bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal and Peripartum Outcomes in Vanishing Twin Pregnancies Achieved by In Vitro Fertilization
Authors: Romanski Phillip A. , Carusi Daniela A. , Farland Leslie V. , Missmer Stacey A. , Kaser Daniel J. , Walsh Brian W. , Racowsky Catherine , Brady Paula C.
Published: May 2018

OBJECTIVE:

To compare perinatal and peripartum outcomes of vanishing twin gestations with singleton and dichorionic twin gestations in pregnancies conceived by in vitro fertilization.

METHODS:

We conducted a retrospective cohort study of vanishing twin pregnancies after fresh and cryopreserved autologous in vitro fertilization cycles performed at our institution from 2007 to 2015. Singleton, dichorionic twin, and dichorionic twin pregnancies with spontaneous reduction to one by 14 weeks of gestation (vanishing twins) were included. Analysis was restricted to patients with a live birth delivery at our institution at or beyond 24 weeks of gestation. The primary outcomes were gestational age and birth weight at delivery; secondary outcomes included peripartum morbidities. A subanalysis further differentiated the vanishing twin pregnancies between those in which demise of the twin occurred before compared with after identification of fetal cardiac activity. Logistic regression models were used to estimate the adjusted odds ratio (OR) with a 95% CI of outcomes.

RESULTS:

There were 1,189 pregnancies that met inclusion criteria (798 singleton, 291 twin, and 100 vanishing twin). The mean gestational age at birth and birth weights were 38.6±2.3 weeks of gestation and 3,207±644 g in singleton pregnancies, 35.5±2.7 weeks of gestation and 2,539±610 g in twin pregnancies, and 38.5±1.8 weeks of gestation and 3,175±599 g in vanishing twin pregnancies. When compared with twins, those with a vanishing twin had lower odds of preterm delivery (OR 0.13, 95% CI 0.07–0.23; adjusted OR 0.12, 95% CI 0.07–0.22) and small-for-gestational-age birth weight (OR 0.24, 95% CI 0.13–0.45; adjusted OR 0.14, 95% CI 0.07–0.28).

CONCLUSION:

In pregnancies conceived by in vitro fertilization that progress to at least 24 weeks of gestation, vanishing twin and singleton pregnancies had similar perinatal and peripartum outcomes. Both were significantly better than twin pregnancies.
Trends in Use and Survival Associated With Fertility-Sparing Trachelectomy for Young Women With Early-Stage Cervical Cancer
Authors: Cui Rosa R. , Chen Ling , Tergas Ana I. , Hou June Y. , St. Clair Caryn M. , Neugut Alfred I. , Ananth Cande V. , Hershman Dawn L. , Wright Jason D.
Published: May 2018

OBJECTIVE:

To assess the trends in use of trachelectomy in the United States and to examine the outcomes of the procedure compared with hysterectomy in young women with cervical cancer.

METHODS:

Data were analyzed from women younger than 50 years of age with stage IA2–IB2 cervical cancer treated with hysterectomy or trachelectomy from 2004 to 2014 who were registered in the National Cancer Database. After propensity score matching, we used Cox proportional hazard models to examine the association between treatment and survival.

RESULTS:

We identified 15,150 patients with cervical cancer, including 14,714 (97.1%) who underwent hysterectomy and 436 (2.9%) who underwent trachelectomy. Trachelectomy rates increased from 1.5% in 2004 to 3.8% by 2014 (P<.001). The greatest increase in the rate of trachelectomy was seen in women younger than 30 years of age (4.6% in 2004 to 17.0% in 2014, P<.001). Among women who underwent trachelectomy, 29.6% had tumors greater than 2 cm in diameter. In a multivariable model, younger women and those more recently diagnosed were more likely to undergo trachelectomy, whereas Medicaid recipients (risk ratio 0.39, 95% CI 0.28–0.54) and the uninsured (risk ratio 0.67, 95% CI 0.45–1.00) were less likely to undergo trachelectomy. After propensity score matching, there was no association between trachelectomy and the risk of mortality (hazard ratio 1.24, 95% CI 0.70–2.22) (mortality rate was 6.0% for hysterectomy vs 5.2% for trachelectomy). Similarly, 5-year survival rates were similar between trachelectomy and hysterectomy for all of the stages examined.

CONCLUSIONS:

Use of trachelectomy for early-stage cervical cancer has increased in the United States, particularly among women younger than 30 years of age. Within this population, survival is similar for trachelectomy and hysterectomy.
Total Laparoscopic Hysterectomy Under Regional Anesthesia
Authors: Moawad Nash S. , Santamaria Flores Estefania , Le-Wendling Linda , Sumner Martina T. , Enneking F. Kayser
Published: May 2018

BACKGROUND:

Laparoscopic hysterectomies comprise a large proportion of all hysterectomies in the United States. Procedures completed under regional anesthesia pose a number of benefits to patients, but laparoscopic hysterectomies traditionally have been performed under general anesthesia. We describe a case of total laparoscopic hysterectomy under epidural anesthesia with the patient fully awake.

CASE:

A 51-year-old woman with abnormal uterine bleeding underwent an uncomplicated total laparoscopic hysterectomy, bilateral salpingectomy, and excision of endometriosis. The procedure was completed under epidural anesthesia without intravenous sedation or systemic narcotics. Pneumoperitoneum with a pressure of 12 mm Hg and Trendelenburg to 15° allowed for adequate visualization. Anesthesia was achieved with midthoracic and low lumbar epidural catheters. Bilevel positive airway pressure was used for augmentation of respiratory function.

