bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA Gm4419 Regulates Myocardial Ischemia/Reperfusion Injury Through Targeting the miR-682/TRAF3 Axis
Authors: Zhao Guixiang , Hailati Juledezi , Ma Xiaoyun , Bao Zhen , Bakeyi Maerjiaen , Liu Zhiqiang
Published: June 2020

Myocardial cell death during acute myocardial infarction occurs because of acute ischemia, persistent ischemia, reperfusion-associated injury, and the inflammatory infiltrate as a response to cell necrosis. In the present study, quantitative real-time PCR showed that lncRNA Gm4419 was highly upregulated in ischemia/reperfusion myocardial tissues and hypoxia/reoxygenation H9C2 cells, whereas miR-682 was downregulated. Knocking down Gm4419 with sh-Gm4419 resulted in the rescue of myocardial infarction and apoptosis induced by ischemia/reperfusion or hypoxia/reoxygenation. Our study further demonstrated that Gm4419 may bind with miR-682 directly. Moreover, in vitro experiments further demonstrated that miR-682 could bind to tumor necrosis factor receptor-associated factor 3 (TRAF3) directly. Most importantly, TRAF3 overexpression could counteract the effect of sh-Gm4419. Taken together, our study indicated that Gm4419 may target miR-682 via sponging to increase TRAF3 expression, thereby contributing to myocardial I/R injury. Therefore, the Gm4419/miR-682/TRAF3 axis may be an important regulatory mechanism in myocardial ischemia/reperfusion injury.
A Potential Role for CXCR2 in Early-onset Preeclampsia: Placental CXCR2 Expression is Related to Increased Blood Pressure and Serum LDH Levels
Authors: Zhang Yan-Ping , Liu Xi-Jing , Jia Jin , Wang Tao , Li Li , Zhou Rong
Published: June 2020

Objective:

This study was aimed to determine the changes in CXCR2 expression in preeclampsia placenta and its correlation with clinical parameters.

Methods:

Sixty-four gravidas ranging in age from 25 to 42 years referred to the obstetrics unit of the West China Second University Hospital from April 2012 to October 2012 were recruited in this case-control study; women were diagnosed and divided into early-onset preeclampsia group (n = 22), late-onset preeclampsia group (n = 22), and healthy pregnancy group (n = 20). After immunolocalized in human placenta, the levels of CXCR2 protein and messenger ribonucleic acid (mRNA) were detected by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Correlations between placental CXCR2 protein expression with systolic blood pressure and lactate dehydrogenase (LDH) in early-onset preeclampsia were examined using Pearson or Spearman's correlation coefficients.

Results:

Placental CXCR2 protein and mRNA expression in early-onset preeclampsia was significantly lower than it was in placentas from healthy pregnancy pregnancies and late-onset preeclampsia (P < 0.05). The placental CXCR2 protein expression correlated negatively with systolic blood pressure and LDH in early-onset preeclampsia (r = −0.51, P < 0.05; r = −0.43, P < 0.05).

Conclusion:

Significant abnormal placental CXCR2 expression in early-onset preeclampsia, and its correlations with some clinical parameters (systolic blood pressure and LDH) were discovered, suggesting that CXCR2 may play a role in the pathogenesis of early-onset preeclampsia.
Preterm Birth, From the Biological Knowledges to the Prevention: An Overview
Authors: Tosto Valentina , Giardina Irene , Tsibizova Valentina , Renzo Gian Carlo Di
Published: June 2020

The time of birth is a critical determinant of perinatal and long-term outcomes, and even trans-generational effects. Preterm birth is still the leading cause of infant mortality and morbidity. Unfortunately, rates of preterm birth remain high worldwide. Preterm parturition is a complex syndrome, which can be induced by several factors such as infection, cervical pathology, uterine overdistension, progesterone deficiency, vascular alterations (utero-placental ischemia, decidual hemorrhage), maternal and fetal stress, allograft reaction, allergic phenomena, and probably other several unknown factors. The mechanisms responsible for early labor activation have been partially identified and involve receptors, chemokines, and inflammatory cytokines. It is very useful to understand the cellular and biochemical pathways responsible for preterm labor activation to identify, treat, and prevent negative outcome in a timely manner. Researchers and clinicians play a key role in improving biochemical knowledge on preterm delivery, identifying risk factors, and applying multilevel preventive strategies.
New Concept and Management for Sepsis in Pregnancy and the Puerperium
Authors: Fan Shang-Rong , Liu Ping , Yan Shao-Mei , Huang Lei , Liu Xiao-Ping
Published: June 2020

