bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hodgkin lymphoma in elderly patients
Authors: Borchmann Sven , Engert Andreas , Böll Boris 
Published: July 2018

Purpose of review
We aim to summarize the current knowledge on the treatment of elderly Hodgkin lymphoma patients with a focus on evidence from clinical trials and novel drugs.

Recent findings
For elderly Hodgkin lymphoma patients above 60 years without precluding comorbidities a curative treatment approach is warranted. Early favorable stage patients should receive two cycles of multiagent chemotherapy followed by 20 Gy localized radiotherapy. Early unfavorable stage patients should receive four cycles of multiagent chemotherapy followed by 30 Gy localized radiotherapy. For advanced stage patients six cycles of multiagent chemotherapy can be recommended and should be followed by localized radiotherapy on residual disease manifestations. Relapsed or refractory patients should be treated in an individually tailored approach that considers both the patient's objectives and comorbidities. The antibody–drug conjugate brentuximab vedotin is a very effective option for elderly patients with a high response rate albeit limited durability. Anti-programed cell death protein 1 antibodies might also be effective in elderly Hodgkin lymphoma patients with a mechanism of action distinct from chemotherapy.

Summary
In conclusion, the goal of treatment in newly diagnosed elderly Hodgkin lymphoma patients is curative whenever possible and prospective and retrospective evidence has shown that this is feasible for all disease stages with a variety of multiagent chemotherapy regimen. Relapsed and refractory elderly Hodgkin lymphoma patients can mostly only be treated with the goal of palliation. However, it remains to be seen if novel substances and new combination regimen are able to change that.
Targeting CD47 as a cancer therapeutic strategy: the cutaneous T-cell lymphoma experience
Authors: Folkes Alecia S. , Feng Mingye , Zain Jasmine M. , Abdulla Farah , Rosen Steven T. , Querfeld Christiane 
Published: July 2018

Purpose of review
To describe the relevance of CD47 in the tumor microenvironment and summarize data on anti-CD47 therapies, including its role in cutaneous T-cell lymphoma (CTCL).

Recent findings
CD47 is expressed on all normal cells and targets SIRPα on the surface of myeloid cells. However, CD47 is found to be overexpressed on cancer cells. CD47–SIRPα interaction inhibits macrophage phagocytosis, allowing cancer cells to escape immune surveillance. Current focus in immunotherapy has been targeted toward inhibiting CD47–SIRPα interaction via anti-CD47 antibodies. This activates innate immunity, promoting cancer cell destruction by macrophages. It also activates adaptive immunity resulting in antigen-presentation, mostly by dendritic cells, leading to antitumor cytotoxic reactions. Current CD47 antagonists undergoing clinical trials include Hu5F9 (an anti-CD47 antibody that directly inhibits the CD47–SIRPα interaction) and TTI-621, (a fusion protein composed of CD47 binding domain of human SIRPα and linked to the Fc region of IgG1). These agents have continued to show strong efficacy against solid and hematological tumors.

Summary
In the CTCL tumor microenvironment, increased immune checkpoint inhibition expression via CD47 bound to SIRPα correlates with a more advanced disease state. Continued success in treating these patients requires further studies on CD47 antagonists, specifically when combined with other antibodies.
Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis
Authors: Soman Midhun , Huang Li-Cong , Cai Wen-Hui , Xu Jun-Bi , Chen Jun-Yao , He Ren-Ke , Ruan Heng-Chao , Xu Xiang-Rong , Qian Zhi-Da , Zhu Xiao-Ming 
Published: July 2018

Abstract

Objective:
This meta-analysis aims to investigate serum androgen profiles (testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin) in women with premature ovarian failure and to establish if there is evidence of diminished androgen levels in these women.

Methods:
Various Internet sources of PubMed, Cochrane library, and Medline were searched systematically until February, 2018. Out of a pool of 2,461 studies, after applying the inclusion/exclusion criterion, 14, 8, 10, and 9 studies were chosen for testosterone, dehydroepiandrosterone sulfate, androstenedione, and sex hormone-binding globulin, respectively, for this meta-analysis. The effect measure was the standardized mean difference with 95% confidence interval (95% CI) in a random-effects model.

Results:
The testosterone concentrations in premature ovarian insufficiency were compared with fertile controls: stamdard mean difference (IV, random, 95% CI) −0.73 [−0.99, −0.46], P value < 0.05. The dehydroepiandrosterone sulfate concentrations in premature ovarian insufficiency compared to fertile controls: standard mean difference (IV, random, 95% CI) −0.65 [−0.92, −0.37], P value < 0.05. Androstenedione in premature ovarian insufficiency were compared with fertile controls: standard mean difference (IV, random, 95% CI) −1.09 [−1.71, −0.48], P value < 0.05. Sex hormone-binding globulin levels did not show statistical significance. The dehydroepiandrosterone sulfate levels were reduced in premature ovarian insufficiency cases, but still showed a higher level than in postmenopausal women.

