrolled 10 patients of distal radius fracture malunion with a mean age of 59.3 years. All patients had bone healing within 3 months after surgery. The mean lengthened distance was 5 mm. The radial inclination and volar tilt could be corrected with improved functional results.
Assessment of Inequality Alongside Policy-oriented Trials
Authors: Søgaard Rikke , Lindholt Jes S.
Published: June 2019

Background:

Despite the dual objectives of many health care systems of improving total health and reducing health inequality, trial designs seem to ignore the assessment of inequality effects. Our study aimed to illustrate an empirical framework for the assessment of inequality effects alongside policy-oriented trials to inform a possible efficiency versus equality trade-off.

Methods:

We measured inequality in the concentrations of all-cause and disease-related mortality and hospital admissions across ranks of socioeconomic status in a randomized controlled trial that tested the efficacy of general population screening of men for vascular disease. We used alternative definitions of inequality (relative/absolute, in attainment/shortfall, ranked by education/income), and supplemented the classical “frequentist” approach to statistical inference with Bayesian posterior probabilities. Equality contours for health improvement that leave inequality unaffected are illustrated graphically. We used bootstrapping for interpretation.

Results:

We estimated the posterior probability of screening increasing inequality to be between 0.21 and 0.93 depending on the inequality definition. Income-ranked inequality appeared to be generally higher than education-ranked inequality but less affected by screening. For the shortfall-relative index based on education-rank, the mean health improvement of a 7% relative reduction in all-cause mortality generated by screening incurred a mean relative increase in inequality of 28%. For the income-based indices, there was no evidence of a trade-off.

Discussion:

We illustrated how decision uncertainty can be reduced by explicit assessment of inequality alongside trials and found some evidence of a possible equity–efficiency trade-off in the context of screening, although this depended on the definition of equality.
Higher Anxiety and Will to Live Are Associated With Poorer Adherence to Cardiac Rehabilitation
Authors: Harris Kristie M. , Anderson Derek R. , Landers Jacob D. , Emery Charles F.
Published: June 2019

Purpose:

Cardiac rehabilitation (CR) session attendance and rates of completion remain suboptimal. Greater distress (ie, depression and anxiety) has been associated with both better and poorer adherence. Will to live (ie, desire, determination and effort to survive) has been associated with survival among cardiac patients and thus may be relevant for CR adherence. It was hypothesized that depression and anxiety would be negatively associated with adherence, and that will to live would moderate these relationships.

Methods:

Sixty patients (mean age = 56.9 ± 10.8 yr; 38 males) entering outpatient CR completed self-report measures of will to live (Wish to Prolong Life Questionnaire) and distress (Hospital Anxiety and Depression Scale). Hierarchical regression analyses were performed to predict CR session attendance (%) and program completion (yes/no) from depression and anxiety, as well as the interaction of those variables with will to live.

Results:

Neither depression nor anxiety was associated with CR adherence (Ps > .33). However, there was a significant interaction of will to live with anxiety in predicting attendance (β= −0.31, P = .03, Model R
2 = .19, P = .01), reflecting that anxiety predicted lower attendance only among patients reporting greater will to live.

Conclusions:

These data help clarify the complex relationship between distress and CR adherence. Findings suggest that higher anxiety is associated with poorer adherence, but only in combination with greater motivation for living. Patients higher in anxiety and will to live may benefit from additional strategies to make actionable behavioral change in the context of CR.
Effects of a Cardiac Rehabilitation Program Versus Usual Care on Cardiopulmonary Function in Patients With Cardiac Syndrome X
Authors: Rahmani Reza , Niyazi Sepideh , Sobh-Rakhshankhah Amir , Guazzi Marco , Mazaheri Reza , Hashemi Naeimeh , Khoddami-Vishteh Hamid-Reza
Published: June 2019

Purpose:

Because of uncertainty in the pathophysiological process, the treatment of cardiac syndrome X (CSX) is still under study. Addressing the effects of cardiac rehabilitation (CR) can help promote the prescription of this modality as an adjuvant therapy for these patients.

Methods:

This study was performed on 30 patients with effort-induced angina pectoris using a positive exercise test and/or myocardial perfusion scan in the absence of obvious stenosis or a stenosis of <50% on coronary angiography. The patients were divided into the CR and usual care (UC) groups and underwent cardiopulmonary exercise testing with gas exchange analysis before and after the study. The Duke Treadmill Score was used to compare prognosis and survival estimates of patients.

