bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term study of the safety and maintenance of efficacy of solriamfetol (JZP-110) in the treatment of excessive sleepiness in participants with narcolepsy or obstructive sleep apnea
Authors: Malhotra Atul , Shapiro Colin , Pepin Jean-Louis , Hedner Jaz , Ahmed Mansoor , Foldvary-Schaefer Nancy , Strollo Patrick J , Mayer Geert , Sarmiento Kathleen , Baladi Michelle , Chandler Patricia , Lee Lawrence , Schwab Richard
Published: November 2019

Study Objectives

To evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA).

Methods

Participants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI-C, respectively). After approximately 6 months of treatment, a subgroup entered a 2-week placebo-controlled randomized withdrawal (RW) phase. Change in ESS from beginning to end of the RW phase was the primary endpoint; PGI-C and CGI-C were secondary endpoints. Safety was assessed throughout the study.

Results

In the maintenance phase, solriamfetol-treated participants demonstrated clinically meaningful improvements on ESS, PGI-C, and CGI-C. In the RW phase, least squares mean change on ESS was 1.6 in participants continuing solriamfetol versus 5.3 in participants switched to placebo (p < .0001). For both secondary endpoints, higher percentages of participants receiving placebo were reported as worse at the end of the RW phase versus solriamfetol (p < .0001). Common treatment-emergent adverse events (TEAEs) with solriamfetol were headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection; 27 (4.2%) participants experienced at least one serious TEAE, and 61 (9.5%) withdrew because of TEAEs.

Conclusions

This study demonstrated long-term maintenance of efficacy of solriamfetol under open-label and double-blind, placebo-controlled conditions. Safety profile of solriamfetol was consistent with previous 12-week studies; no new safety concerns were identified.

Trial Registration

NCT02348632
The Long Road to Gender Equality
Authors: Daly Mary
Published: November 2019

This piece reflects upon the significance of The Logics of Gender Justice. I make the case that this is one of the most significant works on the development of women's rights and gender justice. It offers depth of understanding of the policy and politics precipitating or blocking the roll-out of a range of such rights across time and place. Its geographical scope is both global and local. It offers a framework of analysis and a set of empirical insights that will galvanize scholarship, and not just in the field of gender. I am particularly intrigued by the differentiation between class- and status-based gender policies. I can see promise here—especially from a politics perspective—but to my mind this is not a watertight differentiation between policies. The possibility of an intersectional understanding of gender-related rights and policies is also downplayed by the Htun and Weldon's framework on my reading.
On Reading The Logics of Gender Justice
Authors: Madhok Sumi
Published: November 2019

This ambitious and remarkable book provides us with a new, creative, and critical site for feminist scholarship and leads the way in producing historically and contextually specific empirical datasets and analysis of the deeply complex area of global women's rights. As is often the case with important work, the book engenders a supplementary set of hard questions to be asked both of itself and of the wider literature. In particular, the book enables us to raise two sets of further questions: first, about the links between law, policy making, women's rights, and social transformation, and second, to raise methodological and conceptual questions in the wake of empirically operationalizing intersectionality on a global scale.
Technical Fixes as Challenges to State Legitimacy: Australian Separated Fathers’ Suggestions for Child Support Policy Reform
Authors: Cook Kay , Skinner Christine
Published: November 2019

This article assesses fathers’ evidence presented to an Australian inquiry into the child support scheme. We examine these data in order to address how fathers’ proposed child support policy solutions compared against Eekelaar’s critique of parents’ moral responsibilities to children and his identification of three substitute social bases for parents’ continued support. We find that despite the inquiry’s technical remit, fathers’ solutions challenged the very basis of child support as maintaining, reinforcing, or redressing their responsibilities to children. Here, we illustrate that such procedures may be unable to contain fundamental challenges to state legitimacy when dealing with contested social issues.
Differential Susceptibility of Tree Tomato (Solanum betaceum) Cultivars to Late Blight Caused by Phytophthora betacei
Authors: Mideros Maria F. , Mayton Hilary , Danies Giovanna , Lagos Luz E. , Fry William E. , Restrepo Silvia
Published: November 2019

Host–pathogen interactions of a new species of Phytophthora, causal agent of late blight of tree tomato (Solanum betaceum Cav.), identified as Phytophthora betacei, were investigated with four different cultivars. Thirty-six P. betacei isolates, collected from southern Colombia between 2008 and 2009, were used to inoculate common tree tomato cultivars, Común, Híbrido, Injerto, and Holandés. Data on incubation and latent periods as well as infection efficiency, lesion development, and total sporulation were collected via detached leaf assays. Significant differences in susceptibility, based on the parameters measured, were observed. Común was the most susceptible cultivar, followed by Injerto, Híbrido, and Holandés. The mean incubation period was lowest for Común at 125.6 h post-inoculation (hpi) and highest for Híbrido at 139.4 hpi. No significant differences in latent period were observed. All 36 isolates produced necrotic lesions on Común, and 33, 24, and 21 caused infection on Injerto, Híbrido, and Holandés, respectively. Two isolates were able to cause infection only on Común, and 13 isolates were able to infect all four cultivars. Infection efficiency was significantly higher for the cultivar Común, followed by Injerto, Híbrido, and Holandés. Average lesion size was larger on Común than on any other cultivar. An inverse relationship of lesion size and total sporulation was observed. Común had significantly lower total sporulation than Híbrido and Holandés, which had the smallest average lesion sizes. These data show variation in pathogenicity of P. betacei isolates, under controlled conditions, and differential susceptibility of four distinct S. betaceum cultivars.
Distribution of Candidatus Liberibacter asiaticus in Citrus and the Asian Citrus Psyllid in Texas Over a Decade
Authors: Sétamou Mamoudou , Alabi Olufemi J. , Kunta Madhurababu , Dale Jon , da Graça John V.
Published: November 2019

