bluuebunny/crossref_metadata_2025 huggingface dataset:
Ketamine Action in the In Vitro Cortical Slice Is Mitigated by Potassium Channel Blockade
Authors: Voss Logan J. , Karalus Sebastian , Englund Vilhelm , Sleigh James W.
Published: March 2018

Background

Ketamine is a general anesthetic thought to act by antagonizing N-methyl-d-aspartate receptors. However, ketamine acts on multiple channels, many of which are potential targets―including hyperpolarization-activated cyclic nucleotide-gated and potassium channels. In this study we tested the hypothesis that potassium leak channels contribute to the anesthetic action of ketamine.

Methods

Adult mouse cortical slices (400 µm) were exposed to no-magnesium artificial cerebrospinal fluid to generate seizure-like event activity. The reduction in seizure-like event frequency after exposure to ketamine (n = 14) was quantified as a signature of anesthetic effect. Pharmacologic manipulation of hyperpolarization-activated cyclic nucleotide-gated and potassium channels using ZD7288 (n = 11), cesium chloride (n = 10), barium chloride (n = 10), low-potassium (1.5 mM) artificial cerebrospinal fluid (n = 10), and urethane (n = 7) were investigated.

Results

Ketamine reduced the frequency of seizure-like events (mean [SD], –62 [22]%, P < 0.0001). Selective hyperpolarization-activated cyclic nucleotide-gated channel block with ZD7288 did not significantly alter the potency of ketamine to inhibit seizure-like event activity. The inhibition of seizure-like event frequency by ketamine was fully antagonized by the potassium channel blockers cesium chloride and barium chloride (8 [26]% and 39 [58%] increase, respectively, P < 0.0001, compared to ketamine control) and was facilitated by the potassium leak channel opener urethane (–93 [8]%, P = 0.002 compared to ketamine control) and low potassium artificial cerebrospinal fluid (–86 [11]%, P = 0.004 compared to ketamine control).

Conclusions

The results of this study show that mechanisms additional to hyperpolarization-activated cyclic nucleotide-gated channel block are likely to explain the anesthetic action of ketamine and suggest facilitatory action at two-pore potassium leak channels.
Oral Presentations Have a Significantly Higher Publication Rate, But Not Impact Factors, Than Poster Presentations at the International Society for Study of Lumbar Spine meeting
Authors: Ohtori Seiji , Orita Sumihisa , Eguchi Yawara , Aoki Yasuchika , Suzuki Miyako , Kubota Gou , Inage Kazuhide , Shiga Yasuhiro , Abe Koki , Kinoshita Hideyuki , Inoue Masahiro , Kanamoto Hirohito , Norimoto Masaki , Umimura Tomotaka , Furuya Takeo , Masao Koda , Maki Satoshi , Akazawa Tsutomu , Takahashi Kazuhisa
Published: March 2018

Study Design.

A retrospective study.

Objective.

The aim of this study was to determine the publication rate and impact factors (IFs) among all abstracts presented at the 2010 and 2012 meetings of the International Society for the Study of Lumbar Spine (ISSLS).

Summary of Background Data.

The publication rate of abstracts presented at overseas meetings was reported to be around 50%. However, the publication rate and IFs of oral and poster presentations made at ISSLS meetings were unclear. Moreover, whether the publication rates and IFs differed for papers associated with oral or poster presentations at ISSLS meetings was unknown.

Methods.

We investigated all 1,126 abstracts (oral, special posters, general posters) presented at ISSLS meetings held between 2010 and 2012. PubMed was searched to identify publications and IFs were determined using journal citation reports. We also compared the publication rates and IFs between oral and poster presentations.

Results.

The overall publication rate was 50.1% for three ISSLS meetings (564 publications/1126 abstracts). The overall publication rate for oral presentations, special posters, and general posters given in the 2010 to 2012 meetings was 62.0%, 48.3, and 46.6%, respectively. Overall, papers related to oral presentations had significantly higher publication rates than those of special and general posters (P = 0.0002). The average IFs of publications associated with abstracts presented at three ISSLS meetings was 2.802 for oral presentations, 2.593 for special posters, and 2.589 for general posters. There were no significant differences in average IFs between oral and poster presentations (P > 0.05).

Conclusion.

The publication rate for abstracts presented at ISSLS meetings was high and similar to publication rates for abstracts presented at other meetings concerning orthopedic and spine research. However, there was no significant difference in IFs between oral and poster presentations, suggesting that abstract evaluations cannot predict IFs of the eventual publication.

Level of Evidence: 4
Perioperative Care Protocols in Ankle Fracture Treatment: A Review of the Literature
Authors: Jo Jacob , Matuszewski Paul E. , Swart Eric
Published: March 2018

Although ankle fractures are common injuries and often treated with surgery, there are still many unanswered questions with regard to the optimal perioperative protocols for pain control, venous thromboembolism prophylaxis, and rehabilitation. The purpose of this article is to review the best available literature in these areas and provide evidence-based recommendations.

