bluuebunny/crossref_metadata_2025 huggingface dataset:
Poor Evertor Muscle Activity Is a Predictor of Recurrence in Idiopathic Clubfoot Treated by the Ponseti Method: A Prospective Longitudinal Study With a 5-Year Follow-up
Authors: Little Zoe , Yeo Andrea , Gelfer Yael
Published: March 2019

Background:

After successful primary correction of the deformity in idiopathic clubfoot with the Ponseti method, recurrence has been reported to affect up to 40% of children. So far, it has been difficult to predict which feet are at risk of recurrence, despite numerous studies investigating various potential risk factors. The foot abduction brace (FAB) has been the standard of care in preventing recurrence but, even with excellent compliance, recurrences still occur. Increasingly, evidence points to a congenital neuromuscular imbalance constituting the deforming forces present in clubfoot. Poor evertor muscle activity has been cited specifically as a potential risk factor for recurrence. The aim of this study is to evaluate whether poor evertor muscle activity on clinical examination can predict recurrence in idiopathic clubfoot at 5-year follow-up.

Methods:

Data were collected prospectively on patients treated at our tertiary physiotherapy-led Ponseti service between 2010 and 2015. Hospital ethical approval was obtained. Sex, age, laterality, Pirani score, number of casts, brace compliance, and evertor activity were recorded. Evertor muscle activity was scored in a semiquantitative repeatable manner: 0, 0.5, or 1 as previously described. Recurrence was defined as deterioration of any of the 4 components of the deformity following a previously complete correction.

Results:

In total, 104 patients (172 feet) were included in the study, 76 patients had good evertor activity, and 28 demonstrated poor evertor activity. The mean follow up was 62 months (range, 41 to 71 mo); 18.3% of the patients (19/104) had recurrence treated with repeat casting; 13.5% (14/104) of the patients required additional surgery following recasting. Recurrence was highly associated with poor evertor activity (P<0.01).

Conclusions:

Results at 5 years confirm that a semiquantitative evertor muscle activity assessment can predict recurrence and should be added to the routine clinical assessment in order to assist with individualizing patient’s treatment strategies.

Level of Evidence:

Level II.
The emergence of long-term survivors in recurrent and metastatic squamous cell head and neck cancer
Authors: Castet Florian , Brenes Jesús , Taberna Miren , Mesía Ricard
Published: March 2019

Purpose of review

The systemic therapies available in recurrent and metastatic head and neck squamous cell carcinoma to date are palliative-intent treatments in most cases. However, a small subgroup of patients derives unconventional benefit and become long-term survivors, achieving cure in some cases. This review focusses on this group of patients, discusses recent literature and suggests plausible molecular hypothesis.

Recent findings

Human papillomavirus-related disease is known to confer a better prognosis in metastatic patients, probably because of its greater sensitivity to systemic therapies. This group of patients seems to have a greater immune activation, which could partly explain this fact. Moreover, the use of antiepidermal growth factor receptor therapies in the metastatic setting has doubled the prevalence of long-term survivors. One of the most plausible explanations is the immune-modulatory effect of cetuximab mediated by antibody-dependent cell-mediated cytotoxicity.

These facts, along with the recent encouraging results of checkpoint inhibitors in this disease, give hope that these therapies will not only improve survival but also increase the prevalence of long-term survivors.

Long-term survivors merit our utmost attention as an in-depth study of these patients could help us to better understand the tumour biology and allow us to develop robust biomarkers and effective targeted therapies, which could in turn lead to a true paradigm shift.
Activated Allogeneic Donor-derived Marrow-infiltrating Lymphocytes Display Measurable In Vitro Antitumor Activity
Authors: Biavati Luca , Noonan Kimberly , Luznik Leo , Borrello Ivan
Published: March 2019

A major limitation in current allogeneic hematopoietic stem cell transplantation (alloHSCT) is disease relapse after transplant, indicating that donor-derived T cells are inadequate in imparting an effective antitumor response. The current standard treatment approach to relapse utilizes donor lymphocyte infusions that have limited documented efficacy and are also associated with significant morbidity mainly related to graft-versus-host disease. We have previously shown that marrow-infiltrating lymphocytes (MILs) have a broader antigenic specificity compared with their peripheral blood counterpart in an autologous adoptive T-cell therapy setting. Here, we extend these observations to examine the ability of MILs obtained from patients after an alloHSCT to generate measurable tumor-specific immunity. We show here that allogeneic donor-derived marrow-infiltrating lymphocytes (ddMILs) obtained from patients who underwent alloHSCT with posttransplant cyclophosphamide could be reproducibly expanded and activated with anti-CD3/CD28 beads. Phenotypic characterization of ddMILs subpopulations revealed the prevalence of a central memory phenotype. Polyclonally activated ddMILs displayed measurable in vitro antitumor activity. Furthermore, activated ddMILs from all patients effectively targeted third-party allogeneic antigens, but showed no reactivity toward self-antigens presented in an HLA-restricted manner. Collectively, these results underscore the intrinsic polyclonal tumor-specificity of activated ddMILs and describe a novel approach for the generation of tumor-specific T cells that are suitable for adoptive immunotherapy of hematological malignancies relapsed after alloHSCT. This approach has a potential to significantly increase the tumor-specificity and reduce the toxicities associated with current standard donor lymphocyte infusion approaches.
Chimeric Antigen Receptor-modified Donor Lymphocyte Infusion Improves the Survival of Acute Lymphoblastic Leukemia Patients With Relapsed Diseases After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Wang Tao , Gao Lei , Hu Xiaoxia , Liu Bin , Chen Jie , Zhang Weiping , Wang Jianmin , Yu Xuejun , Feng Dongge , Chang Alfred E. , Max Wicha , Tang Gusheng , Li Qiao , Yang Jianmin
Published: March 2019