Huanglongbing (HLB, citrus greening disease) in the major citrus-producing states of the United States is associated with Candidatus Liberibacter asiaticus (CLas), which is vectored by the Asian citrus psyllid (ACP). Surveys were conducted in Texas from 2007 to 2017 to assess the prevalence and titer of CLas in ACPs and citrus trees. ACP and citrus leaf tissue samples were collected from suspect trees in residential areas and commercial groves (orchards) and assayed for CLas by quantitative PCR. CLas detection in ACPs (2011) preceded that of citrus trees (2012) by several months. Annual incidences of CLas-positive ACPs and leaf tissue followed an exponential growth pattern over the survey period, varying from 0.03 to 28.7% in ACPs and 0.6 to 36.5% in citrus trees. There was a significant and positive relationship between the monthly incidences of CLas-positive ACP and leaf tissue samples. The proportion of HLB detection sites also increased with time, reaching 26 and 40% of commercial groves and residential sites, respectively, by 2017. Seasonal variations were observed in the incidences of CLas-positive ACPs and citrus trees such that significantly more CLas-positive ACPs and trees were recorded during the fall and winter of a given year relative to the hot summer. A temporal analysis of the class distribution of cycle threshold values revealed a trend of increased bacterial accumulation in ACPs and trees over time, with the trend more pronounced for the former than the latter host type. These findings provide a comprehensive insight into the ongoing CLas/HLB epidemic in Texas, with potential lessons for California and other citrus-producing areas where the disease is not yet established.
Stem Canker on Cyclocarya paliurus Is Caused by Botryosphaeria dothidea
Authors: Zheng Xiang-rong , Zhang Mao-jiao , Shang Xu-lan , Fang Sheng-zuo , Chen Feng-mao
Published: November 2019

Cyclocarya paliurus, an important endangered plant in China, has considerable medicinal, timber, and horticultural value. However, little is known about diseases that affect its health. In recent years, stem canker diseases on C. paliurus have been observed frequently in newly established nurseries in Jiangsu Province, China. Symptomatic trees showed elliptical, sunken lesions on the bark, with internal discoloration, leading to enlarging cankers with delineated margins. Pathogenicity tests with fungi isolated from symptomatic samples reproduced typical canker symptoms on both detached branches and potted plants of C. paliurus. Moreover, conidia from pycnidia of isolate ZB-23 could also cause stem canker on C. paliurus. Through combined morphological observation and DNA sequences of ITS region, β-tubulin, and translation elongation factor 1-α genes, the pathogen was identified as Botryosphaeria dothidea. Multigene maximum likelihood and maximum parsimony phylogenetic analyses further supported the identification of the pathogen. To our knowledge, this is the first report of B. dothidea causing stem canker on C. paliurus in China.
The Plasmodium falciparum Hsp70‐x chaperone assists the heat stress response of the malaria parasite
Authors: Day Jemma , Passecker Armin , Beck Hans‐Peter , Vakonakis Ioannis
Published: November 2019

Plasmodium falciparum is the most lethal of human‐infective malaria parasites. A hallmark of P. falciparum malaria is extensive remodeling of host erythrocytes by the parasite, which facilitates the development of virulence properties such as host cell adhesion to the endothelial lining of the microvasculature. Host remodeling is mediated by a large complement of parasite proteins exported to the erythrocyte; among them is a single heat shock protein (Hsp)70‐class protein chaperone, P. falciparum Hsp70‐x (PfHsp70‐x). PfHsp70‐x was previously shown to assist the development of virulent cytoadherence characteristics. Here, we show that PfHsp70‐x also supports parasite growth under elevated temperature conditions that simulate febrile episodes, especially at the beginning of the parasite life cycle when most of host cell remodeling takes place. Biochemical and biophysical analyses of PfHsp70‐x, including crystallographic structures of its catalytic domain and the J‐domain of its stimulatory Hsp40 cochaperone, suggest that PfHsp70‐x is highly similar to human Hsp70 chaperones endogenous to the erythrocyte. Nevertheless, our results indicate that selective inhibition of PfHsp70‐x function using small molecules may be possible and highlight specific sites of its catalytic domain as potentially of high interest. We discuss the likely roles of PfHsp70‐x and human chaperones in P. falciparum biology and how specific inhibitors may assist us in disentangling their relative contributions.—Day, J., Passecker, A., Beck, H.‐P., Vakonakis, I. The Plasmodium falciparum Hsp70‐x chaperone assists the heat stress response of the malaria parasite. FASEB J. 33, 14611‐14624 (2019). www.fasebj.org
Neuromuscular Electrical Stimulation (NMES) in the Management of Glioblastoma Multiforme: A Case Report
Authors: O'Connor Dominic , Caulfield Brian , Wright Sarah , Lennon Olive
Published: November 2019

Background and Purpose:

Glioblastoma multiforme (GBM) is associated with debilitating physical and psychosocial side effects. Voluntary exercise recommended as an adjunct therapy is often limited by physical and neurological impairments. The potential effect of aerobic and muscle-strengthening neuromuscular electrical stimulation (termed concurrent NMES) exercise (4 weeks, 2-5 times/week, 30 minutes to 1 hour) delivered to the lower limbs in patients with GBM has not been examined. This case study explores the effect of a short-term concurrent NMES intervention progressing to NMES and supervised voluntary exercise (aerobic and resistance training) over a 10-week period in a patient with GBM undergoing adjuvant treatment.

