Δευτέρα, 19 Ιουνίου 2017

Go-Wish Pediatrics: Pilot Study of a Conversation Tool in Pediatric Palliative Care

Research Poster Presented at NAPNAP's 2017 Posters On The Move, 38th National NAPNAP Conference on Pediatric Health Care, March 16, 2017, Denver, CO.

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Writing for Publication: Your Obligation to the Profession

Editor's note: Dr. Bobbie Crew Nelms, the first editor for the Journal of Pediatric Health Care, was and continues to be a proponent of encouraging practitioners to write for publication and to contribute to the profession through clinical scholarship. Her early editorials would often speak to this topic, and we are pleased to offer this reprint of one of her columns in this issue.

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Implementation of New Tools in the Evaluation and Management of Newborns at Risk for Sepsis

Practice Innovation Poster Presented at NAPNAP's 2017 Posters On The Move, 38th National NAPNAP Conference on Pediatric Health Care, March 16, 2017, Denver, CO.

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Safety in the Agricultural Work Camp: Comic Book Development & Evaluation for Latino MSAW Families

Emerging Knowledge for Clinical Practice Podium Presentations focusing on the Research Agenda Priority of Safety, Presented at the 38th National NAPNAP Conference on Pediatric Health Care, March 17, 2017, Denver, CO.

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Information for Readers



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Table of Contents



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The Power of Language Nutrition for Children's Brain Development, Health, and Future Academic Achievement

Language Nutrition, a term created to describe language exposure that is rich in quality and quantity and delivered in the context of social interactions, is crucial for a child's development and is strongly associated with his/her future literacy, academic achievement, and health. However, significant differences in children's early language environments contribute to disparities in their educational and health trajectories. Interventions, including book distribution programs, coaching parents to enrich their child's language environment, and public awareness campaigns, have all been shown to positively influence a child's access to language-rich interactions.

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Editorial Board



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Looking Through My Eyes: A Photovoice Study on Influences of Obesity in Multi-Ethnic Inner-City Adolescents

Emerging Knowledge for Clinical Practice Podium Presentations focusing on the Research Agenda Priority of Obesity, Presented at the 38th National NAPNAP Conference on Pediatric Health Care, March 17, 2017, Denver, CO.

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Society



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The Power of Language Nutrition for Children’s Brain Development, Health, and Future Academic Achievement—Continuing Education Posttest



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Welcome to My Happy Time: Summer

Thank you for the opportunity to serve as president of the National Association of Pediatric Nurse Practitioners (NAPNAP). It is a great honor and privilege to be your leader and steward of NAPNAP's culture and image. A significant part of my role is to amplify and communicate the culture of our organization and profession by reaching out to current and prospective members, interdisciplinary health care partners, patients, and parents. Outreach is important, because we are immersed in a time of great change.

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Complication Rates for Pediatric PICCs after Rewire

Emerging Knowledge for Clinical Practice Podium Presentations focusing on the Research Agenda Priority of Self-management of Acute and Chronic Conditions, Presented at the 38th National NAPNAP Conference on Pediatric Health Care, March 17, 2017, Denver, CO.

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Evaluating Depressive Symptomatology, Maternal Loneliness, and Maternal Self-Esteem in Mothers Who Attend a New Moms Peer Support Group

Emerging Knowledge for Clinical Practice Podium Presentations focusing on the Research Agenda Priority of Mental Health, Presented at the 38th National NAPNAP Conference on Pediatric Health Care, March 17, 2017, Denver, CO.

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The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions

http://orlhealth.blogspot.com/2017/06/the-absence-of-cd56-expression-can.html

The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. Aim: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. Statistical Analysis Used: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Results: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. Conclusions: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Estimated Blood Loss: In the Equation of the Beholder

imageNo abstract available

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Determination of Perioperative Blood Loss: Accuracy or Approximation?

imageBACKGROUND: Various different interventions can be used to reduce surgical blood loss; however, there is no "gold standard" for accurately measuring the volume of perioperative blood loss, and this makes it difficult to assess the efficacy of these interventions. METHODS: We used data from a previous multicenter double-blind randomized clinical trial in patients undergoing total hip arthroplasty in which we compared 2 regimens for administering tranexamic acid versus placebo. We assessed direct measures (external blood loss) and indirect estimates (using the formulas of Bourke, Gross, Mercuriali, and Camarasa and a new formula we have developed) using analysis of variance to compare estimated volumes of blood loss among the study groups. In addition, intraclass correlation coefficients (ICCs) and Bland–Altman diagrams were used to compare the estimated volumes of blood loss obtained with each formula. RESULTS: The mean estimated external blood loss was 909 ± 324 mL, and the mean estimates of blood loss calculated using the formulas of Gross, Bourke and Smith, and Camarasa were 1308 ± 555, 1091 ± 454, and 1641 ± 945 mL, respectively, whereas we obtained a value of 1511 ± 919 mL with the new formula at day 2. In all cases, the results favored the use of tranexamic acid (P

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Irregular Outcomes: Predictors of New Atrial Fibrillation After Noncardiac Surgery

imageNo abstract available

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Predictors, Prognosis, and Management of New Clinically Important Atrial Fibrillation After Noncardiac Surgery: A Prospective Cohort Study

imageBACKGROUND: Despite the frequency of new clinically important atrial fibrillation (AF) after noncardiac surgery and its increased association with the risk of stroke at 30 days, there are limited data informing their prediction, association with outcomes, and management. METHODS: We used the data from the PeriOperative ISchemic Evaluation trial to determine, in patients undergoing noncardiac surgery, the association of new clinically important AF with 30-day outcomes, and to assess management of these patients. We also aimed to derive a clinical prediction rule for new clinically important AF in this population. We defined new clinically important AF as new AF that resulted in symptoms or required treatment. We recorded an electrocardiogram 6 to 12 hours postoperatively and on the 1st, 2nd, and 30th days after surgery. RESULTS: A total of 211 (2.5% [8351 patients]; 95% confidence interval, 2.2%–2.9%) patients developed new clinically important AF within 30 days of randomization (8140 did not develop new AF). AF was independently associated with an increased length of hospital stay by 6.0 days (95% confidence interval, 3.5–8.5 days) and vascular complications (eg, stroke or congestive heart failure). The usage of an oral anticoagulant at the time of hospital discharge among patients with new AF and a CHADS2 score of 0, 1, 2, 3, and ≥4 was 6.9%, 10.2%, 23.0%, 9.4%, and 33.3%, respectively. Two independent predictors of patients developing new clinically important AF were identified (ie, age and surgery). The prediction rule included the following factors and assigned weights: age ≥85 years (4 points), age 75 to 84 years (3 points), age 65 to 74 years (2 points), intrathoracic surgery (3 points), major vascular surgery (2 points), and intra-abdominal surgery (1 point). The incidence of new AF based on scores of 0 to 1, 2, 3 to 4, and 5 to 6 was 0.5%, 1.0%, 3.1%, and 5.3%, respectively. CONCLUSIONS: Age and surgery are independent predictors of new clinically important AF in the perioperative setting. A minority of patients developing new clinically important AF with high CHADS2 scores are discharged on an oral anticoagulant. There is a need to develop effective and safe interventions to prevent this outcome and to optimize the management of this event when it occurs.

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A case of nivolumab-related cholangitis and literature review: how to look for the right tools for a correct diagnosis of this rare immune-related adverse event

Summary

Anti-programmed cell death-1 (PD-1) monoclonal antibodies, such as nivolumab, used for the treatment of several tumors, can trigger effector T-cells against tumor- and self-antigens, leading to the occurrence of different immune-related adverse events. Among them, liver injuries are rare and usually transient. To date, only four cases of immune-related cholangitis in non-small cell lung cancer (NSCLC) patients have been described during nivolumab treatment. Here, we describe laboratory tests, imaging and liver biopsy features that confirm this diagnosis as opposed to other forms of autoimmune liver disease; nevertheless, we also provide evidence of the presence of different clinical-pathological patterns of immune-related cholangitis.



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Phase II study of Amrubicin monotherapy in elderly or poor-risk patients with extensive disease of small cell lung cancer

Summary

Background Previous study indicated that an optional anti-cancer drug for the treatment of small-cell lung cancer (SCLC) is amrubicin. However, no prospective studies have evaluated amrubicin in chemo-naive elderly or poor-risk patients with SCLC. Therefore, this study aimed to evaluate the efficacy of amrubicin as first-line chemotherapy for elderly or poor-risk patients with extensive-disease SCLC (ES-SCLC). Methods Patients with chemotherapy-naive ES-SCLC received multiple cycles of 40 mg/m2 amrubicin for 3 consecutive days every 21 days. The primary endpoint was the overall response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results Between March 2011 and August 2015, 36 patients were enrolled in this study. Each patient received a median of four treatment cycles (range, 1–6 cycles). ORR was 52.8% [95% confidence interval (CI), 37–69%]. The median PFS and OS periods were 5.0 months (95% CI, 3.4–6.6 months) and 9.4 months (95% CI, 5.2–13.6 months), respectively. Neutropenia was the most common grade 3 or 4 adverse event (69.4%), with febrile neutropenia developing in 13.9% of patients. No treatment-related death occurred. At the time of starting second-line chemotherapy, 19 of 22 patients (86%) had significantly improved or maintained their performance status (PS) relative to their PS at the time of starting amrubicin monotherapy as first-line chemotherapy (P = 0.027). Conclusions The results of the present study suggest that amrubicin could be considered as a viable treatment option for chemotherapy-naive elderly or poor-risk patients with ES-SCLC (Clinical trial registration number: UMIN000011055 http://ift.tt/PmpYKN).