Level of Evidence: Diagnostic Level III (therapeutic). See Instructions for Authors for a complete description of levels of evidence.
Clinical Significance of Molecular Micrometastasis in the Sentinel Lymph Node of Early-stage Non–Small Cell Lung Cancer Patients
Authors: Lafuente-Sanchis Aránzazu , Estors-Guerrero Miriam , Zúñiga Ángel , Martínez-Hernández Néstor J. , Cremades Antonio , Aparisi-Aparisi Francisco , Galbis-Caravajal José M.
Published: March 2018

Objectives:

Metastatic affectation of lymph node is the main prognostic factor in localized lung cancer. A pathologic study of the obtained samples, even after adequate lymphadenectomy, showed tumor relapses for 20% of stage I patients after oncological curative surgery. We evaluated the prognostic value of molecular micrometastasis in the sentinel lymph node of patients with early-stage lung cancer.

Patients and Methods:

The sentinel node was marked immediately after performing thoracotomy by peritumorally injecting 0.25 mCi of nanocoloid of albumin (Nanocol1) labeled with Tc-99m in 0.3 mL. Guided by a Navigator1 gammagraphic sensor, we proceeded to its resection. The RNA of the tissue was extracted, and the presence of genes CEACAM5, BPIFA1, and CK7 in mRNA was studied. The significant association between the presence of micrometastasis, clinicopathologic characteristics, and patients’ outcome was assessed.

Results:

Eighty-nine stage I-II non–small cell lung cancer patients were included in the study. Of the 89 analyzed sentinel lymph nodes, 44 (49.4%) were positive for CK7, 24 (26.9%) for CEACAM5, and 17 (19.1%) for BPIFA1, whereas 10 (11.2%) were positive for the 3 analyzed genes. A survival analysis showed no significant relation between the presence of molecular micrometastasis in the sentinel node and patients’ progression.

Conclusions:

The molecular analysis of the sentinel node in patients with early-stage lung cancer shows node affectation in cases staged as stage I/II by hematoxylin-eosin or an immunohistochemical analysis. However, this nodal affectation was not apparently related to patients' outcome.
In people living with HIV (PLWH), menopause (natural or surgical) contributes to the greater symptom burden in women: results from an online US survey
Authors: Schnall Rebecca , Jia Haomiao , Olender Susan , Gradilla Melissa , Reame Nancy
Published: March 2018

Objective:

The majority of people living with HIV in the United States are now over the age of 50, but symptom burden research has seldom included older women or the potential role of menopause. The aim of the study was to examine the influence of menopause as part of sex differences in HIV symptom burden.

Methods:

A cross-sectional study was conducted that included both a sex-based analysis of previously reported HIV symptom characteristics of 1,342 respondents to an online survey (males, n = 957; female, n = 385) and a follow-up online survey of menstrual bleeding patterns (inferred menopause) in eligible females (n = 242) from the respondent pool. Using linear mixed models, we identified predictors of symptom burden scores in female respondents.

Results:

For the most troublesome symptoms assessed in the sex-based analysis, depression scores were similar (P > 0.05), but higher (worse) burden scores for fatigue (P = 0.013) and muscle aches/pains (P = 0.004) were exclusively observed in females after adjusting for covariates. Respondents to the female survey (n = 222) were predominantly Black, heterosexual, nonsmokers, and obese, with an HIV diagnosis of approximately 16 years and at least one comorbid condition. Burden scores were higher in women reporting amenorrhea due to natural menopause or hysterectomy (n = 104) versus the menstruating group (n = 118) for muscle aches/pains (P = 0.05), fatigue (P = 0.03), and difficulty falling asleep (P = 0.04), independent of age, HIV duration, and number of HIV-associated non-AIDS conditions.

Conclusions:

Two of the most common symptoms in people living with HIV—fatigue and muscle aches/joint pains—invoke additional burden in women. Independent of aging, symptom burden may be exacerbated after menopause, supporting a shifting paradigm for HIV care management.
The Functional Impact of Breast Reconstruction: An Overview and Update
Authors: Nelson Jonas A. , Lee Iris T. , Disa Joseph J.
Published: March 2018

As rates of bilateral mastectomy and immediate reconstruction rise, the aesthetic and psychosocial benefits of breast reconstruction are increasingly well understood. However, an understanding of functional outcome and its optimization is still lacking. This endpoint is critical to maximizing postoperative quality of life. All reconstructive modalities have possible functional consequences. Studies demonstrate that implant-based reconstruction impacts subjective movement, but patients’ day-to-day function may not be objectively hindered despite self-reported disability. For latissimus dorsi flap reconstruction, patients also report some dysfunction at the donor site, but this does not seem to result in significant, long-lasting limitation of daily activity. Athletic and other vigorous activities are most affected. For abdominal free flaps, patient perception of postoperative disability is generally not significant, despite the varying degrees of objective disadvantage that have been identified depending on the extent of rectus muscle sacrifice. With these functional repercussions in mind, a broader perspective on the attempt to ensure minimal functional decline after breast surgery should focus not only on surgical technique but also on postoperative rehabilitation. Early directed physical therapy may be an instrumental element in facilitating return to baseline function. With the patient’s optimal quality of life as an overarching objective, a multifaceted approach to functional preservation may be the answer to this continued challenge. This review will examine these issues in depth in an effort to better understand postoperative functional outcomes with a focus on the younger, active breast reconstruction patient.
Treatment of Painful Nerves in the Abdominal Wall Using Processed Nerve Allografts
Authors: Bi Andrew , Park Eugene , Dumanian Gregory A.
Published: March 2018