Case Description:

The case was a 61-year-old man with GBM who had completed radiotherapy treatment (40 Gy) and was undergoing adjuvant chemotherapy. Eastern Cooperative Oncology Group level was 3. Assessments were conducted at baseline, and at weeks 4 and 10 of the intervention. Outcomes included 30-second sit-to-stand (30STS), Timed Up and Go (TUG), European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and Godin Leisure Time Questionnaire.

Outcomes:

The intervention was well tolerated, with more than 70% NMES exercise adherence over 10 weeks and progression to combined NMES and voluntary exercise at week 5. No adverse events were reported. Despite self-reported increases in fatigue levels, clinically meaningful improvements were observed at weeks 4 and 10 for 30STS, TUG, and physical quality of life (QoL). Self-report physical activity levels increased at week 10.

Discussion:

In this first clinical case report, a 10-week NMES/voluntary exercise intervention led to improvements in physical and QoL outcomes. This initial evidence suggests NMES exercise is safe and feasible and may act as a bridge to voluntary exercise. NMES demonstrated promise as an effective supportive intervention in the management of GBM. Future clinical trials are required to expand on these initial findings.
Urinary Placental Growth Factor for Prediction of Placental Adverse Outcomes in High-Risk Pregnancies
Authors: Lecarpentier Edouard , Gris Jean Christophe , Cochery-Nouvellon Eva , Mercier Erick , Abbas Houria , Thadhani Ravi , Karumanchi Subbian Ananth , Haddad Bassam
Published: November 2019

OBJECTIVE:

To evaluate whether urinary levels of placental growth factor (PlGF) during pregnancy are associated with the subsequent development of composite adverse outcomes (preeclampsia, fetal growth restriction, placental abruption, perinatal death, maternal death) occurring at less than 34 weeks of gestation.

METHODS:

This is a preplanned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive either low-molecular-weight (LMW) heparin or aspirin alone. For this substudy we measured urinary levels of PlGF and urinary creatinine at the following gestational windows: 10–13 6/7, 14–17 6/7, 18–21 6/7, 22–25 6/7, 26–29 6/7, 30–33 6/7, and 34–37 6/7 weeks of gestation.

RESULTS:

Urine samples were available from 187 patients: LMW heparin plus aspirin (n=93) and aspirin alone (n=94). The two groups had comparable baseline characteristics and had similar adverse composite outcomes at less than 34 weeks of gestation (14/93 [15.1%] vs 11/94 [11.7%]; P=.50). There were no significant differences in urine PlGF levels in the patients who received LMW heparin plus aspirin compared with those who received aspirin alone. However, median [interquartile range] urinary PlGF/creatinine concentrations (pg/mg) measured at mid-pregnancy (22–26 weeks of gestation) were significantly lower among women who developed composite adverse outcome at less than 34 weeks of gestation (42.7 [32.4–80.8] vs 255.6 [118.7–391.8] P<.001) and significantly lower among women who developed preeclampsia at less than 34 weeks of gestation (42.7 [27.5–80.7] vs 244.6 [112.9–390.6] P<.001). For a fixed false-positive rate of 10% the sensitivity of urinary PlGF concentrations at mid-pregnancy was 75.2% (area under the curve 0.93) for the subsequent development of composite adverse outcomes.

CONCLUSION:

Decreased urinary PlGF at mid-gestation (22–26 weeks of gestation) is associated with the subsequent development of preeclampsia-related adverse outcomes at less than 34 weeks of gestation.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00986765.
Consent for the Pelvic Examination Under Anesthesia by Medical Students
Authors: Hammoud Maya M. , Spector-Bagdady Kayte , O'Reilly Meg , Major Carol , Baecher-Lind Laura
Published: November 2019

The pelvic examination is a critical tool for the diagnosis of women's health conditions and remains an important skill necessary for students to master before becoming physicians. Recently, concerns regarding student involvement in pelvic examinations—specifically those performed while a woman is under anesthesia—have been raised in the scientific, professional, and lay literature. These concerns have led to calls to limit or halt the performance of pelvic examinations by students while a woman is under anesthesia. Although ensuring adequate informed consent for teaching pelvic examinations is a priority, we must not lose sight of the critical pedagogical value of teaching pelvic examination in familiarizing students with the female anatomy and instilling a physician workforce with confidence in pelvic examination skills. A compromise that addresses all of these values is possible. In this commentary, we review the educational and legal aspects of the pelvic examination under anesthesia, then provide strategies that individuals and institutions can consider to optimize processes regarding consent for pelvic examination under anesthesia.
Evaluation of Risk-Assessment Tools for Severe Postpartum Hemorrhage in Women Undergoing Cesarean Delivery
Authors: Kawakita Tetsuya , Mokhtari Neggin , Huang Jim C. , Landy Helain J.
Published: November 2019

OBJECTIVE:

To examine and compare the validity of three known risk-assessment tools (CMQCC [California Maternal Quality Care Collaborative], AWHONN [Association of Women's Health, Obstetric and Neonatal Nurses], and NYSBOH [New York Safety Bundle for Obstetric Hemorrhage]) in women undergoing cesarean delivery.