Sepsis, which is life-threatening organ dysfunction resulting from a dysregulated host response to infection, remains a major cause for the admission of pregnant women to the intensive care unit and is one of the leading causes of maternal morbidity and mortality. The obstetric causes include uterine infection, septic abortion, and wound infection. The non-obstetric causes include pyelonephritis and pneumonia. Maternal sepsis may also be from obstetrical critical illness, such as obstetric severe hemorrhage, obstetric (amniotic fluid/pulmonary) embolism, acute fatty liver of pregnancy, and congestive heart failure, cardiopulmonary arrest, and major trauma. The most commonly reported pathogens in maternal sepsis include Escherichia coli, Streptococcus, Staphylococcus, and other gram-negative bacteria. Maternal sepsis may cause intrauterine infection, which results in (1) preterm premature rupture of membranes or preterm labor or birth, (2) cerebral white matter damage or cerebral palsy or neurodevelopmental delay, (3) stillbirth, (4) early- or late-onset sepsis, and (5) perinatal death. The “Hour-1 bundle” should be initiated within the first hour of the recognition of sepsis. The use of early, appropriate antibiotics is crucial in the management of maternal sepsis. Fetal status should be monitored. Appropriate and early source control should be provided. The decision for delivery is often quite complex and should be individualized to each patient's clinical scenario while taking into consideration the suspected source of infection, maternal status, fetal well-being, and gestational age. Extracorporeal membrane oxygenation has been increasingly used in refractory sepsis during pregnancy and the puerperium.
Health Literacy of Patients Attending Cardiac Rehabilitation
Authors: Beauchamp Alison , Sheppard Robyn , Wise Frances , Jackson Alun
Published: June 2020

Purpose:

Cardiac rehabilitation (CR) is effective at reducing further cardiac events. However, dropout rates are high, and maintenance of behavioral change post-CR is challenging. Health literacy (HL) may influence self-management of cardiac risk, yet few studies have explored this association. This study aimed to describe HL among CR attendees; first to describe the HL profiles of people commencing CR and second to examine HL changes between program entry and completion.

Methods:

CR attendees in Melbourne, Australia, completed the Health Literacy Questionnaire (HLQ) at program admission and completion. The HLQ measures HL across 9 scales. Cluster analysis grouped participants according to their HL profile. Effect sizes were used to determine changes in HLQ scores. Post-program interviews explored the role of HL in participant recovery.

Results:

Participants completed baseline (n = 60) and post-program (n = 38) data collection. Mean age was 60.3 ± 11.7 yr, and 38.3% had myocardial infarction and/or percutaneous coronary intervention. Approximately 18% of participants did not complete the program. Five HL clusters were revealed. The clusters most likely to drop out were confident users of the health system. The cluster least likely to drop out reported lower confidence in their ability to find health information and navigate services. Information-seeking ability improved over time, but no other HL improvements were seen.

Conclusion:

There is a wide range of HL profiles in people attending CR. Findings suggest that CR programs should consider a variety of approaches to meet the diverse HL requirements of attendees.
The Effects of Maintenance Cardiac Rehabilitation
Authors: Sánchez-Delgado Juan Carlos , Camargo Sepulveda Diana Carolina , Cardona Zapata Adalgiza , Franco Pico Mayra Yulieth , Santos Blanco Lina Marcela , Jácome Hortúa Adriana Marcela , Dutra de Souza Hugo Celso , Angarita-Fonseca Adriana
Published: June 2020

Purpose:

Maintenance cardiac rehabilitation (M-CR) programs aim to preserve the health benefits achieved during phase II cardiac rehabilitation (CR). The aim of this study was to establish the effects of M-CR on functional capacity, quality of life, risk factors, costs, mortality, and morbidity, among other outcomes.

Methods:

Scopus, ISI Web of Science, PubMed, Embase & Embase classic OVID, and Lilacs were searched. Randomized controlled trials, published between 2000 and 2016, on the effects of M-CR in patients with cardiovascular disease, who had graduated from CR, having a control or comparison arm were included. Citations were processed by two authors, independently. Methodological quality was assessed using PEDro, and level of evidence graded with the Scottish scale. Outcomes were qualitatively synthesized.

Results:

The searches retrieved 1901 studies with 26 articles meeting inclusion criteria (3752 participants). Some trials tested M-CR in nonclinical settings, and others used resistance or high-intensity interval training. The methodological quality of 11 articles was good, with a level of evidence (1+) and a grade B recommendation. Results showed M-CR resulted in increased or maintained functional capacity, quality of life, and physical activity levels, when compared with the control. No adverse events were reported. Few studies assessed rehospitalizations and mortality.

Conclusion:

Quality of included trials was low because it is not possible to double-blind in M-CR trials and also due to the heterogeneity of M-CR interventions. Understanding, availability, and use of M-CR programs should be increased.
Visual performance after bilateral toric extended depth-of-focus IOL exchange targeted for micromonovision
Authors: Georgiev Stefan , Palkovits Stefan , Hirnschall Nino , Döller Birgit , Draschl Petra , Findl Oliver
Published: June 2020

Purpose:

To evaluate overall patient satisfaction, spectacle independence, binocular visual acuity, rotational stability, prevalence of optical phenomena, and decentration and tilt after bilateral toric extended depth-of-focus intraocular lens (EDOF IOL) implantation targeted for micromonovision.

Setting:

Department of Ophthalmology, Hanusch Hospital, Vienna, Austria.

Design:

Prospective case series.

Methods:

The study included 52 eyes of 26 patients with regular corneal astigmatism from 0.75 to 2.60 diopters (D) that were implanted bilaterally with a toric EDOF IOL targeted for micromonovision. Postoperative visual acuity, astigmatism reduction, rotation, tilt, decentration, spectacle independence, patient satisfaction, and photic phenomena were assessed.

