bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-DFS70 autoantibodies in HIV-1-positive individuals
Authors: Pérez Dolores , Azoulay Danielle 
Published: February 2018

Purpose of review
The aim of this review is to summarize the recent studies regarding the relationship between anti-DFS70 antibodies and HIV-1 infection. Examining the interaction between HIV-1 integrate (HIV-IN) and DFS70 and its role in the integration into the host's chromatin. Then, summarizing the importance of anti-DFS70 autoantibodies binding the DFS70 in the same region as the HIV-IN.

Recent findings
The interaction between HIV-IN and DFS70 protein could be a proficient target in the treatment against HIV-1 infection. The blockade of DFS70 is more effective than the blockade of HIV-IN as anti-HIV-1 drug. The anti-DFS70 autoantibodies could be an interesting therapeutic target for anti-HIV-1 treatment. Currently, there are no studies that measured the levels of anti-DFS70 autoantibodies in HIV-1-infected individuals.

Summary
The anti-DFS70 antibodies bind to the DFS70 autoantigen in the same region as the HIV-IN. This fact makes the autoantibodies a potential treatment for HIV-1-infected individuals. Blood levels of anti-DFS70 antibodies have not been measured in HIV-1-infected individuals. This issue opens new lines of research about the protective role of antibodies against HIV-1 infection.
Chimeric Antigen Receptor‐T Cell Therapy
Authors: Buechner Jochen , Kersten Marie José ,   HOVON/LLPC (Lunenburg Lymphoma Phase I/II Consortium) working group, Fuchs Miriam , Salmon Florence , Jäger Ulrich 
Published: February 2018

AbstractChimeric antigen receptor (CAR)‐T cell therapy is a new class of cellular immunotherapies that involves ex vivo genetic modification of T cells to incorporate an engineered CAR. After infusion into the patient, the CAR‐expressing T cells recognize specific tumor targets and induce an immune response against them. The technology utilized is fundamentally different from previously available cancer treatments. Currently, most CAR‐T cell therapies use autologous T cells. Tisagenlecleucel (formerly CTL019) is an anti‐CD19 CAR‐T cell therapy that was recently approved in the United States for the treatment of pediatric and young adult patients with relapsed/refractory B‐cell acute lymphoblastic leukemia (B‐ALL). Tisagenlecleucel has shown robust in vivo expansion and long‐term persistence, clinically meaningful durable response and remission rates, and overall survival benefit in pediatric and young adult patients with relapsed/refractory B‐ALL and in relapsed/refractory diffuse large B‐cell lymphoma. Common adverse events (AEs) include cytokine release syndrome, which may require hospitalization and admission to an intensive care unit, neurological toxicities, and B‐cell aplasia. These AEs are manageable when treated by an appropriately trained team. Additional research is required to further develop AE management protocols. In this review, we describe regulatory requirements, clinical considerations, and site‐level requirements for clinical study implementation of CAR‐T cell therapy in Europe. We also provide a case study of the European experience from the first global clinical trial for tisagenlecleucel, which may serve as a useful starting point for investigators and clinicians looking to implement CAR‐T cell therapy at their institutions.
Higher Adherence to Treatment With Low‐Molecular‐Weight‐Heparin Nadroparin Than Enoxaparin Because of Side Effects in Cancer‐Associated Venous Thromboembolism
Authors: van der Wall Sake J. , Klok Frederikus A. , den Exter Paul L. , Barrios Deisy , Morillo Raquel , Cannegieter Suzanne C. , Jimenez David , Huisman Menno V. 
Published: February 2018

AbstractCurrent guidelines recommend low‐molecular‐weight‐heparins (LMWH) monotherapy for 3 to 6 months as first‐line treatment for cancer‐associated venous thromboembolism (VTE). In clinical practice, enoxaparin and nadroparin are common agents used. However, differences in therapy adherence between these LMWHs have never been reported. Therefore, our aim was to compare adherence to enoxaparin and nadroparin in patients with cancer‐associated VTE. Consecutive patients with active cancer and objectively confirmed VTE, treated at a Dutch or a Spanish hospital, were followed during LMWH therapy with a maximum of 180 days. Cumulative incidences of discontinuation of both LMWHs were estimated and compared according to the Kaplan‐Meier method, applying a competing risk analysis to correct for mortality. A total of 366 patients were analyzed during LMWH treatment, of whom 284 patients (78%) were treated with enoxaparin and 82 (22%) with nadroparin. The cumulative incidence of discontinuation of enoxaparin and nadroparin treatment because of side effects was 30% (95% confidence interval [CI] 24–36) and 8.8% (95% CI 1.1–15), respectively. Competing risk analysis revealed a higher number of patients discontinuing enoxaparin due to side effects (adjusted hazard ratio [HR]: 2.8; 95% CI 1.06–7.2). Pain at the injection site was the most common reason of discontinuation in patients using enoxaparin, occurring in 32 patients, while it occurred in 1 patient using nadroparin (adjusted HR: 4.0; 95% CI 0.52–31). This analysis reveals that enoxaparin was associated with a higher risk of discontinuation because of side effects compared to nadroparin. However, given the nature of the patient groups, these findings should be followed by future studies.
ACUTE EFFECT OF CAFFEINE ON MACULAR MICROCIRCULATION IN HEALTHY SUBJECTS
Authors: Karti Omer , Zengin Mehmet Ozgur , Kerci Suleyman Gokhan , Ayhan Ziya , Kusbeci Tuncay 
Published: February 2018