METHODS:

We conducted a retrospective cohort study that evaluated all women undergoing cesarean delivery at 23 weeks of gestation or longer from 2012 to 2017 at an urban hospital with average of 1,200 cesarean deliveries per year. Data were obtained by chart review. Severe postpartum hemorrhage was defined as transfusion of at least four units of packed red blood cells during the intrapartum or postpartum period. For each risk-assessment tool, women were stratified into low-risk, medium-risk, and high-risk groups. Risk factors were examined using multivariable logistic regression.

RESULTS:

Of 6,301 women who underwent cesarean delivery, a total of 76 (1.2%) had severe postpartum hemorrhage. Women classified as low- or medium-risk had lower rates of severe postpartum hemorrhage (0.4–0.6%) compared with women classified as high-risk (1.8–5.1%) (P<.001). Risk factors that were included in all three tools that were associated with severe postpartum hemorrhage included placenta accreta, placenta previa or low-lying placenta, placental abruption, hematocrit less than 30%, and prior uterine scar. Factors included in only one or two tools that were associated with severe postpartum hemorrhage included having more than four previous vaginal deliveries (CMQCC and AWHONN), stillbirth (AWHONN), and more than four prior births (NYSBOH). Area under the curve and 95% CI for CMQCC, AWHONN, and NYSBOH were all moderate—CMQCC 0.77 (0.71–0.84), AWHONN 0.69 (0.65–0.74), and NYSBOH 0.73 (0.67–0.79), respectively (AWHONN being most sensitive [88% with high-risk as cut-off] and CMQCC being most specific [87% with high-risk as cut-off]).

CONCLUSIONS:

Risk-assessment tools had moderate prediction to identify high-risk groups at risk for severe postpartum hemorrhage after cesarean delivery.
Opioid Analgesia for Medical Abortion
Authors: Colwill Alyssa Covelli , Bayer Lisa L. , Bednarek Paula , Garg Bharti , Jensen Jeffery T. , Edelman Alison B.
Published: November 2019

OBJECTIVE:

To estimate the effect of oral opioids on patient pain during first-trimester medical abortion.

METHODS:

We conducted a randomized, double-blind, placebo-controlled trial where patients up to 10 0/7 weeks of gestation undergoing a medical abortion with mifepristone and misoprostol took 10 mg oral oxycodone or placebo at onset of painful cramping. Additionally, all patients received 800-mg ibuprofen tablets, 4-mg ondansetron oral dissolving tablets, and a written prescription for adjunctive pain medication (six tablets oxycodone 5 mg). Participants used a text-messaging service to report pain scores on a numerical rating scale from 0 to 10 (0 being no pain, 10 being worst pain) for 24 hours at start of misoprostol dosing. The primary outcome was maximum pain experienced within 24 hours postmisoprostol. Our secondary outcomes were maximum pain stratified by gestational age (less than 7 weeks of gestation, 7–10 weeks of gestation), duration of maximum pain, use of adjunctive medication, presence of nausea or vomiting, and satisfaction. We needed at least 76 participants per group to differentiate a clinically important pain difference of 2 points on the numerical rating scale.

RESULTS:

From May 2017 to May 2018, we randomized 172 participants (placebo group with 86, oxycodone group with 86). The study groups had comparable baseline characteristics. We found no difference between groups in median maximum pain scores (placebo 8 [range 1–10], oxycodone 8 [range 2–10], P=.92) and the median duration of maximum pain (placebo 0.75 hours range 0.01–15 vs oxycodone 1 hour range 0.02–10, P=.39). Groups were also similar in the proportion obtaining (placebo 62%, oxycodone 49%, P=.09) and using (placebo 48%, oxycodone 40%, P=.28) adjunctive medication, experiencing nausea or vomiting (placebo 59%, oxycodone 65%, P=.43) and reported satisfaction with pain medications (placebo 62%, oxycodone 65%, P=.63).

CONCLUSION:

Oxycodone does not reduce the maximum level of pain experienced by women undergoing medical abortion up to 10 0/7 weeks of gestation or improve satisfaction.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03139240.
Preemptive Oral Compared With Intravenous Acetaminophen for Postoperative Pain After Robotic-Assisted Laparoscopic Hysterectomy
Authors: Lombardi Tresa M. , Kahn Bruce S. , Tsai Lily J. , Waalen Jill M. , Wachi Nicole
Published: November 2019

OBJECTIVE:

To compare pain after robotic-assisted laparoscopic hysterectomy when giving preoperative oral compared with intravenous acetaminophen.

METHODS:

This double-blind randomized trial included women undergoing robotic-assisted laparoscopic hysterectomy for benign indications. Participants received either acetaminophen 1 g orally then normal saline 100 mL intravenously before surgery, or a placebo orally then acetaminophen 1 g intravenously. The primary outcome measured was difference in pain between the groups 2 hours postoperatively. A sample size of 74 participants (37/group) was needed to achieve 80% power to detect noninferiority using a one-sided, two-sample t-test with an alpha of 0.025 and a noninferiority margin of 10 mm.