Conclusions:
Women with premature ovarian insufficiency are at risk for decreased concentrations of testosterone, dehydroepiandrosterone sulfate, and androstenedione. Dehydroepiandrosterone sulfate levels were more reduced in postmenopausal controls when compared with premature ovarian insufficiency cases.
The many menopauses: searching the cognitive research literature for menopause types
Authors: Edwards Hannaford , Duchesne Annie , Au April S. , Einstein Gillian 
Published: July 2018

AbstractObjective:Recent evidence suggests that early or induced menopause increases the risk for cognitive impairment and dementia. Given the potential for different cognitive outcomes due to menopause types, it is important that present research on menopause and cognition distinguishes between types. The aim of this project was to determine to what extent research looking at cognition in postmenopausal women published in one year, 2016, accounted for menopausal type.Methods:We searched MEDLINE, EMBASE, and PsychINFO using keywords and MeSH terms for menopause and cognition. We included any research paper reporting a cognitive outcome measure in a menopausal human population. Differentiation between the types of menopause was defined by four categories: undifferentiated, demographic differentiation (menopause type reported but not analyzed), partial differentiation (some but not all types analyzed), and full differentiation (menopause types factored into analysis, or recruitment of only one type).Results:Fifty research articles were found and analyzed. Differentiation was distributed as follows: undifferentiated, 38% (19 articles); demographic differentiation, 16% (8); partial differentiation, 28% (14); and full differentiation, 18% (9).Conclusions:This review revealed that although some clinical studies differentiated between the many menopauses, most did not. This may limit their relevance to clinical practice. We found that when menopause types are distinguished, the differing cognitive outcomes of each type are clarified, yielding the strongest evidence, which in turn will be able to inform best clinical practice for treating all women.
Functional Improvement with Free Vascularized Toe-to-hand Proximal Interphalangeal (PIP) Joint Transfer
Authors: Kuzu İsmail Melih , Kayan Reşit Burak , Öztürk Kahraman , Güneren Ethem 
Published: July 2018

Background:
Reconstruction of small joints of fingers is still challenging in hand surgery. Implant arthroplasty and arthrodesis have some limitations in the reconstruction of small finger joints. Free vascularized PIP joint transfer from second toe to finger is a promising autogenous reconstructive alternative.

Methods:
In this prospective study, 7 cases of free vascularized PIP joint transfer were analyzed. The measurements for active and passive range of motion (ROM), grip, and pinch strength has been done preoperatively and 1-year postoperatively. The functional change in daily life quality and work-related activities was evaluated with Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire.

Results:
Mean follow-up period was 20.3 months (12–25). Preoperative mean active and passive ROM values were 3.6° (0–14°) and 11.9° (0–29°), respectively. Postoperative 1-year measurements revealed a mean active ROM of 24.1° and a mean passive ROM of 31.6°. Mean grip and pinch strength increased from 52.1 to 58.6 lbs and from 5.1 to 5.9 lbs, respectively. Mean preoperative and postoperative DASH-scores were 41.3 and 30.3.

Conclusion:
The improvement in ROM, increasing grip strength, and declining DASH scores in our study support that free vascularized joint transfer improves patients’ daily life quality and work-related activities via providing a functional joint if performed with appropriate indications, careful planning, and meticulous surgical execution. Free vascularized joint transfer provides an autogenous, painless, mobile, and stable joint. It also has the advantages of composite tissue reconstruction and lacks the disadvantages of arthrodesis and synthetic joint implants.
Electrophysiological characterisation of central sensitisation in canine spontaneous osteoarthritis
Authors: Hunt James R. , Goff Megan , Jenkins Helen , Harris John , Knowles Toby G. , Lascelles B. Duncan X. , Enomoto Masataka , Mendl Michael , Whay Helen R. , Murrell Joanna C. 
Published: July 2018

Abstract
In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.
Preventing Exercise-Associated Collapse Using Online Runner Education: A Randomized, Controlled Trial
Authors: Worley David M. , Renier Colleen M. , Woehrle Theo A. , Stovitz Steven D. , Nelson Benjamin D. 
Published: July 2018

Objective:
To determine whether online exercise-associated collapse (EAC) prevention education decreases medical tent EAC visits among first-time marathoners.

Design:
A prospective controlled study, with age- and sex-stratified randomization, evaluated rates of medical tent diagnosed EAC among runners randomized to the intervention group and intervention participants, compared with a control group.

Setting:
Grandma's Marathon Medical Tent in Duluth, MN, June 2016.

Participants:
Runners in the 2016 Grandma's Marathon who never previously ran a marathon (n = 2943), randomized into control (n = 1482) and intervention (n = 1461) groups. Intervention participants opened the EAC prevention video (n = 590).