Results:

For the 52 eyes studied, binocular means expressed in logarithm of the minimum angle resolution for postoperative corrected distance, uncorrected distance, uncorrected intermediate, and uncorrected near visual acuities were −0.10 (±0.12), −0.01 (±0.13), 0.01 (±0.14), and 0.13 (±0.14), respectively. Mean refractive astigmatism reduction was 1.31 ± 0.67 D resulting in a mean refractive cylinder of 0.47 ± 0.46 D at the 3-month visit. Mean postoperative rotation was 3.5 ± 3.5 degrees, at the 3-month time point. Most prevalent dysphotopsia were halos, starburst, and glare affecting 6 (23%), 6 (23%), and 5 (19%) of 26 patients, respectively; 20 (77%) of 26 patients reported spectacle independence, with 19 (95%), 19 (95%), and 14 (70%) of 20 patients questioned being satisfied with distance, intermediate, and near vision, respectively.

Conclusions:

Toric EDOF IOL implantation targeted for micromonovision resulted in reliable reduction of preoperative astigmatism with a high degree of postoperative rotational predictability and centration, enabling functional distance, intermediate, and near vision, which manifested itself in high patient satisfaction.
Comparative study of topical steroids vs nonsteroidal anti-inflammatory drugs to control postcataract surgery inflammation
Authors: Deka Amarendra
Published: June 2020

Purpose:

To evaluate the efficacy of bromfenac ophthalmic solution 0.09% in comparison with topical steroids after phacoemulsification cataract surgery, while specifically looking at differences in visual acuities, anterior chamber reaction, and central retinal thickness changes.

Setting:

Mission Nethralaya, India.

Design:

Prospective, randomized, investigator-masked, comparative clinical trial.

Methods:

Patients were randomly assigned to 3 treatment groups: In group I, bromfenac was prescribed 3 times a day for 1 month; in group II, prednisolone acetate 1% eye suspension was prescribed 4 times a day for 1 month; and in group III, prednisolone acetate 1% was prescribed 4 times a day for 2 weeks and bromfenac 2 times a day for 1 month. All patients received anti-infective preoperative and postoperative standards of care. Study visit assessments included corrected distance visual acuity, biomicroscopy, intraocular pressure, adverse events, and concomitant medication review. Optical coherence tomography was performed on postoperative days 7, 21, and 60.

Results:

Each group included 150 eyes. All treatment groups had similar baseline measurements. There was a significant difference in anterior chamber reaction observed between group I and group II (P < .001) and group I and group III (P < .001) on postoperative days 1 and 7. On postoperative day 21, thickening of the central fovea was observed in group II as compared with group I and group III. This difference was statistically significant (P < .001).

Conclusions:

The combination of topical nonsteroidal anti-inflammatory drugs and topical steroids resulted in positive clinical outcomes after cataract surgery.
Decreased Pulmonary Function Over 5 Years in US Firefighters
Authors: Mathias Kevin C. , Graham Elliot , Stewart Donald , Smith Denise L.
Published: June 2020

Objective:

To examine changes in pulmonary function over a 5-year period in US firefighters.

Methods:

Spirometry values from occupational medical examinations separated by 5 years (2009 to 2016) were examined from 662 career firefighters in Virginia. Predicted values and expected 5-year changes in one-second forced expiratory volume (FEV1), forced vital capacity (FVC), and FEV1/FVC were estimated using reference equations generated from the Third National Health and Nutrition Examination Survey (NHANES III) data. Paired t-tests were used to identify significant changes over time and between the observed and expected changes.

Results:

FEV1 and FVC (percentage of predicted) decreased (P < 0.001) from 100.9 ± 0.6% to 92.3 ± 0.5% and 99.0 ± 0.6% to 91.9 ± 0.5%, respectfully. The observed decreases in FEV1, FVC, and FEV1/FVC were two to four times greater (P < 0.001) than the expected decrease over 5 years.

Conclusion:

Increased efforts are needed to ensure respiratory protection for US firefighters to minimize their risk of pulmonary damage.
Longitudinal Changes in Prevalence of Colorectal Cancer in Farm and Non-Farm Residents of Saskatchewan
Authors: Watara Abubakari Ibrahim , Ahmed Shahid , Khan Shahedul , Karunanayake Chandima , Dosman James , Pahwa Punam
Published: June 2020

Objective:

To determine predictors associated with longitudinal changes in colorectal cancer (CRC) prevalence in farm and non-farm rural residents in Saskatchewan, Canada.

Methods:

Data from the Saskatchewan Rural Health Study were collected from 8261 individuals nested within 4624 households at baseline survey in 2010 and 4867 individuals (2797 households) at follow-up survey in 2014. The study sample consists of 5599 individuals (baseline) and 3933 at (follow-up) (more than or equal to 50 years).

Results:

The prevalence of CRC increased over time among rural farm (baseline: 0.8%; follow-up: 1.3%,P < 0.05) and non-farm (baseline: 1.4%; follow-up: 2.0%,P > 0.05) residents. Longitudinal predictors of CRC prevalence were: quadrant, location of home, mother ever had cancer, age, body mass index (BMI), sex, radiation, natural gas.

Conclusions:

Longitudinal changes in prevalence of CRC among farm and non-farm residents appear to depend on a complex combination of individual and contextual factors.
Reliability of an Assessment Tool and Outcomes of a Comprehensive Worksite Wellness Intervention
Authors: Ablah Elizabeth , Kellogg Melinda , Okut Hayrettin , Usher Jeff , Lester Ryan
Published: June 2020

Objective:

The purpose of this study was to determine the reliability of a comprehensive worksite-level assessment and identify which worksite wellness best practices were implemented following a workshop.

