bluuebunny/crossref_metadata_2025 huggingface dataset:
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls
Authors: Momozawa Yukihide , Iwasaki Yusuke , Hirata Makoto , Liu Xiaoxi , Kamatani Yoichiro , Takahashi Atsushi , Sugano Kokichi , Yoshida Teruhiko , Murakami Yoshinori , Matsuda Koichi , Nakagawa Hidewaki , Spurdle Amanda B , Kubo Michiaki
Published: June 2019

Background

Genetic testing has been conducted in patients with prostate cancer (PCa) using multigene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants.

Methods

We sequenced eight genes associated with hereditary PCa in 7636 unselected Japanese patients with PCa and 12 366 male, cancer-free control individuals. We assigned clinical significance for all 1456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and control participants with calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided.

Results

We identified 136 pathogenic variants, and 2.9% of patients and 0.8% of control individuals had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P < .001, odds ratio [OR] = 5.65, 95% confidence interval [CI] = 3.55 to 9.32), HOXB13 (P < .001, OR = 4.73, 95% CI = 2.84 to 8.19), and ATM (P < .001, OR = 2.86, 95% CI = 1.63 to 5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis and more often had smoking and alcohol drinking histories as well as family histories of breast, pancreatic, lung, and liver cancers.

Conclusions

This largest sequencing study of PCa heredity provides additional evidence supporting the latest consensus among clinicians for developing genetic testing guidelines for PCa.
Stereotactic body radiotherapy for primary non-small cell lung cancer patients with clinical T3-4N0M0 (UICC 8th edition): outcomes and patterns of failure
Authors: Narita Atsuya , Takeda Atsuya , Eriguchi Takahisa , Saigusa Yusuke , Sanuki Naoko , Tsurugai Yuichiro , Enomoto Tatsuji , Kuribayashi Hidehiko , Mizuno Tomikazu , Yashiro Kae , Hara Yu , Kaneko Takeshi
Published: June 2019

The evidence for stereotactic body radiotherapy (SBRT) is meagre for patients with clinical T3-4N0M0 non-small cell lung cancer (8th Edition of the Union for International Cancer Control (UICC)). This study retrospectively investigated clinical outcomes following SBRT for such patients. Among consecutive patients treated with SBRT, patients staged as cT3-4N0M0 by all criteria were examined, most of whom were unsuitable to chemoradiotherapy due to their fragile characters. Clinical outcomes were evaluated and factors associated with outcomes were investigated. Between 2005 and 2017, 70 eligible patients (T3: 58, T4: 12; median age 81 (63–93) years) were identified. Median follow-up duration was 28.6 (1.0–142.5) months. No adjuvant chemotherapy was administered. The 3-year local recurrence rates were 15.8% and 16.7% in T3 and T4 patients, respectively, and they were significantly lower in the high-dose group (3.1% vs 28.6%, P < 0.01). Multivariate analyses showed that the dose-volumetric factor was the significant factor for local recurrence. The 3-year regional and distant metastasis rates, cancer-specific mortality, and overall survival in T3 and T4 patients were 22.7% and 25.0%, 26.5% and 33.3%, 32.2% and 41.7%, and 39.5% and 41.7%, respectively. Only age was correlated with overall survival. Radiation pneumonitis ≥grade 3 and fatal hemoptysis occurred in 3 and 1 patients, respectively. SBRT for cT3-4N0M0 lung cancer patients achieved good local control. Survival was rather good considering that patients were usually frail, staged with clinical staging, and were not given adjuvant chemotherapy, and it may be comparable to surgery. To validate these outcomes following SBRT, a prospective study is warranted.
Radiotherapy for localized sebaceous carcinoma of the eyelid: a retrospective analysis of 83 patients
Authors: Takagawa Yoshiaki , Tamaki Wakana , Suzuki Shigenobu , Inaba Koji , Murakami Naoya , Takahashi Kana , Igaki Hiroshi , Nakayama Yuko , Shigematsu Naoyuki , Itami Jun
Published: June 2019

The current study retrospectively analyzed the results of radiotherapy for clinically localized sebaceous carcinoma of the eyelid.We reviewed records of 83 patients with histologically confirmed sebaceous carcinoma who were treated radiotherapeutically between 1983 and 2015. Sixty-five patients (78%) were initially treated with radiotherapy of curative intent, while the remaining 18 patients underwent postoperative radiotherapy due to tumor recurrence or positive surgical margins. Thirty-seven patients belonged to T1–2, while 46 belonged to T3–4. All 83 patients were treated with radiotherapy with a median radiation dose of 60 Gy. The median follow-up period was 92.1 months (range, 2.8–310.3 months).

At the time of analysis, 13 patients (15.1%) died, and 36 patients (43.3%) had local recurrence. The 7-year overall survival, freedom from neck lymph node recurrence, and local control (LC) rates for all patients were 83.5%, 75.5%, and 52.3%, respectively. Patients with a tumor size ≤10 mm had a higher 7-year LC rate than those with a tumor size >10 mm (58.8% vs 46.6%, P = 0.054). Neck lymph node recurrence was observed in 17 patients (20%) and significantly related to the tumor size. Late toxicity of an eyelid dysfunction of grade 3 was observed in 1 patient with T3 tumor.