Purpose:
To evaluate the acute effects of caffeine on macular microvasculature using quantitative optical coherence tomography angiography analysis.

Methods:
Fifty-two healthy subjects aged 24 to 48 years were randomly divided into 2 groups: a control group, which received placebo, and a study group, which was subjected to caffeine. All participants underwent optical coherence tomography angiography at baseline and 1 hour after 200-mg oral caffeine intake in the study group and after oral placebo in the control group. Macular flow area, macular vessel density, and foveal avascular zone (FAZ) area were analyzed in both the groups.

Results:
The study group consisted of 14 men and 12 women with a mean age of 40.6 ± 8.9 years. The mean age of control group was 39.5 ± 9.4 years, which consisted of 13 men and 13 women. Baseline macular flow area, vessel density, and FAZ area measurements of the study and control groups showed no significant difference (P > 0.05). Oral caffeine intake caused a significant reduction in macular flow area (superficial, deep, and choriocapillaris) and vessel density (P < 0.05). However, there was no statistically significant difference in FAZ area after caffeine intake when compared with baseline measurements (P = 0.063).

Conclusion:
We found a significant decrease in macular flow area (superficial, deep, and choriocapillaris) and vessel density after caffeine intake. Our findings are consistent with previous studies using other techniques. We believe that the results of this preliminary study will be useful in future studies about this topic.
CORRELATIONS BETWEEN CHANGES IN PHOTORECEPTOR LAYER AND OTHER CLINICAL CHARACTERISTICS IN CENTRAL SEROUS CHORIORETINOPATHY
Authors: Yu Jia , Jiang Chunhui , Xu Gezhi 
Published: February 2018

Purpose:
To clarify the correlations between changes in the photoreceptor layer (PRL) and other clinical characteristics during central serous chorioretinopathy.

Methods:
Patients with central serous chorioretinopathy with one eye affected were enrolled. Photoreceptor layer appearance within the detached area was evaluated, and its correlations with symptom duration, best-corrected visual acuity, and the difference in the foveal outer nuclear layer thickness between the affected and contralateral eyes were analyzed.

Results:
A total of 222 patients were included. The PRL outer border appeared either smooth, granulated, or as scattered dots attached to external limiting membrane. These different appearances were associated with elongation in symptom duration (18, 180, and 1,855 days), decreases in best-corrected visual acuity (6/10, 6/15, and 6/120), and increases in the difference of foveal outer nuclear layer thickness (−16, −32, and −60 μm). Among eyes with smooth PRL outer border, which had similar symptom duration, eyes with foveal PRL defect had poorer best-corrected visual acuity and greater reduction in outer nuclear layer thickness than the other eyes (all P = 0.00).

Conclusion:
Morphologic changes in PRL, best-corrected visual acuity, the reduction in foveal outer nuclear layer thickness, and symptom duration correlate closely but may behave asynchronously. These objective parameters, besides symptom duration, could be helpful when considering the timing of central serous chorioretinopathy treatment.
OPHTHALMIC ARTERY OCCLUSION AFTER FOREHEAD AUTOLOGOUS FAT INJECTION
Authors: Liu Hongtao , Chen Danian , Zhang Junjun 
Published: February 2018

Purpose:To present clinical findings of ophthalmic artery occlusion, a devastating ocular complication because of forehead autologous fat injection.Methods:Retrospective study of three eyes of three patients whereby ophthalmic artery occlusion and/or hemiplegia occurred after forehead autologous fat injection in China.Results:All patients suffered severe ocular pain, vomiting, and vision loss immediately after the injections and had unilateral permanent blindness.Conclusion:Physicians performing cosmetic facial surgery involving autologous fat injection need to be aware of this potential risk and should inform the patient before the surgery.
Corneal Endothelial Tolerance After Iris-Fixated Phakic Intraocular Lens Implantation: A Model to Predict Endothelial Cell Survival
Authors: Chebli Sabrina , Rabilloud Muriel , Burillon Carole , Kocaba Viridiana 
Published: February 2018

Purpose:
To evaluate the long-term endothelial tolerance of iris-fixated phakic intraocular lenses (pIOLs) over a 10-year period, to identify predictive factors for endothelial decompensation, and to develop a model to predict endothelial cell survival after pIOL implantation.