Neuromas can be a debilitating cause of pain and often negatively affect patients’ quality of life. One effective method of treatment involves surgical resection of the painful neuroma and use of a processed nerve allograft to repair the injured nerve segment. Giving the nerve “somewhere to go and something to do” has been shown to effectively alleviate pain in upper and lower extremities. We present the first report of this concept to treat a painful neuroma of the abdominal wall that developed following a laparoscopic gastric bypass. The neuroma was excised, and the affected nerve was reconstructed using a processed nerve allograft as an interposition graft, with resolution of pain and gradual return of normal sensation. Patient-reported outcomes were measured using the Patient Reported Outcomes Measurement Information System. Neuroma excision with concurrent interposition grafting using processed nerve allografts may be a promising method of treatment for postsurgical painful neuromas of the trunk.
Development of “Core Syllabus” for Facial Anatomy Teaching to Aesthetic Physicians: A Delphi Consensus
Authors: Kumar Narendra , Swift Arthur , Rahman Eqram
Published: March 2018

Background:

A detailed understanding of facial anatomy, specifically the vascular framework, is crucial for delivering safe nonsurgical aesthetic procedures. To date, there is no core document based on consensus for the teaching of facial anatomy to aesthetic physicians exists. The aim of this study was to ascertain the most critical anatomical structures for avoiding disastrous complications during nonsurgical aesthetic procedures.

Methods:

After a detailed literature review, Delphi questionnaire was developed listing 154 anatomical structures of the face and neck for consensus review. Thirty-five international experts in surgical and nonsurgical facial aesthetics were invited to complete an online survey designed to rank the relevance of each anatomical element on a Likert scale from 1 (not at all important) to 4 (very important) or 5 (no opinion). Consensus for items included in the core syllabus was predefined as achieving a Cronbach’s α ≥ 0.90 and an agreement score of ≥ 80%.

Results:

Thirty-four international experts (97.14%) completed the iterative online Delphi survey. The consensus among the specialists polled was achieved after 1 round of the survey (Cronbach’s α = 0.94). The expert panel reached an agreement score of ≥ 80% on 137 of the 154 anatomical structures listed.

Conclusion:

The outcome of this Delphi study represents an essential first step in systematizing an evidence-based facial anatomy “Core Syllabus” for the teaching of aesthetic physicians and practitioners. This “Core Syllabus” will act as a blueprint for the educators while crafting a program.
A Clinical Evidence-Based Approach to Examine the Effects of mTBI and PTSD Symptoms on ANAM Performance in Recently Deployed Active Duty Soldiers: Results From the Warrior Strong Study
Authors: Betthauser Lisa M. , Brenner Lisa A. , Cole Wesley , Scher Ann I. , Schwab Karen , Ivins Brian J.
Published: March 2018

Objective:

Service members are frequently diagnosed with comorbid mild traumatic brain injury (mTBI) and posttraumatic stress disorder after returning from Afghanistan and Iraq. Little is known about how mTBI in the postacute and chronic phases combined with current posttraumatic stress disorder symptoms (PTS) affects performance on the Automated Neuropsychological Assessment Metrics, Version 4, Traumatic Brain Injury—Military (ANAM4) battery used by the US military. We examined postdeployment ANAM4 performance using conventional statistical methods, as well as rates of poor performance, below established cutoffs (<10th and ≤2nd percentile).

Methods:

A total of 868 soldiers were assessed for history of mTBI during the most recent deployment, as well as, lifetime mTBI, current PTS, and current pain-related symptoms. The ANAM4 was also administered.

Results:

Soldiers with PTS and/or mTBI performed worse on ANAM4 relative to controls with those with both conditions performing worst. However, a nontrivial minority (∼10%-30%) of individuals with mTBI, PTS, or both had scores that were at or below the second percentile.

Conclusion:

Our results illustrate that a combination of mTBI and PTS is associated with worse ANAM4 performance than either condition alone. Furthermore, only a minority of soldiers with any, or both, of the conditions had ANAM deficits. The long-lasting impacts and unique contribution of each condition have yet to be determined.
LONGITUDINAL CHANGES IN CHOROIDAL AND RETINAL THICKNESSES IN CHILDREN WITH MYOPIC SHIFT
Authors: Jin Peiyao , Zou Haidong , Xu Xun , Chang Ta Chen , Zhu Jianfeng , Deng Junjie , Lv Minzhi , Jin Jiali , Sun Sifei , Wang Ling , He Xiangui
Published: March 2018

Purpose:

To elucidate the development of the choroid and retina in children, and to explore changes in these during myopic shift.

Methods:

A total of 118 children aged 7 to 12 years participated in this 1-year longitudinal study. Children underwent several examinations at baseline and follow-up, including cycloplegic refraction, axial length measurement, and swept-source optical coherence tomography. Thickness changes in the choroid and retina were compared among children with or without myopic shift.

Results:

Eighty-eight children (74.6%) developed a myopic shift after 1 year, and their central foveal choroid was significantly attenuated (P < 0.01). No significant change was observed in choroids of children without myopic shift (P = 0.83). Choroidal thickness decreased in all subfields during myopic shift, whereas the thickness of the retinal layers increased or were unchanged in most subfields. Axial length increase and central foveal choroidal thinning were associated with myopic shift (R2 = 0.157, P < 0.01), but axial length increase was not significantly related to choroidal thinning (P > 0.05).