The value of chimeric antigen receptor-modified donor lymphocyte infusion (CAR-DLI) is unclear in B-cell acute lymphoblastic leukemia (B-ALL), particularly in patients with relapsed diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, 5 B-ALL patients who relapsed after allo-HSCT received CAR-DLI (CAR-DLI group), and the outcome was compared with 27 relapsed B-ALL patients who received DLI therapy (DLI group). The median complete remission duration of CAR-DLI group was significantly (P=0.020) longer when compared with DLI group: 9 months (range, 2–29) versus 3.2 months (range, 0–17.4). Furthermore, patients receiving CAR-DLI showed significant (P=0.049) survival advantage over DLI group, with median overall survival of 12 months (range, 3–29) and 3.7 months (range, 0–65), respectively. Of note, no patient developed acute graft versus host disease in the CAR-DLI group, while incidence of acute graft versus host disease grades I–II and grades III–IV were 2 (7%) and 4 (14.8%) in the DLI group, respectively. In addition, cytokine release syndrome in CAR-DLI group was manageable. Overall, our study demonstrated that CAR-DLI significantly improved the survival of B-ALL patients relapsed after allo-HSCT, thus indicating that CAR-DLI may represent an alternative and more effective therapy for B-ALL patients with relapsed diseases.
Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells
Authors: Kianmehr Zahra , Khorsandi Khatereh , Mohammadi Maryam , Hosseinzadeh Reza
Published: March 2019

p-Coumaric acid (PCA) is a kind of phenolic compound, and as one of the cinnamic acid derivatives, it has many biological functions such as antioxidants, anti-inflammatory, antiplatelet, and anticancer activity. Low-level laser irradiation has received increasing interest in the fields of tissue regeneration and wound healing. In this study, the effect of low-level laser irradiation on human fibroblast cells (human dermal fibroblast) and human melanoma cancer cells (A375 and SK-MEL-37) treated with PCA was investigated. The human dermal fibroblast, A375, and SK-MEL-37 cells were exposed to low-level laser at 660-nm wavelength with 3 J/cm2for 90 s, and then the cells were treated with different concentrations of PCA (0–1000 μg/ml for 24 h), separately. In another experiment, first the cells were treated by PCA and then irradiated with low-level laser as described before. The effect of various irradiation energy (1–6 J/cm2) on the melanoma cells, which were then treated by PCA, was studied. The cell viability using MTT assay and lactate dehydrogenase assay was determined. Morphological changes owing to apoptosis induction by irradiation and PCA were detected by fluorescence microscopy using acridine orange/ethidium bromide double staining. The results showed that pretreatment with low-level laser irradiation and then PCA reduced the survival and growth of melanoma cells more than the early treatment with PCA and then low-level laser irradiation. Lactate dehydrogenase activity was reduced significantly by preirradiation and then PCA treatment in comparison with the dark group in melanoma cells. The cell cytotoxicity at different irradiation energy and then IC50concentration of PCA was increased up to 3 J/cm2and then decreased following increasing irradiation energy. The morphology study with light microscopy and apoptotic assay using acridine orange/ethidium bromide dual staining confirmed the MTT results. This study showed that low-level laser irradiation alone is not able to kill human normal fibroblast and human melanoma cancer cells. Preirradiation followed by treatment with PCA did not change the cell viability in human fibroblast significantly but reduced the cell viability in melanoma cells presumably through the apoptosis pathway.
Combating Food Insecurity
Authors: Wilkinson Mark
Published: March 2019

Individuals and food-insecure households who rely on food banks have a higher likelihood of chronic health conditions. A study of the Action Family Program at a faith-based community center demonstrated how nurses can impact food bank recipients' health measures through health promotion interventions. Providing healthier food options with the weekly food distribution box, cooking demonstrations, health screenings, and health education resulted in reduced weight, and decreased systolic and diastolic blood pressure measurements.
Ukrainian Faith Community Nursing
Authors: Martin Mary , D'Andre Pam
Published: March 2019

Ukraine has been an independent country since the fall of Communism in 1991. Its history has been and continues to be marked by war. Through the story of one patient, this article describes the ministry of faith community nursing in the capital city, Kiev. Through an ongoing partnership, the Association for Christian Nurses and Volunteers-Welfare Organization (BLAGO) teaches nurses and volunteers the principles of faith community nursing, with the goal of establishing faith community nursing practice in each state/oblast.
Christ-Focused Service-Learning
Authors: Matthew Stephanie , Roark Elizabeth , Hockett Eloise
Published: March 2019