Results:

An increase in peak oxygen uptake (

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2) was significantly higher in the CR group than in the control group (P = .017). Resting

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2 was also increased in the CR group, but its difference with the UC group was not statistically significant. Resting O2 pulse was increased in the CR group, which significantly differed between groups (P = .041). Exercise test duration and the Duke Treadmill Score significantly increased in the CR group as compared with the UC group (P = .003 and P = .002, respectively). Also, recovery heart rate in the first minute was significantly improved in CR group.

Conclusion:

Adding a 4-wk course of CR to UC for patients with CSX not only increased the Duke Treadmill Score and exercise test duration but also improved the resting O2 pulse, peak

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2, and first-minute recovery heart rate.
EVALUATION OF ACCURACY AND UNIFORMITY OF THE NOMENCLATURE OF VITREORETINAL INTERFACE DISORDERS
Authors: Benyamini Shira , Loewenstein Anat , Moisseiev Elad
Published: June 2019

Purpose:

To evaluate the accuracy and uniformity of the definitions used to diagnose vitreoretinal (VR) interface disorders and to assess it after review of its definitions.

Methods:

A case-series study, consisting of a questionnaire of 46 optical coherence tomography images of six VR interface disorders: vitreomacular adhesion, vitreomacular traction, epiretinal membrane, full-thickness macular hole, lamellar macular hole, and pseudohole. Images were presented to 41 practicing ophthalmologists (13 residents, 11 VR specialists, and 17 non-VR specialists), and a diagnosis was recorded for each image. The questionnaire was repeated after review of the International Vitreomacular Traction Study (IVTS) group classification. Rates of accuracy and uniformity for each condition were analyzed.

Results:

Overall correct identification rates according to the IVTS classification were achieved in 67.4% of cases and were highest for epiretinal membrane and full-thickness macular hole, followed by vitreomacular adhesion, vitreomacular traction, and lamellar macular hole, and were significantly lower for pseudohole (P < 0.001). Accuracy was higher among VR specialists and was associated with previous familiarity with the IVTS classification (P = 0.043) but not with length of experience in ophthalmology (P = 0.74). After review of the IVTS classification, overall correct identification rates improved to 71.7% (P = 0.004), with the significant improvement in pseudohole identification (P = 0.002).

Conclusion:

The IVTS classification is effective in standardizing the diagnosis of VR interface disorders. It is expected to become increasingly assimilated among ophthalmologists over time, leading to higher rates of accuracy and uniformity in diagnosing VR interface disorders.
Audiologic and Otologic Complications of Cryptococcal Meningoencephalitis in Non-HIV Previously Healthy Patients
Authors: King Kelly A. , Ansari Ghedak , Panackal Anil A. , Zalewski Chris , Anjum Seher , Bennett John E. , Beri Andrea , Kim Hung Jeff , Hammoud Dima , Brewer Carmen C. , Williamson Peter R.
Published: June 2019

Objective:

To identify audiologic and otologic outcomes in previously healthy non-HIV patients with cryptococcal meningoencephalitis (CM).

Study Design:

Retrospective case review of a subset of patients recruited in a prospective observational study following previously healthy individuals who developed CM.

Setting:

Tertiary referral center, National Institutes of Health Clinical Center.

Patients:

Previously healthy adult patients with CM without immune suppressive therapy before disease onset.

Interventions:

Diagnostic evaluations included audiometry, acoustic immittance, otoacoustic emissions, and auditory brainstem response studies, in addition to neurotologic assessment.

Results:

Twenty-nine patients (58 years) underwent audiologic evaluation between 6 months and 3.5 years after CM diagnosis; 21 patients were seen for longitudinal assessment with an average duration of follow up of 20.3 months. Nearly three-quarters (73%) of the cohort presented with hearing loss, most commonly (90%) sensorineural in origin. The most frequent degree of loss was mild and then moderate, although some patients had severe or profound impairment. Hearing loss improved (43%) or remained stable (38%) in most cases. Ears with internal auditory canal enhancement on magnetic resonance imaging (MRI) had significantly more hearing loss than those without enhancement, although a similar finding was not observed with gyral enhancement or the presence of ependymitis or ventricular volume expansion. Hearing loss was not associated with reduced cerebrospinal fluid (CSF) glucose, CSF total protein, cryptococcal antigen, or total cell count.