CONCLUSION:

With a committed patient, adequate planning, and knowledge of the potential intraoperative complications, regional anesthesia is an option for select women undergoing laparoscopic hysterectomy.
Risk of Gynecologic Cancer According to the Type of Endometriosis
Authors: Saavalainen Liisu , Lassus Heini , But Anna , Tiitinen Aila , Härkki Päivi , Gissler Mika , Pukkala Eero , Heikinheimo Oskari
Published: May 2018

OBJECTIVE:

To assess the risks of gynecologic cancer according to the type of endometriosis in women with surgically verified endometriosis.

METHODS:

This is a population-based study of women with surgically verified endometriosis retrieved from the Finnish Hospital Discharge Register 1987–2012 (N=49,933); the subtypes of ovarian (n=23,210), peritoneal (n=20,187), and deep infiltrating (n=2,372) endometriosis were analyzed separately. Gynecologic cancers were obtained from the Finnish Cancer Registry. The outcome measure was the standardized incidence ratio (95% CI) calculated as the ratio between the observed to the expected number of cancers and defined for each gynecologic cancer and further stratified according to the histology, follow-up time since surgery, and age at follow-up. The follow-up was 838,685 person-years, and the Finnish female population served as the reference.

RESULTS:

Endometriosis was associated with increased risk of ovarian cancer (standardized incidence ratio 1.76 [95% CI 1.47–2.08]), especially with endometrioid (3.12 [2.15–4.38]) and clear cell (5.17 [3.20–7.89]) histologic type and to a lesser extent with serous type (1.37 [1.02–1.80]). The risk of ovarian cancer was highest among women with ovarian endometriosis and especially for endometrioid (4.72 [2.75–7.56]) and clear cell (10.1 [5.50–16.9]) ovarian cancer, occurring 5–10 years after the index surgery. The overall risk of ovarian cancer was not increased among women with peritoneal and deep infiltrating endometriosis. However, peritoneal endometriosis was associated with a twofold increase in risk of endometrioid histology. The risk of endometrial cancer was not altered in the entire cohort. The standardized incidence ratio for precancerous cervical lesions was 0.81 (0.71–0.92) and for invasive squamous cell carcinoma of the cervical cancer 0.46 (0.20–0.91).

CONCLUSION:

The excess risk of ovarian cancer among women with ovarian endometriosis translates into two excess cases per 1,000 patients followed for 10 years. Acknowledging these risks is important when planning long-term management of women with endometriosis.
A Comparison of Adjuvant Techniques on Setting Time of Octyl-2-Cyanoacrylate (DERMABOND Advanced)
Authors: Niedermeier Steven R. , Balch Samora Julie
Published: May 2018

Octyl-2-cyanoacrylate is a topical skin adhesive (TSA) that has gained popularity over the last decade for wound and incisional wound closure. TSAs have been used with or without suture when closing lacerations or operative incisions. One brand of octyl-2-cyanoacrylate, DERMABOND, was shown to have high wound bursting strength and tensile force, large number of normal tensile loading cycles to failure, long time to failure, and short setting time. Many intraoperative methods have been used by surgical staff in an effort to reduce curing time (ie, time for the tissue adhesive to set), including waving a hand or towels over the incision or bringing the operating room lights into closer proximity to the wound. Two investigators applied the TSA to their own volar forearms and measured the time to complete dryness in the operative room. A total of 112 applications of DERMABOND was performed and recorded at 1 mm TSA thickness (n=56) and at 2 mm TSA thickness (n=56). Mean drying times from each group and subgroup were calculated and compared using student’sttest and multivariate analysis. We found that no adjuvant methods commonly used in the operating room to speed up drying times were effective. If DERMABOND is utilized for wounds and surgical closure, we recommend applying only a thin layer utilizing the small applicator for more expeditious setting times and cost-effectiveness.
The impact of patient characteristics and disease-specific factors on first-line treatment decisions for BRAF-mutated melanoma: results from a European expert panel study
Authors: Ascierto Paolo A. , Bastholt Lars , Ferrucci Pier F. , Hansson Johan , Márquez Rodas Iván , Payne Miranda , Robert Caroline , Thomas Luc , Utikal Jochen S. , Wolter Pascal , Kudlac Amber , Tuson Harriet , McKendrick Jan
Published: May 2018

Treatment decisions for advanced melanoma are increasingly complex and guidelines provide limited advice on how to choose between immunotherapy and targeted therapy for first-line treatment. A Delphi study was carried out to understand which patient characteristics and disease-related factors inform clinicians’ choices of first-line treatment for BRAF-mutated melanoma. Twelve European melanoma specialists experienced in using immunotherapies and targeted agents participated in a double-blind two-phase Delphi study. In phase 1, participants completed a questionnaire developed after reviewing patient characteristics and disease-related factors reported in trials, clinical guidelines, and health technology assessments. Phase 2 was an expert panel meeting to explore outstanding issues from phase 1 and seek consensus, defined as 80% agreement. Twenty patient-related and disease-related characteristics were considered. There was consensus that tumor burden (83% of clinicians) and disease tempo (83%) are very or extremely important factors when selecting first-line treatment. Several components were deemed important when assessing tumor burden: brain metastases (82% of clinicians) and location of metastases (89%). There was consensus that disease tempo can be quantified in clinical practice, but not on a formal classification applicable to all patients. Lactate dehydrogenase level is a component of both tumor burden and disease tempo; all clinicians considered lactate dehydrogenase important when choosing first-line treatment. The majority (92%) did not routinely test programmed death ligand-1 status in patients with melanoma. Clinicians agreed that choosing a first-line treatment for advanced melanoma is a complex, multifactorial process and that clinical judgment remains the most important element of decision-making until research can provide clinicians with better scientific parameters and tools for first-line decision-making.
Gastrointestinal Bleeding During Continuous-Flow Left Ventricular Assist Device Support
Authors: Kataria Rachna , Jorde Ulrich P.
Published: May 2018

Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used for the management of advanced heart failure refractory to optimal medical therapy. Despite the encouraging outcomes with CF-LVADs, gastrointestinal bleeding (GIB) continues to be a rather concerning complication resulting in increased rates of readmission and increased morbidity. The exact pathophysiology of CF-LVAD-associated GIB remains poorly understood, and this lack of knowledge limits our ability to control this morbid complication. What is clear, however, is that the majority of GIB episodes in LVAD patients are due to fragile GI arteriovenous malformations or angiodysplasias, in the setting of CF-LVAD-associated acquired von Willebrand syndrome. We will, herein, appraise the proposed interactions between different pathophysiological processes thought to be causing angiodysplasias and GIB in patients on CF-LVAD support.
PD-L1 Expression is Increased in Metastasizing Squamous Cell Carcinomas and Their Metastases
Authors: García-Díez Irene , Hernández-Ruiz Eugenia , Andrades Evelyn , Gimeno Javier , Ferrándiz-Pulido Carla , Yébenes Mireia , García-Patos Vicenç , Pujol Ramón M. , Hernández-Muñoz Inmaculada , Toll Agustí
Published: May 2018

Programmed cell death ligand 1 (PD-L1) expression by tumor cells plays an important role in the inhibition of T cell–mediated immune response in cancer. PD-L1 expression by tumor cells has been linked to poor prognosis in a wide variety of cancers. However, PD-L1 expression in cutaneous squamous cell carcinoma (cSCC) has been scarcely studied, and its role as a prognosis biomarker remains controversial. The association of PD-L1 expression and the metastatic risk in a series of cSCC was assessed. PD-L1 and CD8 immunostainings of full excision sections of 99 primary tumors and 24 lymphatic metastases were semiquantitatively evaluated. Primary cSCCs were grouped according to the development of lymphatic metastatic spread [metastasizing squamous cell carcinoma (MSCC)] (n = 48) or the absence of progression [nonmetastasizing squamous cell carcinoma (NMSCC)] (n = 51). PD-L1–positive expression (cut off ≥1%) was found in 26% NMSCCs and in 50% MSCCs (P = 0.02). PD-L1 association with an increased metastatic risk was confirmed in the multivariate analysis (P < 0.05), along with the following features: recurrence, poor differentiation, and perineural invasion. Ninety percent of the metastases of PD-L1–positive tumors were also positive for PD-L1, displaying a trend toward a higher PD-L1 expression when compared with their primary tumors (P = 0.058). No significant differences in the peritumoral inflammatory infiltrate or in the expression of CD8 were found between metastasizing and nonmetastasizing primary tumors. Our results suggest that PD-L1 may play a relevant role in metastatic spread and may be a candidate prognostic biomarker in cSCC.
Two Cases of Chronic Candidiasis in Keratitis–Ichthyosis–Deafness Syndrome
Authors: Bartenstein Diana , Chung Hye Jin , Hussain Sadaf
Published: May 2018

Keratitis–ichthyosis–deafness (KID) syndrome is a rare genodermatosis that typically results from mutations of the GJB2 gene or, less commonly, the GJB6 gene. Patients with KID syndrome are at higher risk of malignancy and infections. Here, we present 2 patients with KID syndrome who developed verrucous plaques. Given that patients with KID syndrome are at high risk of developing squamous cell carcinoma, biopsies were performed. Both cases revealed histologic findings of marked papillomatous epidermal hyperplasia with numerous fungal spores and pseudohyphae in the stratum corneum. For one case, daily oral fluconazole was initiated. The patient demonstrated dramatic resolution of his foot plaques over the course of 2 years. These cases highlight that, for the dermatopathologist, chronic fungal infection should be sought for verrucous plaques in patients with KID syndrome as, if present, this finding may alter treatment and quality of life.
Impact of Mohs Micrographic Surgery on Tumor Staging of Cutaneous Squamous Cell Carcinoma: A Comparison of the 7th and 8th Editions of the American Joint Committee on Cancer Guidelines
Authors: Montuno Michael A. , Brown Brandon , Konda Sailesh , Motaparthi Kiran
Published: May 2018

BACKGROUND

Based on current AJCC-7 guidelines for staging cutaneous squamous cell carcinoma (cSCC), patients with T2 tumor staging represent a prognostically heterogeneous group. The new AJCC-8 guidelines seek to provide improved stratification by inclusion of independent risk factors in the T3 category. These features may be identified in tissue stages during Mohs micrographic surgery (MMS). Thus, low-risk cSCC may be upstaged after MMS, impacting prognosis, additional evaluation, and adjuvant nonsurgical treatment.

OBJECTIVE

To examine the impact of MMS on cSCC staging under AJCC-7 and AJCC-8 guidelines.