Methods:

Kansas worksites attended a WorkWell Kansas Phase I workshop from 2012 through 2014 and completed a 155-item assessment before the workshop and 1 year later. Cronbach alpha measured the internal consistency of the WorkWell KS Phase I Assessment, and McNemar test assessed differences in proportions from baseline to follow-up.

Results:

Two hundred eighty five worksites completed a baseline assessment, of which, 109 completed the follow-up assessment (32%). The internal consistency of the instrument was 0.96, and worksites reported significant improvements at follow-up from baseline for nine variables.

Conclusions:

Improvements predominantly included creating a wellness committee, assessing needs, and developing goals. There was a lack of policy and systems level improvements at the worksite.
Evaluating Covid-19 Injury Claims With a Focus on Workers’ Compensation
Authors: Hyman Mark H. , Talmage James B. , Hegmann Kurt T.
Published: June 2020

COVID-19 illness can cause multiorgan illness. Some States have passed legislation granting a rebuttable presumption of causation by workplace exposure in certain occupations. This paper summarizes methodology for evaluating claimants utilizing known science and as well as information from the American Medical Association Guides resources.
Association of Co-Exposure to Psychosocial Factors With Depression and Anxiety in Korean Workers
Authors: Park Jungsun , Kim Yangho
Published: June 2020

Introduction:

This study assessed the association of co-exposure to psychosocial factors with depression and anxiety in Korean workers.

Methods:

All data were from the 2017 Korean Working Conditions Survey.

Results:

Males and females who perceived organizational injustice, hid their emotions at the workplace, felt they were paid inappropriately, and had no support from managers were more likely to report depression and anxiety. Males who reported long working hours, no ability to influence decisions, work pressure, and no ability to apply their own ideas at the workplace were more likely to report depression and anxiety. Co-exposure to a greater number of psychosocial factors had stronger associations with depression and anxiety in men and women.

Conclusion:

Employers should reduce depression and anxiety in their workers by providing comprehensive interventions that protect them from co-exposure to work stressors.
Beethoven: His Hearing Loss and His Hearing Aids
Authors: Perciaccante Antonio , Coralli Alessia , Bauman Neil G.
Published: June 2020

To celebrate the 250th anniversary of the birth of the great classical composer, Ludwig van Beethoven (1770–1827), we point out how his hearing loss affected him and how the primitive hearing aids at that time helped mitigate his hearing loss. From the age of 26, Beethoven began to suffer from a fluctuating, progressive hearing loss (“my hearing grew worse and worse”), This started in his left ear (“in my left ear, with which this illness of my ears had started”), where he had difficulty hearing higher pitched tones (“I don’t hear the high notes of the instruments and voices”) and words (“Sometimes, I cannot hear people who speak quietly, I can hear the sounds, but not the words”) and associated with tinnitus (“my ears, they still keep buzzing and humming day and night”) and loudness recruitment (“if someone yells, it is unbearable to me”).

However, in spite of his hearing loss, Beethoven never lost his love for music and continued composing music, at times using some of the acoustic hearing aids that were just being developed. We analyze and describe the ear trumpets, and the resonant plate that engineer Johan Nepomuk Maelzel and piano-maker Conrad Graf, respectively, constructed to try to improve Beethoven's hearing. Moreover, we discuss the possible use of a wooden drumstick Beethoven might have used to improve his perception of the piano's sound.
Exercise Trials in Pediatric Brain Tumor: A Systematic Review of Randomized Studies
Authors: Sharma Bhanu , Allison David , Tucker Patricia , Mabbott Donald , Timmons Brian W.
Published: June 2020

In pediatric brain tumor patients, treatment advances have increased survival rates to nearly 70%, while consequently shifting the burden of disease to long-term management. Exercise has demonstrated potential in improving multiple health impairments secondary to brain tumor treatment. However, these effects have not been consolidated through review. Therefore, we performed a systematic review of 6 health sciences databases (Medline, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Central Database). Two reviewers screened studies against predefined inclusion criteria, namely that the study must: (i) be pediatric-specific; (ii) examine the effects of an exercise intervention; and (iii) employ a randomized or quasi-randomized trial design. The same 2 reviewers performed data extraction and analyses. From a pool of 4442, 5 articles—based on 2 independent trials—were included in our review (N=41). Exercise interventions were primarily aerobic, but included balance or muscle building components. Exercise had a positive effect on volumetric or diffusion-based neuroimaging outcomes, as well as motor performance and cardiorespiratory fitness. The effects of exercise on cognition remains unclear. Exercise did not worsen any of the outcomes studied. This review captures the state of the science, suggesting a potential role for exercise in children treated for brain tumor.
Successful Liver Transplantation for Adolescent Patient With Pyruvate Kinase Deficiency-induced Cirrhosis
Authors: Rinehardt Hannah N. , Villella Anthony D. , Milanes-Yearsley Martha , Kelly Sean , El-Hinnawi Ashraf
Published: June 2020

We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Explant pathology demonstrated a lack of significant iron deposition indicating that PK deficiency predisposes the liver to injury independent of transfusion-related iron overload.
Clinicoepidemiologic Profile and Outcome Predicted by Minimal Residual Disease in Children With Mixed-phenotype Acute Leukemia Treated on a Modified MCP-841 Protocol at a Tertiary Cancer Institute in India
Authors: Myint Htar H. , Tandon Sneha , Narula Gaurav , Prasad Maya , Subramanian Papagudi , Patkar Nikhil , Tembhare Prashant , Gujral Sumeet , Banavali Shripad
Published: June 2020

Introduction:

Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL.