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Decorin gene upregulation mediated by an adeno-associated virus vector increases intratumoral uptake of nab-paclitaxel in neuroblastoma via inhibition of stabilin-1

Summary

The availability of effective medication for the treatment of refractory or recurrent neuroblastoma remains limited. This study sought to investigate the effects of increased decorin (DCN) expression on the intratumoral uptake of nab-paclitaxel as a potential novel approach to NB. Correlation between the clinical characteristics of neuroblastoma and the expression of DCN, secreted protein acidic and rich in cysteine (SPARC) and stabilin-1 was evaluated. The anticancer effect of recombinant adeno-associated virus-DCN (rAAV-DCN) was assessed in vivo and in vitro. And the effect of rAAV-DCN on the intratumoral uptake of paclitaxel was also studied in neuroblastoma-grafted nude mice. Overall, 12.5%, 17.7%, and 71.9% of the tumors stained positive for DCN, SPARC and stabilin-1 respectively and correlated to age, stage and N-MYC status in 96 children and adolescents with neuroblastoma. Transfected neuroblastoma cells stably expressed DCN, with in vivo and in vitro studies demonstrating rAAV-DCN sensitized the anticancer effect of nab-paclitaxel. Systemic rAAV-DCN in neuroblastoma-grafted nude mice inhibited stabilin-1, up-regulated SPARC, and increased the intratumoral uptake of paclitaxel. Macrophage depletion or anti-stabilin-1 monoclonal antibody increased the intratumoral uptake of nab-paclitaxel and its anticancer effects to a degree comparable to that achieved by systemic rAAV-DCN. The systemic administration of rAAV-DCN up-regulates DCN in neuroblastoma and accelerates the intratumoral uptake of nab-paclitaxel by inhibiting stabilin-1 mediated SPARC degradation.



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Urolithins impair cell proliferation, arrest the cell cycle and induce apoptosis in UMUC3 bladder cancer cells

Summary

Ellagitannins have been gaining attention as potential anticancer molecules. However, the low bioavailability of ellagitannins and their extensive metabolization in the gastrointestinal tract into ellagic acid and urolithins suggest that the health benefits of consuming ellagitannins rely on the direct effects of their metabolites. Recently, chemopreventive and chemotherapeutic activities were ascribed to urolithins. Nonetheless, there is still a need to screen and evaluate the selectivity of these molecules and to elucidate their cellular mechanisms of action. Therefore, this work focused on the antiproliferative effects of urolithins A, B and C and ellagic acid on different human tumor cell lines. The evaluation of cell viability and the determination of the half-maximal inhibitory concentrations indicated that the sensitivity to the studied urolithins varied markedly between the different cell lines, with the bladder cancer cells (UMUC3) being the most susceptible. In UMUC3 cells, urolithin A was the most active molecule, promoting cell cycle arrest at the G2/M checkpoint, increasing apoptotic cell death and inhibiting PI3K/Akt and MAPK signaling. Overall, the present study emphasizes the chemopreventive/chemotherapeutic potential of urolithins, highlighting the stronger effects of urolithin A and its potential to target transitional bladder cancer cells.



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High Prevalence of Resistance to Fluoroquinolones and Tetracycline Campylobacter Spp. Isolated from Poultry in Poland

Microbial Drug Resistance , Vol. 0, No. 0.


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“Make OSA great again” Report from the 113th American Thoracic Society International Conference (2017) in Washington DC



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Stereotyped episodes of aphasia and immobility: how cataplexy mimics stroke in an elderly patient

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Publication date: Available online 19 June 2017
Source:Sleep Medicine
Author(s): E. Antelmi, F. Pizza, S. Vandi, G. Plazzi




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Risk of obstructive sleep apnea among patients with Cushing's syndrome: a nationwide longitudinal study

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Publication date: August 2017
Source:Sleep Medicine, Volume 36
Author(s): Ling-Uei Wang, Tsung-Yang Wang, Ya-Mei Bai, Ju-Wei Hsu, Kai-Lin Huang, Tung-Ping Su, Cheng-Ta Li, Wei-Chen Lin, Tzeng-Ji Chen, Mu-Hong Chen
ObjectivePrevious studies have demonstrated the association between Cushing's syndrome (CS), obstructive sleep apnea (OSA), and the risk factors for OSA, but rarely provided the evidence within a large population. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between CS and OSA, and to provide persuading evidences.MethodsIn our study, 1612 patients with CS and 1612 age-, sex-, and comorbidities-matched controls were included, and followed up to the end of 2011. Cases of OSA were identified during the follow-up.ResultsAmong patients with CS, 53 developed OSA (incidence: 4.11 per thousand person-year) compared with 22 in the control group (incidence: 1.70 per thousand person-year) during the follow-up (p < 0.001). CS patients had a 2.82-fold higher risk of developing OSA (HR = 2.82; 95% CI: 1.67–4.77) in later life.DiscussionOur study was the first longitudinal study to support the temporal association between CS and risk of OSA. Patients with CS were associated with an increased likelihood of OSA. Further studies would be required to investigate the exact underlying mechanisms between CS and OSA, and elucidate whether the prompt intervention for CS may reduce the risk of subsequent OSA.



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“Make OSA great again” Report from the 113th American Thoracic Society International Conference (2017) in Washington DC



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Post-catastrophe Analysis of the Fundão Tailings Dam Failure in the Doce River System, Southeast Brazil: Potentially Toxic Elements in Affected Soils

Abstract

On November 5, 2015, after the collapse of the Fundão tailings dam, a massive amount of iron mine waste was released into the Doce River system in southeast Brazil. The aim of our study was to determine the mass fractions of potentially toxic elements in soil affected by the deposition of material by the waste wave. A preliminary screening was performed with portable X-ray fluorescence spectrometry (PXRF) and principal component analysis (PCA). The EPA 3050B method was further applied to digest the samples for quantitative determination of As, Ba, Cr, Cu, Mn, Ni, Pb, V, and Zn by inductively coupled plasma mass spectrometry. PCA was useful to classify the mine waste samples based on the Fe signal from the PXRF spectra, in spite of the heterogeneous nature of the material discharged into the Doce River system. The anomalous levels of As (up to 164 mg kg−1) and Mn (as high as 2410 mg kg−1) found in some mine waste and affected soil samples are within the background ranges typically observed in the soils of the Iron Quadrangle region. The toxicity characteristic leaching procedure shows no evidence of hazards regarding As, but a high natural background level of Mn was found in the mobile fraction. This preliminary environmental assessment highlights the importance of evaluation of long-term effects on soil directly impacted, as well as on the aquatic biota of the Doce River system and adjacent coastal environment given the large affected area, which includes regions with varying background levels of toxic elements.



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Impact of evolving isoprene mechanisms on simulated formaldehyde: An inter-comparison supported by in situ observations from SENEX

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Publication date: September 2017
Source:Atmospheric Environment, Volume 164
Author(s): Margaret R. Marvin, Glenn M. Wolfe, Ross J. Salawitch, Timothy P. Canty, Sandra J. Roberts, Katherine R. Travis, Kenneth C. Aikin, Joost A. de Gouw, Martin Graus, Thomas F. Hanisco, John S. Holloway, Gerhard Hübler, Jennifer Kaiser, Frank N. Keutsch, Jeff Peischl, Ilana B. Pollack, James M. Roberts, Thomas B. Ryerson, Patrick R. Veres, Carsten Warneke
Isoprene oxidation schemes vary greatly among gas-phase chemical mechanisms, with potentially significant ramifications for air quality modeling and interpretation of satellite observations in biogenic-rich regions. In this study, in situ observations from the 2013 SENEX mission are combined with a constrained 0-D photochemical box model to evaluate isoprene chemistry among five commonly used gas-phase chemical mechanisms: CB05, CB6r2, MCMv3.2, MCMv3.3.1, and a recent version of GEOS-Chem. Mechanisms are evaluated and inter-compared with respect to formaldehyde (HCHO), a high-yield product of isoprene oxidation. Though underestimated by all considered mechanisms, observed HCHO mixing ratios are best reproduced by MCMv3.3.1 (normalized mean bias = −15%), followed by GEOS-Chem (−17%), MCMv3.2 (−25%), CB6r2 (−32%) and CB05 (−33%). Inter-comparison of HCHO production rates reveals that major restructuring of the isoprene oxidation scheme in the Carbon Bond mechanism increases HCHO production by only ∼5% in CB6r2 relative to CB05, while further refinement of the complex isoprene scheme in the Master Chemical Mechanism increases HCHO production by ∼16% in MCMv3.3.1 relative to MCMv3.2. The GEOS-Chem mechanism provides a good approximation of the explicit isoprene chemistry in MCMv3.3.1 and generally reproduces the magnitude and source distribution of HCHO production rates. We analytically derive improvements to the isoprene scheme in CB6r2 and incorporate these changes into a new mechanism called CB6r2-UMD, which is designed to preserve computational efficiency. The CB6r2-UMD mechanism mimics production of HCHO in MCMv3.3.1 and demonstrates good agreement with observed mixing ratios from SENEX (−14%). Improved simulation of HCHO also impacts modeled ozone: at ∼0.3 ppb NO, the ozone production rate increases ∼3% between CB6r2 and CB6r2-UMD, and rises another ∼4% when HCHO is constrained to match observations.