Conclusions:

Hearing loss is a common manifestation of cryptococcal meningitis in previously healthy patients and may involve a cochlear or neural site of lesion, or both. Routine surveillance of hearing in patients is recommended, regardless of symptomatology, to ensure early and appropriate intervention and care.
Standardization of the Punch Technique for the Implantation of Bone Anchored Auditory Devices: Evaluation of the MIPS Surgical Set
Authors: Kim Harold Hyon Soo , Kari Elina , Copeland Benjamin J. , Moore Gary F. , Shaia Wayne T. , Cosetti Maura K. , Wazen Jack J. , Wanna George B. , Chang Chin-Yen Joseph
Published: June 2019

Objective:

To describe and assess intraoperative and postoperative outcomes in the insertion of osseointegrated auditory implants with a newly designed surgical instrumentation set through a punch type technique.

Study Design:

Retrospective case series.

Methods:

Patients who underwent bone anchored auditory implant surgery using the Minimally Invasive Ponto Surgery (Oticon Medical, Somerset, NJ) surgical set through a punch technique at nine neurotology tertiary referral based practices were identified. Demographic data, skin thickness at implant site, implant used, duration of surgery, adverse intraoperative events, and postoperative outcomes were recorded.

Results:

Seventy-five patients comprised the study cohort (32 males, 43 females). Most patients (57. 3%) were aged 51 to 75 years while 30.7% of the cohort comprised those aged 18 to 50 years and 12% were over 75 years. All but two patients received 4 mm fixtured implants and 68% received the Oticon Medical BioHelix implant. Two patients received 3 mm fixture implants and 32% received the Oticon Medical Wide Ponto implant. Mean surgical time was 12.2 minutes (6–45 min, standard deviation of 6.88 min). In three instances, surgery was converted to a linear incision to control brisk bleeding. Skin condition was Holgers 0 to 1 in 91.8%, while 5.5% had Holgers 2, and 2.7% had Holgers 3 at the first postoperative visit. At second postoperative visit, 94.3% had Holgers 0 to 1, 4.3% had Holgers 2, and 1.4% had Holgers 3. All instances of adverse skin reactions were treated with topical or systemic antibiotics and/or local debridement. There were no instances of implant loss. One patient had his implant traumatically displaced to a 45-degree angle necessitating implant replacement at a second site.

Conclusion:

Punch technique placement of osseointegrated auditory implants using the Minimally Invasive Ponto Surgery surgical set represents a safe technique that further simplifies a progressively minimally invasive surgery.
Audiologic Improvement Following MCF Approach for Spontaneous Cerebrospinal Fluid Leaks
Authors: Alwani Mohamedkazim , Bandali Elhaam , Van Buren Lauren , Yates Charles W. , Nelson Rick F.
Published: June 2019

Objective:

To determine the audiologic improvement after middle cranial fossa (MCF) approach to repair spontaneous cerebrospinal fluid (sCSF) leaks.

Study Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients:

Twenty-four consecutive patients (27 ears) with temporal bone sCSF leak over a 4-year period. Patient age, sex, ethnicity, body mass index (BMI), location of CSF leak, recurrence of CSF leak, and presence of encephalocele(s) were recorded.

Intervention:

Audiometric testing in patients undergoing MCF repair of temporal bone sCSF leak.

Main Outcome Measures:

Comparison of preoperative and postoperative pure-tone average (PTA), air-bone gap (ABG), and word recognition score (WRS) in the sCSF leak ear.

Results:

Out of 27 ears, 55% had multiple tegmen defects and 82% had more than or equal to 1 encephaloceles. There were no recurrent CSF leaks at a median follow up of 4 months. The mean (SD) preoperative PTA and ABG were 40.58 [15.67] and 16.44 [6.93] dB, respectively. There was significant improvement in mean PTA (10.28 [8.01] dB; p < 0.001; Cohen d = 0.95) and ABG (9.31 [7.16] dB; p < 0.001; Cohen d = 0.88) after sCSF repair. Mean WRS improved (by 3.07 [6.11] %; p = 0.024; Cohen d = 0.46) from a mean preoperative WRS of 93.16 [9.34]% to a mean postoperative WRS of 96.26 [6.49]%.