Methods:

Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1.

Results:

Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×109/L. Common immunophenotypes were B/myeloid—12 (50%), T/myeloid—9 (37.5%), and B/T-lymphoid—3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry–based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo).

Conclusion:

MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia–type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease–negativity rate of 69% in evaluated patients, which was also predictive of better outcome.
Grief among Neonatal Intensive Care Nurses
Authors: Rodriguez Alison , Spilker Arlene , Goyal Deepika
Published: June 2020

Background:

Nurses working in the high-stress environment of the neonatal intensive care unit (NICU) are at high risk of experiencing grief after death of a baby.

Design:

Using a quantitative cross-sectional design, a convenience sample of nurses working in a Level IV NICU in Northern California, United States completed online surveys. Level of grief among NICU nurses, perceptions of grief support available at their institution, and past and future grief coping methods were assessed.

Participants:

A diverse sample of 55 NICU nurses, mean age 45.5 (SD = 11.7) years. Setting: A high-acuity NICU in one large Northern California hospital.

Methods:

Participant demographic data and the Revised Grief Experience Inventory were completed online.

Results:

Total grief scores ranged between 22 and 82 with a mean of 46.9 (SD = 17.4). Sixty percent (n = 33) moderately/strongly disagreed on adequacy of current grief support services at their institution and 81% (n = 45) reported hospital staff could benefit from additional grief support. Nurses' past grief support included family, friends, and church. Future grief resources would include family, friends, and co-workers. Participants indicated need for debriefing and additional nurse staffing resources at the time of a patient death.

Conclusions:

Neonatal intensive care unit nurses in our study reported experiencing grief. Debriefing and bereavement support may be helpful for nurses working in high-stress environments where there is a higher likelihood of patient death.
Use of a Novel Couples' Verification Tool in a Male Partner Treatment Study of Women With Recurrent Bacterial Vaginosis
Authors: Muzny Christina A. , Pontius Angela , Woznicki Nicole , Hudak Kathryn E. , Lensing Shelly Y. , Sobel Jack D. , Schwebke Jane R.
Published: June 2020

Verification of relationship status beyond self-report is an important aspect in sexually transmitted infection research, including partner treatment studies where primary sexual partners are targeted for enrollment. This exploratory study describes the use of a novel couples' verification tool in a male partner treatment study of women with recurrent bacterial vaginosis.
Neuroendocrine Cells Are Commonly Absent in the Intestinal Crypts in Autoimmune Enteropathy
Authors: Lee Hee Eun , Yuan Lin , Wu Tsung-Teh
Published: June 2020

The absence of neuroendocrine (NE) cells in the intestinal mucosa in autoimmune enteropathy (AIE) has been occasionally reported. However, the status of NE cells has not been studied in detail in AIE. Small bowel and colonic biopsies were retrospectively retrieved from 18 AIE patients (26 baseline [18 small bowel and 8 colon]; and 15 follow-up [11 duodenum and 4 colon] biopsies in 11 patients). Thirty-three common variable immunodeficiency (CVID) patients (30 small bowel and 16 colon), 15 inflammatory bowel disease patients (5 duodenum and 10 colon), 13 immunoglobulinA deficiency patients (13 duodenum and 5 colon), and 10 normal controls (5 colon and 5 duodenum) were selected as control groups. Histologic features (villous atrophy, intraepithelial lymphocytosis, acute inflammation, crypt apoptosis, and absence or presence of goblet cells, Paneth cells and plasma cells) were recorded. Chromogranin immunostain was performed and chromogranin-positive NE cells were counted per 10 consecutive, well-oriented crypts. On the basis of the number of chromogranin-positive NE cells, cases were graded as being absent (≤3 NE cells), markedly decreased (≤15), and intact (>15). The NE cell status correlated with histologic features. The median age of 18 AIE patients was 38.5 years (range: 11 to 74 y) and 14 patients were male. Fourteen of 18 (78%) patients showed loss (absent or markedly decreased) of NE cells in the small bowel and/or colon in the baseline biopsies including 12 (of 18) small bowel and 6 (of 8) colon biopsies. Follow-up biopsy was available in 11 patients. Six of 7 (85%) patients who showed loss of NE cells in the baseline biopsies regained NE cells in the follow-up biopsies, and 1 patient continued to show loss of NE cells. Four patients who showed intact NE cells in the baseline remained unchanged in the follow-up. Among the control groups, 3 of 33 (9%) CVID patients showed loss of NE cells. NE cells were not lost in the biopsies of all 15 and 13 patients with inflammatory bowel disease and immunoglobulinA deficiency, respectively, or the 10 normal controls. In all 41 biopsies (26 baseline plus 15 follow-up) with AIE, NE cell loss was significantly associated with increased crypt apoptosis and loss of goblet cells (P=0.001, both) but not with other histologic findings. In conclusion, our study suggests that NE cells may also be the target cells in AIE and commonly lost in the intestinal crypts in AIE, and consequently loss of NE cells can be used as an adjunct histologic feature for diagnosis of AIE.
Lower Rate of CTNNB1 Mutations and Higher Rate of APC Mutations in Desmoid Fibromatosis of the Breast
Authors: Norkowski Emma , Masliah-Planchon Julien , Le Guellec Sophie , Trassard Martine , Courrèges Jean-Baptiste , Charron-Barra Céline , Terrier Philippe , Bonvalot Sylvie , Coindre Jean-Michel , Laé Marick
Published: June 2020