Radiotherapy for sebaceous carcinoma of the eyelid is a reasonable alternative to surgical resection for tumors <10 mm in size with few severe complications, while larger tumors should be treated with surgery if feasible.
Surgical excision of a giant pedunculated hydatid cyst of the liver
Authors: Mohammed Ayad Ahmad , Arif Sardar Hassan
Published: June 2019

Hydatid disease is caused by a tape worm Echinococcus Granulosus that lives in the intestines of the definitive host which is the dog or other carnivore. Human is the accidental intermediate host and become infected by ingesting contaminated vegetables or water with the eggs of the parasite.

A-37-year old male presented with right side abdominal pain for 2 months. Abdominal examination showed a large right side abdominal mass extending from the right subcostal region to the right iliac fossa. CT-scan showed two cystic lesions in the right lobe of the and a third one extending to the pelvis. During surgery aspiration of 10 liters of bile stained fluid done. Excision of the cysts done. Tube drain put inside the cyst cavity with omentoplasty. There was bile leak to the drain which stopped over one month. The patient received anthelminthic medication for 3 months.
Mechanics of a plant in fluid flow
Authors: Gosselin Frédérick P
Published: June 2019

Plants live in constantly moving fluid, whether air or water. In response to the loads associated with fluid motion, plants bend and twist, often with great amplitude. These large deformations are not found in traditional engineering application and thus necessitate new specialized scientific developments. Studying fluid–structure interaction (FSI) in botany, forestry, and agricultural science is crucial to the optimization of biomass production for food, energy, and construction materials. FSIs are also central in the study of the ecological adaptation of plants to their environment. This review paper surveys the mechanics of FSI on individual plants. I present a short refresher on fluid mechanics then dive into the statics and dynamics of plant–fluid interactions. For every phenomenon considered, I examine the appropriate dimensionless numbers to characterize the problem, discuss the implications of these phenomena on biological processes, and propose future research avenues. I cover the concept of reconfiguration while considering poroelasticity, torsion, chirality, buoyancy, and skin friction. I also assess the dynamical phenomena of wave action, flutter, and vortex-induced vibrations.
The binary millisecond pulsar PSR J1023+0038 – II. Optical spectroscopy
Authors: Shahbaz T , Linares M , Rodríguez-Gil P , Casares J
Published: June 2019

We present time-resolved optical spectroscopy of the ‘redback’ binary millisecond pulsar system PSR J1023+0038 during both its radio pulsar (2009) and accretion disc states (2014 and 2016). We provide observational evidence for the companion star being heated during the disc state. We observe a spectral type change along the orbit, from ∼G5 to ∼F6 at the secondary star’s superior and inferior conjunction, respectively, and find that the corresponding irradiating luminosity can be powered by the high-energy accretion luminosity or the spin-down luminosity of the neutron star. We determine the secondary star’s radial velocity semi-amplitude from the metallic (primarily Fe and Ca) and Hα absorption lines during these different states. The metallic and Hα radial velocity semi-amplitude determined from the 2009 pulsar-state observations allows us to constrain the secondary star’s true radial velocity K2 = 276.3 ± 5.6  km s−1 and the binary mass ratio q = 0.137 ± 0.003. By comparing the observed metallic and Hα absorption-line radial velocity semi-amplitudes with model predictions, we can explain the observed semi-amplitude changes during the pulsar state and during the pulsar/disc-state transition as being due to different amounts of heating and the presence of an accretion disc, respectively.
Dynamics of magnetic flux tubes in accretion discs of T Tauri stars
Authors: Dudorov A E , Khaibrakhmanov S A , Sobolev A M
Published: June 2019

Dynamics of slender magnetic flux tubes (MFTs) in the accretion discs of T Tauri stars is investigated. We perform simulations taking into account buoyant, aerodynamic, and turbulent drag forces, radiative heat exchange between MFT and ambient gas, and magnetic field of the disc. The equations of MFT dynamics are solved using Runge–Kutta method of the fourth order. The simulations show that there are two regimes of MFT motion in absence of external magnetic field. In the region r < 0.2 au, the MFTs of radii $0.05 \le a_0 \le 0.16\, H$ (H is the scale height of the disc) with initial plasma beta of 1 experience thermal oscillations above the disc. The oscillations decay over some time, and MFTs continue upward motion afterwards. Thinner or thicker MFTs do not oscillate. MFT velocity increases with initial radius and magnetic field strength. MFTs rise periodically with velocities up to 5–15 km s−1 and periods of 0.5–10 yr determined by the toroidal magnetic field generation time. Approximately 20 per cent of disc mass and magnetic flux can escape to disc atmosphere via the magnetic buoyancy over characteristic time of disc evolution. MFTs dispersal forms expanding magnetized corona of the disc. External magnetic field causes MFT oscillations near the disc surface. These magnetic oscillations have periods from several days to 1–3 months at r < 0.6 au. The magnetic oscillations decay over few periods. We simulate MFT dynamics in accretion discs in the Chameleon I cluster. The simulations demonstrate that MFT oscillations can produce observed IR-variability of T Tauri stars.
Mechanism for APOBEC3G catalytic exclusion of RNA and non-substrate DNA
Authors: Solomon William C , Myint Wazo , Hou Shurong , Kanai Tapan , Tripathi Rashmi , Kurt Yilmaz Nese , Schiffer Celia A , Matsuo Hiroshi
Published: June 2019

