bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient-Reported Outcome Measures in Neurosurgery: A Review of the Current Literature
Authors: Ghimire Prajwal , Hasegawa Harutomo , Kalyal Nida , Hurwitz Victoria , Ashkan Keyoumars
Published: October 2017

BACKGROUND

Patient-reported outcome measures (PROMs) play an important role in the evaluation of health outcomes, quality of life, and satisfaction, and have been successfully utilized in many areas of clinical medicine and surgical practice. The prevalence of PROMs in neurosurgery is not known.

OBJECTIVE

To review the PROMs that have been utilized in the published neurosurgery literature to date.

METHODS

Articles were searched in MEDLINE, EMBASE, HMIC Health Management Information Consortium, PsycARTICLES, and PsycINFO using search terms related to neurosurgery and PROMs, published from 1806 to August 2016. A total of 268 articles were identified that were stratified by the inclusion and exclusion criteria leading to a total of 137 articles. Twenty-six PROMs, involving both adult and pediatric populations, were identified.

RESULTS

A large number of generic and disease-specific PROMs are used in the neurosurgical literature. Generic PROMs are usually nonspecific measures of health status. Disease-specific PROMs may not address issues relevant to neurosurgical procedures. There are very few neurosurgery-specific PROMs that take into account the impact of a neurosurgical procedure on a specific condition.

CONCLUSION

PROMs that currently feature in the neurosurgical literature may not address the specific outcomes relevant to neurosurgical practice. There is an emergent need for generic and disease-specific PROMs to be validated in neurosurgical patients and neurosurgery-specific PROMs developed to address unmet needs of patients undergoing neurosurgical procedures.
Limited Midline Myelotomy for Intractable Visceral Pain: Surgical Techniques and Outcomes
Authors: Vedantam Aditya , Koyyalagunta Dhanalakshmi , Bruel Brian Mendoza , Dougherty Patrick M , Viswanathan Ashwin
Published: October 2017

BACKGROUND

Limited midline myelotomy targets the midline nociceptive pathway for intractable visceral pain. Multiple techniques are available for limited midline myelotomy; however, outcome data for each technique are sparse.

OBJECTIVE

To review our experience with open and percutaneous approaches for limited midline myelotomy for intractable visceral pain.

METHODS

Patients who underwent limited midline myelotomy for intractable visceral pain were reviewed. Myelotomy was performed using 3 techniques: open limited myelotomy, percutaneous radiofrequency myelotomy, and percutaneous mechanical myelotomy. Demographic and perioperative clinical data were recorded. In addition to the visual analog scale and Karnofsy performance score, outcomes were categorized as excellent (no pain), good (considerable reduction in pain, not requiring opioids stronger than codeine), fair (minimal reduction in pain, but no change in opioid medication requirement), and poor (no reduction in pain).

RESULTS

Eight patients (median age 56.5 yr, 6 females) underwent limited myelotomy. Four patients underwent open limited thoracic myelotomy with excellent pain outcomes. Three patients underwent percutaneous radiofrequency lesioning with fair (n = 1) and poor outcomes (n = 2). One patient underwent percutaneous mechanical lesioning with a good outcome (n = 1). The median duration of follow-up was 11 wk (2-54 wk). Two patients reported minor sensory complications after the procedure.

CONCLUSION

In our preliminary experience, outcomes for open limited thoracic myelotomy were superior to percutaneous approaches. Given the limited utilization of this technique, multicenter registries are needed to further evaluate the best surgical technique for limited midline myelotomy.
Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome
Authors: Rao Avinash , Soliman Hesham , Kaushal Mayank , Motovylyak Olesya , Vedantam Aditya , Budde Matthew D , Schmit Brian , Wang Marjorie , Kurpad Shekar N
Published: October 2017

BACKGROUND

Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM).

OBJECTIVE

To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery.

METHODS

Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. Functional status was measured using the modified Japanese Orthopedic Association (mJOA) scale preoperatively and at follow-up up to 2 yr. Regression analysis between FA and mJOA was performed. DTI at C4-7 was obtained in controls.

RESULTS

Forty-four CSM patients enrolled prior to decompression were compared with 24 controls. FA at the level of maximal compression correlated positively with preoperative mJOA score. Preoperative FA correlated inversely with recovery throughout the postoperative period. This was statistically significant at 12 mo postoperation and nearly so at 6 and 24 mo. Patients with preoperative FA <0.55 had a statistically significant difference in outcome compared to FA >0.55.

CONCLUSION

In the largest longitudinal study of this kind, FA promises a valid biomarker for severity of CSM and postoperative improvement. FA is an objective measure of function and could provide a basis for prognosis. FA is particularly useful if preoperative values are less than 0.55.
Hemodynamics Associated With Intracerebral Arteriovenous Malformations: The Effects of Treatment Modalities
Authors: Fennell Vernard S , Martirosyan Nikolay L , Atwal Gursant S , Kalani M Yashar S , Ponce Francisco A , Lemole G Michael , Dumont Travis M , Spetzler Robert F
Published: October 2017