Conclusion:

Choroidal thinning occurs early in myopic progression. Axial length increase and choroidal thinning are independently associated with myopic shift.
EFFECT OF INTRAOCULAR PRESSURE–LOWERING MEDICATIONS ON NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATMENT OUTCOMES IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS
Authors: Rahimy Ehsan , Ying Gui-shuang , Pan Wei , Hsu Jason ,   on behalf of the CATT Research Group
Published: March 2018

Purpose:

To evaluate the effect of intraocular pressure-lowering medications on treatment outcomes in the Comparison of AMD Treatments Trials.

Methods:

Secondary analysis of Comparison of AMD Treatments Trials data. Medication logs were reviewed for continuous 2-year use of agents that increased aqueous outflow (Group A: topical prostaglandins) or suppressed aqueous production (Group B: topical beta blockers and carbonic anhydrase inhibitors). Eyes were excluded if mixed-mechanism intraocular pressure–lowering agents or medications from more than one group were taken. Anatomical and vision responses to treatment at years 1, 2, and over the entire 2-year period in each group were compared with controls (no intraocular pressure–lowering medications).

Results:

Inclusion criteria were met by 28 Group A patients, 19 Group B patients, and 857 controls. After 2 years, the control group had a mean visual acuity improvement of +6.3 letters from baseline, compared with +3.5 letters in Group A (P = 0.38), and +13.8 letters in Group B (P = 0.052). Mean retinal thickness change from baseline was −54.9 μm in controls, −80.6 μm in Group A (P = 0.26), and −96.8 μm in Group B (P = 0.13). Mean total thickness change from baseline was −163 μm in controls, −180 μm in Group A (P = 0.63), and −238 μm in Group B (P = 0.08). In longitudinal analysis with adjustment by their baseline values, anti–vascular endothelial growth factor treatment drug and regimen, Group B had more visual acuity improvement (difference of 2.6 letters, 95% confidence interval: −3.4–8.5 letters), more reduction in the retinal thickness (−17.9 μm, 95% confidence interval: −36.5 to 0.7 μm), and total thickness from baseline (mean difference of −54.7 μm, 95% confidence interval: −103 to 6.2 μm) compared with the control group.

Conclusion:

Concurrent aqueous suppressant use during anti–vascular endothelial growth factor therapy for neovascular age-related macular degeneration was associated with a trend toward greater reductions in retinal and total thickness as well as improved visual outcomes over 2 years. A similar effect was not observed to the same extent with agents that increase aqueous outflow. Because of the small sample size and secondary analysis, these findings must be cautiously interpreted and perhaps serve as a basis for future prospective studies.
Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study
Authors: Donker Dirk W. , Brodie Daniel , Henriques José P. S. , Broomé Michael
Published: March 2018

Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (−800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella™ enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.
Left Ventricular Assist Device Thrombosis—Amiodarone-Induced Hyperthyroidism: Causal Link?
Authors: Rajapreyar Indranee , Acharya Deepak , Tallaj José , Hornbuckle Lauren , Sharpton Jessica , Joly Joanna , Pamboukian Salpy
Published: March 2018

Ventricular arrhythmias occurs in 20–50% of patients supported with left ventricular assist devices (LVAD). Ventricular arrhythmias are well tolerated with LVAD support but long-term consequences include worsening right ventricular function. Management of ventricular arrhythmias in LVAD patients includes use of antiarrhythmic agents or ablation. Amiodarone has been used a first-line agent to treat ventricular arrhythmias post-LVAD implantation. Chronic treatment with amiodarone for arrhythmias can result in hyperthyroidism and hypothyroidism in 5–10% of patients. Hyperthyroidism is known to cause endothelial dysfunction, alterations in coagulation, and fibrinolytic pathways favoring hypercoagulable state. We describe two cases of left ventricular assist device (LVAD) thrombosis potentiated by amiodarone-induced hyperthyroidism (AIT) and discuss pathophysiological mechanisms for hypercoagulable state induced by hyperthyroidism.
Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection
Authors: Peng Songxu , Wan Zhihua , Liu Tingting , Zhu Huiping , Du Yukai
Published: March 2018

Goals:

To identify the potential risk factors of hepatitis B virus (HBV) intrauterine transmission and predict the incidence of HBV intrauterine transmission among hepatitis B surface antigen–positive pregnant women with diverse viral load.

Background:

The intrauterine transmission of HBV significantly contributes to the persistence of a high number of patients infected with HBV. However, its risk factors remain unclear.

Materials and Methods:

A prospective study was performed on hepatitis B surface antigen–positive pregnant women who delivered from June 2012 to December 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China.

Results:

In total, 1200 women paired with 1219 infants were enrolled. In total, 11 (0.9%) infants were identified with intrauterine transmission. We observed that all infants with intrauterine transmission were born to hepatitis B e antigen–positive mothers who had serum HBV DNA levels >7 log10 copies/mL. Our study suggested that the HBV DNA levels (for each log10 copies/mL increase, odds ratio=5.43; 95% confidence interval, 1.31-22.43; P=0.019) had independent effects on HBV intrauterine transmission in a multivariate logistic regression model. Moreover, cesarean section (odds ratio=0.18; 95% confidence interval, 0.04-0.74; P=0.018) was associated with a reduced risk of HBV intrauterine transmission. The predictive rates of intrauterine transmission were 0.06%, 0.50%, 2.81%, 8.89% in infants with maternal HBV DNA levels of 105, 106, 107, 108 copies/mL, respectively.