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Evidence for Adaptive Introgression of Disease Resistance Genes Among Closely Related Arabidopsis Species

The generation and maintenance of functional variation in the pathogen defense system of plants is central to the constant evolutionary battle between hosts and parasites. If a species is susceptible to a given pathogen, hybridisation and subsequent introgression of a resistance allele from a related species can potentially be an important source of new immunity and is therefore expected to be selected for in a process referred to as adaptive introgression. Here we survey sequence variation in ten resistance (R) genes and compare with 37 reference genes in natural populations of the two closely related and interfertile species Arabidopsis lyrata and A. halleri. The R-genes are highly polymorphic in both species and show clear signs of trans-species polymorphisms. We show that A. lyrata and A. halleri have had a history of limited introgression for the reference genes. For the R-genes the introgression rate has been significantly higher than for the reference genes, resulting in fewer fixed differences between species and a higher sharing of identical haplotypes. We conclude that R-genes likely cross the species boundaries at a higher rate than reference genes and therefore also that some of the increased diversity and trans-specific polymorphisms in R-genes is due to adaptive introgression.



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Sleep in Adolescents and Young Adults in the Year After Cancer Treatment

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.


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Fractionated dosing improves preclinical therapeutic index of pyrrolobenzodiazepine-containing antibody drug conjugates

                Purpose:  To use preclinical models to identify a dosing schedule that improves tolerability of highly potent pyrrolobenzodiazepine dimers (PBD) antibody drug conjugates (ADCs) without compromising anti-tumor activity.  <p>                Experimental design:   A series of dose-fractionation studies were conducted to investigate the pharmacokinetic drivers of safety and efficacy of PBD ADCs in animal models.  The exposure-activity relationship was investigated in mouse xenograft models of human prostate cancer, breast and gastric cancer by comparing anti-tumor activity after single and fractionated dosing with tumor-targeting ADCs conjugated to SG3249, a potent PBD dimer.  The exposure-tolerability relationship was similarly investigated in rat and monkey toxicology studies by comparing tolerability, as assessed by survival, body weight, and organ-specific toxicities, after single and fractionated dosing with ADCs conjugated to SG3249 (rats) or SG3400, a structurally related PBD (monkeys).    </p> <p>Results:  Observations of similar anti-tumor activity in mice treated with single or fractionated dosing suggests that anti-tumor activity of PBD ADCs is more closely related to total exposure (AUC, area under the curve) than peak drug concentrations (Cmax).  In contrast, improved survival and reduced toxicity in rats and monkeys treated with a fractionated dosing schedule suggests that tolerability of PBD ADCs is more closely associated with Cmax than AUC </p>                 Conclusions:  We provide the first evidence that fractionated dosing can improve preclinical tolerability of at least some PBD ADCs without compromising efficacy.  These findings suggest that preclinical exploration of dosing schedule could be an important clinical strategy to improve the therapeutic window of highly potent ADCs and should be investigated further.



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Mechanisms of primary drug resistance in FGFR1 amplified lung cancer

Purpose: <br />The 8p12-p11 locus is frequently amplified in squamous cell lung cancer (SQLC); the receptor tyrosine kinase fibroblast growth factor receptor 1 (FGFR1) being one of the most prominent targets of this amplification. Thus, small molecules inhibiting FGFRs have been employed to treat FGFR1-amplified SQLC. However, only about 11% of such FGFR1-amplified tumors respond to single agent FGFR inhibition and several tumors exhibited insufficient tumor shrinkage, compatible with the existence of drug-resistant tumor cells.<br />Experimental Design: <br />To investigate possible mechanisms of resistance to FGFR inhibition we studied the lung cancer cell lines DMS114 and H1581. Both cell lines are highly sensitive to three different FGFR-inhibitors, but exhibit sustained residual cellular viability under treatment, indicating a subpopulation of existing drug-resistant cells. We isolated these subpopulations by treating the cells with constant high doses of FGFR inhibitors.<br />Results: <br />The FGFR inhibitor resistant cells were cross-resistant and characterized by sustained mitogen-activated protein kinase (MAPK) pathway activation. In drug resistant H1581 cells we identified NRAS amplification and DUSP6 deletion, leading to MAPK-pathway reactivation. Furthermore, we detected subclonal NRAS amplifications in 3 out of 20 (15%) primary human FGFR1 amplified SQLC specimens. By contrast, drug resistant DMS114 cells exhibited transcriptional up-regulation of MET that drove MAPK-pathway reactivation. As a consequence, we demonstrate that rational combination therapies resensitize resistant cells to treatment with FGFR inhibitors.<br />Conclusions:<br />We provide evidence for the existence of diverse mechanisms of primary drug resistance in FGFR1-amplified lung cancer and provide a rational strategy to improve FGFR inhibitor therapies by combination treatment.



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Dose-Finding Methods: Moving Away from the 3+3 to Include Richer Outcomes

The most commonly used method for dose-finding, the 3+3, has poor performances. New adaptive designs are more efficient. Nevertheless, they have reached a maximum performance level, and further improvement requires either larger sample sizes, or outcomes measures richer than the simplistic severe toxicity measured at cycle 1.



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Patient-derived interstitial fluids and predisposition to aggressive sporadic breast cancer through collagen remodeling and inactivation of p53.

Purpose: Despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood body fluid in medicine. Increased IF pressure is thought to result from the increased deposition of extracellular matrix in the affected tissue preventing its reabsorption. In the cancer field, increased rigidity surrounding a cancerous mass remains the main reason that palpation and radiological examination, such as mammography, are used for cancer detection. While the pressure produced by IF has been considered, the biochemical composition of IF has not been considered in its effect on tumors.<br /><br />Experimental Design: We classified 135 IF samples from bilateral mastectomy patients based on their ability to promote the invasion of breast cancer cells. <br /><br />Results: <p>We observed a wide range of invasion scores. Patients with high-grade primary tumors at diagnosis had higher IF invasion scores. In mice, injections of high-score IF (IFHigh) in a normal mammary gland promotes ductal hyperplasia, increased collagen deposition, and local invasion. In a mouse model of residual disease, IFHigh increased disease progression and promoted aggressive visceral metastases. Mechanistically, we found that IFHigh induces myofibroblast differentiation and collagen production through activation of CLIC4. IFHigh also down-regulates RYBP, leading to degradation of p53. Further, in mammary glands of heterozygous p53-mutant knock-in mice, IFHigh promotes spontaneous tumor formation.</p> <br /><br />Conclusions:Our study indicates that IF can increase the deposition of extracellular matrix and raises the provocative possibility that they play an active role in the predisposition, development, and clinical course of sporadic breast cancers



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A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma

Purpose: <p>While stereotactic body radiation therapy (SBRT) can reduce tumor volumes in metastatic renal cell carcinoma (mRCC) patients, little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of mRCC patients and analyze the immunological impact of high-dose radiation.</p> <br /><br />Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, mRCC patients were treated with 15 Gray (Gy) SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).<br /><br />Results: RCC cells treated in vitro with radiation had increased TAA expression compared to untreated tumor cells. Fourteen patients received SBRT followed by surgery and treatment was well tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens.<br /><br />Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared to archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC.



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Brevundimonas diminuta infection in a case of nephrotic syndrome

Abhilash Chandra, Anupam Das, Manodeep Sen, Meenakshi Sharma

Indian Journal of Pathology and Microbiology 2017 60(2):279-281

Brevundimonas has rarely been isolated from clinical specimens. We here report a case of Brevundimonas diminuta infection in an 18-year-old male patient with nephrotic syndrome. B. diminuta was identified by the VITEK 2 Compact system, following isolation from his blood sample. To the best of our knowledge, B. diminuta has not been reported in patients with nephrotic syndrome.

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Leiomyosarcoma of inferior vena cava with intracardiac extension presenting as Budd-Chiari syndrome: Report of a rare case

Kaniyappan Nambiyar, Arvind Ahuja, Minakshi Bhardwaj

Indian Journal of Pathology and Microbiology 2017 60(2):256-258

Primary leiomyosarcoma of vascular origin is a rare malignant smooth muscle tumor. This report describes a case of primary leiomyosarcoma of the inferior vena cava (IVC) in a 52-year-old male who presented with complaints of abdominal pain, chest pain, and bilateral lower limb swelling for 4 months. Imaging of the chest and abdomen revealed a mass in the IVC extending into right atrium, heterogeneous enhancement of liver, hepatosplenomegaly, and ascites. Histopathological examination showed a malignant spindle cell tumor with cells arranged in fascicular and hemangiopericytomatous pattern. Immunohistochemistry for smooth muscle actin and desmin confirmed smooth muscle origin of the tumor. Recognition of this tumor in this rare location and Budd-Chiari syndrome-like presentation is imperative for proper management of the patient.