The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of substrate ssDNA from non-substrate. Using 2′-deoxy-2′-fluorine substituted cytidines, we show that a 2′-endo sugar conformation of the target deoxycytidine is favored for substrate binding and deamination. Trajectories of the MD simulation indicate that a ribose 2′-hydroxyl group destabilizes the π-π stacking of the target cytosine and H257, resulting in dislocation of the target cytosine base from the catalytic position. Interestingly, APOBEC3A, which can deaminate ribocytidines, retains the ribocytidine in the catalytic position throughout the MD simulation. Our results indicate that A3Gctd catalytic selectivity against RNA is dictated by both the sugar conformation and 2′-hydroxyl group.
Transcriptome signature of cellular senescence
Authors: Casella Gabriel , Munk Rachel , Kim Kyoung Mi , Piao Yulan , De Supriyo , Abdelmohsen Kotb , Gorospe Myriam
Published: June 2019

Cellular senescence, an integral component of aging and cancer, arises in response to diverse triggers, including telomere attrition, macromolecular damage and signaling from activated oncogenes. At present, senescent cells are identified by the combined presence of multiple traits, such as senescence-associated protein expression and secretion, DNA damage and β-galactosidase activity; unfortunately, these traits are neither exclusively nor universally present in senescent cells. To identify robust shared markers of senescence, we have performed RNA-sequencing analysis across eight diverse models of senescence triggered in human diploid fibroblasts (WI-38, IMR-90) and endothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubicin, and expression of the oncogene HRASG12V. The intersection of the altered transcriptomes revealed 50 RNAs consistently elevated and 18 RNAs consistently reduced across all senescence models, including many protein-coding mRNAs and some non-coding RNAs. We propose that these shared transcriptome profiles will enable the identification of senescent cells in vivo, the investigation of their roles in aging and malignancy and the development of strategies to target senescent cells therapeutically.
Noise-reducing optogenetic negative-feedback gene circuits in human cells
Authors: Guinn Michael Tyler , Balázsi Gábor
Published: June 2019

Gene autorepression is widely present in nature and is also employed in synthetic biology, partly to reduce gene expression noise in cells. Optogenetic systems have recently been developed for controlling gene expression levels in mammalian cells, but most have utilized activator-based proteins, neglecting negative feedback except for in silico control. Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback. We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-inhibiting peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain. These LITers provide a range of nearly 4-fold gene expression control and up to 5-fold noise reduction from existing optogenetic systems. Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation. Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology and other biomedical fields of research.
Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging
Authors: Buchanan Charlotte E , Mahmoud Huda , Cox Eleanor F , McCulloch Thomas , Prestwich Benjamin L , Taal Maarten W , Selby Nicholas M , Francis Susan T
Published: June 2019

Background

Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD).

Methods

We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated.

Results

MRI evidenced excellent reproducibility in CKD (coefficient of variation <10%). Significant differences between CKD and HVs included cortical and corticomedullary difference (CMD) in T1, cortical and medullary apparent diffusion coefficient (ADC), renal artery blood flow and cortical perfusion. MRI measures correlated with kidney function in a combined CKD and HV analysis: estimated GFR correlated with cortical T1 (r = −0.68), T1 CMD (r = −0.62), cortical (r = 0.54) and medullary ADC (r = 0.49), renal artery flow (r = 0.78) and cortical perfusion (r = 0.81); log urine protein to creatinine ratio (UPCR) correlated with cortical T1 (r = 0.61), T1 CMD (r = 0.61), cortical (r = −0.45) and medullary ADC (r = −0.49), renal artery flow (r = −0.72) and cortical perfusion (r = −0.58). MRI measures (cortical T1 and ADC, T1 and ADC CMD, cortical perfusion) differed between low/high interstitial fibrosis groups at 30–40% fibrosis threshold.

Conclusion

Comprehensive multi-parametric MRI is reproducible and correlates well with available measures of renal function and pathology. Larger longitudinal studies are warranted to evaluate its potential to stratify prognosis and response to therapy in CKD.
Central venous catheter use increases ischemic stroke risk: a nationwide population-based study
Authors: Liao P -H , Lai C -Y , Wu C -H , Su Y -C , Wei C -W , Kao C -H
Published: June 2019

Background

Central venous catheter (CVC) placement is a common procedure used for the treatment of critically ill patients. However, ischemic stroke is a complication after CVC placement.

Aim

This study investigated the association between CVC placement and ischemic stroke risk in an Asian population.

Design

Population-based retrospective study.

Methods

We enrolled 37 623 patients who ever-received CVC placement over 2000–10 and propensity score-matched individuals without CVC placement as the comparison cohort from the Taiwan National Health Insurance Research Database. We determined the cumulative incidence rates and adjusted hazard ratios (aHRs) for ischemic stroke.