Conclusions:

Our data confirmed that increasing maternal viral load has the ability to predict intrauterine HBV transmission. Vaginal delivery increased risk of HBV transmission in infants compared with cesarean section. Further studies are warranted to clarify the possible mechanism underlying these associations.
Comparative Efficacy of Anti-TNF Therapies For The Prevention of Postoperative Recurrence of Crohn’s Disease
Authors: Bakouny Ziad , Yared Fares , El Rassy Elie , Jabbour Rita , Hallit Rachel , Khoury Nathalie , Honein Khalil , Bou Jaoude Joseph
Published: March 2018

Introduction:

There is a lack of studies on the optimal anti–tumor necrosis factor (anti-TNF) agent for postoperative prophylaxis of Crohn’s disease (CD) recurrence. Therefore, we conducted a network meta-analysis (NMA) of prospective trials to compare the efficacy of anti-TNF agents in the prevention of postoperative endoscopic and clinical recurrence of CD following ileocolonic resection.

Methods:

We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and recent American gastroenterology association (AGA) meeting abstracts through August 2017. We selected prospective studies comparing anti-TNF agents among each other or to other agents in the setting of postoperative prevention of CD recurrence. We performed a NMA using a frequentist approach with generalized pairwise modeling and inverse variance heterogeneity method.

Results:

We identified 9 studies, including 571 patients and 5 treatment agents, among which 2 anti-TNF drugs (adalimumab and infliximab). Compared with infliximab, our NMA yielded the following results for endoscopic recurrence: adalimumab [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.18-4.75], thiopurines (OR, 4.11; 95% CI, 0.68-24.78), placebo (OR, 4.39; 95% CI, 0.70-27.68), and Mesalamine (OR, 37.84; 95% CI, 3.77-379.42). For clinical recurrence: adalimumab (OR, 1.03; 95% CI, 0.17-6.03), thiopurines (OR, 1.40; 95% CI, 0.20-10.02), placebo (OR, 1.77; 95% CI, 1.01-3.10), and mesalamine (OR, 16.54; 95% CI, 1.55-176.24).

Conclusions:

On the basis of a NMA combining direct and indirect evidence either adalimumab or infliximab may be used in the postoperative prophylaxis of CD recurrence. There is currently a lack of evidence on the use of other anti-TNF agents in this setting.
Digital Pancreaticocholangioscopy for Mapping of Pancreaticobiliary Neoplasia
Authors: Tyberg Amy , Raijman Isaac , Siddiqui Ali , Arnelo Urban , Adler Douglas G. , Xu Ming-ming , Nassani Najib , Sejpal Divyesh V. , Kedia Prashant , Nah Lee Yun , Gress Frank G. , Ho Sammy , Gaidhane Monica , Kahaleh Michel
Published: March 2018

Introduction:

In patients with pancreaticobiliary lesions anticipating surgical resection, digital pancreaticocholangioscopy can be used to identify the extent of disease. This presurgical“mapping” could change the surgical plan and optimize patient care.

Materials and Methods:

Patients with pancreaticobiliary lesions anticipating surgery who underwent endoscopic retrograde cholangiopancreatography with digital pancreaticocholangioscopy from 9 international centers were included. Primary outcome was whether pancreaticocholangioscopy altered the surgical plan. Secondary outcome was correlation between surgical and endoscopic histology and adverse events.

Results:

A total of 118 patients were included (64% male, mean age 69 y): cholangioscopy in 105 patients (89%), pancreatoscopy in 13 patients (11%). Pancreaticocholangioscopy changed the surgical plan in 39 (34%) of patients: 8 of 13 in the pancreatic duct, 32 of 105 in the bile duct. In the bile duct, 6 patients (5%) had less extensive surgery, 26 patients (25%) avoided surgery. In the pancreatic duct, 4 patients (31%) had more extensive surgery and 4 patients (31%) had less extensive surgery. Four patients with downstaged surgery had positive margins on surgical resection; 1 required additional surgical intervention. Overall correlation between endoscopy and surgical histology was 88%. Adverse events included post endoscopic retrograde cholangiopancreatography pancreatitis in 3 patients (2.5%).

Conclusion:

Digital pancreaticocholangioscopy can be effectively used as a mapping tool to delineate the degree of involvement of biliary lesions before surgical resection, in some cases altering the surgical plan. Prospective studies are needed, especially when downstaging surgery.
Clinical Significance of Histological Effect and Intratumor Stromal Expression of Tenascin-C in Resected Specimens After Chemoradiotherapy for Initially Locally Advanced Unresectable Pancreatic Ductal Adenocarcinoma
Authors: Hayasaki Aoi , Murata Yasuhiro , Usui Masanobu , Hibi Taemi , Ito Takahiro , Iizawa Yusuke , Kato Hiroyuki , Tanemura Akihiro , Azumi Yoshinori , Kuriyama Naohisa , Kishiwada Masashi , Mizuno Shugo , Sakurai Hiroyuki , Yoshida Toshimichi , Isaji Shuji
Published: March 2018

Objectives

Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens and the histologic effect of chemoradiotherapy (CRT) as prognostic indicators in initially locally advanced unresectable (UR-LA) PDAC.