The understanding of the physiology of cerebral arteriovenous malformations (AVMs) continues to expand. Knowledge of the hemodynamics of blood flow associated with AVMs is also progressing as imaging and treatment modalities advance. The authors present a comprehensive literature review that reveals the physical hemodynamics of AVMs, and the effect that various treatment modalities have on AVM hemodynamics and the surrounding cortex and vasculature. The authors discuss feeding arteries, flow through the nidus, venous outflow, and the relative effects of radiosurgical monotherapy, endovascular embolization alone, and combined microsurgical treatments. The hemodynamics associated with intracranial AVMs is complex and likely changes over time with changes in the physical morphology and angioarchitecture of the lesions. Hemodynamic change may be even more of a factor as it pertains to the vast array of single and multimodal treatment options available. An understanding of AVM hemodynamics associated with differing treatment modalities can affect treatment strategies and should be considered for optimal clinical outcomes.
Diversity and Pathogenicity of Rhizoctonia Species from the Brazilian Cerrado
Authors: Blanco Angel José Vieira , Costa Marília Oliveira , Silva Roberto do Nascimento , Albuquerque Fábio Suzart de , Melo Arthur Tavares de Oliveira , Lopes Fabyano Alvares Cardoso , Steindorff Andrei Stecca , Barbosa Elder Tadeu , Ulhoa Cirano José , Lobo Junior Murillo
Published: October 2017

Eighty-one Rhizoctonia-like isolates were identified based on morphology and nuclei-staining methods from natural and agricultural soils of the Cerrado (Brazilian savanna). The nucleotide similarity analysis of ITS1-5.8S-ITS2 regions identified 14 different taxa, with 39.5% of isolates assigned to Waitea circinata (zeae, oryzae, and circinata varieties), while 37.0% belonged to Thanatephorus cucumeris anastomosis groups (AGs) AG1-IB, AG1-ID, AG1-IE, AG4-HGI, and AG4-HGIII. Ceratobasidium spp. AG-A, AG-F, AG-Fa, AG-P, and AG-R comprised 23.5%. Rhizoctonia zeae (19.8%), R. solani AG1-IE (18.6%), and binucleate Rhizoctonia AG-A (8.6%) were the most frequent anamorphic states found. Root rot severity caused by the different taxa varied from low to high on common beans, and tended to be low to average in maize. Twenty-two isolates were pathogenic to both hosts, suggesting difficulties in managing Rhizoctonia root rots with crop rotation. These results suggest that cropping history affects the geographical arrangement of AGs, with a prevalence of AG1 in the tropical zone from central to north Brazil while the AG4 group was most prevalent from central to subtropical south. W. circinata var. zeae was predominant in soils under maize production. To our knowledge, this is the first report on the occurrence of W. circinata var. circinata in Brazil.
A Systematic Review of Atypical Antipsychotics in Chronic Pain Management
Authors: Jimenez Xavier F. , Sundararajan Tharani , Covington Edward C.
Published: October 2017

Introduction:

Many psychopharmacologic agents are used as primary or adjuncts in pain management. Atypical antipsychotics (AAs) have also been used as adjuncts in pain management regimens in a variety of manners; however, their efficacy in this capacity is unclear.

Methods:

A systematic review of all studies examining AA use for pain was conducted. Three literature databases were utilized to search for word combinations of “pain” and a variety of commonly prescribed AAs ie, (olanzapine, quetiapine, risperidone, aripiprazole, ziprasidone, clozapine, paliperidone, iloperidone, lurasidone). Articles chosen for review included retrospective analyses, randomized control trials, and case series/reports. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses diagram illustrates the study selection process.

Results:

Olanzapine, quetiapine, risperidone, aripiprazole, and ziprasidone are the only AAs with published studies in pain management. Among these, olanzapine and quetiapine have the most studies (11 and 6, respectively). Olanzapine shows preliminary and consistent efficacy in fibromyalgia and headache/migraine, although only 1 study was a randomized controlled trial with level I evidence of efficacy. Other AAs eg, (quetiapine) fail to demonstrate efficacy in pain syndromes and/or lack robust study designs.

Conclusions:

Few studies have been conducted to evaluate the analgesic effects of AAs. The collective findings of multiple studies evaluating olanzapine in pain syndromes suggest a high, yet preliminary level of evidence of efficacy, warranting prospective studies in various pain syndrome contexts. Pharmacological mechanisms of AA action are elaborated, and the findings of this review are discussed. Risk and benefits of using AAs in chronic pain are described, and investigational implications and future directions are explored.
Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation During Angiotensin II Therapy in Septic Acute Kidney Injury
Authors: Lankadeva Yugeesh R. , Kosaka Junko , Evans Roger G. , Bellomo Rinaldo , May Clive N.
Published: October 2017

Objectives:

Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action induces renal hypoxia. We therefore examined the effects of angiotensin II on intrarenal Po
2 in ovine sepsis. We also assessed the validity of urinary Po
2 as a surrogate measure of medullary Po
2.

Design:

Interventional study.

Setting:

Research Institute.

Subjects:

Sixteen adult Merino ewes (n = 8/group).

Interventions:

Sheep were instrumented with fiber-optic probes in the renal cortex, medulla, and within a bladder catheter to measure Po
2. Conscious sheep were infused with Escherichia coli for 32 hours. At 24–30 hours, angiotensin II (0.5–33.0 ng/kg/min) or saline vehicle was infused.

Measurements and Main Results:

Septic acute kidney injury was characterized by hypotension and a 60% ± 6% decrease in creatinine clearance. During sepsis, medullary Po
2 decreased from 36 ± 1 to 30 ± 3 mm Hg after 1 hour and to 20 ± 2 mm Hg after 24 hours; at these times, urinary Po
2 was 42 ± 2, 34 ± 2, and 23 ± 2 mm Hg. Increases in urinary neutrophil gelatinase-associated lipocalin (12% ± 3%) and serum creatinine (60% ± 23%) were only detected at 8 and 24 hours, respectively. IV infusion of angiotensin II, at 24 hours of sepsis, restored arterial pressure and improved creatinine clearance, while not exacerbating medullary or urinary hypoxia.