MATERIALS AND METHODS

The medical record was queried for patients who underwent MMS for cSCC. Data were recorded for 190 MMS specimens and corresponding biopsies. Tumor staging according to AJCC-7 and AJCC-8 was assigned.

RESULTS

High-risk histologic features are more likely identified with MMS than biopsies. Cutaneous squamous cell carcinoma was equally likely to be upstaged during MMS under both AJCC-7 and AJCC-8, with 10.5% being classified as AJCC-8 T3. Seventy percent of these were only classified as T3 after MMS. Upstaging to T3 during MMS under AJCC-8 is less likely than upstaging to T2 under AJCC-7.

CONCLUSION

Mohs surgeons have a significant impact on accurate staging of high-risk cSCC. AJCC-8 improves risk stratification of cSCC.
A Comparison Study of the Nonablative Fractional 1565-nm Er:glass and the Picosecond Fractional 1064/532-nm Nd:YAG Lasers in the Treatment of Striae Alba: A Split Body Double-Blinded Trial
Authors: Zaleski-Larsen Lisa A. , Jones Isabela T. , Guiha Isabella , Wu Douglas C. , Goldman Mitchel P.
Published: May 2018

BACKGROUND

Few effective treatments exist for striae alba, which are the mature stage of stretch marks.

OBJECTIVE

To evaluate the efficacy of the nonablative fractional 1,565-nm Erbium-glass (Er:glass) and the picosecond fractional 1,064/532-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers in the treatment of striae alba.

MATERIALS AND METHODS

Twenty subjects with striae alba on the bilateral abdomen were treated with either the nonablative fractional 1565-nm Er:glass or the picosecond fractional 1,064/532-nm Nd:YAG laser, with a total of 3 treatments 3 weeks apart.

RESULTS

A 31% (1.25/4) texture improvement was noted for both the fractional 1,565-nm Er:glass laser and the picosecond fractional 1,064/532-nm Nd:YAG laser. The degree of atrophy was improved by 30% (1.19/4) with the 1,565-nm Er:glass laser and 35% (1.38/4) with the picosecond 1,064/532-nm Nd:YAG laser. A 48% (1.9/4) subject overall assessment of improvement was noted with the fractional 1565-nm Er:glass laser and 45% (1.8/4) improvement with the picosecond fractional 1,064/532-nm Nd:YAG laser. There was no significant change in striae density with either laser. The picosecond laser was rated as less painful during all 3 sessions (p = .002) and had a shorter healing time (p = .035). The nonablative fractional 1,565-nm Er:glass and the picosecond fractional 1,064/532-nm Nd:YAG lasers were equally efficacious in improving striae alba.
Survival-related Selection Bias in Studies of Racial Health Disparities
Authors: Howe Chanelle J. , Robinson Whitney R.
Published: May 2018

The impact of survival-related selection bias has not always been discussed in relevant studies of racial health disparities. Moreover, the analytic approaches most frequently employed in the epidemiologic literature to minimize selection bias are difficult to implement appropriately in racial disparities research. This difficulty stems from the fact that frequently employed analytic techniques require that common causes of survival and the outcome are accurately measured. Unfortunately, such common causes are often unmeasured or poorly measured in racial health disparities studies. In the absence of accurate measures of the aforementioned common causes, redefining the target population or changing the study design represents a useful approach for reducing the extent of survival-related selection bias. To help researchers recognize and minimize survival-related selection bias in racial health disparities studies, we illustrate the aforementioned selection bias and how redefining the target population or changing the study design can be useful.
Pharmacokinetics of Doripenem in Healthy Koreans and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients With Normal and Enhanced Renal Function
Authors: Kim So Won , Choe Sangmin , Kim Dong Jin , Zang Dae Young , Lee Dong-Hwan
Published: May 2018

Background:

Dose adjustment is often required in patients with normal or enhanced renal function. The aim of this study is to investigate the pharmacokinetic (PK) properties of doripenem and explore optimal dosing regimens in patients with normal or enhanced renal function according to various minimum inhibitory concentrations (MICs).

Methods:

The authors conducted a clinical trial and analyzed PK samples in 11 healthy Korean subjects applying noncompartmental analysis and a population approach. The population PK parameter estimates were used in Monte Carlo simulations to explore optimal dosing regimens for a probability of target attainment of 90% at 40% fTMIC (free drug concentrations above MIC).

Results:

The time course of doripenem concentrations was well described by a 2-compartment model. The population typical values of clearance and steady-state volume were 22.9 L/h and 19.1 L, respectively, and were consistent with our noncompartmental analysis results. When the MIC was greater than 1 mcg/mL, at least increasing the dose or prolonging the infusion time was essential in patients with normal or enhanced renal function.

Conclusions:

These results suggest that dosage adjustment such as increasing the dose or lengthening the infusion time should be considered in patients with normal or enhanced renal function.
Impact of Drug Interactions on Clobazam and N-Desmethylclobazam Concentrations in Pediatric Patients With Epilepsy
Authors: Russell Gabrielle R. , Phelps Stephanie J. , Shelton Chasity M. , Wheless James W.
Published: May 2018

Background:

Clobazam (CLB) is approved as adjunctive treatment for seizures associated with Lennox–Gastaut syndrome in patients aged 2 years and older. It is converted to an active metabolite N-desmethylclobazam (NCLB) by CYP3A4, which is then broken down to an inactive metabolite by CYP2C19. This study characterizes the impact of CYP3A4 and CYP2C19 drug interactions on CLB and NCLB serum concentrations (Cp) and concentration/dose (Cp/D) ratios in pediatric patients with epilepsy.