Service-learning is an experiential process of action and reflection that allows students to expand their knowledge through real-world activities that benefit others. Service-learning opportunities for baccalaureate nursing students in Kenya have provided many ongoing examples of learning from our Kenyan collaborators. Receiving ministry from those we came to serve, allows allows us, in turn, to demonstrate Christ's humility. In this article, we share specific stories of how various community partners ministered in unexpected ways to our teams of students and faculty, as we served in Kenya through healthcare and education.
Comparison of Mohs Surgery and Surgical Excision in the Treatment of Localized Sebaceous Carcinoma
Authors: Su Chang , Nguyen Kevin A. , Bai Harrison X. , Christensen Sean R. , Cao Ya , Tao Yongguang , Karakousis Giorgos , Zhang Paul J. , Zhang Guiying , Xiao Rong
Published: March 2019

BACKGROUND

It remains controversial if Mohs surgery is superior to surgical excision in treating localized sebaceous carcinoma.

OBJECTIVE

To compare Mohs surgery and surgical excision for treating patients with localized sebaceous carcinoma.

MATERIALS AND METHODS

The US National Cancer Database was used to identify patients with histologically confirmed Stage 0 to 2 sebaceous carcinoma from 2004 to 2014. Clinicopathologic and socioeconomic factors were compared between treatment groups using the chi-square test. Overall survival (OS) was evaluated by log-rank test, multivariable Cox proportional hazard regression, and propensity score–matched analysis. Relative survival analyses compared with age- and sex-matched US population were performed.

RESULTS

Of 1,265 patients, 234 received Mohs surgery and 1,031 received surgical excision. Mohs surgery had a higher rate of negative margin (p = .004). On multivariate Cox regression analysis, Mohs surgery was associated with longer OS than surgical excision (HR: 0.703, 95% CI: 0.496–0.995, p = .047). The survival benefit of Mohs surgery persisted on relative survival analysis and propensity score–matched analysis (p = .0385), after matching the 2 groups on patient and disease characteristics.

CONCLUSION

Patients who received Mohs surgery had significantly longer OS when compared with those who received surgical excision. Prospective clinical trials comparing these treatment paradigms are warranted.
Expertise in Head and Neck Cutaneous Reconstructive Surgery
Authors: Deng Min , Higgins H. William , Lesiak Kendra , Decker Ashley B. , Regula Christie G. , Stevenson Mary L. , Raphael Brian , Depry Jennifer , Scott Jeffrey F. , Bangash Haider , Ochoa Shari A. , Ibrahimi Omar A. , Shafai Aria , Bordeaux Jeremy S. , Carucci John A. , Cook Jonathan L. , Goldman Glenn D. , Rohrer Thomas E. , Lawrence Naomi
Published: March 2019

BACKGROUND

The management of skin cancers has evolved with the development of Mohs micrographic surgery and a greater emphasis on surgical training within dermatology. It is unclear whether these changes have translated into innovations and contributions to the reconstructive literature.

OBJECTIVE

To assess contributions from each medical specialty to the cutaneous head and neck oncologic reconstructive literature.

METHODS

The authors conducted a systematic review of the head and neck reconstructive literature from 2000 through 2015 based on a priori search terms relating to suture technique, linear closure, advancement, rotation, transposition and interpolation flaps, and identified the specialty of the senior authors.

RESULTS

The authors identified 74,871 articles, of which 1,319 were relevant. Under suture technique articles, the senior authors were primarily dermatologists (58.2%) and plastic surgeons (20.3%). Under linear closure, the authors were dermatologists (48.1%), plastic surgeons (22.2%), and otolaryngologists (20.4%). Under advancement and rotation flaps, the senior authors were plastic surgeons (40.5%, 38.9%), dermatologists (38.1%, 34.2%), and otolaryngologists (14.4%, 21.6%). Under transposition and interpolation flaps, the senior authors were plastic surgeons (47.3%, 39.4%), dermatologists (32.3%, 27.0%), and otolaryngologists (15.3%, 23.4%).

CONCLUSION

The primary specialties contributing to the cutaneous head and neck reconstructive literature are plastic surgery, dermatology, and otolaryngology.
Assessing Skin Biopsy Rates for Histologic Findings Indicative of Nonpathological Cutaneous Disease
Authors: Solomon James A. , Oswalt Michael , Nodzenski Michael , Glener Julie , Schaeffer Matthew R. , Cartee Todd V. , Maher Ian A. , Sobanko Joseph F. , Waldman Abigail , Yoo Simon S. , Lewis Suzanna , Barr Morgan , Marous Molly , Sledge Brigitte , Duke Jodi Kay , Armstrong April W. , Poon Emily , Veledar Emir , Dellavalle Robert P. , Alam Murad
Published: March 2019

BACKGROUND

Recent increase in skin biopsies has been attributed to an epidemic of skin cancer. This may be avoidable, with potential savings.