Conclusions:

MCF approach for repair of sCSF leaks yields significant improvement in conductive hearing loss and is highly effective in management of the entire lateral skull base where multiple bony defects are often identified.
Arterial stiffness is associated independently with liver stiffness in biopsy-proven nonalcoholic fatty liver disease: a transient elastography study
Authors: Bilgin Beyza O. , Sunbul Murat , Kani Haluk T. , Demirtas Coskun O. , Keklikkiran Caglayan , Yilmaz Yusuf
Published: June 2019

Background

Nonalcoholic fatty liver disease (NAFLD) has been associated with an increased arterial stiffness. However, the question as to whether an association exists between the extent of vascular and liver stiffness in patients with biopsy-proven NAFLD remains open. In this study, we sought to investigate whether pulse wave velocity (PWV) and augmentation index (AIx) – two common indices of arterial stiffness – are associated with (a) liver stiffness measurement (LSM) on transient elastography (TE) and (b) histological liver fibrosis.

Patients and methods

We examined 125 patients with biopsy-proven NAFLD and 55 age-matched and sex-matched controls. Arterial stiffness of the brachial artery was measured using a Mobil-O-Graph arteriography system. LSM was assessed using TE, whereas the presence of advanced fibrosis (F ≥ 3) was determined on histology.

Results

Patients with NAFLD had higher PWV [median: 7.2 (6.3−8.2) and 6.2 (5.5−6.7) m/s, respectively, P < 0.001] and AIx (mean: 21.3 ± 13.5 and 17.2 ± 11.9%, respectively, P=0.01) compared with the controls. LSM showed positive correlations with both PWV (ρ = 0.300; P<0.01) and AIx (ρ = 0.223, P = 0.02). Both indices of arterial stiffness were higher in patients with advanced fibrosis than in those with nonadvanced fibrosis (F ≤ 2).

Conclusion

The severity of arterial and liver stiffness increases in parallel in patients with biopsy-proven NAFLD. Systematic risk assessment for reducing arterial stiffness is recommended in the presence of TE-determined advanced fibrosis.
Offset Effects of Outpatient Cost-sharing for the Poor in Korea
Authors: Ko Hansoo
Published: June 2019

Objective:

The objective of this study was to evaluate the impacts of the implementation of patient cost-sharing for an outpatient visit and prescription drugs for poor and nonable bodied Koreans in 2007.

Data Sources/Study Settings:

Nationally-representative longitudinal data sets (Korea Welfare Panel Study and the Korean Longitudinal Study of Ageing) in 2006, 2008, and 2010.

Research Design:

Propensity score matching with difference-in-differences framework exploiting within-person variation in cost-sharing.

Results:

Decreases in the probability of outpatient visit are offset by increases in the likelihood of hospitalization after the policy change. Cost-sharing also decreases drug adherence by 20%, particularly among chronically-ill persons.

Conclusion:

Because the costs of increased hospitalization among Medical Aid enrollees accrue to the government, the introduction of outpatient cost-sharing does not achieve the goal of cost control.
Disputes of Self-reported Chronic Disease Over Time
Authors: Quiñones Ana R. , Melekin Amanuel , Cigolle Christine T. , Nagel Corey L.
Published: June 2019

Background:

Respondents in longitudinal health interview surveys may inconsistently report their chronic diseases across interview waves. Racial/ethnic minority adults have an increased burden of chronic diseases and may dispute chronic disease reports more frequently.

Objective:

We evaluated the longitudinal association between race/ethnicity, nativity, and language of interview with disputing previously reported chronic diseases.

Methods:

We performed secondary data analysis of nationally representative longitudinal data (Health and Retirement Study, 1998–2010) of adults 51 years or older (n=23,593). We estimated multilevel mixed-effects logistic models of disputes of previously reported chronic disease (hypertension, heart disease, lung disease, diabetes, cancer, stroke, arthritis).

Results:

Approximately 22% of Health and Retirement Study respondents disputed prior chronic disease self-reports across the entire study period; 21% of non-Latino white, 20.5% of non-Latino black, and 28% of Latino respondents disputed. In subgroup comparisons of model-predicted odds using postestimation commands, Latinos interviewed in Spanish have 34% greater odds of disputing compared with non-Latino whites interviewed in English and 35% greater odds of dispute relative to non-Latino blacks interviewed in English.