Methods

Among 110 UR-LA PDAC patients enrolled in the CRT protocol from February 2005 to December 2015, 46 who underwent curative-intent resection were classified as high (tumor destruction >50%) and low (≤50%) responders according to the Evans grading system. Tenascin-C expression was immunohistologically evaluated in all patients except one with complete response.

Results

The 12 high responders achieved a significantly higher R0 rate than did the 34 low responders (83.3 vs 47.1%), but disease-specific survival (DSS) time was not significantly different (median survival time, 29.8 vs 21.0 months). Tenascin-C expression was inversely correlated with histologic effect of CRT. The 22 patients with negative TN-C had significantly longer DSS time than did the 23 with positive TN-C (29.3 vs 17.1 months). In multivariate analysis, only TN-C expression was a significant prognostic factor for DSS.

Conclusions

Intratumor stromal expression of TN-C is a strong prognostic indicator in UR-LA PDAC patients with resection after CRT.
Induced Pluripotent Stem Cell‐Derived Hepatocytes and Precision Medicine in Human Liver Disease
Authors: Kulkarni Sakil , Rudnick David A.
Published: March 2018

Liver‐like human cells can be generated from human skin by converting fibroblasts to “induced pluripotent stem cells” (iPSCs), then differentiating the iPSCs into “induced hepatocytes”. Although still primarily used as a research tool, emerging applications involving iPSC‐derived induced hepatocytes have exciting and provocative clinical and translational potential. This review provides a brief summary of the current status of this field and obstacles that must be overcome before this novel tool will enable precision medicine‐based approaches to human liver disease.
Hydronephrosis From Ureteropelvic Junction Obstruction Discovered on Point-of-Care Ultrasound in Patients With Trauma
Authors: Melvin Jennifer E. , Ost Michael C. , Marin Jennifer R.
Published: March 2018

We present 2 cases of patients with abdominal trauma who were found to have hydronephrosis on point-of-care ultrasound secondary to previously undiagnosed ureteropelvic junction obstructions. We review the ultrasound findings, technique, and relevant literature regarding renal point-of-care ultrasound and ureteropelvic junction obstruction.
Chlamydia Conjunctivitis in 2 Prepubertal Children
Authors: Brownell Amanda D. , Miraldi Utz Virginia , Makoroff Kathi L. , Shapiro Robert A. , Mortensen Joel E.
Published: March 2018

Sexually transmitted infection as the result of child sexual abuse in prepubertal children is uncommon. Chlamydia trachomatis conjunctivitis is an even less common entity in prepubertal children outside the newborn period. This report details the presentation of 2 children with conjunctivitis who were subsequently diagnosed as having C. trachomatis conjunctivitis. One child was also diagnosed as having rectal and pharyngeal C. trachomatis infection, and the other also had genital C. trachomatis infection. Even with multisite C. trachomatis infection as an indication of sexual abuse, neither child gave a detailed disclosure of abuse to account for their infections. The absence of a clear disclosure is not uncommon. Previous literature reports that a disclosure in these circumstances occurs in less than half of cases. In this report, we review the recommendations for diagnosis of C. trachomatis using nucleic acid amplification testing and culture as well as treatment. Specific clinical features should alert the clinician to C. trachomatis conjunctivitis and lead to timely diagnosis and protection of the child from further sexual abuse.
C-Reactive Protein Concentration Can Help to Identify Bacteremia in Children Visiting the Emergency Department: A Single Medical Center Experience
Authors: Chiu I-Min , Huang Ying-Hsien , Su Chih-Min , Kung Chia-Te , Li Chao-Jui , Chen Chih-Ho , Tang Kuo-Su , Kuo Kuang-Che
Published: March 2018

Background

For febrile children who are evaluated in a pediatric emergency department (PED), blood culture can be considered the laboratory criterion standard to detect bacteremia. However, high rates of negative, false-positive, or contaminated blood cultures in children often result in this testing being noncontributory. This study determined the factors associated with true-positive blood cultures in children.

Methods

This retrospective study was conducted at a tertiary medical center's PED. The blood culture use reports were prepared by an infectious disease specialist and were classified as bacteremia, nonbacteremia, and contamination.

Results

We registered a total of 239,459 PED visits during the 8-year period, and 21,841 blood culture samples were taken. Of the laboratory test studies, higher C-reactive protein (CRP) levels and lower hemoglobin levels were observed in the bacteremia group compared with other groups (all P < 0.001). The cut-off value calculated for each age group was adjusted for better clinical usage and significantly improved the blood culture clinical utility documented in the following age groups: 0 to 1 years (CRP level = 30 mg/L, odds ratio [OR] = 5.4, P < 0.001), 1 to 3 years (CRP level = 45 mg/L, OR = 3.7, P < 0.001), and 12 to 18 years (CRP level = 50 mg/L, OR = 6.3, P = 0.006). Using the CRP cut-off value established in this study, we could reduce the blood culture samples in the PED by 14,108 (64.6%).