OBJECTIVE

To determine whether the increase in skin biopsies is attributable to increasing frequency of biopsies associated with histology lacking pathological cutaneous disease. Pathological cutaneous disease was defined as (1) a malignancy, precancerous lesion, or lesion of uncertain behavior; or (2) disease symptomatic or associated with adverse quality of life impact.

PATIENTS AND METHODS

Retrospective cohort study, 2006 to 2013 of dermatology practice serving Florida and Ohio. Data were a consecutive sample of skin biopsies for diagnosis of dermatologic disease.

RESULTS

A total of 267,706 biopsies by an average of 52 providers per month from January 06 to December 13 were analyzed. Number of biopsies per visit increased 2% per year (RR: 1.02, CI: 1.00–1.04). Likelihood of biopsy associated with histology indicative of nonpathological cutaneous disease did not increase over time (OR: 0.99, CI: 0.95–1.03, p = .6302).

CONCLUSION

Rates of biopsies associated with nonpathological cutaneous disease is not increasing. Overall biopsy rates per visit have gradually increased; this seems attributable to greater rates of detection of pathological dermatologic disease.
Safety Profile of Sclerosing Agents: An Analysis From the World Health Organization Pharmacovigilance Database VigiBase
Authors: Roselli Audrey , Khouri Charles , Roustit Matthieu , Blaise Sophie , Cracowski Jean-Luc
Published: March 2019

BACKGROUND

Several sclerosing agents are used to treat chronic venous diseases. Although they do not seem to differ in terms of efficacy, their safety profiles might differ.

OBJECTIVE

To compare the safety profile of sclerosing agents through an analysis of the World Health Organization pharmacovigilance database.

METHODS

The authors performed a disproportionality analysis using the proportional reporting ratio (PRR) method to compare pharmacovigilance signals between each sclerosing agent among 6 adverse event syndromes of interest: hypersensitivity reactions, arterial thromboembolic disorders, venous thromboembolic disorders, cardiac arrhythmias, visual/neurological disturbances, and skin ulcerations. The cutoff for signal detection was defined by a logPRR lower boundary 95% confidence interval (CI) ≥0 and number of cases n ≥3.

RESULTS

Of 1,227 Individual Case Safety Reports (ICSRs) identified, after removal of ICSRs with unselected indications, the authors selected 472 reports for the analysis. The authors found that polidocanol is associated with more reporting of venous embolic/thrombotic events (logPRR = 1.38 [95% CI 1.27–1.49]), ethanolamine with the higher pharmacovigilance disproportionality signal of cardiac arrhythmias (logPRR = 0.80 [95% CI 0.51–1.09]), and STS with more reporting of allergic reactions (logPRR = 1.79 [95% CI 1.59–1.98]).

CONCLUSION

The safety profile of sclerosing agents significantly differs and should guide benefit-risk ratio assessment of such agents.
Direct Oral Anticoagulants in Octogenarians With Atrial Fibrillation: It Is Never Too Late
Authors: Russo Vincenzo , Carbone Andreina , Rago Anna , Golino Paolo , Nigro Gerardo
Published: March 2019

Atrial fibrillation is the most common arrhythmia in clinical practice, and age is one of the strongest predictors/risk factors for ischemic stroke in patients with atrial fibrillation. Elderly patients, in particular patients aged 80 years and older, are at higher risk of both ischemic and bleeding events compared with younger patients. Vitamin K antagonists (VKAs) reduce the risk of ischemic stroke, especially in the elderly, but increase the bleeding risk. In addition, frequent international normalized ratio monitoring is needed to ensure the optimal level of anticoagulation. Furthermore, VKAs have multiple drug and food interactions. Direct oral anticoagulants (DOACs) have recently emerged as alternatives to VKAs and are gradually increasing their popularity mainly because of their fewer drug and food interactions and ease of use. Their effectiveness and safety have been well-established in the general population, but the benefit in the very elderly (≥80 years old) is still unclear. Data about the safety and the effectiveness of DOACs in patients older than 75 years are available in literature, but the evidences of the use of DOACs in patients aged 80 years and older are lacking. This review aims to give light to the differences, in terms of benefits and safety, of the DOACs in this subset of patients.
Allopurinol Administration for the Prevention of Contrast-Induced Nephropathy: A Network Meta-analysis With Trial Sequential Analysis
Authors: Bellos Ioannis , Iliopoulos Dimitrios C. , Perrea Despina N.
Published: March 2019

Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09–0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien–Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.
Individualized luteal phase support
Authors: Lawrenz Barbara , Coughlan Carol , Fatemi Human M.
Published: March 2019

Purpose of review

The aim of this review is to summarize the different aspects of luteal phase deficiency in IVF treatment and the possibilities of individualized luteal phase support.

Recent findings

After the application of human chorionic gonadotrophin (hCG) for final oocyte maturation, the vaginal route for progesterone administration is sufficient to maintain an adequate luteal phase support. New data point toward the possibility of oral medication; however, those data have yet to be confirmed in larger studies. Luteolysis after gonadotropinrealzing hormone (GnRH) agonist trigger is patient specific and not always severe. According to the progesterone level, individualized low dosages of hCG can be applied as luteal phase support without the risk of ovarian hyperstimulation syndrome (OHSS) development.

