bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet-to-lymphocyte ratio as a potential prognostic factor in nasopharyngeal carcinoma
Authors: Cen Rui-Xiang , Li Yu-Gang
Published: October 2019

Background:

The aim of this study was to investigate the use of pretreatment platelet-to-lymphocyte ratio (PLR) as a prognostic marker in patients with nasopharyngeal carcinoma (NPC).

Methods:

A literature search was conducted using online databases such as MEDLINE, EMBASE, Cochrane Library, and WangFang. Overall survival (OS), progression-free survival (PFS), and clinicopathological features were generated and compared.

Results:

Ten studies that included 3388 patients were analyzed in this meta-analysis. Among them, 8 studies with 3033 patients with NPC investigated the prognostic role of PLR for OS and showed that elevated PLR was associated with poor OS (HR: 1.77, 95% CI: 1.46–2.15, P < .001). Five studies that included 1156 patients investigated the role of PLR in predicting PFS, and showed that high PLR was associated with poor PFS (HR: 1.65, 95% CI: 1.26–2.17, P < .001). Moreover, high PLR correlated with the N stage (N2-3 vs N0-1; OR: 1.55, 95% CI: 1.02–2.34, P = .04).

Conclusion:

Our study suggested that high PLR is associated with worse prognosis in patients with NPC. Pretreatment PLR could serve as a simple, promising indicator for prognostic evaluation in patients with NPC.
Risk factors of degenerative lumbar scoliosis in patients with lumbar spinal canal stenosis
Authors: Wang Chunlei , Chang Hengrui , Gao Xianda , Xu Jiaxin , Meng Xianzhong
Published: October 2019

Lumbar spinal canal stenosis (LSCS) associated with degenerative scoliosis has being increasingly aware by the public and studied by many researchers. Degenerative changes leading to spinal stenosis can precede a spinal deformity which will develop into the de novo scoliosis. There are few studies focusing on the risk factors contributing to the degenerative lumbar scoliosis (DLS) in lumbar spinal stenosis patients.

From September, 2017 to December, 2017, 181 patients who were diagnosed with LSCS in the outpatient department of our hospital were enrolled in this retrospective investigation. The patients were divided into 2 groups: DLS group (Cobb angle >10°) and LSCS group. Sex, age, smoking status (yes or no), occupation (heavy or light labor), body mass index (BMI), bone mineral density (BMD) and radiographic parameters including the lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), thoracic kyphosis (TK), coronal vertical axis, and sagittal vertical axis (SVA) are all evaluated as potential risk factors. Multivariate logistic regression analysis and receiver-operating characteristic curves were used to identify potential risk factors.

Forty-five of 181 patients were diagnosed with DLS and involved in the DLS group. There were significant differences between the 2 groups in BMI (P < .001), LL (P = .0046), BMD (P < .001), SVA (P < .001), and TK (P = .047). BMD < −1.85 g/cm2 (adjusted odds ratio [AOR] 0.030, 95% confidence interval [CI] 0.008–0.107, P < .001), BMI >25.57 kg/m2 (AOR 1.270, 95% CI 1.040–1.551, P = .019), and SVA >3.98 cm (AOR 3.651, 95% CI 2.226–5.990, P < .001) had good accuracy to predict the formation of degenerative lumbar scoliosis based on degenerative lumbar spinal stenosis.

Degenerative lumbar scoliosis has a high incidence in degenerative lumbar spinal stenosis. BMD <−1.85 g/cm2, BMI >25.57 kg/m2, and SVA >3.98 cm were the potential risk factors for the formation of degenerative lumbar scoliosis based on degenerative lumbar spinal stenosis.
Comparison of psychiatric disturbances in patients with multiple sclerosis and neuromyelitis optica
Authors: Shin Joon Sung , Kwon Young Nam , Choi Yoobin , Lee Jae Yeon , Lee Yoonji Irene , Hwang Ju Hyun , Choi Soo-Hee , Kim Sung-Min
Published: October 2019

Although both multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases, their psychiatric disturbances may differ given differences in the neurological manifestations. We used subjective and objective measurements to compare the psychiatric disturbances in patients with MS and NMO.

Psychiatric disturbances were assessed in 24 MS and 35 NMO patients using the Beck Hopelessness Scale, Symptom Checklist-95 and the brief version of World Health Organization Quality of Life. Personality was assessed using the Big Five Inventory-10. Disease-related function was assessed using the Fatigue Severity Scale, Short-Form McGill Pain Questionnaire, and the Global Assessment of Function. Positivity offset (PO) and negativity bias (NB) and heart rate variability (HRV) were measured using a modified implicit affect test and photoplethysmograph, respectively. Data were analyzed using analysis of covariance with age and sex as covariates.