RESULTS:

From April 2016 through August 2017, 77 patients were enrolled, with 75 participants included in the final analysis. Characteristics were similar between groups. No difference in average pain score was noted 2 hours after surgery, nor at any of the measured time points. Average scores for the oral and intravenous group, respectively, at 2 hours were 35 and 36 mm (P=.86), at 4 hours 36 and 37 mm (P=.96), and at 24 hours 35 and 36 mm (P=.79). Thirty-eight percent of participants in the oral group and 19% of participants in the intravenous group experienced nausea (P=.12). The oral group used 9.7 morphine equivalents in the recovery room, and the intravenous group used 9.5 morphine equivalents (P=.9). The oral group requested analgesia in 45 minutes on average, and the intravenous group requested analgesia in 43 minutes (P=.79).

CONCLUSION:

No difference in pain was observed 2 hours postoperatively when comparing preoperative administration of oral compared with intravenous acetaminophen. Given the ease of administration and lower cost of oral dosing, this study supports the oral route as part of the enhanced recovery after surgery protocol for minimally invasive gynecologic surgery.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03391284.
Effects of Gastrointestinal-Type Chemotherapy in Women With Ovarian Mucinous Carcinoma
Authors: Kurnit Katherine C. , Sinno Abdulrahman K. , Fellman Bryan M. , Varghese Aaron , Stone Rebecca , Sood Anil K. , Gershenson David M. , Schmeler Kathleen M. , Malpica Anais , Fader Amanda N. , Frumovitz Michael
Published: November 2019

OBJECTIVE:

To estimate whether gastrointestinal-type chemotherapy was associated with improved survival compared with standard gynecologic regimens for women with ovarian mucinous carcinoma.

METHODS:

We conducted a retrospective cohort study of patients with ovarian mucinous carcinoma who received postoperative adjuvant chemotherapy at two academic centers. Demographic and clinical information was abstracted from the medical records. Gastrointestinal-type chemotherapy contained 5-fluorouracil, capecitabine, irinotecan, or oxaliplatin. Gynecologic regimens included standard carboplatin or cisplatin. Bevacizumab treatment was allowed in both groups. Summary statistics were used to compare baseline characteristics; Kaplan-Meier product-limit estimator was used to compare survival outcomes.

RESULTS:

Fifty-two patients received either gastrointestinal-type chemotherapy (n=26; 50%) or a standard gynecologic regimen (n=26; 50%). Three-quarters of tumors were early-stage (I or II), 68% grade 1 or 2 and 88% of patients had no gross residual disease after surgery. Patients receiving gastrointestinal-type chemotherapy were more likely to receive bevacizumab (50% vs 4%; P<.001), but there were no other differences in clinical or demographic characteristics. Unadjusted overall survival analyses showed that gastrointestinal-type chemotherapy was associated with better overall survival (hazard ratio 0.2, 95% CI 0.1–0.8), as were early stage tumors and having no gross residual disease.

CONCLUSION:

Gastrointestinal-type chemotherapy with or without bevacizumab was associated with improved survival and should be considered in patients with ovarian mucinous carcinoma requiring adjuvant therapy.
Caring for Patients With Uterine Cancer in Rural and Public Hospitals in New York State
Authors: Gamble Charlotte R. , Huang Yongmei , Frey Melissa K. , Wright Jason D.
Published: November 2019

OBJECTIVE:

To evaluate perioperative outcomes for women with uterine cancer undergoing hysterectomy at rural and public hospitals in New York State.

METHODS:

The New York Statewide Planning And Research Cooperative System database was used to identify women with uterine cancer who underwent hysterectomy from 2000 to 2015. Perioperative complications, inpatient mortality, and resource utilization were compared at rural, public and private hospitals. Multilevel mixed effect log-linear models were developed to evaluate the association between hospital type and outcomes of interest. Patient characteristics, hospital and surgeon clustering were accounted for within the model.

RESULTS:

Over the years studied, there were 193 hospitals that cared for 46,298 women with uterine cancer. Of these, 9.8% were public, 15.0% were rural, and 75.1% were private metropolitan. They cared for 11.0%, 2.2% and 86.8% of patients, respectively. The proportion of patients cared for at rural hospitals decreased significantly from 5.2% in 2000 to 0.6% in 2014 (P<.001). There was no change in the volume of patients cared for at public hospitals (11.3 to 10.3%, P>.05). In a multivariable model adjusting for patient risk, there were no significant differences in perioperative morbidity, transfusion and length of stay across the three hospital types (P>.05). Compared with private hospitals, treatment at a rural hospital was associated with increased inpatient mortality (adjusted risk ratio 4.03, 95% CI 1.02–15.97).

CONCLUSION:

In New York State, operative uterine cancer care is shifting away from rural hospitals. Public hospitals have similar risk-adjusted outcomes compared with private metropolitan facilities.
Does ACDF Utilization and Reimbursement Change Based on Certificate of Need Status?
Authors: Ziino Chason , Bala Abiram , Cheng Ivan
Published: November 2019

Introduction:

Anterior cervical discectomy and fusion (ACDF) remain an effective treatment option for multiple pathologies of the cervical spine. As the health care economic climate has changed, so have reimbursements with a concomitant push toward outpatient procedures. Certificate of Need (CON) programs were established in response to burgeoning health care costs which require states to demonstrate need before expansion of medical facilities. The impact of this program on spine surgery is largely unknown. The purpose of this study was to examine the impact of CON status on reimbursement and utilization trends of ACDF in both inpatient and outpatient settings.