Desmoid fibromatosis (DF) is a rare, locally aggressive, nonmetastasizing fibroblastic/myofibroblastic tumor with a tendency to recur and an unpredictable clinical course. A “wait-and-see” policy is the new standard of care. DF are characterized by activating alterations of the wnt/β-catenin pathway:CTNNB1or adenomatous polyposis coli gene (APC) mutations (these mutations being mutually exclusive). Desmoid-type fibromatosis of the breast (DFB) is rare with an incidence of 0.2% of breast tumors. The diagnosis of DFB is difficult, as it must be distinguished from metaplastic carcinoma and other spindle cell lesions. Sequencing of 128 DFB identified a lower rate ofCTNNB1mutations using Sanger (65.6%) or Sanger+next-generation sequencing (77.7%) and a higher rate ofAPCmutations (11.8%) than in all-site DF. By excluding patients with familial adenomatous polyposis (n=2), the rate ofAPCmutations in DFB was high (10.7%). The distribution ofCTNNB1mutations in DFB was different from all-site DF, with a higher rate of T41A (68.9%), a lower rate of S45F (5.7%), and a similar rate of S45T (12.6%). By combining the 2 molecular techniques in a 2-step manner (Sanger, then next-generation sequencing), we increased the detection rate ofCTNNB1mutations and lowered the rate of wild-type tumors from 34.4% to 9.8%, therefore improving the diagnosis of DFB. The identification of the exon 3CTNNB1mutation in breast spindle cell lesions is a highly specific tool for the diagnosis of DFB, in addition to extensive immunohistochemical analysis. Our study also underlines the importance ofAPCin DFB tumorigenesis. These findings have significant implications for patient care and management.
Genomic and Immunophenotypic Landscape of Aggressive NK-Cell Leukemia
Authors: El Hussein Siba , Patel Keyur P. , Fang Hong , Thakral Beenu , Loghavi Sanam , Kanagal-Shamanna Rashmi , Konoplev Sergej , Jabbour Elias J. , Medeiros L. Jeffrey , Khoury Joseph D.
Published: June 2020

Aggressive natural killer-cell leukemia (ANKL) is a rare, lethal disease with pathologic features that are underdescribed in the literature, particularly in Western nations. In addition, although data on the molecular pathogenesis of ANKL has been reported, evaluation of such data in a clinicopathologic context remains limited. Patients diagnosed with ANKL were identified retrospectively. Detailed demographic and clinicopathologic data were analyzed. We assessed novel markers by immunohistochemistry and performed targeted next-generation sequencing analysis. The study group included 9 men and 3 women with a median age at diagnosis of 47.5 years (range, 20 to 75 y). Two distinct patterns of bone marrow involvement were identified: interstitial and sinusoidal. The neoplastic cells were positive for CD56 and CD94, and negative for surface CD3, CD5, and CD57 in all cases assessed. They were also positive for CD2 (10/12), c-MYC (6/8), BCL2 (6/8), CD16 (5/7), EBER (9/12), CD7 (6/11), pSTAT3Tyr705 (3/8), CD8 (2/6), PD-L1 (2/8), CD4 (2/11), CD8 (2/6), and CD158 (1/5). Aberrant p53 expression was identified in most (7/8) cases; p53 was strongly expressed in 4 cases. Conventional cytogenetic analysis showed clonal abnormalities in 5 of 12 cases. TP53 mutations were detected in 3 of 6 cases, whereas ASXL1 and TET2 mutations were each detected in 2 of 6 cases. Patients had very poor outcomes despite intensive chemotherapy, with a median survival of 2 months. ANKL exhibits 2 distinct patterns of tissue involvement. Neoplastic cells in ANKL are commonly positive for c-MYC and EBER, and they have a high frequency of p53 overexpression, frequently with corresponding TP53 mutations.
CNS Low-grade Diffusely Infiltrative Tumors With INI1 Deficiency, Possessing a High Propensity to Progress to Secondary INI1-deficient Rhabdoid Tumors
Authors: Nobusawa Sumihito , Nakata Satoshi , Nakano Yoshiko , Kawamura Atsufumi , Yoshida Makiko , Tamura Akihiro , Hasegawa Daiichiro , Kosaka Yoshiyuki , Ito Ichiro , Watanabe Reiko , Oishi Takuma , Hayashi Nakamasa , Ishikawa Eiichi , Sakamoto Noriaki , Okura Naoki , Murakami Chiaki , Ichimura Koichi , Hirato Junko , Yokoo Hideaki
Published: June 2020