It is the task of the reproductive medicine specialist to individualize luteal phase support according to the patient's specific characteristics, needs and desires and the type of treatment performed. The greatest indication for individualization of the luteal phase is following GnRH agonist trigger in high responder patients in order to tailor luteal phase support to the patient-specific pattern of luteolysis and minimize the risk of causing OHSS with unnecessary high hCG dosages.
Treatment potential of bone marrow-derived stem cells in women with diminished ovarian reserves and premature ovarian failure
Authors: Herraiz Sonia , Pellicer Nuria , Romeu Mónica , Pellicer Antonio
Published: March 2019

Purpose of review

We review the techniques recently tested in both animal models and humans to provide a state-of-the-art on adult stem cell ovarian transplant to achieve ovarian rejuvenation in patients with diminished ovarian reserves.

Recent findings

As the firsts reports of spontaneous pregnancies achieved after bone marrow transplantation in oncologic women with primary ovarian insufficiency, increasing evidence supports the regenerative effects of stem cell-based therapies in the ovarian niche. Adult stem cells from several origins promote follicular development, increase ovarian local vascularization, increase follicle and stromal cell proliferation and reduce cell apoptosis and follicular atresia, although they do not modify embryo quality. Therefore, residual quiescent follicles of aged or damaged ovaries might produce competent oocytes in an adequate ovarian environment. Nevertheless, further research is needed to properly evaluate underlying mechanisms, identify best cell sources and design less invasive infusion techniques.

Stem cells may be a relevant therapeutic alternative for ovary regeneration and follicular development in patients with impaired ovaries, such as poor ovarian responders or women diagnosed with primary ovarian insufficiency.
Androgen supplementation in assisted reproduction: where are we in 2019?
Authors: Montoya-Botero Pedro , Rodriguez-Purata Jorge , Polyzos Nikolaos P.
Published: March 2019

Purpose of review

The purpose of this review is to provide an overview of androgen supplementation in ART with the most updated evidence, from animal studies to its clinical applications in poor ovarian responders (POR) and the future studies to be published.

Recent findings

Animal studies, has shown that testosterone supplementation, can be an option to increase the recruitable follicular pool in POR. However, the potential mechanism of action, dose, and duration of treatment is still under investigation. Early studies in humans reported promising results in favor of androgens [dehydroepiandrosterone (DHEA) or testosterone] in POR. Nevertheless, recent evidence does not appear to follow the initial results, whereas the type, dose, and duration of testosterone administration appear to be crucial for treatment effect.

Testosterone seems to play an essential role in regulating ovarian function. However, it is worrisome that androgens are used off-label, despite that the available evidence is weak. Although testosterone supplementation may be beneficial in POR, published studies have used inconsistent doses and duration of administration. An ongoing trial (T-TRANSPORT trial) for the first time aims to provide conclusive evidence on whether transdermal testosterone administration can improve the reproductive outcomes in patients undergoing IVF/ICSI.
Computation Speeds and Memory Requirements of Mesh-Type ICRP Reference Computational Phantoms in Geant4, MCNP6, and PHITS
Authors: Yeom Yeon Soo , Han Min Cheol , Choi Chansoo , Han Haegin , Shin Bangho , Furuta Takuya , Kim Chan Hyeong
Published: March 2019

Recently, Task Group 103 of the International Commission on Radiological Protection completed the development of new adult male and female mesh-type reference computational phantoms, which are planned for use in future International Commission on Radiological Protection dose coefficient calculations. In the present study, the performance of major Monte Carlo particle transport codes, i.e., Geant4, MCNP6, and PHITS, were investigated for the mesh-type reference computational phantoms by performing transport simulations of photons, electrons, neutrons, and helium ions for some external and internal exposures, and simultaneously measuring the memory usage, initialization time, and computation speed of the adult male mesh-type reference computational phantom in the codes. The measured results were then compared with the values measured with the current adult male voxel-type reference computational phantom in International Commission on Radiological Protection Publication 110 as well as five voxel phantoms produced from the adult male mesh-type reference computational phantom with different voxel resolutions, i.e., 0.1 × 0.1 × 0.1 mm3, 0.6 × 0.6 × 0.6 mm3, 1 × 1 × 1 mm3, 2 × 2 × 2 mm3, and 4 × 4 × 4 mm3. From the results, it was found that in all of the codes, the memory usage of the mesh-type reference computational phantom is greater than that of the voxel-type reference computational phantom and the lowest resolution voxelized phantom, but it is sufficiently lower than the maximum memory, 64 GB, that can be installed in a personal computer. The required initialization time of the mesh-type reference computational phantom and of the voxel-type reference computational phantom and voxelized phantoms in resolutions lower than 0.6 × 0.6 × 0.6 mm3 was less than a few minutes in all of the codes. As for the computation speed among the codes, MCNP6 showed the worst performance for the mesh-type reference computational phantom, which was slower than that for the voxel-type reference computational phantom by up to ~50 times and slower than that for all of the voxelized phantoms by up to ~40 times. By contrast, PHITS showed the best performance for the mesh-type reference computational phantom, which was faster than that for the voxel-type reference computational phantom by up to ~3 times and faster than that for all of the voxelized phantoms by up to ~20 times. This high performance of PHITS is indeed encouraging considering that it is used nowadays by the International Commission on Radiological Protection for most dose coefficient calculations.
Suicide in European Hodgkin Lymphoma Patients
Authors: Kim Austin I. , Goergen Helen , Engert Andreas , LaCasce Ann S. , Maranda Louise , Barton Bruce , Borchmann Sven
Published: March 2019