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Ameloblastoma: A 16-year clinicopathological study on Goan population

Karla Maria Carvalho, Anita Dhupar, Anita Spadigam, Shaheen Syed

Indian Journal of Pathology and Microbiology 2017 60(2):157-160

Background: Ameloblastoma is a benign slow growing tumor of odontogenic origin composed of epithelial cells that resemble enamel forming cells namely the ameloblasts however these lesional cells do not differentiate to produce enamel. They are locally aggressive and can cause severe abnormalities of the face and jaw. Aim: This study aimed to correlate the incidence and recurrence rates of ameloblastoma to the different clinical and histopathological parameters. Methods: A study on ameloblastomas in the Goan population for 16 years (1999–2014) was carried out. Archived documented data of surgically treated cases of ameloblastomas were used in this study. Results: It was revealed that out of 52 cases of ameloblastomas, a male preponderance was seen. Age predisposition was seen to favor the third-fourth decade, the most common site was the posterior aspect of lower jaw for new and recurrent cases. Conclusion: The study highlights, the possible etiological role of location influencing the incidence and recurrence rates of ameloblastomas.

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Fine needle aspiration cytology of thyroid metastasis: An unusual presentation of cervical carcinoma; a case report and review of literature

Monika Singh, Prajwala Gupta, Minakshi Bhardwaj

Indian Journal of Pathology and Microbiology 2017 60(2):298-299



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The absence of CD56 expression can differentiate papillary thyroid carcinoma from other thyroid lesions

Ioana Golu, Mihaela Maria Vlad, Alis Dema, Lavinia Cristina Moleriu, Anca Tudor, Mihaela Iacob, Oana Popa, Marioara Cornianu

Indian Journal of Pathology and Microbiology 2017 60(2):161-166

Context: The neural cell adhesion molecule CD56 is an antigen important for the differentiation of the follicular epithelium. Recent studies have reported low or absent expression of CD56 in papillary thyroid carcinoma (PTC) and its presence in normal thyroid tissue, benign thyroid lesions, and most follicular non-PTC tumors. Aim: We wish to estimate the value of CD56 in the differentiation of PTC (including follicular variant-PTC [FV-PTC]) from other nontumoral lesions and follicular thyroid neoplasias. Settings and Design: This was a retrospective, case–control study. Subjects and Methods: We analyzed the expression of CD56 in normal thyroid follicular tissue, 15 nonneoplastic thyroid lesions (nodular hyperplasia, Graves' disease, and chronic lymphocytic thyroiditis/Hashimoto), and 38 thyroid follicular cell neoplasms (25 cases of PTC). The immunohistochemical reactions were performed on sections stained with anti-CD56 antibody. Statistical Analysis Used: We used the Chi-square test, values of P< 0.05 being considered statistically significant. Risk analysis was applied on these studied groups, by calculating the odds ratio (OR) value. Results: Our results indicated that CD56 immunoexpression had differentiated PTC from benign nonneoplastic lesions (P = 0.002), as well as from follicular neoplasias (P = 0.046). There were no significant differences regarding CD56 expression between FV-PTC and classical PTC (P = 0.436). The immunoexpression of CD56 has differentiated PTC from other thyroid non-PTC lesions (P < 0.001), with 26.4 OR value. Conclusions: CD56 has been proved to be a useful marker in the diagnosis of PTC, including FV-PTC. Its absence can help differentiate FV-PTC from other thyroid nodules with follicular patterns.

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Primary cutaneous large B-cell lymphoma of scalp: Case report of a rare variant

Yasmeen Khatib, Madhura Dande, Richa D Patel, Meena Makhija

Indian Journal of Pathology and Microbiology 2017 60(2):268-271

Primary cutaneous large B-cell lymphoma (Bcl) is defined as a lymphoma composed of large cells constituting more than 80% of the infiltrate and absence of extracutaneous involvement after staging investigations. In the new World Health Organization/European Organization for Research and Treatment of Cancer classification, cutaneous Bcls with large cells are of three types - primary cutaneous large Bcl leg type (PCLBCLLT), primary cutaneous follicle center lymphoma diffuse type (PCFCLDT), and primary cutaneous large Bcls other (PCLBCLO). These three different types are distinct in terms of their clinicopathological features and survival. The PCLBCLO has intermediate features between those of PCLBCLLT and PCFCLDT. We present a case of PCLBCLO in a 57-year-old male who presented with a scalp swelling. Ultrasonography examination was suggestive of a sebaceous cyst. Computed tomography scan revealed the presence of an ill-defined hyperdense region in the soft tissue of the scalp region extending into the deeper layers of the scalp. Fine-needle aspiration cytology (FNAC) revealed the presence of atypical lymphoid cells. Diagnosis was confirmed by biopsy and immunohistochemistry. Patient received rituximab combined with doxorubicin, vincristine, cyclophosphamide, and prednisolone regimen with complete resolution of the lesion. We present this case for its rarity, the utility of FNAC in early diagnosis, and to discuss the differential diagnosis.

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Poorly differentiated thyroid carcinoma: A hospital-based clinicopathological study and review of literature

Thin Thin Win, Nor Hayati Othman, Irfan Mohamad

Indian Journal of Pathology and Microbiology 2017 60(2):167-171

Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare aggressive malignancy of thyroid follicular cells and has unique features in morphology and behavior. This study was aimed to describe the experience of a tertiary medical center with PDTC within a 10-year period. Materials and Methods: This is a descriptive retrospective study of eight cases of PDTC among 418 various thyroid carcinomas. All cases of PDTC were retrieved along with the clinicopathological information. Results: Only eight cases (1.9%) of PDTC were diagnosed among 418 thyroid carcinomas. Mean age was 48.12 with 3:5 (male:female) and tumor size ranged 3–12 cm. PDTC were diagnosed coexisting with one or more other pathologies; nodular hyperplasia (four cases), papillary carcinoma (one case), follicular carcinoma (three cases), and Hashimoto thyroiditis (two cases); with ≥60% PDTC component. Six cases associated with high-grade features died within 3 years after diagnosis. Discussion: Mean age in this study was younger including a 20-year-old girl. Younger age was associated with better prognosis. Most of the cases had underlying benign thyroid lesions and differentiated thyroid carcinoma. Most of the PDTC had poor prognosis associated with PDTC component ≥60%, tumor necrosis, high mitotic count, lymph node involvement, vascular invasion and distant metastasis; and these cases died within 3 years after diagnosis. Conclusion: Although treatment of PDTC remains surgery followed by radioiodine therapy, correct histopathological diagnosis is important for clinicians and oncologists to predict the prognosis. All thyroid carcinoma should be sampled thoroughly not to miss small foci of PDTC component.

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Crescentic C3 glomerulopathy with acquired partial lipodystrophy: An unusual cause of rapidly progressive renal failure

Smita Mary Matthai, Shibu Jacob, Raiyani Palak, K Jagdish, Santosh Varughese, V Tamilarasi

Indian Journal of Pathology and Microbiology 2017 60(2):290-291



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Diagnostic value of immunohistochemistry staining of Bcl-2, CD34, CD20 and CD3 for distinction between discoid lupus erythematosus and lichen planus in the skin

Mazaher Ramezani, Bita-Sadat Hashemi, Sedigheh Khazaei, Mansour Rezaei, Ali Ebrahimi, Masoud Sadeghi

Indian Journal of Pathology and Microbiology 2017 60(2):172-176

Background: Cluster of differentiation (CD) markers is a classification system for monoclonal antibodies against cell surface molecules on leukocytes and antigens from other cells. Aims: The aim of this study is to evaluate immunohistochemical markers in patients with discoid lupus erythematosus (DLE) and lichen planus (LP) and correlation of these markers in two groups and with the normal group in the West of Iran. Settings and Design: Analytical cross-sectional study. Materials and Methods: This study was performed on paraffin blocks of DLE and LP patients with normal group (21, 21 and 16 cases, respectively) between 2009 and 2012. Formalin-fixed, paraffin-embedded tissue sections from each DLE, LP, and normal skin biopsy specimen were cut into 4-μ thick sections and mounted on glass slides. Initial sections were stained with hematoxylin and eosin. Primary antihuman antibodies against CD3, CD20, CD34, and Bcl-2 were applied. Positive control samples for CD3, CD20, and Bcl-2 were received from lymph nodes and for CD34 from dermal microvessels. Statistical Analysis Used: SPSS version 19 (SPSS, Inc., Chicago, USA) and Microsoft Excel 2007. Results: The mean staining for four markers was more significant in DLE and LP groups compared to normal group and for CD34 and CD3 was more significant in LP groups versus DLE group. Conclusions: CD3+, CD34+, Bcl-2+, and CD20+ cells are significantly higher in DLE and LP lesional skins versus normal skin. In addition, there were higher expressions of CD3 and CD34 in LP lesional skin versus DLE lesional skin.