Conclusions:

In septic acute kidney injury, renal medullary and urinary hypoxia developed several hours before increases in currently used biomarkers. Angiotensin II transiently improved renal function without worsening medullary hypoxia. In septic acute kidney injury, angiotensin II appears to be a safe, effective therapy, and urinary Po
2 may be used to detect medullary hypoxia.
Paracrine interactions of cancer-associated fibroblasts, macrophages and endothelial cells: tumor allies and foes
Authors: Ronca Roberto , Van Ginderachter Jo A. , Turtoi Andrei
Published: October 2017

Purpose of review

Tumor stroma is composed of many cellular subtypes, of which the most abundant are fibroblasts, macrophages and endothelial cells. During the process of tissue injury, these three cellular subtypes must coordinate their activity to efficiently contribute to tissue regeneration. In tumor, this mechanism is hijacked by cancer cells, which rewire the interaction of stromal cells to benefit tumor development. The present review aims at summarizing most relevant information concerning both pro-tumorigenic and anti-tumorigenic actions implicating the three stromal cell subtypes as well as their mutual interactions.

Recent findings

Although stromal cells are generally regarded as tumor-supportive and at will manipulated by cancer cells, several novel studies point at many defaults in cancer cell-mediated stromal reprograming. Indeed, parts of initial tissue-protective and homeostatic functions of the stromal cells remain in place even after tumor development. Both tumor-supportive and tumor-suppressive functions have been well described for macrophages, whereas similar results are emerging for fibroblasts and endothelial cells.

Recent success of immunotherapies have finally brought the long awaited proof that stroma is key for efficient tumor targeting. However, a better understanding of paracrine stromal interactions is needed in order to encourage drug development not only aiming at disruption of tumor-supportive communication but also re-enforcing, existing, tumor-suppressive mechanisms.
Expression of KLF6-SV2 in colorectal cancer and its impact on proliferation and apoptosis
Authors: Zhang Biao , Guo Dan-Dan , Zheng Jia-Ying , Wu Yan-An
Published: October 2017

Kruppel like factor 6 (KLF6), a member of KLF family, which has classic zinc finger structure, is broadly considered to have anticancer activity. The role of SV2 variant, one of KLF6 alternative splicing isoforms has not yet been definite in the colorectal cancer. This study aimed to detect the expression of the KLF6-SV2 in colorectal cancer and investigate its impact on cell proliferation and apoptosis. qRT-PCR was used to quantitatively determine KLF6-SV2 mRNA expression in colorectal cancer samples, corresponding normal tissue, normal colonic mucosal cell line FHC and seven colorectal cancer cell lines. SW480 and SW620 cell models with over-expressing KLF6-SV2 were constructed. Cell proliferation, cell cycle and apoptosis were measured respectively using MTT assay, DNA ploidy detection and Annexin V flow cytometry. Meanwhile, expression of p53, p21 and Bax were detected by qRT-PCR and western blot. The mRNA expression level of KLF6-SV2 in colorectal cancer tissues (0.783±0.409) was decreased than in corresponding normal tissues (1.086±0.449) (P<0.01), and expression in SW480 and SW620 were lower than in FHC, HCT116, LoVo, HT29, Caco-2 and RKO. In cell lines over-expressing KLF6-SV2, cell proliferation was markedly suppressed, cell cycle was blocked and cell apoptosis was significantly induced. Simultaneously, expression of p21 and Bax were remarkably up-regulated, while p53 remained unchanged. Decreased expression of KLF6-SV2 may be associated with the occurrence and development of colorectal cancer. KLF6-SV2 plays a role as tumor suppressor by efficiently blocking cell proliferation, arresting cell cycle and inducing apoptosis in colorectal cancer, which may be related to increased expression of p21 and Bax.
Life-threatening Autoimmune Cardiomyopathy Reproducibly Induced in a Patient by Checkpoint Inhibitor Therapy
Authors: Tajmir-Riahi Azadeh , Bergmann Tanja , Schmid Michael , Agaimy Abbas , Schuler Gerold , Heinzerling Lucie
Published: October 2017

Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%–50% to 15%. Ischemia and viral infections were ruled out. Histopathology showed hypertrophic myocarditis with interstitial lymphocytes. Prednisolone improved the patient’s condition within 3 days, leading to a 25% and 30% ejection fraction after 2 and 8 weeks, respectively, and clinical symptoms subsided completely. Importantly, reinduction of anti-PD1 therapy resulted in a flare of myocarditis. Awareness for potentially life-threatening irAE of checkpoint inhibitors like autoimmune cardiomyopathy and myocarditis is crucial to rapidly initiate adequate treatment.
Multidirectional Cranial Distraction Osteogenesis with Simplified Modifications for Treating Sagittal Synostosis
Authors: Sunaga Ataru , Sugawara Yasushi , Kamochi Hideaki , Gomi Akira , Chi Daekwan , Asahi Rintaro , Mori Masanori , Sarukawa Shunji , Uda Hirokazu , Yoshimura Kotaro
Published: October 2017

Background:

Multidirectional cranial distraction osteogenesis (MCDO) is a procedure of ours developed earlier for treating craniosynostosis. However, the numerous bone flaps led to prolonged operative time and occasional bone detachment from dura. We have since simplified the osteotomy design. In treating sagittal synostosis, required bone flaps have been reduced to 11 (from ~20).