Results

We finally identified and enrolled 34 164 propensity score-matched pairs of individuals. Compared with the comparison group, CVC placement increased the average annual ischemic stroke incidence [19.5 vs. 11.6 per 10 000 person-years; crude HR=1.28, 95%, confidence interval (CI)=1.21–1.35; adjusted subhazard ratio (aSHR)=1.4, 95% CI = 1.33–1.47; P<0.001). In addition, compared with those aged >35 years, stroke risk was significantly higher in <35-year-old patients with CVC placement (aSHR=14.3, 95% CI=6.11–33.4; P<0.001). After <1-year follow-up, the ischemic stroke incidence rate in the CVC placement group was ∼3.25-fold higher than that in the comparison group (aHR=3.25, 95% CI=2.9–3.63; P<0.0001).

Conclusion

CVC placement increases ischemic stroke risk, particularly in those aged ≤35 years; this trend warrants further investigation.
Gender and Citizenship in Australia: Government Approaches to Paid Parental Leave Policy 1996–2017
Authors: Newsome Lucie
Published: June 2019

In Western welfare states women’s citizenship rights are increasingly conferred on the basis of labor force participation rather than maternalism. This article examines the policy positions and discourse associated with paid parental leave of successive Australian governments from 1996 to 2017 to examine the extent to which this has occurred in the Australian context. It reveals a slow movement away from maternalism that has been constrained by path dependencies associated with the male breadwinner model and is shaped by philosophies of liberalism and small government.
Evolutionary dynamics and molecular epidemiology of West Nile virus in New York State: 1999–2015
Authors: Bialosuknia Sean M , Tan Yi , Zink Steven D , Koetzner Cheri A , Maffei Joseph G , Halpin Rebecca A , Mueller Emmi A , Novotny Mark , Shilts Meghan , Fedorova Nadia B , Amedeo Paolo , Das Suman R , Pickett Brett , Kramer Laura D , Ciota Alexander T
Published: June 2019

Following its introduction into New York State (NYS) in 1999, West Nile virus (WNV; Flavivirus, Flaviviridae) underwent a rapid expansion throughout the USA and into Canada and Latin America. WNV has been characterized as being evolutionarily stable, with weak geographic structure, a dominance of purifying selection and limited adaptive change. We analyzed all available full-genome WNV sequences, focusing on the 543 available sequences from NYS, which included 495 newly sequenced 2000–15 isolates. In addition, we analyzed deep-sequencing data from 317 of these isolates. While our data are generally in agreement with the limited pace of evolutionary change and broad geographic and temporal mixing identified in other studies, we have identified some important exceptions. Most notably, there are 14 codons which demonstrated evidence of positive selection as determined by multiple models, including some positions with evidence of selection in NYS exclusively. Coincident with increased WNV activity, genotypes possessing one or more of these mutations, designated NY01, NY07, and NY10, have increased in prevalence in recent years and displaced historic strains. In addition, we have found a geographical bias with many of these mutations, which suggests selective pressures and adaptations could be regional. Lastly, our deep-sequencing data suggest both increased overall diversity in avian tissue isolates relative to mosquito isolates and multiple non-synonymous minority variants that are both host-specific and retained over time and space. Together, these data provide novel insight into the evolutionary pressures on WNV and the need for continued genetic surveillance and characterization of emergent strains.
Sexual Assault in the Military and Increased Odds of Sexual Pain Among Female Veterans
Authors: Pulverman Carey S. , Creech Suzannah K. , Mengeling Michelle A. , Torner James C. , Syrop Craig H. , Sadler Anne G.
Published: June 2019

OBJECTIVE:

To examine whether the relationship between childhood sexual abuse and sexual function in civilian women is also found among female veterans, and to consider the additional effects of sexual assault in the military.

METHODS:

Using a retrospective cohort design, participants (N=1,004) from two midwestern Department of Veterans Affairs medical centers and associated clinics completed a telephone-assisted interview on sexual assault, sexual pain, and mental health. Binary logistic regression was used to compare the rates of sexual pain between women with no sexual assault history, histories of childhood sexual abuse alone, histories of sexual assault in the military alone, and histories of childhood sexual abuse and sexual assault in the military.

RESULTS:

Female veterans with histories of childhood sexual abuse and sexual assault in the military reported the highest rates of sexual pain (χ2(3)=40.98, P<.001), posttraumatic stress disorder (PTSD, χ2(3)=88.18, P<.001), and depression (χ2(3)=56.07, P<.001), followed by women with sexual assault in the military histories alone, women with childhood sexual abuse histories alone, and women with no sexual assault. Female veterans with histories of childhood sexual abuse and sexual assault in the military were 4.33 times more likely to report sexual pain, 6.35 times more likely to report PTSD, and 3.91 times more likely to report depression than female veterans with no sexual assault.