Materials and Methods:

We queried a combined private payer and Medicare database from 2007 to 2015. All single-level ACDFs were identified. We then split each procedure into those performed in CON versus non-CON states. We then further split each group into the inpatient and outpatient settings. Compound annual growth rate (CAGR) was used to compare utilization and reimbursement trends. Reimbursement was adjusted for inflation using the United States Bureau of Labor Statistics consumer price index.

Results:

A total of 32,727 single-level ACDFs were identified, of which 28,441 were performed in the inpatient setting, and 4286 were performed in the outpatient setting. Reimbursement decreased across all settings, with the most pronounced decrease in the non-CON outpatient setting with an adjusted CAGR of −11.0%. Utilization increased across all groups, although the fastest growth was seen in the outpatient CON setting with a CAGR of 47.7%, and the slowest growth seen in the inpatient non-CON setting at a CAGR of 12.9%.

Conclusions:

ACDF utilization increased most rapidly in the outpatient setting, and CON status did not appear to hinder growth. Reimbursement decreased across all settings, with the outpatient setting in non-CON states most affected. Surgeons should be aware of these trends in the changing health care environment.
Extracranial Abscopal Effects Induced by Brain Radiation in Advanced Lung Cancer
Authors: D’Andrea Mark A. , Reddy G. Kesava
Published: November 2019

An extracranial abscopal effect induced by central nervous system (CNS)-radiation therapy is considered an unusual event because of the belief that brain has a distinctive immune microenvironment. Regular immune responses from radiation therapy or other interventions were thought to be very limited in the CNS. In addition, CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounters with CNS antigens. Moreover, the traditional assumption is that nascent tumor-associated antigens produced by radiation therapy could not pass through the blood-brain barrier back into the rest of the body to modulate the immune system and induce extracranial abscopal responses. Emerging data from a small number of case series and individual case reports of various malignancies have radically altered our earlier understanding by revealing that the CNS is neither isolated nor passive in its interactions with the body’s immune system. Furthermore, current data indicate that the CNS is both immune-competent and interacts actively with the peripheral immune system. Therefore, radiation treatment to ≥1 location of CNS metastases can induce abscopal responses in tumors away from the treated CNS metastatic sites. These observations suggest the abscopal effect traverses the blood-brain barrier. In this article, we reviewed and assessed the clinical evidence of extracranial abscopal responses of CNS-radiation therapy in patients with advanced lung cancer.
The Effect of Metformin on Prognosis in Patients With Locally Advanced Gastric Cancer Associated With Type 2 Diabetes Mellitus
Authors: Seo Ho Seok , Jung Yoon Ju , Kim Ji Hyun , Lee Han Hong , Park Cho Hyun
Published: November 2019

Objectives:

This study examined the effect of metformin use on the prognosis of gastric cancer patients.

Materials and Methods:

The study population comprised 2187 patients who underwent curative gastrectomy for the treatment of gastric cancer. They were divided into 3 groups: metformin (n=103), non-metformin (n=139), and non-diabetes mellitus (DM) (n=1945) according to their history of type 2 DM and metformin use. Survival, disease recurrence, and the pathologic stage were analyzed.

Results:

Overall survival was better in the metformin group than in the non-DM group (P=0.005). Metformin use was an independent prognostic factor of overall survival, cancer recurrence, and peritoneal recurrence. An effect of metformin use was especially notable in patients with T4 or N0 disease.

Conclusions:

Metformin improves the survival of patients with gastric cancer and type 2 DM.
A Pilot Study of Radiation Therapy in Combination With Pembrolizumab in Patients With Metastatic Renal Cell Cancer
Authors: Lin Jianqing , Song Andrew J. , Hoffman-Censits Jean , Leiby Benjamin E. , Tuluc Madalina , Shaw Colette , Harshyne Larry , Kean Rhonda , Bar-Ad Voichita , Den Robert B. , Hurwitz Mark D. , Louie Jennifer , Philipose Sherin , Deshmukh Sandeep P. , Johnson Jennifer M. , Dicker Adam P. , Hooper Douglas C. , Kelly William K. , Lu Bo
Published: November 2019

Objectives:

There is no study published regarding the benefit of radiation therapy (RT) in combination with immune checkpoint inhibitors (ICIs) for the treatment of metastatic renal cell cancer (mRCC). This report is part of an exploratory study aiming to determine the immunomodulatory activity of RT alone or in combination with pembrolizumab in solid tumors.

Materials and Methods:

mRCC patients were treated with a combination of RT (8 Gy×1 or 4 Gy×5) followed by pembrolizumab with or without lead-in dose of pembrolizumab. Treatment response was measured based on the modified Response Evaluation Criteria in Solid Tumors criteria. Adverse events were monitored and graded. Pre-RT and post-RT tumor biopsies were obtained to evaluate programmed death-ligand 1 expression. Immune markers from peripheral blood before, during, and after treatment were analyzed using flow cytometry.