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Poly immunophenotypic expression in a case of diffuse large B-cell lymphoma

Neha Singh, Aniruddha Ketkar, Sumeet Gujral

Indian Journal of Pathology and Microbiology 2017 60(2):304-306



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Ki-67 evaluation in breast cancer: The daily diagnostic practice

Lukasz Fulawka, Agnieszka Halon

Indian Journal of Pathology and Microbiology 2017 60(2):177-184

Context: Breast cancer is the most common malignancy in females. It is routinely classified according to the WHO histological typing. However, there is also a molecular classification of breast cancer which is routinely substituted with surrogate subtypes based on expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors and proliferation index (PI). PI is defined as the percentage of Ki-67-positive cells among overall cell population. The method commonly applied by pathologists to determine PI is visual scoring of the sample. Strict recommendations for PI assessment do not exist. Thus, the mode of PI evaluation differs significantly between pathologists. Aims: The aim of our study was to evaluate the daily approach to defining the PI. Settings and Design: Four practicing nonscholar pathologists were asked to evaluate PI in cases of invasive breast carcinoma. Subjects and Methods: The study was performed on a group of 98 patients diagnosed with invasive breast carcinoma. Immunohistochemical reaction was performed with monoclonal antibody against human Ki-67 antigen using Ventana BenchMark XT. Statistical Analysis Used: Results were compared using Pearson's and Spearman's rank correlation coefficients and Fleiss and Cohen's kappa values. Results: Statistical analysis showed pairwise Pearson's coefficients ranging between 0.77 and 0.84 (P < 0.001) and Spearman's rank correlation coefficients ranging between 0.68 and 0.83 (P < 0.001). The Fleiss kappa value for the 14% cutoff point was 0.58 whereas for the 20% cutoff point was 0.60. The pairwise Cohen's kappa values ranged from 0.45 to 0.69 for the 14% cutoff point and 0.53 to 0.67 for the 20% cutoff point. Friedman's rank ANOVA test showed significant differences among the four pathologists (P < 0.001). Conclusions: Our study shows a significant difference in results and methods of evaluation of PI between pathologists.

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Extraskeletal mesenchymal chondrosarcoma at unusual location involving spleen and kidney with review of literature

Krushna Chandra Pani, Mahima Yadav, P Valli Priyaa, Niraj Kumari

Indian Journal of Pathology and Microbiology 2017 60(2):262-264

Mesenchymal chondrosarcoma (MC) is a rare malignant neoplasm bearing characteristic dimorphic pattern histologically. We describe two rare cases of primary MC involving two different visceral organs (1) a 24-year-old man with solid renal mass and, (2) a 42-year-old man with cystic splenic mass. The histological and immunophenotypical features of both lesions were classical of MC. Although this lesion is uncommon in visceral organs, the possibility of this rare entity must be kept in differential diagnosis with compatible morphology.

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Risk of cardiac pacemaker pocket infection in a tertiary care hospital

Jaswinder Singh Gill, Navreet Singh, SP Khanna

Indian Journal of Pathology and Microbiology 2017 60(2):185-188

Background: The risk of pacemaker pocket infections (PPIs) is rare with good antisepsis techniques and use of advanced antibiotics. However, injudicious antibiotic usage leads to the rise of multidrug-resistant bacteria, which may cause PPI. Few reports exist about the microbial spectrum of the PPI from our country, prompting us to study the same. Methods: We conducted this retrospective observational study for 3 years (January 2013–February 2016) from all the patients with PPI. We collected the relevant clinical samples (blood and pus) for the microbial culture using a standard protocol. We included 100 samples collected from the medical staff and the hospital environment as a control sample. The data were analyzed using appropriate statistical methods and a P< 0.05 was considered statistically significant. Results: Our data showed that 17 out of 160 (10.6%) patients had PPI. Coagulase negative Staphylococcus sp. was isolated in 7 (41.2%) patients, followed by Staphylococcus aureus in 4 patients (23.5%). Other isolated bacteria include multidrug-resistant Burkholderia cepacia (n = 3), Mycobacterium abscessus (n = 2) and polymicrobial infection in a single patient. One out of hundred surveillance samples grew B. cepacia. Conclusion: Our data revealed a high incidence of Gram-positive cocci causing PPI. Every hospital should formulate their antibiotic policy based on the pattern of the hospital flora and their drug sensitivity.

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Composite lymphoma with coexistence of diffuse large B-cell lymphoma and anaplastic large cell lymphoma: Diagnostic pitfalls

Meyyappa Devan Rajagopal, Rakhee Kar, Debdatta Basu, Sunu Lazar Cyriac

Indian Journal of Pathology and Microbiology 2017 60(2):275-278

Composite lymphoma is a rare tumor composed of two or more distinct lymphomas in the same topographic site or tissue. Several combinations of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, and Hodgkin lymphoma can occur with different prognoses and treatments. The coexistence of a B-cell NHL and a T-cell NHL is unusual. The exact etiology of composite lymphoma is unknown; however, few mechanisms have been proposed to explain its pathogenesis. The chemotherapeutic protocols are heterogeneous but are essentially targeted against the high-grade component. Most of the cases show worse outcome with a median survival of 12 months. In this article, we report a case of composite lymphoma which was initially diagnosed as diffuse large B-cell lymphoma, and the presence of CD3-positive atypical cells in the bone marrow urged us to re-evaluate the lymph node biopsy following which a focus of Alk-1-positive anaplastic large cell lymphoma was identified.

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Significance of vascular endothelial growth factor and CD31 and morphometric analysis of microvessel density by CD31 receptor expression as an adjuvant tool in diagnosis of psoriatic lesions of skin

Nitika Chawla, Sant Prakash Kataria, Kamal Aggarwal, Pardeep Chauhan, Dinesh Kumar

Indian Journal of Pathology and Microbiology 2017 60(2):189-195

Background: Pathogenesis of psoriasis is a debated issue. Several mechanisms have been proposed to identify the etiology and pathogenesis so that specific treatments can be given to patients with psoriasis. Aims: (1) To compare pattern and distribution of vascular endothelial growth factor (VEGF) and CD31 in patients with psoriasis and other psoriasiform lesions of skin. (2) To study the correlation between VEGF and CD31 expression, clinical severity, and histopathology of psoriasiform lesions of skin. (3) Evaluation of microvessel density (MVD) by using computer-assisted quantitative image analysis in psoriatic skin lesions. Materials and Methods: This study was conducted on eighty cases, out of which forty were diagnosed cases of psoriasis and forty cases of clinically suspected psoriasiform lesions, submitted in the Department of Pathology, Pt. B.D. Sharma, University of Health Sciences, Rohtak, for histopathological examination. Histopathological sections were stained by routine hematoxylin and eosin staining, and these biopsies were further subjected to immunohistochemical staining with VEGF and CD31 as per standard technique. Results: Assessment of various histopathological features revealed strong correlation between epidermal hyperplasia, suprapapillary thinning, and elongation of rete ridges. Suprabasilar keratinocytes in psoriatic lesions stained intensely for VEGF. The difference for number of microvessels and MVD in psoriasis and psoriasiform lesions was statistically significant. Correlation between intensity of VEGF staining by suprabasilar keratinocytes and MVD was found to be highly significant in psoriatic lesions. Conclusion: The present study concluded that psoriatic lesions exhibit potent angiogenic activity. Early lesions show increased MVD along with other histomorphological parameters such as hypogranulosis, parakeratosis and Munro's microabscesses. Overexpression of VEGF by suprabasilar keratinocytes correlated with increased MVD in papillary dermis.

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A case of Aspergillus tracheobronchitis in a patient with chronic obstructive pulmonary disease

Ming-Li Yuan, Gang Yang, Hong-Ling Hu, Wen Yin, Wei-Jun Tan, Su Zhao

Indian Journal of Pathology and Microbiology 2017 60(2):285-287

Aspergillus tracheobronchitis (AT) is a unique form of invasive pulmonary aspergillosis, which is commonly found in patients with impaired immunity. Early-stage AT presents in a nonspecific way, both clinically and radiographically, thereby delaying diagnosis and resulting in a high mortality. Owing to impaired mucociliary clearance, previous nonfungal infections, and administration of corticosteroids, among other aspects, patients with chronic obstructive pulmonary disease (COPD) are predisposed to AT, although they are mostly immunocompetent. AT in COPD patients has not been well recognized and the condition is often misdiagnosed or missed. We herein report a case of AT diagnosed in a male with past COPD, with the features of pseudomembranous AT upon bronchoscopy. This contradicts the opinion that pseudomembranous AT is found in severely immunocompromised hosts with hematologic malignancies.