Methods:
This retrospective study included 130 eyes in 60 patients who underwent pIOL implantation for correction of high myopia from January 2003 to October 2012 at Edouard Herriot Hospital in Lyon, France. Endothelial cell densities (ECDs) were measured using specular microscopy before and biannually after pIOL implantation. Best-corrected visual acuity was measured before and 6 months after pIOL implantation. The annual postoperative decrease in ECD was estimated using a mixed linear regression model with a random intercept. Patient and eye characteristics were introduced into the model to quantify their effect on ECD change. The main outcome measures were annual postoperative reduction of ECD and best-corrected visual acuity.

Results:
The preoperative ECD was 2770 ± 265 cells/mm2 (2134–3200 cells/mm2). The ECD decreased by 1.83%, on average (95% confidence interval, 1.54–2.10), during the first postoperative year. Thereafter, the mean decrease in annual ECD was estimated to be 0.87% (95% confidence interval, 0.78–0.95). For a cell number of 3500, 3000, 2500, and 2000, the number of years required to reach the threshold of 1500 cells/mm2 was estimated to be approximately 96, 78, 57, and 32 years, respectively. No predictive factors for endothelial decompensation were identified.

Conclusions:
pIOL implantation is a safe surgical means to correct high myopia in phakic patients without compromising corneal endothelium survival.
Clinical presentation of autoimmune and viral encephalitides
Authors: Dubey Divyanshu , Toledano Michel , McKeon Andrew 
Published: February 2018

Purpose of review
We describe clinical and diagnostic features of various autoimmune and viral encephalitis subtypes.

Recent findings
Population-based studies have demonstrated both autoimmune and viral causes have similar prevalence and incident rates. Repertoire of autoimmune biomarkers has considerably increased with discovery of many novel neural antibodies including glial fibrillary acidic proteinα-immunoglobulin G. Similarly, with use of next generation sequencing and DNA libraries, many viral causes are being detected which would have been categorized as encephalitis of unknown cause a decade ago.

Summary
Autoimmune and viral encephalitides can resemble one another and sometimes autoimmune encephalitis may be triggered by viral infections. Early diagnosis and treatment is the key to both causes, which emphasizes the importance of clinical diagnosis before laboratory confirmation.
Is hemoglobin good for cerebral oxygenation and clinical outcome in acute brain injury?
Authors: English Shane W. , McIntyre Lauralyn 
Published: February 2018

Purpose of review
The purpose of this review is to highlight the role of hemoglobin in cerebral physiology and pathophysiology. We review the existing as well as recent evidence detailing the effects of red blood cell transfusion on cerebral oxygenation and clinical outcome.

Recent findings
Hemoglobin is a key component in oxygen delivery, and thus cerebral oxygenation. Higher hemoglobin levels and red blood cell transfusion are associated with higher cerebral oxygen delivery and decreased cerebral ischemic burden. Recent studies suggest that this may be associated with improved clinical outcomes. However, these results are limited to only a few, small studies and the results have not been consistent. Further studies are required.

Summary
Hemoglobin is important for cerebral oxygenation and strategies to minimize anemia should be undertaken. Although higher hemoglobin levels are associated with less cerebral ischemia and better clinical outcome, whether this remains true whenever red blood cell transfusion is used to achieve this result remains unclear.
Autophagy: should it play a role in ICU management?
Authors: Rosenthal Martin D. , Carrott Phil , Moore Frederick A. 
Published: February 2018

Purpose of review
This review is to discuss the role of autophagy in the critically ill patient population. As the understanding of autophagy continues to expand and evolve, there are certain controversies surrounding whether intensivist should allow the benefit of autophagy to supersede gold standard of insulin therapy or early nutritional support.

Recent findings
The review is relevant as the current literature seems to support under-feeding patients, and perhaps the reason these studies were positive could be prescribed to the mechanisms of autophagy. It is well understood that autophagy is a physiologic response to stress and starvation, and that the inducible form could help patients with end-organ dysfunction return to homeostasis.