Methods:

In a 2-year period (2014–2015), 5 boys with sagittal synostosis underwent MCDO using our simplified and fixed-form osteotomy. Mean age at surgery was 9.4 months (range, 8–11 months). Pre- and postoperative cranial morphology was assessed by cephalic index and by mid-sagittal vector analysis.

Results:

Improved cranial shape was confirmed by 3-dimensional CT scans and by mid-sagittal vector index. Mean preoperative cephalic index (68.7) progressively increased to means of 78.5 immediately after distraction device removal, 75.2 at postoperative month 6, and 75.1 at 1 year postoperatively. There were no major complications, although transient cerebrospinal fluid leakage and loosening of anchor pins occurred in 1 patient.

Conclusions:

Simplified MCDO has a number of advantages over conventional distraction procedures such as discretionary reshaping/expansion of cranium and predictable osteogenesis and is a valid treatment option for patients with sagittal synostosis.
TWELVE-MONTH EFFICACY OF INTRAVITREAL BEVACIZUMAB INJECTION FOR CHRONIC, ATYPICAL, OR RECURRENT CENTRAL SEROUS CHORIORETINOPATHY
Authors: Chung Yoo-Ri , Kim Jong Wan , Song Ji Hun , Park Aram , Kim Min Ho
Published: October 2017

Purpose:

To evaluate intravitreal bevacizumab (IVB) injection efficacy for the treatment of chronic, atypical, or recurrent central serous chorioretinopathy (CSC).

Methods:

Clinical data from 77 eyes of 71 patients with chronic, atypical, or recurrent CSC treated with IVB were retrospectively analyzed. After initial 6-weekly IVB administration until no subretinal fluid remained at the fovea, additional as-needed IVBs were administered, based on optical coherence tomography findings. Best-corrected visual acuity and central retinal thickness (CRT) were analyzed at baseline and 3, 6, 9, and 12 months after initial IVB.

Results:

The significant improvement of baseline logarithm of minimum angle of resolution best-corrected visual acuity and CRT at 3 months (both P < 0.001) was maintained throughout the 12-month follow-up period. Best-corrected visual acuity improved significantly in patients with chronic and recurrent CSC, at all time points (all P < 0.05), but not in patients with atypical CSC. The CRT reduction was significant in all subgroups during the follow-up period (all P < 0.05). Definite leakage on initial fluorescein angiography correlated with improved reduction in CRT (P = 0.039).

Conclusion:

As-needed optical coherence tomography–based IVB was effective for reducing CRT in patients with chronic, atypical, or recurrent CSC, and for vision improvement in chronic and recurrent CSC over the 1-year follow-up period.
Comfort, Ocular Dryness, and Equilibrium Water Content Changes of Daily Disposable Contact Lenses
Authors: Insua Pereira Eduardo , Lira Madalena
Published: October 2017

Objectives:

The objective of this investigation was to evaluate the level of comfort and ocular dryness during wear with six daily disposable contact lenses (DDCL) and also determine the changes in contact lens equilibrium water content (EWC) resulting from their wear.

Methods:

In this contralateral open trial, 27 subjects were randomly fitted with six DDCL (stenfilcon A, delefilcon A, nelfilcon A, narafilcon A, nesofilcon A, and omafilcon A). The evaluation of comfort and ocular dryness sensation was recorded by the participants at two moments of the day (11 am and 5 pm) over a period of 10 days of contact lens wear. The assessment was made with the aid of visual analogue scales (0–10). The refractive index of 54 contact lenses was accessed by a single operator using a digital automated refractometer (CLR 12-70; Index Instruments). The EWC of the lenses was estimated based on its refractive index values.

Results:

Comfort ratings were slightly higher for delefilcon A (9.56±0.67, P=0.01) and narafilcon A (9.40±0.93, P=0.01) and these lenses wearers also reported less ocular dryness. The results revealed a pronounced water content reduction for omafilcon A (P=0.002), narafilcon A (P=0.008), and nesofilcon A (P=0.003).

Conclusion:

Although changes in subjective responses and EWC were distinct among the materials analyzed, all the contact lenses performed well during the 10 days of wear.
Chronic and Intermittent Angle Closure Caused by In-The-Bag Capsular Tension Ring and Intraocular Lens Dislocation in Patients With Pseudoexfoliation Syndrome
Authors: Bochmann Frank , Strümer Jörg
Published: October 2017

Purpose:

A subluxation or dislocation of the intraocular lens (IOL) is a well-known complication after cataract surgery in patients with pseudoexfoliation syndrome (PEX). Capsular tension rings (CTR) are frequently used to prevent postoperative complications caused by zonular weakness. Here we present a series of 7 cases, 2 with intermittent and 5 with acute angle closure caused by a combination of PEX-associated zonular weakness and a resulting unstable capsular bag-CTR-IOL complex.

Materials and Methods:

We describe the typical clinical course with elevated intraocular pressure, myopic shift, and shallowing of the anterior chamber in 7 patients with a new type of secondary angle closure. The diagnostic challenges and treatment options are discussed in detail.

Results:

In all cases, the mechanism of angle closure identified by ultrasound biomicroscopy was an anterior dislocation of the peripheral iris by the capsular bag-CTR-IOL complex. The IOL was removed together with the capsular bag and the CTR and replaced by an iris-fixated IOL in all cases.