The purpose of this study was to determine whether there is an increased risk of suicide in European Hodgkin Lymphoma (HL) patients compared to the general European population.

European HL patients enrolled in the German Hodgkin Study Group (GHSG) HD7 through HD15 studies were analyzed and standardized mortality ratio (SMR) was calculated using suicide mortality rates for the general European population. Case‐control analysis was performed to identify characteristics associated with risk of death by suicide. Among 12,202 European HL patients observed for 94,972 person‐years, 19 suicides (17 males and 2 females) were identified resulting in a SMR 1.63 (95% CI: 1.01–2.50, p = 0.046). The only characteristic associated with a statistically significant increased risk of suicide was male sex with an odds ratio (OR) 8.42 (95% CI = 1.04–67.85; p = 0.046) on multivariate analysis. These findings were confirmed in an independently analyzed Surveillance, Epidemiology, and End Results Program (SEER) validation dataset. European HL patients have a significantly increased incidence of suicide compared to the general European population. Male HL patients have a greater than 8‐fold increased risk of suicide compared to female HL patients. Further study of social risk factors associated with an increased risk of suicide in HL patients is needed.
DETECTION OF CLINICALLY UNSUSPECTED RETINAL NEOVASCULARIZATION WITH WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY
Authors: You Qi Sheng , Guo Yukun , Wang Jie , Wei Xiang , Camino Acner , Zang Pengxiao , Flaxel Christina J. , Bailey Steven T. , Huang David , Jia Yali , Hwang Thomas S.
Published: March 2019

Purpose:

To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR).

Methods:

This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV.

Results:

Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm2 (range 0.17–0.54 mm2). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR.

Conclusion:

Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.
Management of Descemet Membrane's Folds After Deep Anterior Lamellar Keratoplasty: Descemet Membrane—Tucking Technique
Authors: Neri Alberto , Moramarco Antonio , Iovieno Alfonso , Fontana Luigi
Published: March 2019

Purpose:

To describe a surgical maneuver that allows for correction of central Descemet membrane (DM) folds at the end of a deep anterior lamellar keratoplasty (DALK) procedure. We term the present technique “DM tucking.”

Methods:

A blunt tip spatula is introduced vertically into the trephination cut, 90 degrees away from the main direction of the DM folds, and advanced until it touches the host layer. Gentle pressure is applied, resulting in tucking of the redundant host layer toward the periphery. The tucking maneuver is repeated at different clock hours until a regular graft–host interface is obtained.

Results:

We applied the present technique to several DALK procedures performed for keratoconus, and found it to be safe and effective.

Conclusions:

DALK is the procedure of choice for the surgical treatment of corneal stromal diseases with a healthy endothelium, such as keratoconus. DM folds are a possible complication after DALK in patients with advanced corneal ectasia, arising from the compression of the redundant host DM by the donor graft, once it is sutured to the recipient. DM folds after DALK, when they involve the visual axis, cause permanent visual disturbances DM tucking allows the displacement of the central DM folds toward the graft margin, where they do not affect the patient's quality of vision.
The Use of Conjunctival Staining to Measure Ocular Surface Inflammation in Patients With Dry Eye
Authors: Yang Soonwon , Lee Hyun Jung , Kim Da-Yeong , Shin Soojung , Barabino Stefano , Chung So-Hyang
Published: March 2019

Purpose:

To investigate the expression levels of inflammatory cytokines in the conjunctival epithelium and correlations with clinical parameters in dry eye disease (DED).

Methods:

This study evaluated 28 patients with Sjögren syndrome (SS) DED, 28 patients with non-SS DED, and 10 controls. The messenger ribonucleic acid (mRNA) expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, interferon (IFN)-γ, IL-17, and matrix metalloproteinase 9 (MMP9) from conjunctival epithelium was investigated by real-time polymerase chain reaction. Protein expression was confirmed by immunofluorescence staining. Correlations were evaluated between the mRNA expression of inflammatory cytokines and clinical DED parameters such as ocular surface disease index score, Schirmer I value, tear film breakup time, and corneal and conjunctival staining scores.