Interventions:
Online EAC education included an introductory webpage and 5-minute professional video describing EAC and prevention.

Main Outcome Measures:
Medical tent visit with EAC diagnosis.

Results:
Intervention participants had no decreased likelihood of EAC, compared with controls [odds ratio (OR), 0.88, 95% confidence interval (CI), 0.46-1.69]. Exercise-associated collapse occurred less frequently in those with longer race times (OR, 0.58, 95% CI, 0.43-0.79). Intervention participation was associated with longer race times (OR, 1.12, 95% CI, 1.10-1.23).

Conclusions:
Those opening the EAC prevention video and controls had similar EAC rates. Slower running speed was associated with lower EAC rates. Video viewing was a predictor of slower running pace.
Preliminary Results With Image-guided Cochlear Implant Insertion Techniques
Authors: Labadie Robert F. , Noble Jack H. 
Published: July 2018

Hypothesis:
Using patient-customized cochlear measurements obtained from preoperative computed tomography (CT) scans to guide insertion of cochlear implant (CI) electrode arrays will lead to more optimal intracochlear positioning.

Background:
Cochlear duct length is highly variable ranging from 25.26 to 35.46 mm, yet CI electrode arrays are treated as one size fits most. We sought to investigate the impact of patient-customized insertion plans on final location of electrode arrays.

Methods:
Twenty cadaveric temporal bone specimens were CT scanned and randomly divided into groups A and B. Group A specimens had an optimal customized insertion plan generated including entry site (e.g., round window versus extended round window), entry vector based on anatomical landmarks (e.g., hug posterior aspect of facial recess and angle 1 mm inferior to stapes), depth to begin advancing off stylet, and final insertion depth. Suboptimal plans were chosen for group B by selecting an approach that was normal yet predicted to result in poor final electrode location. One surgeon, blinded as to group, carried out the CI insertions following which the electrode array was fixed using superglue and the specimen CT scanned to allow assessment of final electrode location.

Results:
Average perimodiolar distances for groups A and B were 0.51 and 0.60 mm, respectively. For group A, full scala tympani insertion was achieved in all specimens while in group B, 4 of 10 specimens had scalar translocation.

Conclusion:
Patient customized cochlear implant insertion techniques achieved better positioning of electrode arrays in this study and have potential for improving electrode positioning in patients.
Low Concentration Intra-Tympanic Gentamicin Treatment for Menière's Disease: A Long-Term Follow Up
Authors: Nathan Shlamkovitch , Lasry Reut , Ephraim Eviatar , Marom Tal , Gavriel Haim 
Published: July 2018

Background:
Intra-tympanic injections of gentamicin (ITG), a known ototoxic agent, have been proven to be effective in controlling Menière's disease (MD) symptoms, in patients who did not respond to conservative therapy, although its safety was questionable.

Objectives:
To study whether low-concentration ITG, in refractory MD, had an effect on the ipsilateral hearing, in comparison to the contralateral ear, and to study the effectiveness of such treatment.

Methods:
A comparative, retrospective cohort study was conducted between 2003 and 2015, and compared the change in the hearing level between the injected ear and the contralateral, untreated ear.

Outcomes:
In 20 of 27 patients (74.1%), one course of ITG treatment was considered as successful. In the short-term, there was improvement of hearing level at 1000 Hz (p = 0.014), and deterioration of hearing level at 8000 Hz (p = 0.039), both in comparison to the control ear. In the long-term and after confounders adjustment, we found there were no differences in the hearing levels between the treated ear and the untreated contralateral ear.

Conclusions:
A high success rates of treating vertigo attacks with low concentration ITG in refractory unilateral MD patients is herein reported, while a significant difference was not observed in the hearing threshold compared with the healthy contralateral ear.
Epitope-based human leukocyte antigen matching for transplantation: a personal perspective of its future
Authors: Duquesnoy René J. 
Published: July 2018

Purpose of review
This study reflects my personal experience with the characterization of human leukocyte antigen (HLA) epitopes and their significance in HLA matching for transplantation. It offers a subjective assessment what further studies are needed to have this concept be applied in the clinical setting.

Recent findings
This study addresses the structural characteristics of antibody-reactive HLA epitopes determined by different methods, eplet-associated antibody analysis and acceptable mismatching for sensitized patients and eplet immunogenicity and determination of mismatch permissibility.