Methods:

This was a retrospective chart review including patients older than 1 month, who received CLB between April 2012 and March 2017. Extracted data included patient demographics, CLB daily dose, CLB and NCLB Cp, calculated CLB and NCLB Cp/Cp and Cp/D ratios, and all concomitant drugs.

Results:

The study included 995 CLB concentration sets from 302 patients (median age 7.6 years and range 0.2–40.1 years). Pharmacokinetic variability was extensive, as seen by widespread ranges of CLB and NCLB Cp, NCLB/CLB Cp ratio, and 3 Cp/D ratios (CLB, NCLB, and CLB + NCLB). Comedications, described as CYP3A4 inducers and/or CYP2C19 inhibitors (carbamazepine, eslicarbazepine, felbamate, (fos)phenytoin, oxcarbazepine, pentobarbital, phenobarbital, rufinamide, and topiramate), generally increased NCLB/CLB Cp ratio (267%–400%), NCLB Cp/D ratio (167%–202%), and CLB + NCLB Cp/D ratio (142%–185%) and decreased CLB Cp/D ratio (47%–76%) compared with a group of concentration sets in patients receiving only neutral comedications (P < 0.025 for all comparisons). Older age was associated with higher Cp/D ratios (mg/kg), indicative of decreased clearance.

Conclusions:

Pharmacokinetic variability of CLB in pediatric patients is extensive, and it is influenced by drug–drug interactions and age. Therapeutic drug monitoring of CLB and active metabolite NCLB with calculation of various Cp/Cp and Cp/D ratios can provide useful insight into CLB pharmacokinetics and help differentiate between causes of variability.
Hormone Therapy in Breast Cancer Survivors and Those at High Risk for Breast Cancer
Authors: REID ROBERT L.
Published: May 2018

Women and health care providers are often fearful of using hormone therapy to deal with distressing menopausal symptoms in circumstances where there is a perceived or real increased risk of breast cancer. This paper examines the evidence for and against hormone therapy use in 3 common clinical situations: the woman with a positive family history in a first-degree relative, the woman who has undergone risk-reducing salpingo-oophorectomy due to a known genetic mutation, and the woman in whom treatment of breast cancer has induced premature menopause.
The effects of emotional intelligence training on the job performance of Australian aged care workers
Authors: Karimi Leila , Leggat Sandra G. , Bartram Timothy , Rada Jiri
Published: May 2018

Background:

Emotional intelligence (EI) training is popular among human resource practitioners, but there is limited evidence of the impact of such training on health care workers.

Purpose:

In the current article, we examine the effects of EI training on quality of resident care and worker well-being and psychological empowerment in an Australian aged care facility. We use Bar-On’s (1997) conceptualization of EI.

Methodology/Approach:

We used a quasiexperimental design in 2014–2015 with experimental (training) and control (nontraining) groups of 60 participants in each group in two geographically separate facilities. Our final poststudy sample size was 27 participants for the training group and 17 participants for the control group. Over a 6-month period, we examined whether staff improved their well-being, psychological empowerment, and job performance measured as enhanced quality of care (self-rated and client-rated) by applying skills in EI.

Results:

The results showed significant improvement among workers in the training group for EI scores, quality of care, general well-being, and psychological empowerment. There were no significant differences for the control group.

Practice Implications:

Through examining the impact of EI training on staff and residents of an aged care facility, we demonstrate the benefits of EI training for higher quality of care delivery. This study demonstrates the practical process through which EI training can improve the work experiences of aged care workers, as well as the quality of care for residents.
Evaluating Plutonium Intake and Radiation Dose Following Extensive Chelation Treatment
Authors: Dumit Sara , Avtandilashvili Maia , Tolmachev Sergei Y.
Published: May 2018

A voluntary partial-body donor (US Transuranium and Uranium Registries case 0785) was accidentally exposed to 239Pu via inhalation and wounds. This individual underwent medical treatment including wound excision and extensive chelation treatment with calcium ethylenediaminetetraacetic acid and calcium diethylenetriaminepentaacetic acid. Approximately 2.2 kBq of 239Pu was measured in the wound site 44 y after the accident. Major soft tissues and selected bones were collected at autopsy and radiochemically analyzed for 238Pu, 239Pu, and 241Am. Postmortem systemic retention of 238Pu, 239Pu, and 241Am was estimated to be 32.0 ± 1.4 Bq, 2,172 ± 70 Bq, and 394 ± 15 Bq, respectively. Approximately 3% of 239Pu whole-body activity was still retained in the lungs 51 y after the accident indicating exposure to insoluble plutonium material. To estimate the intake and calculate radiation dose, urine measurements not affected by chelation treatment, in vivo chest counts, and postmortem radiochemical analysis data were simultaneously fitted using Integrated Modules for Bioassay Analysis Professional Plus software. The currently recommended International Commission on Radiological Protection Publication 130 human respiratory tract model and National Council on Radiation Protection and Measurements Report 156 wound model were used with default parameters. The intake, adjusted for 239Pu removed by chelation treatment, was estimated at approximately 79.5 kBq with 68% resulting from inhalation and 32% from the wound. Inhaled plutonium was predominantly insoluble type S material (74%) with insoluble plutonium fragments deposited in the wound. Only 1.3% reduction in radiation dose was achieved by chelation treatment. The committed effective dose was calculated to be 1.49 Sv. Using urine data available for this case, the effect of chelation therapy was evaluated. Urinary excretion enhancement factors were calculated as 83 ± 52 and 38 ± 17 for initial and delayed calcium ethylenediaminetetraacetic acid treatments, respectively, and as 18 ± 5 for delayed calcium diethylenetriaminepentaacetic acid. The enhancement factor decreases proportionally to an inverse cubic root of time after intake. For delayed calcium ethylenediaminetetraacetic acid treatment, with five consecutive daily administrations, the enhancement factor increased from day 1 to 4, followed by approximately a 50% drop on day 5. The half-time of plutonium ethylenediaminetetraacetic acid complex removal in urine was evaluated to be 1.4 d.
INTRAVITREAL ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT AT 2-MONTH INTERVALS REDUCES FOVEAL AVASCULAR ZONE ENLARGEMENT AND VISION LOSS IN RADIATION MACULOPATHY
Authors: Daruich Alejandra , Matet Alexandre , Schalenbourg Ann , Zografos Leonidas
Published: May 2018