Results:

Patients with non-SS DED expressed significantly more IFN-γ, IL-6, and MMP9 genes in the conjunctival epithelium than the controls (P < 0.05), and all cytokine gene expression was significantly higher in patients with SS DED than in the controls (P < 0.01). Tumor necrosis factor-α, IL-1β, IL-6, and IL-17 gene expression was higher in patients with SS DED than in the non-SS DED group (P < 0.05). Immunofluorescence staining of conjunctival epithelium demonstrated that positive cells with IL-6 or MMP9 were significantly higher in non-SS DED than in controls (P < 0.01) and much higher in SS DED than in non-SS DED (P < 0.05). Conjunctival staining scores significantly correlated with the expression of IFN-γ, IL-6, IL-17, and MMP9 in both DED groups (P < 0.05 in non-SS DED and P < 0.01 in SS-DED). Interestingly, correlation coefficients of all cytokines were much higher in SS DED compared to non-SS DED. Corneal staining scores showed positive correlations with IFN-γ, IL-17, and MMP9 (P < 0.05), and correlation coefficients were lower than those of conjunctival staining scores.

Conclusions:

Conjunctival staining scores may be useful to measure ocular surface inflammation in SS and non-SS DED.
Outcomes of gefitinib therapy for disease recurrence in medically inoperable stage I lung adenocarcinoma patients with active EGFR mutations receiving stereotactic body radiotherapy: a single-institute retrospective study
Authors: Kashiwabara Kosuke , Semba Hiroshi , Fujii Shinji , Tsumura Shinsuke
Published: March 2019

Introduction:

Anticancer therapy for disease recurrence in medically inoperable stage I lung adenocarcinoma patients receiving stereotactic body radiotherapy (SBRT) has not been previously reported. Gefitinib is tolerable and effective in patients with active epidermal growth factor receptor (EGFR) mutations who have an advanced age and/or a low performance status, but whether gefitinib improves the survival of such patients with disease recurrence after SBRT remains unclear.

Patients and methods:

We retrospectively evaluated overall survival after disease recurrence in patients with active EGFR mutations who received gefitinib (GEF group) and patients without active EGFR mutations who did not receive gefitinib (non-GEF group).

Results:

During a follow-up period with a median time of 36.0 months, disease recurrence occurred in 10 of 20 patients with medically inoperable stage I lung adenocarcinoma who received SBRT (2 cases with local tumor recurrence alone and 8 cases with lymph node and/or distant metastasis). The median age or the median Charlson comorbidity index score were 84 years and 2 in the GEF group (n=4) and 81 years and 2 in the non-GEF group (n=6), respectively. Two cases in the GEF group received chemotherapy after first-line gefitinib therapy. Two cases in the non-GEF group received chemotherapy, but the others received best supportive care alone. The median overall survival time from disease recurrence was significantly different between the 2 groups (27.3 vs. 3.6 mo, P=0.038). Two cases with grade 2 radiation pneumonitis did not have a recurrence of pneumonitis during gefitinib therapy.

Conclusions:

Gefitinib might be useful as a salvage therapy in patients who desire to continue anticancer treatment.
Optical Coherence Tomography Segmentation Errors of the Retinal Nerve Fiber Layer Persist Over Time
Authors: Nagarkatti-Gude Nisha , Gardiner Stuart K. , Fortune Brad , Demirel Shaban , Mansberger Steven L.
Published: March 2019

Précis:

There are errors in automated segmentation of the retinal nerve fiber layer (RNFL) in glaucoma suspects or patients with mild glaucoma that appear to persist over time; however, automated segmentation has greater repeatability than manual segmentation.

Purpose:

To identify whether optical coherence tomography (OCT) segmentation errors in RNFL thickness measurements persist longitudinally.

Methods:

This was a cohort study. We used spectral domain OCT (Spectralis) to measure RNFL thickness in a 6-degree peripapillary circle, and exported the native “automated segmentation only” results. In addition, we exported RNFL thickness results after “manual refinement” to correct errors in the automated segmentation, and used the differences in these measurements as “error” in segmentation. We used Bland-Altman plots and linear regression to determine the magnitude, location, and repeatability of RNFL thickness error in all twelve 30-degree sectors and compared the error at baseline to follow-up time points at 6 months, 2 years, 3 years, and 4 years.

Results:

We included 406 eyes from 213 participants. The 95% confidence interval for errors at baseline was −6.5 to +13.2 μm. The correlation between the baseline error and the errors in the follow-up time periods were high (r>0.5, P<0.001 for all). Automated segmentation had a smaller SD of residuals from the longitudinal trend line when compared to manual refinement (1.56 vs. 1.80 μm, P<0.001), and a higher ability (P=0.009) to monitor progression using an analysis of a longitudinal signal-to-noise ratio.

Conclusions:

Errors in automated segmentation remain relatively stable, and baseline error is highly likely to persist in the same direction and magnitude in subsequent time periods. However, automated segmentation (without manual refinement) is more repeatable and may be more sensitive to glaucomatous progression. Future segmentation algorithms could exploit these findings to improve automated segmentation in the future.
Suture Removal After Trabeculectomy With Fornix-based Conjunctival Flap Leads to Faster Visual Recovery but Not Reduced Astigmatism
Authors: Laspas Panagiotis , Leichsenring Verena , Hoffmann Esther , Preussner Rolf , Wahl Jochen , Pfeiffer Norbert
Published: March 2019

Précis:

The closing limbal suture after trabeculectomy with a fornix-based conjunctival flap plays no critical role in the development of corneal astigmatism and intraocular pressure (IOP). A standard removal is not recommended.