Summary
The jury is still out as to how autophagy will play into clinical practice as we review several gold standard therapies for the critically ill.
Clozapine for Treatment-Refractory Behavioral Disturbance in Dementia
Authors: Teodorescu Andreea , Dima Lorena , Ifteni Petru , Rogozea Liliana M. 
Published: February 2018

Background:
Behavioral and psychological symptoms in dementia significantly contribute to caregiver burden and impose patient hospitalization. The goal of treatment of admitted patients is the rapid remission of symptoms to allow their return to home as soon as possible. Intervention requires an intrusive approach with parenteral treatment and physical restraints, with a negative emotional impact on patients and their families. Despite the large utilization of antipsychotics for behavioral and psychological symptoms, there is no antipsychotic approved by the Food and Drug Administration for agitation in dementia.

Study Question:
To evaluate efficacy and tolerability of clozapine in patients with treatment-resistant agitation associated with dementia.

Study Design:
Cohort study with 337 patients, admitted between January 1, 2012 and December 31, 2016, with dementia according to The Diagnostic and Statistical Manual of Mental Disorders 4th ed. criteria. Clozapine was given in standard titration, starting with 6.25 or 12.5 mg.

Measures and Outcomes:
Efficacy was measured by the need for physical restraints and time to discharge and tolerability by recording all side effects. Data collected included demographics, psychotropics used, physical restraints, length of stay, destination after discharge, and comorbidities.

Results:
Of 337 cases, 315 (93.5%) patients received antipsychotics. There were 27 cases treated with clozapine. Before clozapine initiation, haloperidol was given in 16 cases (55.17%, mean = 7.43 mg/d, SD = ±4.01), and the treatment was stopped mainly because of extrapyramidal side effects. Other antipsychotics used were quetiapine (mean dose = 260 mg/d, SD = ±54.77), risperidone (mean dose = 3.3 mg/d, SD = ±0.57), and olanzapine (mean dose = 8.33 mg/d, SD = ±2.88). Mean dose of clozapine was 59.16 mg/d, (SD = ±40.48), ranging from 12.5 to 200 mg/d. There were a lower number of physical restraints after clozapine initiation than before (12 vs. 34, P < 0.05).

Conclusions:
Clozapine therapy seemed beneficial in treatment-resistant agitation in patients with dementia. The risk–benefit balance must be well weighed when clozapine is chosen. More studies are needed.
The Association of Recently Diagnosed Diabetes and Long-term Diabetes With Survival in Pancreatic Cancer Patients
Authors: Jeon Christie Y. , Li Donghui , Cleary Sean , Stolzenberg-Solomon Rachael , Bosetti Cristina , La Vecchia Carlo , Porta Miquel , Toriola Adetunji T. , Hung Rayjean J. , Kurtz Robert C. , Olson Sara H. 
Published: February 2018

Objectives
It is unclear whether long-standing diabetes or new-onset pancreatogenic diabetes contributes to poor prognosis in patients with pancreatic ductal adenocarcinoma (PDAC).

Methods
We investigated the influence of diabetes diagnosed shortly before PDAC and long-term diabetes on overall survival in 2792 PDAC patients who had participated in 3 PDAC case-control studies in the Pancreatic Cancer Case-Control Consortium. There were 300 patients with long-term diabetes of more than 3 years' duration (11%) and 418 patients with recently diagnosed diabetes of 3-year duration or less (15%). We performed Cox regression to determine the association of long-term diabetes and recently diagnosed diabetes with overall survival, adjusting for study site, age, sex, race, stage of disease, surgery, chemotherapy, smoking history, and body mass index at diagnosis.

Results
In the overall population, neither long-term diabetes (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.97–1.26) nor recently diagnosed diabetes (HR, 1.06; 95% CI, 0.94–1.18) was associated with shorter survival. When stratified by stage of disease, long-term diabetes was associated with 42% increase in rate of death in persons with resectable PDAC (HR, 1.42; 95% CI, 1.13–1.78), whereas it was not associated with survival in PDAC patients with more advanced disease.

Conclusion
Long-term diabetes was associated with increased rate of death in patients with resectable PDAC.
Primary and Secondary Organ Failures Cause Mortality Differentially in Acute Pancreatitis and Should be Distinguished
Authors: Padhan Rajesh Kumar , Jain Saransh , Agarwal Samagra , Harikrishnan Suresh , Vadiraja Padmaprakash , Behera Sanatan , Jain Sushil Kumar , Dhingra Rajan , Dash Nihar Ranjan , Sahni Peush , Garg Pramod Kumar 
Published: February 2018

Objective
The aim of this study was to study the development of early and late organ failure (OF) and their differential impact on mortality in patients with acute pancreatitis (AP).