Purpose:

To evaluate, in eyes with radiation maculopathy, the effect of 2-month-interval anti–vascular endothelial growth factor therapy on best-corrected visual acuity and foveal avascular zone (FAZ) enlargement using optical coherence tomography angiography.

Methods:

Consecutive treatment-naive patients with radiation maculopathy after proton beam irradiation for choroidal melanoma were retrospectively included. Clinical and optical coherence tomography angiography data at baseline and the 6-month visit were recorded. Two independent observers measured FAZ area manually on 3 × 3-mm optical coherence tomography angiography images of the superficial capillary plexus and deep capillary plexus. Patients were encouraged to follow strictly a 2-month-interval intravitreal anti–vascular endothelial growth factor treatment by either bevacizumab or ranibizumab. Findings were analyzed based on the adherence to the treatment scheme.

Results:

According to the adherence to the bimonthly anti–vascular endothelial growth factor treatment protocol, patients were categorized into 3 groups: treatment protocol (n = 19, strict adherence), variable intervals (n = 11, intervals other than 2 months), and no treatment (n = 11). The estimated radiation dose to the foveola in each group was 49 ± 16, 46 ± 17, and 46 ± 18 cobalt gray equivalent, respectively (P = 0.85). For the entire cohort, best-corrected visual acuity loss (P < 0.02) and FAZ enlargement (P < 0.0001) were observed over 6 months. Best-corrected visual acuity loss was significantly less pronounced in the treatment-protocol group than in the variable-interval and no-treatment groups (P = 0.007 and P = 0.004). The FAZ enlargement was lower in the treatment-protocol group compared with the variable-interval group for both superficial capillary plexus (P = 0.029) and deep capillary plexus (P = 0.03), and to the no-treatment group for the deep capillary plexus only (P = 0.016).

Conclusion:

Decrease in best-corrected visual acuity and FAZ enlargement on optical coherence tomography angiography occurred over 6 months in eyes with radiation maculopathy and were significantly reduced under 2-month-interval anti-vascular endothelial growth factor therapy.
HEMI-TEMPORAL INTERNAL LIMITING MEMBRANE PEELING IS AS EFFECTIVE AND SAFE AS CONVENTIONAL FULL PEELING FOR MACULAR HOLE SURGERY
Authors: Shiono Akira , Kogo Jiro , Sasaki Hiroki , Yomoda Ryo , Jujo Tatsuya , Tokuda Naoto , Kitaoka Yasushi , Takagi Hitoshi
Published: May 2018

Purpose:

To investigate the efficacy of hemi-temporal internal limiting membrane (ILM) peeling for idiopathic macular hole.

Methods:

The medical records of patients with macular holes who had undergone vitrectomy with ILM peeling were studied. Forty-two eyes with macular hole were divided into 2 groups based on surgical procedure (hemi-temporal ILM peeling [hemi group]: 15 eyes; 360° ILM peeling [360° group]: 27 eyes). The closure rates and distances between the optic disc and the intersection of two retinal vessels most closely located nasally or temporally to the macular hole were compared.

Results:

The primary closure rates were not significantly different between the two groups (hemi group: 93.3%; 360° group: 92.5%, P = 0.92). The temporal retinal vessels in the hemi group were displaced 120.5 ± 102.0 µm toward the optic disc at 1 week postoperatively, which did not differ significantly from the 360° group (136.1 ± 106.1 µm) (P = 0.107). However, the nasal retinal vessels in the hemi group were displaced by 42.4 ± 42.9 µm at 1 week postoperatively, which was significantly less than the 90.1 ± 77.3 µm displacement seen in the 360° group (P = 0.040).

Conclusion:

Hemi-temporal ILM peeling may be preferable to 360° ILM peeling because of less displacement of the retina and greater safety.
COMMUNITY-ASSOCIATED METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS SUBRETINAL ABSCESS IN A NONBACTEREMIC PATIENT TREATED WITH INTERNAL DRAINAGE AND RETINECTOMY
Authors: Yang Jessica F. , Kishore Kamal
Published: May 2018

Purpose:

To report a case of community-associated methicillin-resistant Staphylococcus aureus subretinal abscess that continued to progress, despite intravitreal and systemic antibiotic therapy.