Conclusions

This study provides new evidence that CRP may be a useful indicator for blood culture sampling in certain age groups and may help improve the efficiency of blood culture in the PED.
Interpretation of P53 Immunohistochemistry in Endometrial Carcinomas: Toward Increased Reproducibility
Authors: Köbel Martin , Ronnett Brigitte M. , Singh Naveena , Soslow Robert A. , Gilks C. Blake , McCluggage W. Glenn
Published: March 2018

P53 immunohistochemistry has evolved into an accurate surrogate reflecting the underlying TP53 mutation status of a tumor, and has utility in the diagnostic workup of endometrial carcinomas. Recent work predominantly carried out in tubo-ovarian high-grade serous carcinoma has revealed 4 main patterns of p53 staining (normal/wild-type, complete absence, overexpression, and cytoplasmic); the latter 3 patterns are variably termed abnormal/aberrant/mutation-type and are strongly predictive of an underlying TP53 mutation. The aim of this review is to provide practical advice to pathologists regarding various aspects of p53 immunohistochemical staining. These include laboratory methods to optimize staining, a description of the different patterns of staining, advice regarding the interpretation, and reporting of p53 staining and practical uses of p53 staining in endometrial carcinoma diagnosis. Illustrations are provided to aid in the interpretational problems.
Reconsidering the International Association for the Study of Pain definition of pain
Authors: Cohen Milton , Quintner John , van Rysewyk Simon
Published: March 2018

Introduction:

The definition of pain promulgated by the International Association for the Study of Pain (IASP) is widely accepted as a pragmatic characterisation of that human experience. Although the Notes that accompany it characterise pain as “always subjective,” the IASP definition itself fails to sufficiently integrate phenomenological aspects of pain.

Methods:

This essay reviews the historical development of the IASP definition, and the commentaries and suggested modifications to it over almost 40 years. Common factors of pain experience identified in phenomenological studies are described, together with theoretical insights from philosophy and biology.

Results:

A fuller understanding of the pain experience and of the clinical care of those experiencing pain is achievable through greater attention to the phenomenology of pain, the social “intersubjective space” in which pain occurs, and the limitations of language.

Conclusion:

Based on these results, a revised definition of pain is offered: Pain is a mutually recognizable somatic experience that reflects a person's apprehension of threat to their bodily or existential integrity.
Capsaicin 8% patch reversibly reduces A-delta fiber evoked potential amplitudes
Authors: Papagianni Aikaterini , Siedler Gabriela , Sommer Claudia , Üçeyler Nurcan
Published: March 2018

Introduction:

The capsaicin 8% patch is a treatment option in patients with localized peripheral neuropathic pain. Better understanding of its mechanisms of action and knowledge on predictive biomarkers for a treatment response is warranted.

Objectives:

To use electrically evoked pain-related potentials for investigation of A-delta fiber conduction after capsaicin 8% patch treatment.

Methods:

We studied 11 healthy controls at the dorsal hand and the foot and 12 patients with neuropathic pain at the area affected by neuropathic pain before and 2 hours after application of a capsaicin 8% patch (Qutenza). Patients were additionally phenotyped using quantitative sensory testing and skin biopsy.

Results:

Peak-to-peak N1-P1 amplitudes (PPA) were reduced after Qutenza application by a median of 60% in 6/11 controls and by 33% in patients with neuropathic pain compared with baseline; they were increased in 3 controls that did not develop capsaicin-induced pain. Patients with elevated cold detection thresholds more often had reduced PPA after Qutenza than those with normal cold detection threshold. Patients with reduced PPA after capsaicin application and with capsaicin-induced pain were more likely to achieve pain reduction on Qutenza.

Conclusion:

The capsaicin 8% patch induces a reduction in A-delta PPA in healthy persons and in patients with neuropathic pain adding to the mechanistic understanding of its effect.
Time to First-Line ART Failure and Time to Second-Line ART Switch in the IeDEA Pediatric Cohort
Authors: Wools-Kaloustian Kara , Marete Irene , Ayaya Samuel , Sohn Annette H. , Van Nguyen Lam , Li Shanshan , Leroy Valériane , Musick Beverly S. , Newman Jamie E. , Edmonds Andrew , Davies Mary-Ann , Eboua François T. , Obama Marie-Thérèse , Yotebieng Marcel , Sawry Shobna , Mofenson Lynne M. , Yiannoutsos Constantin T.
Published: March 2018

Background:

Globally, 49% of the estimated 1.8 million children living with HIV are accessing antiretroviral therapy (ART). There are limited data concerning long-term durability of first-line ART regimens and time to transition to second-line.

Methods:

Children initiating their first ART regimen between 2 and 14 years of age and enrolled in one of 208 sites in 30 Asia-Pacific and African countries participating in the Pediatric International Epidemiology Databases to Evaluate AIDS consortium were included in this analysis. Outcomes of interest were: first-line ART failure (clinical, immunologic, or virologic), change to second-line, and attrition (death or loss to program ). Cumulative incidence was computed for first-line failure and second-line initiation, with attrition as a competing event.

Results:

In 27,031 children, median age at ART initiation was 6.7 years. Median baseline CD4% for children ≤5 years of age was 13.2% and CD4 count for those >5 years was 258 cells per microliter. Almost all (94.4%) initiated a nonnucleoside reverse transcriptase inhibitor; 5.3% a protease inhibitor, and 0.3% a triple nucleoside reverse transcriptase inhibitor–based regimen. At 1 year, 7.7% had failed and 14.4% had experienced attrition; by 5 years, the cumulative incidence was 25.9% and 29.4%, respectively. At 1 year after ART failure, 13.7% had transitioned to second-line and 11.2% had experienced attrition; by 5 years, the cumulative incidence was 31.6% and 25.9%, respectively.