Conclusions:

We present a new type of secondary angle closure caused by an anterior dislocated capsular bag-CTR-IOL complex. The cause of both, this atypical presentation and the ineffectiveness of the laser peripheral iridotomy is the large diameter CTR. Therefore CTR implantation might also be the source of late postoperative complications. If a secondary angle closure associated with PEX and unstable capsular bag-CTR-IOL complex is encountered, IOL explantation and replacement by an iris-fixated IOL is a simple and effective treatment option.
Left Versus Biventricular Assist Devices in Cardiac Arrest
Authors: Packer Erik J. S. , Slettom Grete , Solholm Atle , Mongstad Arve , Haaverstad Rune , Tuseth Vegard , Grong Ketil , Nordrehaug Jan Erik
Published: October 2017

Maintaining adequate organ perfusion during cardiac arrest remains a challenge, and various assist techniques have been evaluated. We assessed whether a right ventricular impeller assist device (RVAD) in adjunct to a left ventricular impeller assist device (LVAD) is beneficial. Twenty anesthetized pigs were randomized to maximized circulatory support by percutaneously implanted left- or biventricular assist device(s) during 30 minutes of electrically induced ventricular fibrillation followed by three attempts of cardioversion. Continuous hemodynamic variables were recorded. Cardiac output and myocardial, cerebral, renal, and ileum mucosa tissue perfusion were measured with fluorescent microspheres, and repeated blood gas analyses were obtained. With biventricular support, an increased LVAD output was found compared with left ventricular (LV) support; 3.2 ± 0.2 (SEM) vs. 2.0 ± 0. 2 L/minute just after start of ventricular fibrillation, 3.2 ± 0.1 vs. 2.0 ± 0.1 L/minute after 15 minutes, and 3.0 ± 0.1 vs. 2.1 ± 0.1 L/minute after 30 minutes of cardiac arrest (p
g < 0.001). Biventricular support also increased aortic and LV pressure, in addition to end-tidal CO2. Tissue blood flow rates were increased for most organs with biventricular support. Blood gas analyses showed improved oxygenation and lower s-lactate values. However, myocardial perfusion was degraded with biventricular support and return of spontaneous circulation less frequent (5/10 vs. 10/10; p = 0.033). Biventricular support was associated with high intraventricular pressure and decreased myocardial perfusion pressure, correlating significantly with flow rates in the LV wall. A transmural flow gradient was observed for both support modes, with better maintained subepicardial than midmyocardial and subendocardial perfusion.
Sex-Specific Outcome Disparities in Patients Receiving Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-analysis
Authors: Blumer Vanessa , Mendirichaga Rodrigo , Hernandez Gabriel A. , Zablah Gerardo , Chaparro Sandra V.
Published: October 2017

Continuous-flow left ventricular assist devices (CF-LVADs) decrease mortality and improve quality of life in patients with advanced heart failure (HF). Their widespread utilization has led to concerns regarding increased adverse effects, especially in women. Nevertheless, sex-specific data remain limited. We searched Medline, Embase, Scopus, and the Cochrane Library for publications reporting sex-specific outcomes after CF-LVADs from January 2008 through January 2017. Outcomes were compared under the random-effects model and heterogeneity examined via χ2 test and I
2 statistics. A total of 10 studies including 4,493 CF-LVAD recipients were included in the analysis (23.5% women). The overall rate of stroke was significantly higher in women (odds ratio [OR] 1.94; 95% confidence interval [CI] 1.32–2.84; p = 0.0007). This was true for ischemic strokes (OR 2.03; 95% CI 1.21–3.42; p = 0.008) and hemorrhagic strokes (OR 2.03; 95% CI 1.21–3.42; p = 0.008). Women were also more likely to develop right HF necessitating right ventricular assist device (RVAD) implantation (OR 2.12; 95% CI 1.08–4.15; p = 0.03). Other adverse events including renal failure, bleeding, and device-related infection were comparable for both genders. The overall mortality while on CF-LVAD was similar in both groups (OR 1.05; 95% CI 0.81–1.36; p = 0.71). Our analysis suggests that women are at greater risk of significant complications such as cerebrovascular events and right HF necessitating RVAD after CF-LVAD implantation. Further research is needed to better understand the mechanisms underlying these sex-specific outcome disparities.
Mapping the Informed Consent Process for Left Ventricular Assist Devices
Authors: Fedson Savitri E. , MacKenzie Kelly K. , Delgado Estevan D. , Abraham Mackenzie N. , Estep Jerry D. , Blumenthal-Barby Jennifer S. , Bruce Courtenay R.
Published: October 2017

Ethical, practical, and medical challenges affect decisions about left ventricular assist device (LVAD) implantation. The informed consent document (IC-Doc) is integral to the decision-making process and structures informed consent conversations. The objective of this study was to analyze IC-Docs to identify the information patients and their families receive about LVAD implantation to create a model IC-Doc. We requested IC-Doc for LVAD implantation from LVAD programs in the United States. We analyzed them in three areas: medical and technical content, patient knowledge gaps, and syntax. Nineteen IC-Docs representing all United Network of Organ Sharing regions were included. Seventeen (89.5%) mentioned the indications for LVAD implantation (bridge to transplant or destination therapy), and six indicated which category applied to the patient. Palliative care was mentioned as an alternative in nine (47.4%); no IC-Doc discussed nonsurgical palliative care. Eight forms (42.1%) specifically mentioned turning off the LVAD. Eighteen forms mention general bleeding, and four referred to long-term gastrointestinal bleeding. Two IC-Docs addressed driveline infections. One form was written at an 8th grade reading level. There is wide variation in LVAD IC-Docs and omission of some benefits and risks. We have written an IC-Doc that meets criteria for disclosure, fills many knowledge gaps, and has an acceptable readability score.
A Numerical Simulation of HeartAssist5 Blood Pump Using an Advanced Turbulence Model
Authors: Drešar Primož , Rutten Marcel C. M. , Gregorič Igor D. , Duhovnik Jožef
Published: October 2017