Results:

Twelve mRCC patients who progressed on prior antiangiogenic therapy were enrolled. Half had 2 lines of prior therapy. Two patients (16.7%) had partial responses and were on study for 12.4 and 14.5 months. Three patients had stable disease for a period ranging from 4.2 to 10.4 months, whereas 7 patients had progressive disease. Median progression-free survival was 8.6 months and median overall survival was 32.3 months. Three patients had grade ≥3 events (hyperglycemia, thrombocytopenia, transaminitis). Biopsied tissue programmed death-ligand 1 expression and tumor-infiltrating lymphocytes were numerically higher in responders comparing to nonresponders (Modified Proportion Score 45% vs. 30.45%; tumor-infiltrating lymphocytes odds ratio 4.92).

Conclusion:

Combining RT with pembrolizumab in pretreated mRCC is well-tolerated and appears to have comparable efficacy with single-agent nivolumab.
Metastatic Crohn Disease: A Clinicohistological Appraisal From a Tertiary Care Center in India
Authors: Chatterjee Debajyoti , Bhattacharjee Rajsmita , Khullar Geeti , Kumaran Sendhil , De Dipankar , Saikia Uma N. , Radotra Bishan D.
Published: November 2019

Background:

Granulomatous dermatitis due to noncontiguous involvement of Crohn disease (CD) of the gut has been described as metastatic CD (MCD). MCD is the rarest form of cutaneous manifestations of CD. This study aims to analyze the clinicohistological features of MCD in a tertiary care center of India.

Materials and Methods:

A retrospective review of patients diagnosed clinically and histologically with MCD over past 5 years was performed. Data on cutaneous features, histological findings, and response to treatment were collected.

Results:

Twelve patients (3 men and 9 women) with a mean age of 29 years were identified. All women had vulval involvement in the form of edema (80%), ulceration (60%), and fistula (20%). Among the 3 men, 2 had perineal and scrotal swelling and ulcer, whereas the third patient presented with leg ulcer. Intestinal CD was already diagnosed in 50% patients (5/10) at cutaneous presentation, whereas it was diagnosed subsequently in 30% (3/10) cases. Histological examination revealed nonnecrotizing granulomatous inflammation in the dermis in 11 patients (92%). Additional histological features included eosinophilic infiltrate (58%), panniculitis (33%), and vasculitis (33%). The patients were treated with various combinations of oral prednisolone, metronidazole, minocycline, azathioprine, and subcutaneous adalimumab with partial relief.

Conclusion:

MCD shows a wide spectrum of clinical presentation, with anogenital involvement being the most common. Histology reveals nonnecrotizing granulomas in the dermis in majority of the cases. The diagnosis is extremely challenging in patients without gastrointestinal involvement at presentation, and thus, a high index of suspicion is imperative.
Morphologic, Immunohistochemical, and Molecular Distinction Between Fibroepithelioma of Pinkus and “Fenestrated” Basal Cell Carcinoma
Authors: Russell-Goldman Eleanor , Lindeman Neal I. , Laga Alvaro C. , Hanna John
Published: November 2019

Fibroepithelioma of Pinkus (FEP) is a rare cutaneous neoplasm with a characteristic fenestrated architecture and a prominent spindle cell stromal component and which invariably pursues an indolent course. The classification of FEP has been much debated since its first description in 1953, with some arguing that it represents a variant of a basal cell carcinoma (BCC) while others view it as a variant of a trichoblastoma. Multiple previous immunohistochemical studies aiming to clarify this issue have yielded conflicting results. To date, there have been no molecular studies of FEP. We identified 16 cases of fenestrated follicular neoplasms and classified them as BCC or FEP based solely on histomorphologic criteria. CK20 immunohistochemistry supported this classification scheme, with FEP showing significantly more CK20-positive Merkel cells than BCC. We then analyzed a subset of these tumors by a targeted next-generation DNA sequencing platform. All the BCC cases harbored pathogenic PTCH1 mutations, confirming the diagnosis. By contrast, none of the FEP cases harbored a PTCH1 mutation or indeed any mutation known to be causally linked to the development of BCC. Our results suggest that FEP can be distinguished from BCC on morphologic, immunohistochemical, and molecular genetic grounds. We argue that FEP is better considered a benign follicular neoplasm and support its classification as a variant of trichoblastoma.
Toddler Sleep Challenges: All in a Day's Work
Authors: Barnes Andrew J. , Kroupina Maria , Perry Nicole , Augustyn Marilyn
Published: November 2019

CASE:

Leo is a 26-month-old boy who you are seeing for an urgent care visit due to “sleep difficulty,” particularly sleep onset. Since age 1, he screams, hits, and kicks his mother every day, starting after she gets home from work at 5 pm (or before the family's dinnertime on her days off) and escalating over the course of the evening until he “wears himself out” and falls asleep in a crib in his own room around 9 to 10 pm Once asleep, he sleeps well through the night and wakes easily around 7 am in a pleasant mood; his mother leaves for work soon after he awakens. He naps after lunch for 2 to 3 hours on weekdays at an in-home child care with 1 to 2 adult caregivers and 5 other children aged 0 to 5 years. He refuses to nap at home.