Methods
Consecutive patients (N = 805) with acute pancreatitis were included in an observational study. Organ failure was categorized as primary if it occurred early due to pancreatitis per se and secondary if it occurred late due to infected pancreatic necrosis (IPN). Primary outcome was a relative contribution of primary OF, secondary OF, and IPN to mortality.

Results
Of the 614 patients (mean age, 38.8; standard deviation, 14.6 years; 430 males) in a derivation cohort, 274 (44.6%) developed OF, with 177 having primary OF and 97 secondary OF due to sepsis. Primary OF caused early mortality in 15.8% and was a risk factor for IPN in 76% of patients. Mortality in patients with primary OF and IPN was 49.5% versus 36% in those with IPN and secondary OF (P = 0.06) and 4% in those with IPN but without OF (P < 0.001). The results of the 191 patients in the validation cohort confirmed the relative contribution of primary and secondary OF to mortality.

Conclusion
Primary and secondary OF contributed to mortality independently and are distinct in their timing, window of opportunity for intervention, and prognosis.
The 2012 International Consensus Guidelines of Intraductal Papillary Mucinous Neoplasms of the Pancreas (Fukuoka Criteria) Predict the Malignant Potential, Even in Actual Clinical Situations
Authors: Okamura Yukiyasu , Sano Shusei , Sugiura Teiichi , Ito Takaaki , Yamamoto Yusuke , Ashida Ryo , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Sasaki Keiko , Uesaka Katsuhiko 
Published: February 2018

Objectives
The aim of the present study was to validate the use of the 2012 International Consensus Guidelines for intraductal papillary mucinous neoplasm (IPMN) (Fukuoka criteria) in patients without findings of obstructive jaundice and/or an enhanced solid component.

Methods
This retrospective study included patients who underwent pancreatectomy for IPMN between October 2002 and September 2016. The sensitivity, specificity, and positive and negative predictive values for malignancy were calculated for each feature of high-risk stigmata.

Results
Of the 135 patients who underwent surgery for IPMN, 50 (37.0%) had low/intermediate-grade dysplasia, 25 (18.5%) had high-grade dysplasia, and the remaining 60 (44.5%) had invasive carcinoma. A malignant potential was, thus, present in 63% of all resected cases. Considering an actual clinical situation, the predictors for malignant potential were assessed in 62 patients without findings of obstructive jaundice and/or an enhanced solid component. A multivariate analysis revealed that the Fukuoka criteria were the only independent factor for predicting the malignant potential (odds ratio, 5.69; P = 0.036).

Conclusions
The present study suggested that malignant potential can be accurately detected by faithfully keeping to the Fukuoka criteria. Using these criteria enables us to identify patients with malignant potential, even in the actual clinical situations.
Effect of Reprimo Down-regulation on Malignant Transformation of Intraductal Papillary Mucinous Neoplasm
Authors: Nakazato Tetsuya , Suzuki Yutaka , Tanaka Ryota , Abe Nobutsugu , Masaki Tadahiko , Mori Toshiyuki , Ohkura Yasuo , Sugiyama Masanori 
Published: February 2018

Objectives

Reprimo gene is a cytoplasmic protein belonging to a family of molecules controlled by p53 that inhibits cell cycle progression. Ectopic expression of Reprimo results in cell cycle arrest at the G2 phase. The aim of this study was to investigate the impact of Reprimo expression on tumorigenesis of intraductal papillary mucinous neoplasm (IPMN).

Methods
Thirty-seven surgical cases of IPMN were collected retrospectively. Twenty-eight patients had benign IPMNs (low-grade dysplasia, n = 18; intermediate-grade dysplasia, n = 10), and the remaining 9 had malignant IPMNs (high-grade dysplasia, n = 4; invasive carcinoma, n = 5). DNA from tumor samples was extracted. DNA methylation patterns of Reprimo were determined by the methods of methylation-specific polymerase chain reaction and immunohistochemistry. The methylation status of Reprimo was compared between benign IPMNs and malignant IPMNs.

Results
The incidence of aberrant DNA methylation of Reprimo was significantly higher in malignant IPMNs than in benign IPMNs (78% vs 32%, P = 0.016). Furthermore, the incidence of immunohistochemical Reprimo expression was significantly lower in malignant IPMNs than in benign IPMNs (22% vs 82%, P = 0.002).

Conclusions

Reprimo methylation was found more frequently in malignant IPMNs. Reprimo methylation is involved in malignant transformation of IPMNs.