Conclusions:

The odds of disputing a prior chronic disease report were substantially higher for Latinos who were interviewed in Spanish compared with non-Latino white or black counterparts interviewed in English, even after accounting for other sociodemographic factors, cognitive declines, and time-in-sample considerations. Our findings point toward leveraging of multiple sources of data to triangulate information on chronic disease status as well as investigating potential mechanisms underlying the higher probability of dispute among Spanish-speaking Latino respondents.
Heme Oxygenase-1 Polymorphism Is Associated With the Development of Necrotic Acute Pancreatitis Via Vascular Cell Adhesion Molecule-1 and the E-Selectin Expression Regulation Pathway
Authors: Gulla Aiste , Gulbinas Antanas , Dambrauskas Zilvinas , Strupas Kestutis
Published: June 2019

Objectives

Severe acute pancreatitis can lead to systemic complications. Here, we explore the mechanisms based on our previous study associated with the deregulation of heme oxygenase-1 (HO-1) and development of severe acute pancreatitis.

Methods

Acute pancreatitis patients (n = 135) and age- and sex-matched healthy controls (n = 108) were studied. The polymerase chain reaction products were analyzed with an ABI 3130 genetic analyzer and GeneMapper software. A short allele was defined ≤27 dinucleotide (GT) repeats, whereas a long allele was defined >27 GT. Levels of 12 different cytokines in blood serum were measured by enzyme-linked immunosorbent assay. All samples in this study were consistently stored in −80°C.

Results

Patients with the long long genotype expressed E-selectin and vascular cell adhesion molecule-1 at statistically significantly higher levels in serum compared with short short genotype or short long genotypes. Vascular cell adhesion molecule-1 and E-selectin serum levels significantly correlate with the total allele length of the HO-1 promoter region.

Conclusion

Polymorphism of the GT repeats in the HO-1 promoter region may be a risk factor for developing acute necrotizing pancreatitis due to deregulation of the immune response.
Per Oral Pancreatoscopy Identification of Main-duct Intraductal Papillary Mucinous Neoplasms and Concomitant Pancreatic Duct Stones
Authors: Han Samuel , Raijman Isaac , Machicado Jorge D. , Edmundowicz Steven A. , Shah Raj J.
Published: June 2019

Objectives

Per oral pancreatoscopy (POP) assists in the evaluation and treatment of select benign and neoplastic pancreatic disorders including main-duct intraductal papillary mucinous neoplasm (MD-IPMN). Although pancreatic duct stones are classically thought of as pathognomonic for chronic pancreatitis, its co-occurrence with MD-IPMN as identified via POP may help identify an alternative etiology for presumed idiopathic chronic pancreatitis.

Methods

This was a multicenter retrospective case series of patients found to have pancreatic duct stones with concomitant MD-IPMN by POP.

Results

Thirteen patients with presumed idiopathic chronic calcific pancreatitis were found on POP to have both pancreatic duct stones and MD-IPMN. All patients had a dilated pancreatic duct, and most (92.3%) were symptomatic.

Conclusions

Per-oral pancreatoscopy may identify MD-IPMN as an etiology for patients with presumed idiopathic chronic calcific pancreatitis and associated dilated pancreatic duct. Larger prospective studies are needed to validate these findings.
Lactation Consultation Sustains Breast Milk Intake in Infants With Cystic Fibrosis
Authors: Miller Tami , Antos Nicholas J. , Brock Lisa A. , Wade Thomas , Goday Praveen S.
Published: June 2019

Guidelines recommend breastfeeding in cystic fibrosis (CF) but breastfeeding rates decline rapidly in CF. We initiated a quality improvement project to improve breastfeeding in CF by incorporating International Board‐Certified Lactation Consultants (IBCLC) into the initial CF‐diagnosis visit to support mothers who were breastfeeding at diagnosis. In the preintervention group, only 8/14 (57%) continued to provide breast milk after the first visit, whereas postintervention, 16/17 (94%) mothers continued to do so (P = 0.03). The duration of any (or partial) breastfeeding increased to an average of 7.7 months from an average of 6.4 months preintervention (P = 0.45). The weight z score and weight‐for‐length z score at diagnosis showed no change at 6 or 12 months (all comparisons P value >0.05). We conclude that mothers who met with the IBCLC were less likely to quit breastfeeding and hypothesize that lactation support to mothers can prolong the duration of breastfeeding in infants with CF.
Clinical Nurse Specialist–Led Implementation of an Early Discharge Protocol After Cardiac Surgery
Authors: Kwak Chanyeong , Ko Young
Published: June 2019

Purpose/Aims

Current practice in Korean medical institutions executes prolonged average length of stay post–cardiac surgery, imposing higher risks of mortality and morbidity, along with administrative issues resulting in long waiting lists for future cardiac surgery. The purpose of this article is to develop and evaluate an early discharge protocol after cardiac surgery led by clinical nurse specialist in a Korean medical institution.