The need for mechanical assistance of the failing heart has increased with improvements in medicine and a rapidly aging population. In recent decades, significant progress has been made in the development and refinement of ventricular assist devices (VADs). Such devices operate in mixed laminar, transitional, and turbulent flow regime. One tool that assists in the development of VADs by facilitating understanding of the physical and mechanical properties of these flow regimes is computational fluid dynamics (CFD). In our investigation, we tested an advanced turbulence model that is a further development from standard Reynolds-averaged Navier-Stokes (RANS) models. From estimated pump flow rates (Q

0
) and constant rotation speed (n), pressure head (Δp) was calculated and validated with experimental data. An advanced turbulence model called scale adaptive simulation (SAS) was used in the solving of six different working cases comparing numerical SAS-SST and standard SST-kω models to experimental results.
Review and update on postoperative opioid use after nasal and sinus surgery
Authors: Becker Sophia D. , Becker Daniel G.
Published: October 2017

Purpose of review

We examine the current literature on pain management after sinus and nasal surgery. The goal after surgery is to provide effective pain management without having too many ‘leftovers’, as leftover medications are an important source of opioids that are fueling the current prescription narcotic epidemic in the United States. There are more than 250 000 sinus operations and 260 000 septoplasties performed annually, and surgeons commonly prescribe a narcotic pain medication for postoperative pain management.

Recent findings

The literature suggests that an evidence-based approach may lead surgeons to prescribe significantly less narcotic pain medication for these procedures without affecting pain management.

An evidence-based approach to pain management can result in unchanged pain control and a significant positive impact on the narcotic abuse epidemic.
Resolving Malnutrition With Parenteral Nutrition Before Liver Transplant in Biliary Atresia
Authors: Wendel Danielle , Mortensen Melissa , Harmeson Alisha , Shaffer Michele L. , Hsu Evelyn , Horslen Simon
Published: October 2017

Objective:

Malnutrition is a common complication of end‐stage liver disease (ESLD) associated with poor liver transplant outcomes. Nasogastric feeds are used for nutritional supplementation, but some patients remain malnourished. Parenteral nutrition (PN) can be effective, but has potential complications. The primary objective was to evaluate the effect of PN on anthropometric measures in children with ESLD awaiting liver transplant. Secondary objectives were evaluation of PN‐associated complications, liver function tests, pediatric end‐stage liver disease scores, waitlist time, and post‐transplant length of stay (total and time in the intensive care unit).

Methods:

A single‐center, retrospective chart review analyzing pediatric patients with ESLD receiving PN who were transplanted during a 6‐year period. Data were trended and described over time, as were the relationships between anthropometric data and time receiving PN.

Results:

A total of 44 patients with ESLD were transplanted between January 2010 and December 2015. Eighteen (41%) received PN before transplant; all had biliary atresia with median age at transplant of 10 months (range, 5–18 months). Mid‐upper arm circumference and triceps skinfold thickness showed resolution of malnutrition in 7 patients (39%) with normalization of 1 measure in another 4 patients (22%). Of the remaining, 6 had improved z scores and 1 had worsening malnutrition. No deaths occurred in patients receiving PN. Central line infection rates were 3.8/1000 catheter days with 8 total infections in 6 patients over a total of 2117 catheter days.

Conclusions:

Children with ESLD and malnutrition who have failed enteral feeding may benefit from PN to improve and/or resolve malnutrition before liver transplant.
Long‐term Exposure of Children to a Mixed Lipid Emulsion Is Less Hepatotoxic Than Soybean‐based Lipid Emulsion
Authors: Lam Carol K.L. , Church Peter C. , Haliburton Beth , Chambers Kathryn , Martincevic Inez , Vresk Laura , Courtney‐Martin Glenda , Bandsma Robert , Avitzur Yaron , Wales Paul C. , Mouzaki Marialena
Published: October 2017

Lipid emulsions have been associated with liver injury. Newer mixed emulsions (ML), such as SMOFlipid (Fresenius Kabi, Germany), are thought to be more hepatoprotective than soybean‐based emulsions (SL), such as Intralipid (Baxter). Pediatric studies comparing long‐term use between the 2 are limited. This study compares the severity of hepatic injury between a prospective cohort of hospitalized children on ML (n = 20) and a historical age‐ and diagnosis‐matched cohort of hospitalized children on SL (n = 20). Median exposure to ML and SL were 10 versus 6 weeks (P = 0.030), respectively, at similar median lipid doses (2.2 vs 2.1 g · kg−1 · day−1). Using a generalized estimating equations approach, conjugated bilirubin trajectory was found to be lower in patients on ML compared with SL (P < 0.001), suggesting that prolonged exposure (≥4 weeks) to ML is associated with decreased liver injury compared with SL in hospitalized children.
INSL3 Expression in Leydig Cell Hyperplasia and Leydig Cell Tumors
Authors: Lakis Nelli S. , Lombardo Kara A. , Mangray Shamlal , Netto George J. , Salles Daniela , Matoso Andres
Published: October 2017