Leo goes to bed easily when his father puts him to bed if his mother is not at home, but his mother feels that evenings are the only time she can spend with Leo, and so, she tries to put him to bed most nights. However, because of Leo's behaviors at bedtime with her, she feels inadequate, depressed, and guilty; when she tries to disengage or allow her husband to help, Leo screams, “Mommy, mommy!” and tries to gain access to her and resists his father putting him to bed until his mother returns. Both parents worry that “he would not grow out of this,” and his mother now avoids coming home from work for fear of Leo's behavior. Both parents feel that this situation is causing marital strain.

Leo was born healthy at full-term and is an only child; pregnancy was complicated by hyperemesis gravidarum. Leo has been healthy and meeting developmental milestones. His parents describe his temperament as “like his father at that age,” “easy, but never able to self-soothe,” “intense” in his emotional reactions, persistent, “strong-willed and serious,” and “shy and observant, withdrawn at first and then getting more pleasant after a while” in novel situations. Behaviorally, he engaged in noninjurious head-banging at home when upset between 12 and 15 months; bit children a few times at child care between 20 and 24 months; and lately refuses to share or will push other children at child care every few weeks. His parents recently read a book about parenting “spirited” children but did not find it helpful. What would you do next?
Obstetric complications in pregnancies with life-limiting malformations
Authors: Quaresima Paola , Homfray Tessa , Greco Elena
Published: November 2019

Purpose of review

The implementation of palliative care at birth has led to a significant rise in the number of couples who choose to continue with pregnancies complicated by life-limiting malformations (LLMs). Prenatal counselling and appropriate antenatal/perinatal management in these cases are poorly studied and may pose significant challenges. The purpose of this review is to outline specific obstetric risks and to suggest management for mothers who choose to continue with pregnancies with the most common LLMs.

Recent findings

In pregnancies complicated by LLMs where parents opt for expectant management, clinicians should respect parental wishes, whilst openly sharing potential serious maternal medical risks specific for the identified abnormalities. The focus of both antenatal and perinatal care should be maternal wellbeing rather than foetal survival. Follow-up ultrasound examinations and maternal surveillance should be aimed at achieving timely diagnosis and effective management of obstetric complications. A clear perinatal plan, agreed with the couples by a multi-disciplinary team including a foetal medicine specialist, a neonatologist and a geneticist, is crucial to reduce maternal morbidity.

This review provides a useful framework for clinicians who face the challenges of counselling and managing cases complicated by LLMs where parents opt for pregnancy continuation.
Self-managed abortion
Authors: Conti Jennifer , Cahill Erica P.
Published: November 2019

Purpose of review

To review the current state of self-managed or self-induced abortion in the United States and the emerging legal, political, and research questions surrounding this issue.

Recent findings

With the exponential rise of restrictive antiabortion laws in the United States, it has become increasingly difficult to access safe and legal abortion services. One response to this hostile environment for reproductive care access is an increased interest in methods of self-induced or self-managed abortions, primarily by medications sourced outside the medical setting. Medication abortion is established as a safe and effective method of ending a pregnancy. Compared with clinic-based care, the two most pressing concerns regarding the safety of self-managed abortion are that people seeking abortion will incorrectly self-identifying as appropriate candidates and that they will not know or be able to access medical care if needed. There is therefore an increasing need for medical providers to learn about and researchers to evaluate the incidence, safety and efficacy of self-management of abortion. Simultaneously, reproductive law experts must continue to develop and educate on the legal frameworks to protect and decriminalize people seeking self-managed abortion as well as their care providers.

Emerging research suggests that abortion outside the medical setting, or self-managed abortion, is an overall safe and effective way to end a pregnancy. However, significant legal barriers and stigma remain. The safest environment for self-managed abortion (SMA) is one where accurate information is available, medical care is accessible when needed, and all methods of abortion remain legal.
Hyperbaric Oxygen Preconditioning Can Reduce Postabdominoplasty Complications: A Retrospective Cohort Study
Authors: Friedman Tali , Menashe Shaked , Landau Geva , Sherf Matan , Wiser Itay , Seligman Yaakov , Friedman Mony , Hadanny Amir , Efrati Shai , Heller Lior
Published: November 2019

Background:

Hyperbaric oxygen therapy (HBOT) can improve wound healing and has been found to have positive preconditioning effects in animal models. Among esthetic surgical procedures, abdominoplasty poses the highest rate of postoperative complications. The aim of this study was to evaluate the effect of preoperative HBOT as a preconditioning treatment for expected postsurgical complications.

Methods:

We conducted a retrospective cohort study among patients who underwent abdominoplasty at our institute and private practice between January 2012 and November 2017. Patients who received preoperative HBOT were compared with patients who did not receive HBOT. Surgical complication data and demographic, preoperative and postoperative data from patient records were collected.

Results:

The study included 356 patients. Of them, 83 underwent HBOT preoperatively. Using preoperative HBOT, postoperative complications were significantly reduced from 32.6% (89 patients) to 8.4% (7 patients),P<0.001. Moreover, 17 (6.2%) patients in the comparison group and none in the HBOT group experienced necrosis (P= 0.016). In the multivariate analysis, preoperative HBOT was an independent protective factor against postoperative complications (odds ratio, 0.188; 95% CI, 0.082–0.432;P< 0.001). After propensity score matching, the study results remained the same.

Conclusions:

Preoperative HBOT can reduce postoperative complication rate in abdominoplasty patients. Further prospective studies are necessary to validate the findings and characterize patients who benefit the most from this treatment.