Description of the Project/Program

The project of implementing early discharge protocol seeks to provide an efficient delivery system for patients who are undergoing cardiac surgery. To evaluate the efficacy of this project, a group of cohorts administered with early discharge protocol was compared against the control group for their length of hospital stay, adverse complications, and clinical outcomes such as postoperative mortality and morbidity.

Outcomes

The early discharge protocol group had a decreased hospital length of stay by 30% (P < .05) compared with the control group under the conventional discharge protocol while maintaining patient safety and minimizing exposure of patients to further risks of mortality and morbidity.

Conclusion

Clinical nurse specialist–led early discharge protocol in patients who received cardiac surgery decreases length of stay, thus minimizing exposure of patients to further risks of mortality and morbidity.
Case Study: Schistosomiasis of the Endocervical Canal, A Rarely Reported Localization
Authors: Delavy Martine , Heriniainasolo Josea Lea , Catarino Rosa , Viviano Manuela , Petignat Patrick , Vassilakos Pierre
Published: June 2019

With a challenging diagnosis, schistosomiasis is a major public health issue worldwide, particularly in low-resource countries. The presence of Schistosoma ova in the female genital tract is a common finding, which may engender considerable suffering among women of child-bearing age. We report the asymptomatic case of endocervical schistosomiasis without visible exocervical lesions in a 41-yr-old Malagasy woman with human papillomavirus-positive status detected during a cervical cancer screening campaign in Andilampanahy, Madagascar. Schistosomiasis involving only the endocervical canal is rarely reported and can be diagnosed histologically with endocervical brushing, which therefore represents a minimally invasive and well-tolerated tool for disease detection.
A New Classification of Benign, Premalignant, and Malignant Endometrial Tissues Using Machine Learning Applied to 1413 Candidate Variables
Authors: Downing Michael J. , Papke David J. , Tyekucheva Svitlana , Mutter George L.
Published: June 2019

Benign normal (NL), premalignant (endometrial intraepithelial neoplasia, EIN) and malignant (cancer, EMCA) endometria must be precisely distinguished for optimal management. EIN was objectively defined previously as a regression model incorporating manually traced histologic variables to predict clonal growth and cancer outcomes. Results from this early computational study were used to revise subjective endometrial precancer diagnostic criteria currently in use. We here use automated feature segmentation and updated machine learning algorithms to develop a new classification algorithm. Endometrial tissue from 148 patients was randomly separated into 72-patient training and 76-patient validation cohorts encompassing all 3 diagnostic classes. We applied image analysis software to keratin stained endometrial tissues to automatically segment whole-slide digital images into epithelium, cells, and nuclei and extract corresponding variables. A total of 1413 variables were culled to 75 based on random forest classification performance in a 3-group (NL, EIN, EMCA) model. This algorithm correctly classifies cases with 3-class error rates of 0.04 (training set) and 0.058 (validation set); and 2-class (NL vs. EIN+EMCA) error rate of 0.016 (training set) and 0 (validation set). The 4 most heavily weighted variables are surrogates of those previously identified in manual-segmentation machine learning studies (stromal and epithelial area percentages, and normalized epithelial surface lengths). Lesser weighted predictors include gland and lumen axis lengths and ratios, and individual cell measures. Automated image analysis and random forest classification algorithms can classify normal, premalignant, and malignant endometrial tissues. Highest predictive variables overlap with those discovered independently in early models based on manual segmentation.
Color Vision Deficiency Among Doctors: Can We Make Useful Adaptations to the Color Codes Used in the Clinical Environment?
Authors: Thomas Peter B. M. , Nesaratnam Nisha , Chaudhuri-Vayalambrone Prannoy , Mollon John D.
Published: June 2019

Color vision deficiency (formerly known as color blindness) is common as a congenital and as an acquired condition. Some professions, most famously commercial aviation, require their members to demonstrate normal color vision. In the United States and United Kingdom, no restriction is placed on the ability of the color-deficient doctor to practice medicine, although there is evidence that certain clinical discriminations are harder for such doctors. Generally ignored has been the difficulty and the potential for error that arises from the use of color codes in clinical equipment. In this review, we introduce the basic concepts of color deficiency, summarize evidence for the challenges it poses to the doctor, examine global variation in policy, show the potential for confusion among clinical color codes, and suggest how the current situation could be improved to enhance both patient safety and the well-being of the color-deficient doctor.
Biologics in Acute Burn Injury
Authors: Kogan Samuel , Halsey Jordan , Agag Richard L.
Published: June 2019