CONCLUSION:

The relationship between sexual assault and sexual pain in female veterans is distinct from their civilian peers. For female veterans, sexual assault in the military is more detrimental to sexual function (specifically sexual pain) than childhood sexual abuse alone, and the combination of childhood sexual abuse and sexual assault in the military confers the greatest risk for sexual pain. Given this difference in sexual health, treatments for sexual dysfunction related to a history of childhood sexual abuse in civilian women may not be adequate for female veterans. Female veterans may require a targeted treatment approach that takes into account the particular nature and consequences of sexual assault in the military.
Chemotherapy, Radiation, or Combination Therapy for Stage III Uterine Cancer
Authors: Syeda Sbaa , Chen Ling , Hou June Y. , Tergas Ana I. , Khoury-Collado Fady , Melamed Alexander , St. Clair Caryn M. , Ananth Cande V. , Neugut Alfred I. , Hershman Dawn L. , Wright Jason D.
Published: June 2019

OBJECTIVE:

To compare the outcomes of women with stage III uterine cancer treated with chemotherapy alone, external beam radiation alone, and combination chemotherapy and radiation.

METHODS:

The National Cancer Database was used to identify women with stage III endometrioid, serous, and clear cell uterine cancer treated with either chemotherapy (with or without vaginal brachytherapy) alone, external beam radiation (with or without brachytherapy), or combination chemotherapy and external beam radiation (with or without vaginal brachytherapy) from 2004 to 2015. Survival was estimated using Cox proportional hazards models and adjusted survival curves after propensity score analysis using inverse probability of treatment weighting to balance the clinical and demographic characteristics between the cohorts.

RESULTS:

Of the 20,873 patients identified, 9,456 (45.3%) received chemotherapy alone, 2,417 (11.6%) were treated with radiation alone, and 9,000 (43.1%) received chemotherapy in combination with external beam radiation. Use of combination therapy was 33.0% in 2004, and then rose to 50.5% in 2015. The mortality of the cohort was 33.1% and median survival was 115 months. Within the cohort, combination therapy was associated with a 23% reduction in mortality (hazard ratio [HR]=0.77; 95% CI 0.73–0.80) compared with chemotherapy alone. Similar findings of decreased mortality were noted in subgroup analyses for both stage IIIA (HR=0.81; 95% CI 0.68–0.98) and stage IIIC (HR=0.79; 95% CI 0.75–0.84) tumors. Similarly, when compared with radiation alone, combination therapy was accompanied by a 19% decrease in mortality (HR=0.81; 95% CI 0.73–0.89). Combination chemoradiation was associated with decreased mortality across all of the histologic subtypes.

CONCLUSION:

Among women with stage III uterine cancer, combination chemotherapy and external beam radiation is associated with decreased mortality compared with chemotherapy or radiation alone.
An Opportunity to Engage Obstetrics and Gynecology Patients Through Shared Visit Notes
Authors: Herlihy Mary , Harcourt Kendall , Fossa Alan , Folcarelli Patricia , Golen Toni , Bell Sigall K.
Published: June 2019

OBJECTIVE:

To assess obstetrics and gynecology patients' interest in reading their ambulatory visit notes, identification of documentation errors, and perceptions of sensitive language through a quality improvement (QI) initiative.

METHODS:

Beginning April 2016, as part of a QI project all obstetrics and gynecology patients (except family planning) were invited to read their ambulatory visit notes and provide feedback using a patient reporting tool codeveloped with patients. Two physicians with safety expertise reviewed all patient-reported errors over the first 16 months.

RESULTS:

Among obstetrics and gynecology patients with an active portal account and an available note, 6,594 of 9,550 (69%) read at least one note. Two hundred twelve (3.2%) patients used the electronic reporting tool, submitting a total of 232 reports, in a “natural” environment with no advertisement, incentives, or clinician encouragement. In total, 94% felt they understood the notes, 95% understood the next steps in the care plan, and 92% felt the notes accurately described their visit. Of all reports, 27% of patients identified inaccuracies in the notes, including descriptions of symptoms (29%); family history (21%); medications (15%); health problems (15%); social history and physical examination, including elements that were reportedly documented but not performed (each 11%). Patients rated inaccuracies as important in 58% of reports, and, on clinician review, 75% of patient-reported mistakes had the potential to affect care. Among all reports, 7% of patients indicated bothersome words. More than half (56%) of patients included voluntary positive feedback such as appreciation for the health care provider, reassurance from notes, greater visit recall and care plan adherence, and positive effects on the patient–doctor relationship.

DISCUSSION:

Obstetrics and gynecology patients are interested in reading notes, which can promote engagement and safety. Few patients provided feedback, but those who did identified documentation inaccuracies in about one quarter of reports; the majority were relevant to care. Greater outreach and patient encouragement are needed to further engage patients in safety.
Postpartum Galactostasis of the Vulva in a Case of Bilateral Lactating Ectopic Breast Tissue
Authors: Mayer Richard B. , Enengl Sabine , Witzany Herbert , Trautner Philip , Shebl Omar , Oppelt Peter
Published: June 2019

BACKGROUND:

In the general population, the incidence of accessory breast tissue, a congenital malformation, is 1–5%. The most common site is the lower axilla. Detecting such tissue may be problematic, and accessory breasts below the umbilicus are extremely rare.