Atypical teratoid/rhabdoid tumors (AT/RTs) are highly malignant tumors of the central nervous system that predominantly occur in infants, and are characterized by the presence of rhabdoid cells and inactivation of INI1 or (rarely) BRG1. Most AT/RT are identified as primary tumors; however, rare AT/RT or INI1-deficient RTs arising from other primary tumors have been reported. Here, we report 3 cases of hitherto unclassifiable low-grade tumors with loss of INI1 nuclear expression, for which we propose the designation of central nervous system low-grade diffusely infiltrative tumors with INI1 deficiency (CNS LGDIT-INI1), 2 of which progressed to secondary RT. All 3 CNS LGDIT-INI1 exhibited a similar histology: diffusely distributed small tumor cells with round to oval or irregular nuclei and scant cytoplasm were admixed with degenerative neurons and large reactive astrocytes in an edematous, myxoid, or collagenous background. Mitotic figures were absent. Immunohistochemistry revealed that the tumor cells in all 3 CNS LGDIT-INI1 and 2 RT were negative for INI1. Genetically, total or partial homozygous deletions of theINI1gene were detected in all CNS LGDIT-INI1 and RT excluding 1 CNS LGDIT-INI1 without sufficient DNA quality and quantity. Despite the loss of INI1 expression, these low-grade lesions were clearly distinguishable from AT/RT by their low proliferative activity, diffusely infiltrative growth pattern, and lack of rhabdoid cells and polyphenotypic immunoreactivity. In conclusion, CNS LGDIT-INI1 may represent a rare group of tumors that are clinically indolent but have a high propensity to progress to RT.
Thyroid Papillary Microtumor
Authors: Aliyev Elvin , Ladra-González María J. , Sánchez-Ares María , Abdulkader-Nallib Ihab , Piso-Neira Magalí , Rodríguez-Carnero Gemma , Vieiro-Balo Paula , Pérez-Becerra Raquel , Gude-Sampedro Francisco , Barreiro-Morandeira Francisco , Alvarez Clara V. , Cameselle-Teijeiro José M.
Published: June 2020

Given the high incidence and excellent prognosis of many papillary thyroid microcarcinomas, the Porto proposal uses the designation papillary microtumor (PMT) for papillary microcarcinomas (PMCs) without risk factors to minimize overtreatment and patients’ stress. To validate Porto proposal criteria, we examined a series of 190 PMC series, also studying sex hormone receptors and BRAF
V600E mutation. Our updated Porto proposal (uPp) reclassifies as PMT incidental PMCs found at thyroidectomy lacking the following criteria: (a) detected under the age of 19 years; (b) with multiple tumors measuring >1 cm adding up all diameters; and (c) with aggressive morphologic features (extrathyroidal extension, angioinvasion, tall, and/or hobnail cells). PMCs not fulfilling uPp criteria were considered “true” PMCs. A total of 102 PMCs were subclassified as PMT, 88 as PMC, with no age or sex differences between subgroups. Total thyroidectomy and iodine-131 therapy were significantly more common in PMC. After a median follow-up of 9.6 years, lymph node metastases, distant metastases, and mortality were only found in the PMC subgroup. No subgroup differences were found in calcifications or desmoplasia. Expression of estrogen receptor-α and estrogen receptor-β, progesterone receptor, and androgen receptor was higher in PMC than in nontumorous thyroid tissue. BRAF mutations were detected in 44.7% of PMC, with no differences between subgroups. In surgical specimens, the uPp is a safe pathology tool to identify those PMC with extremely low malignant potential. This terminology could reduce psychological stress associated with cancer diagnosis, avoid overtreatment, and be incorporated into daily pathologic practice.
Effect of Cyclic Compressive Forces on New Bone Formation during the Distraction Period in Mandibular Distraction Osteogenesis Using a Microactuator-Generated Distractor
Authors: Kwon Hyun-Jin , Cha Jung-Yul , Park Jong-Tae , Kim Hyung Jun , Kim Hee-Jin
Published: June 2020

Background:

The traditional method of distraction required a long period until the new bone was fully fused. This study aimed to evaluate the effect of cyclic and repetitive compressive force on new bone formation by applying a newly designed microactuator-generated distractor compared with the traditional distraction protocol.

Methods:

The distraction devices were applied to the right and left mandibles of eight mature beagles, four of which were allocated to the experimental group and the other four to the control group. After a 5-day latency period, in the experimental group, 1.5-mm distraction and 0.5-mm compression were alternately applied every 12 hours; and in the control group, 0.5-mm distraction was repeated every 12 hours to perform a total of 7-mm mandibular lengthening. After an 8-week consolidation period, microstructure analysis using micro–computed tomography and histologic evaluations were performed.

Results:

Bone volume fraction and trabecular number were significantly higher in the experimental group. Trabecular thickness did not show a significant difference, and trabecular separation was significantly higher in the control group. The measurement of new bone was significantly higher in the experimental group, but the difference in mineral apposition rate between the experimental and control groups was not statistically significant.