Conclusions:

High rates of first-line failure and attrition were identified in children within 5 years after ART initiation. Of children meeting failure criteria, only one-third were transitioned to second-line ART within 5 years.
Cango Lyec (Healing the Elephant): Gender Differences in HIV Infection in Post-conflict Northern Uganda
Authors: Spittal Patricia M. , Malamba Samuel S. , Ogwang Martin D. , Musisi Seggane , Ekwaru J. Paul , Sewankambo Nelson K. , Pearce Margo E. , Jongbloed Kate , Patel Sheetal H. , Katamba Achilles , Blair Alden H. , Muyinda Herbert , Schechter Martin T.
Published: March 2018

Background:

As previously encamped resettle, potential for rapid HIV transmission in post-conflict Northern Uganda is concerning. Women in particular may be experiencing heightened vulnerability resulting from war-related sexual violence.

Setting:

Cango Lyec (Healing the Elephant) Project is a cohort involving conflict-affected people in 3 districts in Northern Uganda.

Methods:

Eight randomly selected communities were mapped, and a census was conducted. Participants aged 13–49 years completed questionnaires in Luo on war-related experiences, mental health, sexual vulnerabilities, and sociodemographics. Blood samples were tested for HIV and syphilis. Baseline data from all sexually active participants was used to determine gender differences in HIV prevalence. Multivariate modeling determined correlates of HIV by gender.

Results:

Among 2008 participants, HIV prevalence was higher among women [17.2; 95% confidence interval (CI): 14.7 to 19.7] compared to men (10.6; 95% CI: 8.0 to 13.2, <0.001). Among women, correlates of HIV included: war-related sexual assault [adjusted odds ratio (AOR): 1.95; 95% CI: 1.16 to 3.26]; probable depression (AOR: 2.22; 95% CI: 1.46 to 3.37); probable post-traumatic stress disorder (AOR: 2.03; 95% CI: 1.45 to 2.84); experiencing ≥12 traumatic events (AOR: 2.04; 95% CI: 1.31 to 3.18); suicide ideation (AOR: 1.67; 95% CI: 1.22 to 2.28); living in a female-headed household (AOR: 2.76; 95% CI: 1.70 to 4.49); first sexual partner ≥10 years older (AOR: 1.69; 95% CI: 1.07 to 2.67); sex for exchange (AOR: 5.51; 95% CI: 1.76 to 17.31); having 2 (AOR: 2.54; 95% CI: 1.23 to 5.23) or 3+ (AOR: 4.65; 95% CI: 2.65 to 8.18) sexual partners; inconsistent condom use (AOR: 0.40; 95% CI: 0.29 to 0.57); genital ulcers (AOR: 3.08; 95% CI: 2.16 to 4.38); active syphilis (AOR: 4.33; 95% CI: 1.22 to 15.40); and ill health without medical care (AOR: 2.02; 95% CI: 1.22 to 3.34). Among men, correlates of HIV included no condom at sexual debut (AOR: 1.92; 95% CI: 1.30 to 2.83) and genital ulcers (AOR: 4.40; 95% CI: 1.35 to 14.40).

Conclusion:

Women are disproportionately impacted by HIV, trauma, and depression in this conflict-affected population. Trauma-informed HIV prevention and culturally safe mental health initiatives are urgently required.
Gaps Along the HIV Care Continuum: Findings Among a Population Seeking Sexual Health Care Services in New York City
Authors: Pathela Preeti , Jamison Kelly , Braunstein Sarah L. , Schillinger Julia A. , Tymejczyk Olga , Nash Denis
Published: March 2018

Background:

Linkage/relinkage to HIV care for virally unsuppressed people with new sexually transmitted infections is critical for ending the HIV epidemic. We quantified HIV care continuum gaps and viral suppression among HIV-positive patients attending New York City (NYC) sexual health clinics (SHCs).

Methods:

One thousand six hundred forty-nine HIV-positive patients and a 10% sample of 11,954 patients with unknown HIV status on clinic visit date (DOV) were matched against the NYC HIV registry. Using registry diagnosis dates, we categorized matched HIV-positive patients as “new-positives” (newly diagnosed on DOV), “recent-positives (diagnosed ≤90 days before DOV), “prevalent-positives” (diagnosed >90 days before DOV), and “unknown-positives” (previously diagnosed but status unknown to clinic on DOV). We assessed HIV care continuum outcomes before and after DOV for new-positives, prevalent-positives, and unknown-positives using registry laboratory data.

Results:

In addition to 1626 known HIV-positive patients, 5% of the unknown sample (63/1196) matched to the registry, signifying that approximately 630 additional HIV-positive patients attended SHCs. Of new-positives, 65% were linked to care after DOV. Of prevalent-positives, 66% were in care on DOV; 43% of the out-of-care patients were relinked after DOV. Of unknown-positives, 40% were in care on DOV; 21% of the out-of-care patients relinked after DOV. Viral suppression was achieved by 88% of in-care unknown-positives, 76% in-care prevalent-positives, 50% new-positives, 42% out-of-care prevalent-positives, and 16% out-of-care unknown-positives.

Conclusions:

Many HIV-positive people, including those with uncontrolled HIV infection, attend SHCs and potentially contribute to HIV spread. However, HIV status often is not known to staff, resulting in missed linkage/relinkage to care opportunities. Better outcomes could be facilitated by real-time ascertainment of HIV status and HIV care status.