There have been significant advances in the care of burns over the past decade. As a result of the improved survival of burn patients, attention has shifted to the optimized management of their wounds. Traditionally, autografts have been described as the gold standard treatment in cases of deep second- and third-degree burn wounds; however, they are limited especially in large surface area burns. As such, advancements have been made in the development of biologic dressings, which attempt to mimic the function of the lost epidermis and/or dermis. The ideal biologic dressing is nontoxic, lacks antigenicity, is immunologically compatible, and is sterile. Additionally, easy storage conditions, long shelf lives, and reasonable costs are key determinants of whether biologic dressings may truly be widely used in the clinical setting. Biologic dressings serve an important role as skin substitutes in the setting of acute burn injury. This review aims to summarize the multitude of available biologic dressings and their applications.

Methods

The PubMed and Google Scholar databases were searched for the following terms either alone or in combination: “burn injury,” “biologic membrane,” “skin substitutes,” “biosynthetic dressings,” and “acellular membrane.”
Predator-induced selection on urchin activity level depends on urchin body size
Authors: Pretorius Justin , Lichtenstein James L.L. , Eliason Erika J. , Stier Adrian C. , Pruitt Jonathan N.
Published: June 2019

Temporally consistent individual differences in behavior impact many ecological processes. We simultaneously examined the effects of individual variation in prey activity level, covering behavior, and body size on prey survival with predators using an urchin-lobster system. Specifically, we tested the hypothesis that slow-moving purple sea urchins (Strongylocentrotus purpuratus) and urchins who deploy extensive substrate (pebbles and stones) covering behavior will out-survive active urchins that deploy little to no covering behavior when pitted against a predator, the California spiny lobster (Panulirus interruptus). We evaluated this hypothesis by first confirming whether individual urchins exhibit temporally consistent differences in activity level and covering behavior, which they did. Next, we placed groups of four urchins in mesocosms with single lobster and monitored urchin survival for 108 hours. High activity level was negatively associated with survival, whereas urchin size and covering behavior independently did not influence survival. The negative effect of urchin activity level on urchin survival was strong for smaller urchins and weaker for large urchins. Taken together, these results suggest that purple urchin activity level and size jointly determine their susceptibility to predation by lobsters. This is potentially of great interest, because predation by recovering lobster populations could alter the stability of kelp forests by culling specific phenotypes, like foraging phenotypes, from urchin populations.
Automated Clear Cell Renal Carcinoma Grade Classification with Prognostic Significance
Authors: Tian Katherine , Rubadue Christopher A. , Lin Douglas I. , Veta Mitko , Pyle Michael E. , Irshad Humayun , Heng Yujing J.
Published: June 2019

We developed an automated 2-tiered Fuhrman’s grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n=72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman’s grades between TCGA and Pathologist 1 (training set n=235; held-out test set n=42). Discordant cases (n=118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n=160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21-3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts.
Sex-Biased Trajectories of Amygdalo-Hippocampal Morphology Change Over Human Development
Authors: Fish Ari M. , Nadig Ajay , Seidlitz Jakob , Reardon Paul K. , Mankiw Catherine , McDermott Cassidy L. , Blumenthal Jonathan D. , Clasen Liv S. , Lalonde Francois , Lerch Jason P. , Chakravarty M. Mallar , Shinohara Russell T. , Raznahan Armin
Published: June 2019

The amygdala and hippocampus are two adjacent allocortical structures implicated in sex-biased and developmentally-emergent psychopathology. However, the spatiotemporal dynamics of amygdalo-hippocampal development remain poorly understood in healthy humans. The current study defined trajectories of volume and shape change for the amygdala and hippocampus by applying a multi-atlas segmentation pipeline (MAGeT-Brain) and semi-parametric mixed-effects spline modeling to 1,529 longitudinally-acquired structural MRI brain scans from a large, single-center cohort of 792 youth (403 males, 389 females) between the ages of 5 and 25 years old. We found that amygdala and hippocampus volumes both follow curvilinear and sexually dimorphic growth trajectories. These sex-biases were particularly striking in the amygdala: males showed a significantly later and slower adolescent deceleration in volume expansion (at age 20 years) than females (age 13 years). Shape analysis localized significant hot-spots of sex-biased anatomical development in sub-regional territories overlying rostral and caudal extremes of the CA1/2 in the hippocampus, and the centromedial nuclear group of the amygdala. In both sexes, principal components analysis revealed close integration of amygdala and hippocampus shape change along two main topographically-organized axes – low vs. high areal expansion, and early vs. late growth deceleration. These results bring greater resolution to our spatiotemporal understanding of amygdalo-hippocampal development in healthy males and females and discover focal sex-differences in the structural maturation of the brain components that may contribute to differences in behavior and psychopathology that emerge during adolescence.