Insulin-like 3 (INSL3) is a hormone produced by Leydig cells (LCs) and leads to physiological testicular descent during embryonic development. We investigated the expression of INSL3 by immunohistochemistry in normal LCs, in Leydig cell tumor (LCT) (n=17 including 15 testes and 2 ovaries) and in Leydig cell hyperplasia (LCH) (n=10). Normally distributed LCs showed strong immunostaining in the cytoplasm in all cases. All 10 cases (100%) of LCH were strongly and diffusely positive in the intertubular areas. Six cases of LCH had nodules raging in size from 0.2 to 0.9 cm with variable INSL3 staining. Fifteen of 17 (88.2%) LCTs showed marked decrease INSL3 staining, 10/17 (58.8%) were completely negative, and 5/17 (29.4%) were only focally positive. Two cases with multifocal LCTs showed strong and diffuse cytoplasmic staining of LCs around seminiferous tubules while the LCTs were negative. Two cases diagnosed as LCT were strongly positive for INSL3. Other sex cord stromal tumors tested were consistently negative including Sertoli-cell tumor (n=4), granulosa cell tumor (n=2), and fibrothecoma (n=1). In conclusion, our results contrast with those of previously published studies, and show that the great majority of LCTs are negative or have decreased expression of INSL3 while its expression is retained in LCH. INSL3 negative nodules within LCH may represent early LCTs. INSL3 immunostaining could be helpful to highlight LCs in cases where it is difficult to identify them (ie, small testicular biopsies performed for infertility workup) and in the differential diagnosis between florid LCH and LCT.
Characterization of PD-L1 Immunohistochemical Expression in Cell Blocks With Different Specimen Fixation and Processing Methods
Authors: Lloyd Isaac E. , Zhou Wenhua , Witt Benjamin L. , Chadwick Barbara E.
Published: October 2017

Interpretative criteria for programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) have been largely based on data from formalin-fixed, paraffin-embedded tissues, despite the fact that cytologic specimens, especially cell blocks, are often the only or most readily available tissue for testing. Unlike biopsy specimens, however, cytology sample processing methods can vary markedly. The purpose of this study was to evaluate the effects of several common preanalytic variables on PD-L1 IHC. Two cell lines with strong expression of PD-L1 (H441) and no expression (MCF7) were cultured in vitro. Harvested cells were collected in PreservCyt, CytoLyt, cell culture media (RPMI), saline, and formalin. Cell blocks were prepared by the plasma-thromboplastin method or Cellient automated system and stained with the FDA-approved 28-8 PD-L1 antibody per protocol. PD-L1 expression was scored manually by 3 pathologists for stain intensity and localization and compared across preparation methods. Several IHC staining patterns were observed: complete membranous, partial membranous, globular, and cytoplasmic, with some overlap. Cellient blocks had the best interobserver agreement and cytomorphology, highest proportion of strong complete membranous staining (82%), and least amount of cytoplasmic (11%) and globular staining (8%). RPMI, saline, and formalin samples demonstrated increased amounts of cytoplasmic and globular staining relative to Cellient, while CytoLyt exhibited the poorest performance overall. Interpretation of PD-L1 IHC on cell blocks is feasible for most processing methods examined, but may require recognition of increased cytoplasmic and globular staining in some sample types. Cellient cell blocks demonstrated superior performance compared with other methods.
Tissue Thickness Effects on Immunohistochemical Staining Intensity of Markers of Cancer
Authors: McCampbell Adrienne S. , Raghunathan Varun , Tom-Moy May , Workman Richard K. , Haven Rick , Ben-Dor Amir , Rasmussen Ole F. , Jacobsen Lars , Lindberg Martin , Yamada N. Alice , Schembri Carol
Published: October 2017

High-quality patient samples are required for reliable immunohistochemistry test outcomes that provide a significant benefit for patient care. Among the preanalytic variables in tissue handling, tissue thickness is thought to be easily controlled; however, whether the thickness of the tissue effects the staining intensity for antibody immunohistochemistry has not been quantitatively demonstrated. To investigate, we cut multiblock tissue sections of tonsil, liver, and kidney at 2, 4, 6, and 8 μm thicknesses. Interferometry measurements of the sectioned paraffin showed a <1 μm variation within a preset microtome thickness. Sections were then immunostained with antibodies targeting different cellular localizations; Ki-67 and BCL6 (nuclear), CD7 (membranous), and cytokeratin (cytoplasmic). A pathologist annotated regions of interest for each marker and performed brightfield and whole-slide visual scoring. Then a pixel-wise processing algorithm determined intensity of each pixel in these regions of interest and binned them into predetermined 0, 1+, 2+, or 3+ intensities. Visual scores from brightfield and whole-slide images were highly correlated to the percentage of pixels in each intensity bin. A stepwise increase was observed in pathologist scores and algorithmically defined percentage of pixels in each bin with increasing thickness demonstrating that changes in preset section thickness impacts staining intensity. The use of tissue thickness outside vendors’ recommendations might change the intensity including the proportion of positive and negative cells and eventually the overall diagnosis outcome. Therefore, we recommend that tissue be consistently cut within the middle of thickness range specified by the assay manufacturer.
Columnar Cell Lesion and Apocrine Hyperplasia of the Breast: Is There a Common Origin? The Role of Prolactin-induced Protein
Authors: Sciarra Amedeo , Lopez Gianluca , Corti Chiara , Runza Letterio , Ercoli Giulia , Bonometti Arturo , Despini Luca , Blundo Concetta , Gambini Donatella , Fusco Nicola
Published: October 2017