Conclusions:

This study has revealed that applying cyclic compressive and tensile forces during the distraction period induces better new bone formation than repetitive distraction alone. In addition, the new distraction device produced reliable distraction results during the experiment.
The Functional Anatomy of the Ophthalmic Angiosome and Its Implications in Blindness as a Complication of Cosmetic Facial Filler Procedures
Authors: Taylor G. Ian , Shoukath Sajna , Gascoigne Adam , Corlett Russell J. , Ashton Mark W.
Published: June 2020

Background:

Blindness following facial filler procedures, although rare, is devastating, usually acute, permanent, and attributed to an ophthalmic artery embolus. However, blindness may be delayed for up to 2 weeks, sometimes following injection at remote sites, suggesting alternative pathways and pathogenesis.

Methods:

Seeking solutions, fresh cadaver radiographic lead oxide injection, dissection, and histologic studies of the orbital and facial pathways of the ophthalmic angiosome, performed by the ophthalmic artery and vein, both isolated and together, and facial artery perfusions, were combined with total body archival arterial and venous investigations.

Results:

These revealed (1) arteriovenous connections between the ophthalmic artery and vein in the orbit and between vessels in the inner canthus, allowing passage of large globules of lead oxide; (2) the glabella, inner canthi, and nasal dorsum are the most vulnerable injection sites because ophthalmic artery branches are anchored to the orbital rim as they exit, a plexus of large-caliber avalvular veins drain into the orbits, and arteriovenous connections are present; (3) choke anastomoses between posterior and anterior ciliary vessels supplying the choroid and eye muscles may react with spasm to confine territories impacted with ophthalmic artery embolus; (4) true anastomoses exist between ophthalmic and ipsilateral or contralateral facial arteries, without reduction in caliber, permitting unobstructed embolus from remote sites; and (5) ophthalmic and facial veins are avalvular, allowing reverse flow.

Conclusion:

The authors’ study has shown potential arterial and venous pathways for filler embolus to cause blindness or visual field defects, and is supported clinically by a review of the case literature of blindness following facial filler injection.
Long-Term Outcomes of Spring-Assisted Surgery for Sagittal Craniosynostosis
Authors: Runyan Christopher M. , Gabrick Kyle S. , Park Jungwon G. , Massary Dominic , Hemal Kshipra , Owens Elizabeth S. , Thompson James T. , Couture Daniel , David Lisa R.
Published: June 2020

Background:

Spring-assisted surgery is an accepted alternative to cranial vault remodeling for treatment of sagittal craniosynostosis. The long-term safety and efficacy profiles of spring-assisted surgery have not been established.

Methods:

This study is a retrospective examination of all patients treated with spring-assisted surgery (n = 175) or cranial vault remodeling (n = 50) for sagittal craniosynostosis at the authors’ institution from 2003 to 2017. Data collected included demographic and operative parameters, preoperative and postoperative Cephalic Indices, and complications. Whitaker grades were assigned blindly by a craniofacial surgeon not involved in patients’ care.

Results:

The mean age at surgery was significantly lower for the spring-assisted surgery group compared with the cranial vault remodeling group (4.6 months versus 22.2 months; p < 0.001). Even when combining spring placement with spring removal operations, total surgical time (71.1 minutes versus 173.5 minutes), blood loss (25.0 ml versus 111.2 ml), and hospital stays (41.5 hours versus 90.0 hours) were significantly lower for the spring-assisted surgery cohort versus the cranial vault remodeling group (p < 0.001 for all). There were no differences in infection, reoperation rate, or headaches between the groups. The percentage improvement in Cephalic Index was not significantly different at 1 (p = 0.13), 2 (p = 0.99), and 6 (p = 0.86) years postoperatively. At 12 years postoperatively, the spring-assisted surgery group had persistently improved Cephalic Index (75.7 preoperatively versus 70.7 preoperatively). Those undergoing spring-assisted surgery had significantly better Whitaker scores, indicating less need for revision surgery, compared with the cranial vault remodeling group (p = 0.006).

Conclusion:

Compared with the authors’ cranial vault remodeling technique, spring-assisted surgery requires less operating room time and is associated with less blood loss, but it has equivalent long-term Cephalic Indices and subjectively better shape outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Registration and Management of “Never Events” in Swiss Hospitals—The Perspective of Clinical Risk Managers
Authors: Schwappach David L. B. , Pfeiffer Yvonne
Published: June 2020

Background

In Switzerland, there is no mandatory reporting of “never events.” Little is known about how hospitals in countries with no “never event” policies deal with these incidents in terms of registration and analyses.

Objective

The aim of our study was to explore how hospitals outside mandatory “never event” regulations identify, register, and manage “never events” and whether practices are associated with hospital size.

Methods

Cross-sectional survey data were collected from risk managers of Swiss acute care hospitals.

Results

Clinical risk managers representing 95 hospitals completed the survey (55% response rate). Among responding risk and quality managers, only 45% would be formally notified through a designated reporting channel if a “never event” has happened in their hospital. Averaged over a list of 8 specified events, only half of hospitals could report a systematic count of the number of events. Hospital size was not associated with “never event” management. Respondents reported that their hospital pays “too little attention” to the recording (46%), the analysis (34%), and the prevention (40%) of “never events.” All respondents rated the systematic registration and analysis of “never events” as very (81%) or rather important (19%) for the improvement of patient safety.

Conclusions

A substantial fraction of Swiss hospitals do not have valid data on the occurrence of “never events” available and do not have reliable processes installed for the registration and exam of these events. Surprisingly, larger hospitals do not seem to be better prepared for “never events” management.