CASE:

This report describes the case of a 5-day postpartum 29-year-old woman, G2P2, with painful vulvar swelling 6 cm in diameter. The patient was diagnosed with polymastia in the vulva, without polythelia, with galactostasis due to suturing of a birth laceration covering an excretory duct. The sutures were removed, and the pain decreased. Breastfeeding was continued.

CONCLUSION:

Ectopic breast tissue is rare but should be taken into consideration in the differential diagnosis of a vulvar mass, especially postpartum in lactating women.
Intrauterine Foley Balloon Catheter to Manage Acute Heavy Menstrual Bleeding in a Perimenarchal 10-Year-Old Girl
Authors: Stanley Jennifer , Adeyemi-Fowode Oluyemisi
Published: June 2019

BACKGROUND:

Intrauterine balloon tamponade is commonly used to treat postpartum hemorrhage refractory to pharmacologic interventions. It has not been well-studied in girls or adolescents for treatment of acute heavy menstrual bleeding.

CASE:

A 10-year old girl presented with heavy menstrual bleeding that did not respond to medical management. Placement of a Foley catheter for intrauterine tamponade was used to control bleeding. She was subsequently diagnosed with a platelet function disorder.

CONCLUSION:

Foley catheter placement is a low-risk, low-cost, and readily accessible option for intrauterine tamponade to consider for young girls and adolescents with acute heavy menstrual bleeding resistant to medical management.
Treatment in a Nonpediatric Hospital Is a Risk Factor for Open Reduction of Pediatric Supracondylar Humerus Fractures: A Population-Based Study
Authors: Vorhies John S. , Uzosike Onyemaechi B. , Imrie Meghan N. , Rinsky Lawrence , Hoffinger Scott
Published: June 2019

Objectives:

To describe the distribution of open versus closed treatment and its relationship with the location of care in pediatric specialty versus general hospitals.

Methods:

Patient data were extracted from the Healthcare Cost and Utilization Project's Kid's Inpatient Database for the years 2000–2012. ICD9-CM diagnosis and procedure codes were used to identify open versus closed treatment of closed supracondylar humerus fractures in children younger than 12 years. A multilevel logistic regression model to control for confounders and identify drivers of open treatment was used.

Results:

An estimated 40,706 inpatient surgical fixation procedures met our inclusion criteria. Overall rate of open treatment was 13.65%. Fractures were less likely to be treated open at pediatric hospitals versus general hospitals 7.61% versus 16.13% (P < 0.0001). Over the study period, rates of open treatment have fallen at nonpediatric hospitals from 20.21% in 2000 to 17.42% in 2012 (P < 0.001) but have remained stable at pediatric hospitals: 7.8% in 2000 and 8.62% in 2012 (P = 0.4369). Mean hospital length of stay was higher for patients who had open treatment 1.63 versus 1.20 days (P < 0.0001), and mean hospital charges were higher for patients who had open treatment $21,465 versus $15,026 (P < 0.0001). After controlling for time trends as well as demographic and hospital characteristics with a logistic regression model, treatment at a nonpediatric hospital was the single most significant predictor of open treatment for an isolated closed supracondylar humerus fractures with an odds ratio of 1.96 (95% confidence interval 1.56–2.46; P < 0.001).

Conclusions:

In this comprehensive population-based study of risk factors for open treatment of supracondylar humerus fractures in the United States, we identified differences in practice patterns by hospital type. Pediatric supracondylar fractures of the elbow have almost twice the odds of open treatment at nonpediatric hospitals.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Medial Buttress Plating for Humerus Fractures With Unstable Medial Column
Authors: Park Sam-Guk , Ko Young-Jin
Published: June 2019

The purpose of this study was to report surgical tips and techniques on the use of additional medial buttress plate fixation in proximal humeral fractures with unstable medial column restoration after lateral locking compression plate fixation. Between April 2011 and January 2017, 17 patients with medial cortical deficiency were treated using this technique. The average follow-up period was 30 (range, 12–81) months. Successful fracture healing was achieved in all 17 cases. The mean neck-shaft angle change was 1.33 degree (range, 0–7.4 degree). Anterior glenoid rim erosion occurred in 1 patient. No avascular necrosis of the humeral head or significant loss of reduction, and no implant failure or screw perforation occurred. In the first part of this study, we described in detail the indications and surgical technique applied to these fractures. In the second part, we reviewed the clinical and radiographic outcomes of these patients. Supplemental medial buttress plate fixation after lateral locking compression plate fixation was effective in preventing varus collapse and implant failure for proximal humeral fractures with an unstable medial column.
International Survey: Factors Associated With Operative Treatment of Distal Radius Fractures and Implications for the American Academy of Orthopaedic Surgeons' Appropriate Use Criteria
Authors: Kyriakedes James C. , Crijns Tom J. , Teunis Teun , Ring David , Bafus Blaine T. ,   Science of Variation Group
Published: June 2019

Objectives:

Through an international survey, we assessed whether deciding to operatively treat an intra-articular distal radius fracture (DRF) is guided by identifiable patient and surgeon factors. In addition, we compared surgeons' treatment decisions with the American Academy of Orthopaedic Surgeons' Appropriate Use Criteria (AUC) treatment recommendations.