Noninvasive breast lesions encompass a heterogeneous group of risk indicators and nonobligate precursors of breast cancer, such as apocrine hyperplasia (AH) and columnar cell lesions (CCLs). Given the different expression of ER and ER-regulated genes in AH and CCL, these two alterations are currently considered discrete conditions. However, whether they share early biologic changes is not clear to date. Here, we sought to define the clinicopathologic and immunohistochemical features of a prospective series of combined lesions made up by CCLs and AH forming a continuum within single terminal duct-lobular units. The study group included 19 cases, whereas 25 cases of synchronous contiguous CCLs and AH served as control group. The different components of each case were subjected to immunohistochemical analysis for ER, PR, AR, HER2, BCL2, CCND1, MUC1, and PIP. Although CCLs and AHs arising in continuity showed opposite patterns of ER expression, the PIP-positive apocrine signature was consistently present in both components. In conclusion, apocrine changes are highly recurrent in CCLs growing within foci of AH, regardless of the ER activation. Our results suggest that PIP-positive and PIP-negative CCLs are likely to represent biologically distinct conditions and that apocrine changes might occur earlier than ER activation in the natural history of breast precursor lesions.
Clear Cell Carcinoma of Salivary Glands Is Frequently p16 Positive
Authors: Bishop Justin A. , Rooper Lisa M. , Chiosea Simion I. , Westra William H.
Published: October 2017

Clear cell carcinoma (CCC) is a low-grade malignancy that commonly arises in minor salivary glands of the oropharynx and other sites. EWSR1-ATF1 gene fusions seem to be specific for this salivary neoplasm. Testing for EWSR1-ATF1 has expanded the histologic spectrum of CCC. As one important example, many CCCs have a predominantly squamous phenotype with few clear cells, a finding that can cause confusion with squamous cell carcinoma (SqCC). P16 immunohistochemical staining to determine human papillomavirus (HPV) status has become standard practice for all oropharyngeal carcinomas showing squamous differentiation. The purpose of this study was to determine whether this practice could contribute to the difficulty in distinguishing CCC from p16-positive SqCC. The authors’ surgical pathology archives were searched for cases of CCC. All cases were evaluated with p16 immunohistochemistry, high-risk HPV RNA in situ hybridization (ISH), and EWSR1 gene break-apart fluorescence ISH. Sixteen CCCs were identified. All harbored an EWSR1 rearrangement. Eleven patients were women and 5 were men. They ranged in age from 30 to 85 years (mean, 58 y). The CCCs arose in the oropharynx (tongue base or tonsil) (n=8, 50%), oral cavity (n=4, 25%), and nasopharynx (n=4, 25%). Each case demonstrated clear cells, but the proportion was highly variable (10% to 90%, mean 48%), with 7 of 16 cases having <50% clear cells. Submitted diagnoses included SqCC (n=3) and mucoepidermoid carcinoma (n=2). Of the 3 patients diagnosed with SqCC, 1 was scheduled to undergo chemoradiation, and 1 had already completed chemoradiation. All 16 CCCs demonstrated p16 staining, with the percentage of p16-positive cells ranging from ≥70% (n=2), 50% to 69% (n=3), and 10% to 49% (n=11). Staining was cytoplasmic and nuclear. All cases were negative for high-risk HPV by RNA ISH. CCCs regularly show squamous features, often lack prominent clear cell changes, frequently arise in the oropharynx, and invariably show p16 staining. These features may cause confusion with SqCC, particularly HPV-related oropharyngeal SqCC. P16 staining is not to be taken as unequivocal evidence of an HPV-related SqCC, even for carcinomas showing squamous differentiation and originating in the oropharynx. Failure to recognize this pitfall could result in overly aggressive treatment of a low-grade carcinoma.
Disparities in Zika Virus Testing and Incidence Among Women of Reproductive Age—New York City, 2016
Authors: Lee Christopher T. , Greene Sharon K. , Baumgartner Jennifer , Fine Anne
Published: October 2017

Context:

The New York City Department of Health and Mental Hygiene (NYC DOHMH) performs surveillance for reportable diseases, including Zika virus (ZIKV) infection and disease, to inform public health responses. Incidence rates of other mosquito-borne diseases related to international travel are associated with census tract poverty level in NYC, suggesting that high poverty areas might be at higher risk for ZIKV infections.

Objectives:

We assessed ZIKV testing rates and incidence of travel-associated infection among reproductive age women in NYC to identify areas with high incidence and low testing rates and assess the effectiveness of public health interventions.

Design:

We analyzed geocoded ZIKV surveillance data collected by NYC DOHMH. Women aged 15 to 44 years tested during January-July 2016 (n = 4733) were assigned to census tracts, which we grouped by poverty level and quartile of the number of persons born in countries or territories with mosquito-borne ZIKV transmission as a proxy for risk of travel to these areas. We calculated crude ZIKV testing rates, incidence rates, and incidence rate ratios (IRRs).

Setting:

New York City.

Results:

Eight percent of patients (n = 376) tested had evidence of ZIKV infection. Cumulative incidence was higher both in areas with higher versus lower poverty levels (IRR = 2.4; 95% confidence interval [CI], 2.0-3.0) and in areas with the largest versus smallest populations of persons born in countries or territories with mosquito-borne ZIKV transmission (IRR = 11.3; 95% CI, 6.2-20.7). Initially, ZIKV testing rates were lowest in higher poverty areas with the largest populations of persons born in countries or territories with mosquito-borne ZIKV transmission (15/100 000), but following targeted interventions, testing rates were highest in these areas (80/100 000).

Conclusions:

Geocoded data enabled us to identify communities with low testing but high ZIKV incidence rates, intervene to promote testing and reduce barriers to testing, and measure changes in testing rates.