SIGNIFICANCE STATEMENT

The amygdala and hippocampus are implicated in several developmentally-dynamic and sex-biased psychiatric disorders, but the spatiotemporal organization and sex-biased patterning of amygdalo-hippocampal maturation remains unclear in humans. Here, by integrating new methods for analysis of longitudinal neuroimaging data, we resolve the developmental milestones and spatial gradients that organize human amygdalo-hippocampal maturation. Each structure’s volume follows a tri-phasic, curvilinear growth trajectory which - for the amygdala - shows rapid male-female size divergence in mid-adolescence through delayed growth deceleration in males. Spatially fine-grained shape analyses localize these sex differences, and further reveal highly orchestrated shape changes across the amygdala and hippocampus that are organized by two topographical gradients. These data provide a new framework for understanding amygdalo-hippocampal organization in human development.
MinION Sequencing of colorectal cancer tumour microbiomes – a comparison with amplicon-based and RNA-Sequencing
Authors: Taylor William S , Pearson John , Miller Allison , Schmeier Sebastian , Frizelle Frank A , Purcell Rachel V
Published: June 2019

Recent evidence suggests a role for the gut microbiome in the development and progression of colorectal cancer. In this study we compare MinION sequencing with meta-transcriptomics and amplicon-based sequencing for microbiome analysis of colorectal tumour tissue samples. DNA and RNA were extracted from 11 colorectal tumour samples. RNA-Sequencing, 16S rRNA amplicon sequencing and MinION genomic sequencing was carried out and resulting data used as input for taxonomic classification using Kraken2. Taxonomic concordance between the three platforms at different taxonomic levels was tested on a per sample basis. The average number of reads per sample using RNA-Sequencing was more than 129 times that generated using MinION sequencing. However, the average read length of MinION sequences was more than 13 times that of RNA or 16S rRNA amplicon sequencing. 16S sequencing was less informative beyond the genus level, and both RNA-Sequencing and MinION sequencing could detect more phyla and genera in the same samples, compared to 16S sequencing. Long-read sequences generated using MinION sequencing can compensate for low numbers of reads for bacterial classification. MinION sequencing can discriminate between bacterial strains and plasmids and shows potential as a tool for microbiome sequencing of colorectal cancers in a clinical setting.
Fentanyl depression of respiration: comparison with heroin and morphine
Authors: Hill Rob , Santhakumar Rakulan , Dewey William , Kelly Eamonn , Henderson Graeme
Published: June 2019

Background and Purpose

Fentanyl overdose deaths have reached ‘epidemic’ levels in North America. Death in opioid overdose invariably results from respiratory depression. In the present work we have characterized how fentanyl depresses respiration and by comparing fentanyl with heroin and morphine, the active breakdown product of heroin, we have sought to determine whether there are factors, in addition to high potency, that contribute to the lethality of fentanyl.

Experimental Approach

Respiration (rate and tidal volume) was measured in awake, freely moving mice by whole body plethysmography

Key Results

Intravenously administered fentanyl produced more rapid depression of respiration than equipotent doses of heroin or morphine. Fentanyl depressed both respiratory rate and tidal volume, the effect on tidal volume may reflect increased respiratory muscle stiffness. Fentanyl did not depress respiration in μ opioid receptor knock-out mice. Naloxone, the opioid antagonist widely used to treat opioid overdose, reversed the depression of respiration by morphine more readily than that by fentanyl whereas diprenorphine, a more lipophilic antagonist, was equipotent in reversing fentanyl and morphine depression of respiration. Prolonged treatment with morphine induced tolerance to respiratory depression but the degree of cross tolerance to fentanyl was less than the tolerance to morphine itself.

Conclusion and Implications

We propose that several factors (potency, rate of onset, muscle stiffness, lowered sensitivity to naloxone and lowered cross tolerance to morphine) combine to make fentanyl more likely to cause opioid overdose deaths than other commonly abused opioids.