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Phenotypic and molecular characterization of cefotaximases, temoniera, and sulfhydryl variable β-lactamases in Pseudomonas and Acinetobacter isolates in an Indian tertiary health-care center

Sana Jamali, Mohammed Shahid, Farrukh Sobia, Anuradha Singh, Haris M Khan

Indian Journal of Pathology and Microbiology 2017 60(2):196-201

Background: Cefotaximases (CTX-M), temoniera (TEM), and sulfhydryl variable (SHV) constitute a rapidly growing cluster of enzymes that have disseminated geographically. They are spreading to species other than Enterobacteriaceae and might be responsible for the presence of blaCTX-M,blaTEM, and blaSHVgenes in Pseudomonas and Acinetobacter spp. The present study was designed to characterize CTX-M, TEM, and SHV phenotypically and genotypically in Pseudomonas and Acinetobacter spp. Materials and Methods: A total of 90 isolates (73 Pseudomonas and 17 Acinetobacter spp.), resistant to any of the third-generation cephalosporins, were randomly selected from clinical samples. Results: Of 90 isolates, 64 (71.11%) were tested positive for extended-spectrum β-lactamase (ESBL) production. Among phenotypically tested ESBL producers, forty isolates were randomly selected for molecular characterization. The prevalence of CTX-M, TEM, and SHV was found to be 57.5%, 15%, and 75%, respectively. Multiplex polymerase chain reaction assay categorized blaCTX-Mgenes into Groups 1 and 26 where Group 1 was present in only 5 isolates and Group 25 was present in rest of the 18 isolates. Conclusion: This is among the premier systemic reports from India documenting phenotypic and molecular characterization of CTX-M, TEM, and SHV β-lactamases in Pseudomonas and Acinetobacter spp. With judicious use of antibiotics and strict infection control procedures, it may be possible to limit the effects of these newer β-lactamases.

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Pediatric nasopharyngeal carcinoma with a spectrum of precursor lesions: Cervical lymph node metastasis initially diagnosed by fine needle aspiration cytology

Dilip Kumar Das, Bahia I Haji, Mohmad Jaragh, Bency John, Kenneth C Katchy

Indian Journal of Pathology and Microbiology 2017 60(2):294-296



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Cytocentrifuged biopsy fixative preparation: A simple cost-effective technique facilitating microscopic diagnosis of lumen-dwelling intestinal parasites

Prashant Joshi, Prasenjit Das, Venkateswaran Iyer, Siddharth Datta Gupta

Indian Journal of Pathology and Microbiology 2017 60(2):202-205

Objective: Direct microscopic visualization is the most specific method for detecting intestinal parasites and is commonly achieved by stool examination or mucosal biopsy. However, postfixation, the intestinal biopsy fragment is often curled, and the entire surface of the biopsied mucosa is seldom viewed microscopically. Tissue processing further distorts morphology of the organisms and causes diagnostic difficulties. Examining multiple sections for parasite detection is time-consuming and often requires aid of special stains and/or immunohistochemistry. To overcome these disadvantages, we hypothesized that the fixative in which biopsies are transferred may provide a valid representation of the biopsied mucosal surface and therefore aid in the identification of mucosal surface parasites.Materials and Methods: Formalin in which biopsies were transferred was retained, stored at 4°C and processed with a cytocentrifuge. Totally, 120 consequent duodenal biopsy fixatives were processed in this way and the cytocentrifuged smears visualized after May-Grunwald-Giemsa staining. Findings of these smears were correlated with their corresponding formalin fixed paraffin embedded tissue sections.Results: Cytocentrifuged formalin preparations were found to be representative of the mucosal surface contents. Giardia trophozoites were visualized in 10/120 preparations with distinct morphological characteristics which were seldom appreciable in tissue sections, eliminating the need for special stains. Furthermore, two of the corresponding histology sections did not demonstrate the parasites despite step sections, while in one case few parasites could be identified in the step sections. Conclusions: Cytocentrifuged fixative preparation is a simple and cost-effective technique which can be routinely employed for intestinal parasite characterization.

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5q deletion myelodysplastic syndrome

Preethi S Chari, Smitha Chander, TS Sundareshan, Sujay Prasad

Indian Journal of Pathology and Microbiology 2017 60(2):301-303



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Stereotyped episodes of aphasia and immobility: how cataplexy mimics stroke in an elderly patient

E.A.: acquisition of data, interpretation of data, drafting the manuscript, revision of the manuscript, final approval to the final version to be published.

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Glucose catabolism in liver tumors induced by c-MYC can be sustained by various PKM1/PKM2 ratios and pyruvate kinase activities

Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Due to differential regulation of enzymatic activities, PKM2 but not PKM1 has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC over-expression in murine livers did not affect c-MYC induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased glucose flux into serine biosynthesis and increased flux into lactate and the Krebs cycle, resulting in reduced total levels of serine. However, these changes also did not affect c-MYC-induced liver tumor development. These results suggest that increased expression of PKM2 is not required to support c-MYC-induced tumorigenesis in the liver and that various PKM1/PKM2 ratios and pyruvate kinase activities can sustain glucose catabolism required for this process.

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Infection exposure promotes ETV6-RUNX1 precursor B cell leukemia via impaired H3K4 demethylases

<p>ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss-of-function resulted in increased levels of H3K4me3, which co-precipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches.

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Cyclooxygenase-2 inhibitors and free flap complications after autologous breast reconstruction, a retrospective cohort study

A key component of modern analgesics is the use of multimodal opioid sparing analgesia (MOSA). In the past, our analgesic regime after autologous breast reconstruction (ABR) included either NSAID or a selective cyclooxygenase-2 inhibitor (COX-2). COX-2 inhibitors could be superior to NSAID due to the well-known side effects from NSAID (bleeding/gastrointestinal ulcers). However, COX-2 inhibitors have been suggested to increase flap failure rates. We report our experience with using COX-2 inhibitors as part of our postoperative MOSA after ABR using free flaps.

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Synovial chondromatosis of the temporomandibular joint with intracranial extension—report of two cases

Synovial chondromatosis of the temporomandibular joint is a rare condition, and only 10 cases with intracranial extension have been reported in the literature. Two cases of synovial chondromatosis with intracranial extension, followed up for 3 to 9 years, are reported here. The surgical treatment modality is described for each case.

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Obstructive sleep apnoea in craniofacial microsomia: analysis of 755 patients

A retrospective cohort study was set up to analyse the prevalence and treatment of obstructive sleep apnoea (OSA) in relation to the severity of the deformity in patients with craniofacial microsomia (CFM). This study included a population of 755 patients with CFM from three craniofacial centres. Medical charts were reviewed for severity of the deformity, types of breathing difficulty, age at which breathing difficulty first presented, treatment for OSA, and treatment outcome. In total, 133 patients (17.6%) were diagnosed with OSA.

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Sclerosing odontogenic carcinoma: current diagnostic and management considerations concerning a most unusual neoplasm

Sclerosing odontogenic carcinoma (SOC) is a primary intraosseous carcinoma of the jaws that has been listed as a separate entity for the first time in the latest version of the World Health Organization classification of Head and Neck Tumours (2017). The aim of this study was to analyse and interpret the existing literature on SOC in the context of a clinical case treated in the authors’ department. A systematic search of the PubMed database was performed in accordance with the PRISMA guidelines, yielding nine cases of SOC reported so far.

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Temporomandibular joint disc perforation: a retrospective study



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Evolution of ventral hernia repair

Abstract

Purpose

The aim of this review was to look at relevant data and research on the evolution of ventral hernia repair.

Methods

Resources including books, research, guidelines, and online articles were reviewed to provide a concise history of and data on the evolution of ventral hernia repair.

Results

The evolution of ventral hernia repair has a very long history, from the recognition of ventral hernias to its current management, with significant contributions from different authors. Advances in surgery have led to more cases of ventral hernia formation, and this has required the development of new techniques and new materials for ventral hernia management. The biocompatibility of prosthetic materials has been important in mesh development. The functional anatomy and physiology of the abdominal wall has become important in ventral hernia management. New techniques in abdominal wall closure may prevent or reduce the incidence of ventral hernia in the future.

Conclusion

The management of ventral hernia is continuously evolving as it responds to new demands and new technology in surgery.



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Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

The aim of this review is to update the safety of low-intensity electric stimulation based on available published research and clinical data in animal models and in human studies until the end of 2016. The essentials of the present manuscript were agreed upon at a two-day safety conference held in Göttingen, Germany on 6-7th September, 2016. Participants included research and clinical experts from neurophysiology, neurology, cognitive neuroscience and psychiatry. Representatives of transcranial electrical stimulation (TES) equipment manufacturers contributed to regulatory issues.

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Degeneration of the vestibular nerve in unilateral Meniere’s disease evaluated by galvanic vestibular-evoked myogenic potentials

The staging system of Meniere’s disease utilizes audiograms to probe cochlear dysfunction. We explored the addition of galvanic vestibular-evoked myogenic potentials (VEMP) to further explore vestibular function.

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Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines

The aim of this review is to update the safety of low-intensity electric stimulation based on available published research and clinical data in animal models and in human studies until the end of 2016. The essentials of the present manuscript were agreed upon at a two-day safety conference held in Göttingen, Germany on 6-7th September, 2016. Participants included research and clinical experts from neurophysiology, neurology, cognitive neuroscience and psychiatry. Representatives of transcranial electrical stimulation (TES) equipment manufacturers contributed to regulatory issues.