Methods:

Retrospective chart review of a 77-year-old female patient with well-controlled diabetes mellitus who developed a left eye endophthalmitis and subretinal abscess from methicillin-resistant S. aureus colonization in the absence of any systemic focus of infection.

Results:

The abscess and endophthalmitis resolved after the second pars plana vitrectomy that included drainage of a subretinal abscess after the failure of initial pars plana vitrectomy, and intravitreal and systemic antibiotics. Retinal detachment due to proliferative vitreoretinopathy necessitated the third pars plana vitrectomy 2 weeks after the second pars plana vitrectomy.

Conclusion:

The authors present an unusual case of methicillin-resistant S. aureus subretinal abscess in a patient with methicillin-resistant S. aureus colonization with negative blood, aqueous humor culture, and vitreous culture but a positive culture from subretinal aspirate.
PRESUMED TUBERCULOUS MULTIFOCAL RETINITIS IN PATIENTS UNDER TREATMENT WITH BIOLOGIC AGENTS
Authors: Arantes Tiago E. , Lima Luiz H. , Bressanin Gláucio L. , Marques Cláudia D. , Duarte Ângela B. , Muccioli Cristina
Published: May 2018

Purpose:

To report unique retinal fundus lesions and treatment outcomes of intraocular tuberculosis in patients under anti–tumor necrosis factor treatment.

Methods:

Retrospective review of two patients with laboratorial evidence of tuberculosis who had bilateral ocular signs and symptoms not attributable to other diseases. Multimodal imaging was analyzed at the time of presentation and after the treatment initiation. The study patients underwent standard treatment for tuberculosis.

Results:

Clinical and laboratory findings were consistent with the diagnosis of presumed tuberculosis. Color fundus photograph revealed the presence of multifocal yellowish retinal spots in the study eyes. On fluorescein angiography, the retinal lesions seen on color fundus photograph showed early hypofluorescence with progressive staining of its edges. Occlusive vasculitis with peripheral nonperfusion was also observed in both cases. Spectral domain optical coherence tomography demonstrated increased reflectivity and thickness on the topography of retinitis lesions. After specific antibiotic treatment for tuberculosis, there was complete disappearance of the retinal lesions in all study eyes.

Conclusion:

We report two unique cases of bilateral presumed intraocular tuberculosis presenting as multifocal retinitis in patients under biologic agent treatment. Anti–tumor necrosis factor agents may be related to unusual fundus manifestations of tuberculosis.
Effect of Latanoprost on Choroidal Thickness
Authors: Sahinoglu-Keskek Nedime , Canan Handan
Published: May 2018

Purpose:

The purpose of this study was to evaluate the changes in choroidal thickness during the use of latanoprost eyedrops which shift fluid to the suprachoroidal space and change choroidal perfusion.

Materials and Methods:

This prospective study included 34 eyes of 17 bilateral glaucoma or ocular hypertensive patients who had no previous hypotensive therapy. Each patient had both eyes treated with latanoprost. Each patient also underwent a complete ophthalmological examination and optical coherence tomography measurement. Choroidal thickness measurements by optical coherence tomography were carried out on the first visit before latanoprost use and at time intervals of 7 and 30 days of therapy.

Results:

The patients’ mean age was 62.3±11 years (range, 30 to 83 y). Of 17 patients, 7 were female individuals. There were no significant differences in central choroidal thicknesses at the fovea, or at each point within the horizontal nasal and temporal quadrants between visits (P<0.05 for all comparisons).

Conclusions:

The current study showed that choroidal thickness does not change after latanoprost therapy. However, the choroidal changes of anterior part of the eye can be effected by the latanoprost therapy. Future studies investigating the anterior part of the eye and focusing on both choroidal perfusion and choroidal thickness may give additional information concerning the mechanism of action.
Noninvasive Detection of Mitochondrial Dysfunction in Ocular Hypertension and Primary Open-angle Glaucoma
Authors: Geyman Lawrence S. , Suwan Yanin , Garg Reena , Field Matthew G. , Krawitz Brian D. , Mo Shelley , Pinhas Alexander , Ritch Robert , Rosen Richard B.
Published: May 2018

Purpose:

To assess mitochondrial dysfunction in vivo in ocular hypertension (OHT) and primary open-angle glaucoma (POAG) using retinal metabolic analysis.

Patients and Methods:

This was an observational, cross-sectional study performed from November 2015 to October 2016 at the New York Eye and Ear Infirmary of Mount Sinai. Thirty-eight eyes with varying stages of POAG, 16 eyes with OHT, and 32 control eyes were imaged on a custom fundus camera modified to measure full retinal thickness fluorescence at a wavelength optimized to detect flavoprotein fluorescence (FPF). Optical coherence tomography was used to measure the retinal ganglion cell-plus layer (RGC+) thickness. Macular FPF and the ratio of macular FPF to RGC+ thickness were the primary outcome variables and were compared among the three groups using an age-adjusted linear regression model. A mixed-effects model was used to assess correlations between FPF variables and clinical characteristics.

Results:

Both macular FPF and the macular FPF/RGC+ thickness ratio were significantly increased in OHT compared with control eyes (P<0.05 and <0.01, respectively). In POAG eyes, macular FPF was not significantly increased compared with controls (P=0.24). However, the macular FPF/RGC+ thickness ratio in POAG eyes was significantly increased compared with controls (P<0.001). FPF was significantly correlated to age in POAG eyes.