MS patients had higher levels of depression, anxiety, panic attacks, obsessive–compulsiveness, aggression, paranoia, interpersonal sensitivity, self-regulation problems, stress vulnerability, and lower psychological quality of life (QOL) compared with NMO patients. The PO and NB and HRV values were not significantly different between groups. However, NMO patients had lower QOL, and higher levels of hopelessness, suicidality, and fatigue than the normal range. Disease duration was associated with hopelessness in NMO patients and with several psychiatric disturbances, but not hopelessness, in MS patients.

Subjective psychiatric disturbances were more severe in patients with MS than in those with NMO, whereas PO and NB and HRV in patients with NMO were comparable with those of MS patients. Our findings highlight the need for different clinical approaches to assess and treat psychiatric disturbances in patients with MS and NMO.
Severe infections of Panton-Valentine leukocidin positive Staphylococcus aureus in children
Authors: Hoppe Pia-Alice , Holzhauer Susanne , Lala Birgit , Bührer Christoph , Gratopp Alexander , Hanitsch Leif Gunnar , Humme Daniel , Kieslich Moritz , Kallinich Tilmann , Lau Susanne , Leistner Rasmus , Niebank Michaela , Pokrywka Anna , Ringe Hannelore , Schaper Anne-Sophie , Schröder Jennyver-Tabea , Schwarz Carsten , Staab Doris , Stegemann Miriam Songa , Thee Stephanie , Varnholt Verena , von Bernuth Horst , Weber-Carstens Steffen , Wendt Anke , Krüger Renate
Published: October 2019

Infections caused by Panton-Valentine leukocidin-positive Staphylococcus aureus (PVL-SA) mostly present as recurrent skin abscesses and furunculosis. However, life-threatening infections (eg, necrotizing pneumonia, necrotizing fasciitis, and osteomyelitis) caused by PVL-SA have also been reported.

We assessed the clinical phenotype, frequency, clinical implications (surgery, length of treatment in hospitals/intensive care units, and antibiotic treatments), and potential preventability of severe PVL-SA infections in children.

Total, 75 children treated for PVL-SA infections in our in- and outpatient units from 2012 to 2017 were included in this retrospective study.

Ten out of 75 children contracted severe infections (PVL-methicillin resistant S aureus n = 4) including necrotizing pneumonia (n = 4), necrotizing fasciitis (n = 2), pyomyositis (n = 2; including 1 patient who also had pneumonia), mastoiditis with cerebellitis (n = 1), preorbital cellulitis (n = 1), and recurrent deep furunculosis in an immunosuppressed patient (n = 1). Specific complications of PVL-SA infections were venous thrombosis (n = 2), sepsis (n = 5), respiratory failure (n = 5), and acute respiratory distress syndrome (n = 3). The median duration of hospital stay was 14 days (range 5–52 days). In 6 out of 10 patients a history suggestive for PVL-SA colonization in the patient or close family members before hospital admission was identified.

PVL-SA causes severe to life-threatening infections requiring lengthy treatments in hospital in a substantial percentage of symptomatic PVL-SA colonized children. More than 50% of severe infections might be prevented by prompt testing for PVL-SA in individuals with a history of abscesses or furunculosis, followed by decolonization measures.
An updated systematic review and meta-analysis of the use of octreotide for the prevention of postoperative complications after pancreatic resection
Authors: Zheng Hao , Qin Jiwei , Wang Ning , Chen Wanjing , Huang Qiang
Published: October 2019

Background:

The use of octreotide prophylaxis following pancreatic surgery is controversial. We aimed to evaluate the effectiveness of octreotide for the prevention of postoperative complications after pancreatic surgery through this systematic review and meta-analysis.

Methods:

Literature databases (including the MEDLINE, EMBASE, and Cochrane databases) were searched systematically for relevant articles. Only randomized controlled trials (RCTs) were eligible for inclusion in our research. We extracted the basic information regarding the patients, intervention procedures, and all complications after pancreatic surgery and then performed the meta-analysis.