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Degeneration of the vestibular nerve in unilateral Meniere’s disease evaluated by galvanic vestibular-evoked myogenic potentials

The staging system of Meniere's disease utilizes audiograms to probe cochlear dysfunction. We explored the addition of galvanic vestibular-evoked myogenic potentials (VEMP) to further explore vestibular function.

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Motivations for Interest, Disinterest and Uncertainty in Intrauterine Device Use Among Young Women

Abstract

Objective To elucidate salient contraceptive preferences and priorities as they relate to young women's interest or lack thereof in intrauterine device (IUD) use. Methods Qualitative data were drawn from a 2012 survey on contraceptive preferences and IUD interest. Among 413 young (ages 18–29) women, open-ended responses describing reasons for interest, disinterest or uncertainty in future IUD use were examined using a thematic analysis approach. Results Most participants were unsure about (49.2%) or not interested in (30.0%) future IUD use. Themes regarding IUD interest related to specific facets of IUD use (e.g., risks and side effects, ease of use), as well as broader influences on contraceptive decision-making (e.g., social influences, alignment with pregnancy intentions). For interested participants, a sense of empowerment pervaded the responses, with many references to the ease of use and lack of requisite maintenance. Uninterested participants were concerned about the internal nature of the IUD, with many describing "horror stories" and fears that the IUD would cause injury or infertility. Unsure participants provided more detailed and complex responses, carefully weighing the advantages and disadvantages of IUD use. Uncertainty was often driven by an acknowledged need for specific information, rather than overall lack of knowledge. Conclusions for Practice In this analysis, many women had a clear sense of their contraceptive preferences, which frequently did not align with IUDs. While continuing to remove barriers to IUD access is critical, patient-centered counseling approaches offer the opportunity to support women in best matching with a method that aligns with their preferences.



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Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade

Abstract

Background

Stimulation of the immune system by targeting the PD-1/PD-L1 pathway can result in activation of anti-tumor immunity. Besides its clinical benefit immune checkpoint therapy leads to significant immune-related adverse events (irAEs). Some rare irAEs are not well described yet but are critical in patient management.

Case presentation

Here, we describe a case of autoimmune cerebral vasculitis/encephalitis after PD-1 inhibitor treatment for metastatic adenocarcinoma of the lung. Upon PD-1 blockade, the patient developed cerebral lesions, while having disease stabilization of extracranial metastases. Imaging suggested that the patient had new progressing brain metastases. Despite stereotactic irradiation the lesions progressed further. The largest lesion became symptomatic and had to be surgically resected. On examination, cerebral vasculitis was detected but not evidence of metastatic lung cancer. Analysis of the patient’s serum revealed the presence of antinuclear antibodies that were already present before starting PD-1 blockade. In addition, we also found anti-vascular endothelial antibodies in the serum.

Conclusion

This finding suggests that the patient had preformed autoantibodies and the checkpoint inhibitor induced a clinically relevant autoimmune disease. Taken together, encephalitic lesions in patients under PD-1/PD-L1 blockade can mimic metastatic brain lesions and this rare irAE has to be considered as a differential diagnosis in patients treated with immunotherapy.



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New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31 st Annual Meeting of the Society for Immunotherapy of Cancer, 2016

Abstract

This report is a summary of ‘New Cancer Immunotherapy Agents in Development’ program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy.



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Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma

Abstract

Background

Immunotherapy plays a key role in the treatment of metastatic melanoma. Patients with autoimmune conditions and/or on immunosuppressive therapy due to orthotropic transplants, however, are systematically excluded from clinical trials. Talimogene laherparepvec (T-VEC) is the first oncolytic virus to be approved by the FDA for cancer therapy. To our knowledge, this is the first report of T-VEC being administered in the setting of an organ transplant recipient.

Case presentation

Here we present the case of a patient with recurrent locally advanced cutaneous melanoma receiving salvage T-VEC therapy in the setting of orthotropic heart transplantation. After 5 cycles of therapy, no evidence of graft rejection has been observed to date, and the patient achieved a complete remission, and is currently off therapy.

Conclusion

This case advocates for further investigation on the safety and efficacy of immunotherapeutic approaches, such as T-VEC, in solid organ transplant recipients.



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Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma

Abstract

Background

Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn’t require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs.

Methods

Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5–20 × 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care.

Results

No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy.

Conclusions

Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated.

Trial registration

Clinicaltrials.gov identifier: NCT01525017.



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Adoptive cell therapy using PD-1 + myeloma-reactive T cells eliminates established myeloma in mice

Abstract

Background

Adoptive cellular therapy (ACT) with cancer antigen-reactive T cells following lymphodepletive pre-conditioning has emerged as a potentially curative therapy for patients with advanced cancers. However, identification and enrichment of appropriate T cell subsets for cancer eradication remains a major challenge for hematologic cancers.

Methods

PD-1+ and PD-1 T cell subsets from myeloma-bearing mice were sorted and analyzed for myeloma reactivity in vitro. In addition, the T cells were activated and expanded in culture and given to syngeneic myeloma-bearing mice as ACT.

Results

Myeloma-reactive T cells were enriched in the PD-1+ cell subset. Similar results were also observed in a mouse AML model. PD-1+ T cells from myeloma-bearing mice were found to be functional, they could be activated and expanded ex vivo, and they maintained their anti-myeloma reactivity after expansion. Adoptive transfer of ex vivo-expanded PD-1+ T cells together with a PD-L1 blocking antibody eliminated established myeloma in Rag-deficient mice. Both CD8 and CD4 T cell subsets were important for eradicating myeloma. Adoptively transferred PD-1+ T cells persisted in recipient mice and were able to mount an adaptive memory immune response.

Conclusions

These results demonstrate that PD-1 is a biomarker for functional myeloma-specific T cells, and that activated and expanded PD-1+ T cells can be effective as ACT for myeloma. Furthermore, this strategy could be useful for treating other hematologic cancers.



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Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy

Abstract

Background

We report the first case to our knowledge of a patient with relapsed/refractory classical hodgkin lymphoma and liver failure with encephalopathy along with human immunodeficiency virus/acquired immunodeficiency syndrome infection, successfully treated with nivolumab without major side effects and encouraging prolonged disease control.

Case presentation

In December 2015, at the time of the patient’s progression from his Hodgkin lymphoma after fourth line treatment, he developed persistent fevers, abdominal distension, jaundice and worsening of his liver function tests. Magnetic resonance imaging of abdomen/pelvis demonstrated hepatomegaly with innumerable new liver lesions, splenomegaly with multiple splenic nodules and several new mediastinal, intraperitoneal and retroperitoneal lymphadenopathy. In accordance with the patient’s wishes before admission, and after agreement with the family, nivolumab (3 mg/kg every 2 weeks) was given. Of note, antiretroviral therapy was on hold due to liver function tests, his viral load was undectable and cluster of differentiation 4 counts were 103/uL at the time of nivolumab administration. One week after the first dose of nivolumab both his hepatic encephalopathy and constitutional symptoms started to improve, and after 2 doses, (January 2016) his LFTs were almost back to normal. After 5 months of nivolumab treatment (10 doses), restaging (computerized tomography scans of neck, chest, abdomen, pelvis) done on May 2016 showed resolution of hepatosplenomegaly with two residual small hepatic lesions, heterogeneous spleen with no splenic lesions, and stable non-enlarged retroperitoneal lymph nodes without intraabdominal lymphadenopathy; consistent with partial response.

Conclusions

We report a case of a patient with human immunodeficiency virus/acquired immunodeficiency syndrome -related relapsed/refractory classical Hodgkin lymphoma and acute liver failure with encephalopathy successfully treated with nivolumab after failing all standard therapeutic options. Unlike classic cytotoxic chemotherapy, which relies on preserved organ function to ameliorate potential severe side effects (i.e. myelosuppression), elimination of monoclonal antibodies is fairly independent of baseline renal and hepatic function since they are usually metabolized by circulating phagocytes and/or by their target antigen-expressing cell.



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GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory

Abstract

Background

The expansion of antigen-specific CD8 T cells is important in generating an effective and long-lasting immune response to tumors and viruses. Glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) is a co-stimulatory receptor that binds the GITR ligand (GITRL). Agonism of GITR can produce important signals that drive expansion of effector T cell populations.

Methods

We explored two separate murine tumor models, CT26 and TC-1, for responsiveness to GITR Ligand Fusion Protein(GITRL-FP) monotherapy. In TC-1, GITRL-FP was also combined with concurrent administration of an E7-SLP vaccine. We evaluated tumor growth inhibition by tumor volume measurements as well as changes in CD8 T cell populations and function including cytokine production using flow cytometry. Additionally, we interrogated how these therapies resulted in tumor antigen-specific responses using MHC-I dextramer staining and antigen-specific restimulations.