Conclusions:

Despite lacking clinical evidence of glaucomatous deterioration, OHT eyes displayed significantly elevated macular FPF, suggesting that mitochondrial dysfunction may be detected before structural changes visible on current clinical imaging. Our preliminary results suggest that macular FPF analysis may prove to be a useful tool in assessing and evaluating OHT and POAG eyes.
Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants
Authors: Yeganeh Nava , Watts D. Heather , Xu Jiahong , Kerin Tara , Joao Esau C. , Pilotto Jose Henrique , Theron Gerhard , Gray Glenda , Santos Breno , Fonseca Rosana , Kreitchmann Regis , Pinto Jorge , Mussi-Pinhata Marisa M. , Veloso Valdilea , Camarca Margaret , Mofenson Lynne , Moye Jack , Nielsen-Saines Karin
Published: May 2018

Background:

HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial.

Methods:

Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission.

Results:

Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with <12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2–5.9), with maternal viral load of >1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6–63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤−2, and 22% with height for Z score ≤−2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5–15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01–2.9) and birth weight-for-age Z score ≤−2 (AOR, 5.2; 95% CI, 1.8–14.8).

Conclusions:

There were high rates of undernutrition, stunting and infectious serious adverse effect in this study’s formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.
Ideal and Actual Impact of Rapid Diagnostic Testing and Antibiotic Stewardship on Antibiotic Prescribing and Clinical Outcomes in Children With Positive Blood Cultures
Authors: Reuter Caroline H. , Palac Hannah L. , Kociolek Larry K. , Zheng Xiaotian T. , Chao Yusuf Y. , Patel Rupal M. , Patel Sameer J.
Published: May 2018

Background:

Implementing matrix-assisted laser desorption ionization–time of flight and multiplex polymerase chain reaction has been associated with decreased mortality and hospital length of stay in adults, but the impact in pediatrics is less understood.

Methods:

This pre–post quasi-experimental study compared antibiotic prescribing for positive blood cultures in patients ≤21 years of age collected in 2012 (preintervention) and in 2015 (after matrix-assisted laser desorption ionization–time of flight/multiplex polymerase chain reaction). Time to effective and optimal antimicrobial therapy was evaluated using Cox proportional hazards regression. Time to ideal optimal therapy was estimated as the earliest potential initiation of optimal therapy. Antibiotic use and clinical outcomes were measured.

Results:

There were 242 and 192 positive monomicrobial blood cultures in 2012 and 2015, respectively. Postintervention, time to optimal therapy (73.8 vs. 48.8 hours; P < 0.001) and organism identification (55.6 vs. 29.5 hours; P < 0.001) were reduced, and patients were more likely to receive optimal therapy by 7 days (hazard ratio, 1.85; P < 0.001). In the ideal scenario in 2015, there was an 8.8-hour delay in initiating optimal therapy based on the time that sufficient microbiologic data were available. Postintervention, time to effective therapy (2.8 vs. 2.7 hours; P = 0.782) and clinical outcomes did not differ. Unnecessary antibiotic duration for probable contaminants (skin flora) (43.1 vs. 29.7 hours; P = 0.027), vancomycin for methicillin-sensitive Staphylococcus aureus (54.0 vs. 41.3 hours; P = 0.008) and nonpenicillin/ampicillin antibiotics for group A Streptococcus, group B Streptococcus and Enterococcus faecalis (87.2 vs. 33.4 hours; P < 0.001) were reduced postintervention.

Conclusions:

Rapid diagnostics reduced time to optimal antimicrobial therapy and unnecessary antibiotic use without worse clinical outcomes.
Factors Influencing the Intestinal Microbiome During the First Year of Life
Authors: Zimmermann Petra , Curtis Nigel
Published: May 2018

The intestinal microbiome plays a crucial role in the development of the immune system and regulation of immune responses. Many factors influence the composition of the infant intestinal microbiome and therefore the development and function of the immune system. This, in turn, may alter the risk of subsequent allergies, autoimmune diseases and other adverse health outcomes. Here, we review factors that influence the composition of the intestinal microbiome during the first year of life, including birth location, gestational age, delivery mode, feeding method, hospitalization, antibiotic or probiotic intake and living conditions. Understanding how the early intestinal microbiome is established and how this is perturbed provides many opportunities for interventions to improve health.
NALCN channels enhance the intrinsic excitability of spinal projection neurons
Authors: Ford Neil C. , Ren Dejian , Baccei Mark L.
Published: May 2018

Spinal projection neurons convey nociceptive signals to multiple brain regions including the parabrachial (PB) nucleus, which contributes to the emotional valence of pain perception. Despite the clear importance of projection neurons to pain processing, our understanding of the factors that shape their intrinsic membrane excitability remains limited. Here, we investigate a potential role for the Na+ leak channel NALCN in regulating the activity of spino-PB neurons in the developing rodent. Pharmacological reduction of NALCN current (INALCN), or the genetic deletion of NALCN channels, significantly reduced the intrinsic excitability of lamina I spino-PB neurons. In addition, substance P (SP) activated INALCN in ascending projection neurons through downstream Src kinase signaling, and the knockout of NALCN prevented SP-evoked action potential discharge in this neuronal population. These results identify, for the first time, NALCN as a strong regulator of neuronal activity within central pain circuits and also elucidate an additional ionic mechanism by which SP can modulate spinal nociceptive processing. Collectively, these findings indicate that the level of NALCN conductance within spino-PB neurons tightly governs ascending nociceptive transmission to the brain and thereby potentially influences pain perception.