Methods:

This cross-sectional survey asked 224 surgeons to operatively or nonoperatively treat 28 hypothetical patients with radiographs of an intra-articular DRF. We randomized patient age (50/70 years), gender, mechanism of injury, activity level, and OTA/AO fracture type. We classified 6 fractures as “nonclinically significant displacement” and 22 as “potentially clinically significant displacement.” Multilevel logistic regression analysis was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported. Statistical significance was P < 0.05.

Results:

Patient factors independently associated with surgery included younger age (OR 6.7, P = 0.003), clinically significant fracture displacement (type B: OR 122, CI, 20–739, P < 0.001; type C: OR 59, CI, 12–300, P < 0.001), normal activity level (OR 5.0, P < 0.001), and high-energy mechanisms (OR 1.3, P = 0.002). Surgeon factors associated with recommending surgery included practicing outside the United States (Europe: OR 2.6, P < 0.001; “other”: OR 4.8, P < 0.001). Hand surgeons most often selected surgery, as compared to orthopaedic trauma surgeons (OR 2.3, P = 0.001) and “other orthopaedists” (OR 2.2, P = 0.022). Thirty-seven percent of treatment decisions for patients with normal activity levels were rated by AUC recommendations as “rarely appropriate,” which included 91% disagreement for 70-year-olds with nonclinically significant displacement.

Conclusions:

Surgeons use patient age and fracture displacement to make treatment recommendations for intra-articular DRF. We recommend that the AUC be updated to include these clinical factors as essential components in its algorithm.

Level of Evidence:

Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.
Accurate Prediction of Antegrade and Retrograde Femoral Intramedullary Implant Length From Patient-Reported Height
Authors: Pearson Jeffrey , Hess Matthew , McGwin Gerald , Quade Jonathan
Published: June 2019

Objective:

To determine whether patient height correlates with implant length selection of antegrade or retrograde femoral intramedullary implants.

Design:

Case–control Study.

Setting:

A single level 1 trauma center.

Patients/Participants:

All patients with operatively treated femoral shaft fractures from 2011 to 2017.

Intervention:

All fractures were treated with an intramedullary nail. Retrograde or antegrade insertion was decided at the discretion of the surgeon and fracture location.

Main Outcome Measurements:

Length of femoral implant and patient height.

Results:

Five hundred sixty-seven operatively treated fractures were reviewed, 322 antegrade and 245 retrograde. The correlation between patient height and actual nail length was 0.55 for antegrade implants (P < 0.01) and 0.59 for retrograde implants (P < 0.01). Separate prediction equations for nail length based on patient height were estimated for antegrade and retrograde implants and found accurate prediction of length 86% and 88% of the time, respectively.

Conclusions:

Intramedullary nail length can be accurately predicted based on patient height and the technique using the equations below. This is the first study to establish a simple equation to serve as an adjunct for selecting the most appropriate length implant. This equation can be used in cases of bilateral femur fractures, templating to have appropriate sized implants in close proximity to the odds ratio, and in remote environments where surgical planning is critical for determining implant needs.
Using Trauma Triage Score to Risk-Stratify Inpatient Triage, Hospital Quality Measures, and Cost in Middle-Aged and Geriatric Orthopaedic Trauma Patients
Authors: Konda Sanjit R. , Lott Ariana , Saleh Hesham , Lyon Thomas , Egol Kenneth A.
Published: June 2019

Objectives:

To investigate the efficacy of a novel geriatric trauma risk assessment tool [Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA)] designed to predict inpatient mortality to risk-stratify measures of hospital quality and cost of care in middle-aged and geriatric orthopaedic trauma patients.

Design:

Prospective cohort study.

Setting:

Academic medical center.

Patients:

One thousand five hundred ninety-two patients 55 years of age and older who were evaluated by orthopaedic surgery in the emergency department between October 1, 2014, and September 30, 2016.

Intervention:

Calculation of the inpatient mortality risk score (STTGMA) using each patient's demographics, injury severity, and functional status. Patients were stratified into minimal-, low-, moderate-, and high-risk cohort groups based on risk of <0.9%, 0.9%–1.9%, 1.9%–5%, and >5%.

Main Outcome Measurements:

Length of stay, complications, disposition, readmission, and cost.

Results:

One thousand two hundred seventy-eight patients (80.3%) sustained low-energy injuries and 314 patients (19.7%) sustained high-energy injuries. The average age was 73.8 ± 11.8 years. The mean length of hospital stay was 5.2 days with a significant difference between the STTGMA risk groups. This risk stratification between groups was also seen in complication rate, need for Intensive Care Unit/Step Down Unit care, percentage of patients discharged, and readmission within 30-days. The mean total cost of admission for the minimal-risk group was less than one-third that of the high-risk cohort.

Conclusions:

The STTGMA tool is able to risk-stratify hospital quality outcome measures and cost. Thus, it is a valuable clinical tool for health care providers in identifying high-risk patients in efforts to continue to provide high-quality resource conscious care to orthopaedic trauma patients.