Results

In this study, we demonstrate that a GITR ligand fusion protein (GITRL-FP) is an effective modulator of antigen-specific CD8 T cells. In a CT26 mouse tumor model, GITRL-FP promoted expansion of antigen-specific T cells, depletion of regulatory T cells (Tregs), and generation of long-lasting CD8 T cell memory. This memory expansion was dependent on the dose of GITRL-FP and resulted in complete tumor clearance and protection from tumor rechallenge. In contrast, in TC-1 tumor–bearing mice, GITRL-FP monotherapy could not prime an antigen-specific CD8 T cell response and was unable to deplete Tregs. However, when combined with a vaccine targeting E7, treatment with GITRL-FP resulted in an augmentation of the vaccine-induced antigen-specific CD8 T cells, the depletion of Tregs, and a potent antitumor immune response. In both model systems, GITR levels on antigen-specific CD8 T cells were higher than on all other CD8 T cells, and GITRL-FP interacted directly with primed antigen-specific CD8 T cells.

Conclusions

When taken together, our results demonstrate that the delivery of GITRL-FP as a therapeutic can promote anti-tumor responses in the presence of tumor-specific CD8 T cells. These findings support further study into combination partners for GITRL-FP that may augment CD8 T-cell priming as well as provide hypotheses that can be tested in human clinical trials exploring GITR agonists including GITRL-FP.



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Elucidating the interactions between individual differences and noninvasive brain stimulation effects in visual working memory by using tDCS, tACS and EEG

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Chi-Hung Juan, Wei-Kuang Liang, Neil G. Muggleton, Philip Tseng, Tzu-Yu Hsu




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Editorial Board

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





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E-meditation: A novel paradigm using tDCS to enhance mindfulness meditation

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Bashar W. Badran, Chris W. Austelle, Nicole R. Smith, Chloe E. Glusman, Brett Froeliger, Eric L. Garland, Jeffrey J. Borckardt, Mark S. George, Baron Short




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Table of Contents

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





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Information for Authors

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





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Transcranial Direct Current Stimulation and Mobility Functioning in Older Adults with Knee Osteoarthritis Pain: A Double-Blind, Randomized, Sham-Controlled Pilot Clinical Study

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Hyochol Ahn, Adam J. Woods, Eunyoung Choi, Nikhil Padhye, Roger Fillingim




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Individual Differences in tDCS Augmented Working Memory Training

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Benjamin Katz, Jacky Au, Martin Buschkuehl, Tessa Abagis, Chelsea Zabel, Susanne M. Jaeggi, John Jonides




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Masthead

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4





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The Effects of High Definition Transcranial Direct Current Stimulation (HD-tDCS) on Memory and Metamemory by Task Difficulty

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Sandry Garcia, Rifat Ahmed, Elizabeth F. Chua




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tDCS metaplasticity and astrocytic calcium in mice

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Hajime Hirase, Hiromu Monai




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Feasibility and Dose Tolerability of High Definition Transcranial Direct Current Stimulation in healthy adults

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Christopher A. Turski, Alanna Kessler-Jones, Bruce Hermann, David Hsu, Jana Jones, Susanne Seeger, Rick Chappell, Chrysanthy Ikonomidou




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Off-line rTMS of left Dorsolateral Prefrontal Cortex reduces food cravings in females but not males

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Valentina Cazzato, Huw Williams, Stergios Makris




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Repetitive Transcranial Magnetic Stimulation in Oromandibular Dystonia

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Publication date: July–August 2017
Source:Brain Stimulation, Volume 10, Issue 4
Author(s): Noriyuki Narita, Kazunobu Kamiya, Tomohhiro Ishii, Teruyasu Hirayama




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GDF5 significantly augments the bone formation induced by an injectable, PLGA-fiber reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia

Biodegradable calcium phosphate cement (CPC) represents a promising option for the surgical treatment of osteoporotic vertebral fractures. Due to augmented local bone catabolism, however, additional targeted delivery of bone morphogenetic proteins with the CPC may be needed to promote rapid and complete bone regeneration.

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Report and Abstracts for 17 th Spring ACCP Conference with Training Workshops, and Technology Exhibits



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Virtual Surgical Planning for Mandibular Distraction in Infants with Robin Sequence.

Summary: Mandibular distraction osteogenesis (MDO) successfully relieves obstructive sleep apnea in many infants with Robin sequence. Preoperative virtual surgical planning and fabrication of three-dimensionally printed cutting guides may lead to further improvements in the MDO technique and decrease the risk for damage to adjacent structures such as developing teeth and the inferior alveolar nerve. This report presents an algorithm for virtual surgical planning and three-dimensionally printing of cutting guides for MDO in infants with RS. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Team Work: Mastectomy, Reconstruction, and Radiation.

No abstract available

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fMRI after Phalloplasty with Nerve Anastomosis in a Trans-Man Patient.

Summary: We report on a case of a trans-man patient, who underwent penile reconstruction with the use of a radial forearm flap, urethroplasty, vaginectomy and scrotoplasty, insertion of testicle implants, and penile erection implants, similar to previously described methods. One of the requirements for an ideal phalloplasty is the preservation of erogenous sensitivity, which is often demanded by the patients for fulfilling their sexual well-being. For the first time known to us, we use a functional magnetic resonance imaging following radial forearm flap phalloplasty with nerve anastomosis to assess the cortical activation after clitoral stimulation. The patient was poked with a plastic pen on the neophallus and the groin. Regular block design with T1 and BOLD-T2* images were used. The results contradict the classic Penfield and Rasmussen homunculus, that is, the activations in the primary somatosensory cortex (S1) were bilateral with a left-sided dominance in the lateral parts of the medial postcentral gyrus (same region as the groin), and no activations were observed in the mesial parts of the postcentral gyrus. We also reported bilateral activations with a left-sided dominance in the secondary somatosensory cortex (S2) and near Broca's area at the sylvian fissure just posterior to ramus ascendens. Our findings are similar to previous studies reporting on imaging related to genital sensitivity. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright (C) 2017 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons. All rights reserved.

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Development of a novel simulation model for assessment of laparoscopic camera navigation

Abstract

Background

Laparoscopic camera navigation is vital to laparoscopic surgery, yet often falls to the most junior member of the surgical team who has limited laparoscopic operating experience. Previously published reports on simulation models fail to address qualitative scoring of movement, method of communication and correct physician location with respect to patient position. The purpose of this study was to develop and evaluate a novel laparoscopic camera navigation simulation model that addresses these deficiencies.

Methods

A novel, low-cost laparoscopic camera navigational maze was constructed from pliable foam for use in a standard laparoscopic surgery box trainer. Participants (n = 37) completed a camera navigation exercise by following a pre-recorded set of verbal instructions using correct anatomic terminology that is used in the operating room, to simulate an actual operating room experience of receiving verbal cues from senior surgeons. The sample group consisted of participants at various levels of Obstetrics and Gynecology training, representing novice to expert laparoscopists. Each trial was recorded with a multi-channel video camera. Performances were scored by a blinded evaluator for excess gross and fine camera movements as well as overt errors, including camera collisions and failure to follow directions.

Results

Our model demonstrated evidence of validity by discriminating performance by level of laparoscopic experience with a statistically significant decrease in number of movements and errors in experts compared to novices. A trend emerged toward improvement with each additional year of training, with reduced variability among performances in more experienced participants.

Conclusions

This novel, low-cost box-trainer simulation model for laparoscopic camera navigation offers a mechanism for assessment of laparoscopic camera operation skills. Moreover, this model closely replicates operating room logistics and communication. Given the necessity for improved laparoscopic camera operation education, our model represents a unique, complementary tool to other laparoscopic simulation curricula.



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Esophageal mucosal integrity improves after laparoscopic antireflux surgery in children with gastroesophageal reflux disease

Abstract

Background

Esophageal intraluminal baseline impedance reflects the conductivity of the esophageal mucosa and may be an instrument for in vivo evaluation of mucosal integrity in children with gastroesophageal reflux disease (GERD). Laparoscopic antireflux surgery (LARS) is a well-established treatment option for children with proton pump inhibitory (PPI) therapy resistant GERD. The effect of LARS in children on baseline impedance has not been studied in detail. The aim of this study was to evaluate the effect of LARS on baseline impedance in children with GERD.

Methods

This is a prospective, multicenter, nationwide cohort study (Dutch national trial registry: NTR2934) including 25 patients [12 males, median age 6 (range 2–18) years] with PPI-resistant GERD scheduled to undergo LARS. Twenty-four hour multichannel intraluminal impedance pH monitoring (MII-pH monitoring) was performed before and 3 months after LARS. Baseline impedance was evaluated during consecutive 2-h intervals in the 24-h tracings.

Results

LARS reduced acid exposure time from 8.5 % (6.0–16.2 %) to 0.8 % (0.2–2.8 %), p < 0.001. Distal baseline impedance increased after LARS from 2445 Ω (1147–3277 Ω) to 3792 Ω (3087–4700 Ω), p < 0.001. Preoperative baseline impedance strongly correlated with acid exposure time (r −0.76, p < 0.001); however, no association between symptomatic outcome and baseline impedance was identified.

Conclusions

LARS significantly increased baseline impedance likely reflecting recovery of mucosal integrity. As the change in baseline impedance was not associated with the clinical outcome of LARS, other factors besides mucosal integrity may contribute to symptom perception in children with GERD.



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