Purpose:

To investigate the effect of removal of the conjunctival suture after trabeculectomy with fornix-based conjunctival flap on corneal astigmatism, visual acuity, and IOP.

Methods:

Eighty-seven cases of trabeculectomy with mitomycin C with a fornix-based conjunctival flap performed in the eyes of 82 patients (5 patients underwent bilateral trabeculectomy) were enrolled in a prospective randomized study. All surgeries were conducted by the same surgeon (J.W.) in the Ophthalmology Department of the University Medical Center of Mainz, Germany. All eyes received a corneal-conjunctival, continuous, mattress, interlocked suture for closing the conjunctiva at the limbus. After randomization, in 46 cases the suture was removed 6 weeks postoperatively; in 41 patients, the suture was left in place. All patients were examined preoperatively, and at 6 weeks, 3 months, 6 months, and 12 months after surgery. Astigmatism was measured using objective refraction and corneal topography, IOP and visual acuity were also assessed. Results were compared using a Wilcoxon test or Mann-Whitney U test for single time-points.

Results:

During follow-up, no significant differences between the 2 study groups regarding refractive or topographic values were found. Patients in the suture removal group had a significantly higher visual acuity than controls at 3 months, 6 months, and 1 year after surgery. IOP was similar in both groups throughout the study.

Conclusions:

Removal of the conjunctival suture in trabeculectomy with a fornix-based conjunctival flap leads to a faster rehabilitation of visual acuity but does not significantly affect corneal astigmatism or IOP.
The Sutureless Mullerectomy
Authors: Gildener-Leapman Juliana R. , Sheps Iyar , Stein Ran , Benyamini Oren , Milstein Asher , Hartstein Morris E.
Published: March 2019

Purpose:

Müller’s muscle-conjunctival resection (MMCR) is a well-known approach for ptosis repair. In its standard fashion, it involves resection of Müller’s muscle and conjunctiva, followed by suturing of the conjunctiva and Müller’s muscle to the tarsus with absorbable or nonabsorbable sutures. The authors herein present their experience in performing MMCR without sutures.

Methods:

The study was conducted as a retrospective review of 19 patients (34 eyelids) undergoing sutureless MMCR. Thirty-three eyelids had acquired ptosis and 1 eyelid had congenital ptosis. Surgery consisted of a standard approach and placement of a Putterman clamp. Following excision of the clamped tissues, no internal sutures were placed. Preoperative and postoperative upper margin-to-reflex distances were measured and patients were evaluated for symmetry within 1 mm and the incidence of any complications.

Results:

Nineteen patients underwent 34 sutureless MMCR procedures. Of these, 13 patients had bilateral ptosis repair. Thirty-three of 34 eyelids (97%) showed improvement in margin-to-reflex distances, with an average improvement of 1.4 mm (range, 0–3.5 mm, SD = 0.64) among all patients. Eighteen of the 19 patients (94.7%) showed postoperative symmetry of margin-to-reflex distances within 1 mm (p < 0.001, χ2 test). One patient who underwent unilateral surgery demonstrated a Herring’s response postoperatively, leading to the single case of asymmetry. There was 1 case of corneal abrasion seen postoperatively.

Conclusions:

The sutureless technique is a rapid and effective method for performing MMCR. This technique is especially useful as an adjunct to blepharoplasty where mild ptosis exists for an added rejuvenating effect. It is low-risk and potentially corneoprotective when compared to the standard suture technique. Further studies could determine if a modified algorithm needs to be applied.
Haploinsufficiency of the brain-derived neurotrophic factor gene is associated with reduced pain sensitivity
Authors: Sapio Matthew R. , Iadarola Michael J. , LaPaglia Danielle M. , Lehky Tanya , Thurm Audrey E. , Danley Kristen M. , Fuhr Shannon R. , Lee Mark D. , Huey Amanda E. , Sharp Stephen J. , Tsao Jack W. , Yanovski Jack A. , Mannes Andrew J. , Han Joan C.
Published: March 2019

Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents. Nociceptive responses assessed by quantitative sensory testing demonstrated reduced pain sensitivity only in the WAGR subjects whose deletion boundaries included the BDNF gene. Corresponding behavioral assessments were made in heterozygous Bdnf knockout rats to examine the specific role of Bdnf. These analogous experiments revealed impairment of Aδ- and C-fiber-mediated heat nociception, determined by acute nociceptive thermal stimuli, and in aversive behaviors evoked when the rats were placed on a hot plate. Similar results were obtained for C-fiber-mediated cold responses and cold avoidance on a cold-plate device. Together, these results suggested a blunted responsiveness to aversive stimuli. Our parallel observations in humans and rats show that hemizygous deletion of the BDNF gene reduces pain sensitivity and establishes BDNF as a determinant of nociceptive sensitivity.