Level of Evidence:

Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Anatomic Considerations and Reconstruction of the Thumb Flexor Pulley System
Authors: Schneider Andrew D. , Srinivas Mukund , Hijji Fady Y. , Jerkins David , Wimalawansa Sunishka M.
Published: June 2019

Disruption to the flexor pulley system of the thumb is an infrequent but devastating injury that can lead to significant compromise in both strength and function. Acute rupture leads to pain, weakness, reduced range of motion (ROM), and potential bowstringing of the flexor tendons. Conservative treatment with a pulley ring should be considered in all patients. However, failure of conservative treatment and bowstringing of the thumb are indications for operative intervention. Reconstruction of the oblique pulley system can be performed either in situ or using a free palmaris longus graft. Care should be taken to identify the neurovascular bundles to avoid compression during the reconstruction. Conscious sedation protocols augmented by ultrasound-guided sheath blocks allow the patient to actively and strongly contract the flexor pollicis longus tendon intraoperatively to appropriately tension the construct for optimal results. Rehabilitation should be performed in a stepwise manner beginning with early passive ROM, active ROM, and finally strengthening at around 8 weeks postoperative.
Colonic Surgery in Patients With Familial Adenomatous Polyposis
Authors: Bolshinsky Vladimir
Published: June 2019

Case Summary:

A 34-year-old woman is referred after a colonoscopy that revealed >100 polyps throughout her colon and rectum (Fig. 1). A random selection of 3 polyps is biopsied and reported as adenomas. She is adopted and is unaware of her biological family. She is found to have a deleterious germline variant in APC (c.1967-1974del). She works as a nurse and is married with 4 children (age: 17, 13, 11, and 6 years). She has had no prior abdominal operations.
A single administration of Neurotropin reduced the elongated immobility time in the forced swimming test of rats exposed to repeated cold stress
Authors: Nasu Teruaki , Kubo Asako , Queme Luis F. , Mizumura Kazue
Published: June 2019

Many people suffer from a major depressive disorder, and chronic pain conditions are often associated with depressive symptoms. Neurotropin, an extract from the inflamed skin of rabbits inoculated with vaccinia virus, has been used for pain relief. Decrease of brain-derived neurotrophic factor (BDNF) in the brain is one of the proposed mechanisms for the major depressive disorders, and Neurotropin has been reported to restore the decreased BDNF in the hippocampus. In this experiment, we examined whether Neurotropin had an antidepressant-like effect in a model of fibromyalgia and whether BDNF in the brain was altered after repeated cold stress (RCS) and Neurotropin treatment. Rats were exposed to RCS because these animals have been used as a model for fibromyalgia syndrome. Depression-like behavior was evaluated using elongation of immobility time in a forced swimming test. Change in expression of BDNF in the brain was also examined by western blot analysis of several brain areas. Depression-like behavior in the forced swimming test was significantly increased 10–14 days after RCS, and this increase was reversed by a single injection of an antidepressant, imipramine, but not by PBS. Increased depression-like behavior was also dose-dependently suppressed by a single administration of Neurotropin (50–200 NU/kg, subcutaneously). BDNF expression was not changed in the brain areas examined (hippocampus, amygdala, prefrontal cortex, and striatum) either after RCS or by Neurotropin injected after RCS. These results suggest that RCS induced a depression-like state in rats, and Neurotropin reversed this state. However, we did not observe a BDNF-related mechanism for these effects.
Genetic associations with age of menopause in familial longevity
Authors: Bae Harold , Lunetta Kathryn L. , Murabito Joanne M. , Andersen Stacy L. , Schupf Nicole , Perls Thomas , Sebastiani Paola
Published: June 2019

Objective:

We hypothesize that mechanisms associated with extended reproductive age may overlap with mechanisms for the selection of genetic variants that slow aging and decrease risk for age-related diseases. Therefore, the goal of this analysis is to search for genetic variants associated with delayed age of menopause (AOM) among women in a study of familial longevity.

Methods:

We performed a meta-analysis of genome-wide association studies for AOM in 1,286 women in the Long Life Family Study (LLFS) and 3,151 women in the Health and Retirement Study, and then sought replication in the Framingham Heart Study (FHS). We used Cox proportional hazard regression of AOM to account for censoring, with a robust variance estimator to adjust for within familial relations.

Results:

In the meta-analysis, a single nucleotide polymorphism (SNP) previously associated with AOM reached genome-wide significance (rs16991615; HR = 0.74, P = 6.99 × 10−12). A total of 35 variants reached >10−4 level of significance and replicated in the FHS and in a 2015 large meta-analysis (ReproGen Consortium). We also identified several novel SNPs associated with AOM including rs3094005: MICB, rs13196892: TXNDC5 | MUTED, rs72774935: SSBP2 | ATG10, rs9447453: COL12A1, rs114298934: FHL2 | NCK2, rs6467223: TNPO3, rs9666274 and rs10766593: NAV2, and rs7281846: HSPA13.

Conclusions:

This work indicates novel associations and replicates known associations between genetic variants and AOM. A number of these associations make sense for their roles in aging.

Video Summary:

Supplemental Digital Content 1, http://links.lww.com/MENO/A420.