Basic implications
for clinical practice and research consider the need for further studies of the structural basis of antibody-verified HLA epitopes determined in different techniques and their clinical relevance, the biological basis of epitope immunogenicity and determinations of permissible mismatches and a computerized clinical transplant database with an Artificial Intelligence component that can generate evidence-based information for the practical application of epitope-based HLA matching.
Beyond Early Infant Diagnosis: Changing the Approach to HIV-Exposed Infants
Authors: Modi Surbhi , Broyles Laura N. , Montandon Michele , Itoh Megumi , Ochanda Boniface , Langat Agnes , Sullivan David , Dale Helen 
Published: July 2018

Abstract:
Despite dramatic global progress with implementing prevention of mother-to-child HIV transmission (PMTCT) programs, there were 160,000 new pediatric HIV infections in 2016. More than 50% of infant HIV infections now occur in the postpartum period, reflecting the relatively high coverage of interventions in the antenatal period and the need for greater attention to the breastfeeding mother and her HIV-exposed infant (HEI). Early diagnosis and treatment are critical to prevent morbidity and mortality in HIV-infected children; however, early infant HIV testing rates remain low in most high HIV-burden countries. Furthermore, systematic retention and follow-up of HEI in the postpartum period and ascertainment of final HIV status remain major program gaps. Despite multiple calls to action to improve infant HIV testing rates, progress has been marginal due to a lack of focus on the critical health care needs of HEI coupled with health system barriers that result in fragmented services for HIV-infected mothers and their families. In this paper, we describe the available evidence on the health outcomes of HEI, define a comprehensive care package for HEI that extends beyond early HIV testing, and describe successful examples of integrated services for HEI.
Zvandiri—Bringing a Differentiated Service Delivery Program to Scale for Children, Adolescents, and Young People in Zimbabwe
Authors: Willis Nicola , Napei Tanyaradzwa , Armstrong Alice , Jackson Helen , Apollo Tsitsi , Mushavi Angela , Ncube Getrude , Cowan Frances M. 
Published: July 2018

Abstract:
Since 2004, there has been a dramatic shift in the HIV response for children, adolescents, and young people in low resource settings. Previous programs and services were largely orientated to adults. This is now changing, but there is limited evidence on how to take services for children, adolescents, and young people living with HIV (CAYPLHIV) to scale. Zvandiri is a theoretically grounded, multicomponent-differentiated service delivery model for children, adolescents, and young people in Zimbabwe that integrates peer-led, community interventions within government health services. Africaid analyzed routine program and other data from November 2004 to October 2017 to document Zvandiri scale-up, framed by the World Health Organization framework for scaling up interventions. Since 2004, Zvandiri has evolved from one support group in Harare into a comprehensive model, combining community- and clinic-based health services and psychosocial support for CAYPLHIV. Zvandiri was scaled up across Zimbabwe through phased expansion into 51 of 63 districts, reaching 40,213 CAYPLHIV. Evidence indicates that this approach improved uptake of HIV testing services, adherence, and retention in care. The environment and strategic choices were critical when taking the model to scale, particularly nesting the program within existing services, and capacity strengthening of service providers working jointly with trained, mentored CAYPLHIV. The results provide a firm foundation for programming and from which to build evidence of sustainable impact. Formal impact evaluation is needed and underway. These program data contribute to the essential evidence base on strategic approaches to assist in planning services for this relatively neglected group.
Getting Treatment and Care Services Right for Children and Adolescents to Reach High Viral Suppression
Authors: Penazzato Martina , Sugandhi Nandita , Essajee Shaffiq , Doherty Meg , Ficht Allison , Phelps Benjamin Ryan 
Published: July 2018

Abstract:
In August 2014, PEPFAR and the Children's Investment Fund Foundation launched the Accelerating Children's HIV/AIDS Treatment (ACT) initiative with the aim of doubling the number of children on antiretroviral treatment in 9 African countries. Increasing rates of pretreatment drug resistance and use of suboptimal treatment regimens and formulations result in poor adherence and high rates of viral failure. Supporting adherence and ensuring appropriate treatment monitoring are needed to maximize duration of first-line treatment and enable timely sequencing to subsequent lines of antiretroviral treatment. Although timely antiretroviral treatment is the core of clinical care for infants, children and adolescents living with HIV, ensuring a broader package of biomedical and non-biomedical interventions is also required to address highly prevalent comorbidities among children living with HIV. Providing such a comprehensive package has been challenging for health care workers who lack the necessary skills and confidence to care for pediatric populations. Efforts to simplify clinical management and specific training and mentorship are needed to address these challenges. In this article, we review the progress made during the ACT initiative and the persistent challenges in achieving and maintaining virological suppression across the age spectrum. We identify innovations needed to build on the success of the ACT initiative. Despite the challenges, achieving high levels of virological suppression in children and adolescents is possible. The complexity of pediatric HIV treatment can be offset as antiretroviral regimens become more effective, tolerable, and easier to prescribe and administer. Meanwhile, basic programmatic elements to address comorbidities as well as support health care workers remain critical. In this article we review the progress made through the ACT initiative, as well as identify innovations needed to address persistent challenges to viral suppression across the age spectrum.