Results:

Thirteen RCTs involving 2006 patients were identified. There were no differences between the octreotide group and the placebo group with regard to pancreatic fistulas (PFs) (relative risk [RR] = 0.79, 95% confidence interval [CI] = 0.62–0.99, P = .05), clinically significant PFs (RR = 1.01, 95% CI = 0.68–1.50, P = .95), mortality (RR = 1.21, 95% CI = 0.78–1.88, P = .40), biliary leakage (RR 0.84, 95% CI = 0.39–1.82, P = .66), delayed gastric emptying (RR = 0.83, 95% CI = 0.54–1.27, P = .39), abdominal infection (RR = 1.00, 95% CI = 0.66–1.52, P = 1.00), bleeding (RR = 1.16, 95% CI = 0.78–1.72, P = .46), pulmonary complications (RR = 0.73, 95% CI = 0.45–1.18, P = .20), overall complications (RR = 0.80, 95% CI = 0.64–1.01, P = .06), and reoperation rates (RR = 1.18, 95% CI = 0.77–1.81, P = .45). In the high-risk group, octreotide was no more effective at reducing PF formation than placebo (RR = 0.81, 95% CI = 0.67–1.00, P = .05). In addition, octreotide had no influence on the incidence of PF (RR = 0.38, 95% CI = 0.14–1.05, P = .06) after distal pancreatic resection and local pancreatic resection.

Conclusion:

The present best evidence suggests that prophylactic use of octreotide has no effect on reducing complications after pancreatic resection.
Clinical outcomes of patients with multivessel coronary artery disease treated with robot-assisted coronary artery bypass graft surgery versus one-stage percutaneous coronary intervention using drug-eluting stents
Authors: Su Chieh-Shou , Shen Ching-Hui , Chang Keng-Hao , Lai Chih-Hung , Liu Tsun-Jui , Chen Kuan-Ju , Lin Tzu-Hsiang , Chen Yu-Wei , Lee Wen-Lieng
Published: October 2019

A number of studies have reported on treatment outcomes of coronary stenting (PCI) for multivessel coronary artery diseases (MVD), and compared them with the conventional coronary artery bypass grafting (CABG). However, the clinical outcomes of robot-assisted CABG (R-CABG) in comparison with PCI in MVD patients have not been investigated.

We recruited retrospectively MVD patients receiving R-CABG and PCI with drug-eluting stents for all vessels in one stage between January 2005 and December 2013 at our institution with at least 3 years of outcomes were retrospectively recruited and analyzed.

A total of 638 MVD patients were studied. Among them, 281 received R-CABG, and 357 received PCI. Similar complete revascularizations were achieved in both groups (R-CABG: 40.2%, PCI: 41.5%, P = .751). The residual stenosis was 4.1 ± 4.4 in the R-CABG group, and comparably 3.5 ± 3.7 in the PCI group (P = .077). Patients in the R-CABG group were younger, with more severe coronary artery disease (CAD) and had more background risk factors. The in-hospital and long-term mortalities as well as the incidence of TLR, myocardial infarction (MI), stroke were all similar between groups. But the incidence of TVR and any revascularization were lower in the R-CABG group. The long-term mortality was predicted by age, left ventricular ejection fraction, and chronic kidney disease, but not by the revascularization modality, completeness of revascularization, nor residual SYNTAX scores. The last 3 factors were not predictors of long-term TLR, TVR, MI, and stroke.

The in-hospital and long-term survival rates of MVD were similar for both the R-CABG and PCI groups. But the R-CABG group had rates of TVR and any revascularization lower than PCI. Revascularization modality, completeness of revascularization, and residual SYNTAX scores were not predictors of in-hospital and long-term mortalities, MI, and stroke in real-world practice. R-CABG was associated with lower rates of TLR and TVR, and is likely a safe and effective treatment and an alternative choice of PCI for MVD patients who have low surgical risks.
Increased risk of appendectomy in patients with asthma
Authors: Kim So Young , Oh Dong Jun , Park Bumjung , Park Il-Seok , Choi Hyo Geun
Published: October 2019

The study aimed to expand previous data regarding an association between asthma and appendectomy in children compared with the population of all ages.

The Korean Health Insurance Review and Assessment Service—National Sample Cohort from 2002 through 2013 was used. In all, 22,030 participants who underwent appendectomy were matched for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 88,120 participants who were included as a control group. In both the appendectomy and control groups, previous history of asthma was investigated. Appendectomy for appendicitis was identified based on a surgical code (International Classification of Disease-10 [ICD-10]: K35). Asthma was classified using an ICD-10 code (J45 and J46) and medication history. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of asthma for appendectomy were analyzed using conditional logistic regression analysis. Subgroup analyses were conducted according to age and sex.

Approximately 15.2% (3358/22,030) of individuals in the appendectomy group and 13.3% (11,749/88,120) of those in the control group had asthma (P < .001). The appendectomy group demonstrated a higher adjusted odds of asthma than the control group (adjusted OR 1.18, 95% CI 1.13–1.23, P < .001). This result was consistent in the subgroups divided according to age and sex.

The odds for asthma were higher in the appendectomy group than in the control group.
Gait turning patterns in chronic ischemic stroke males and its relationship to recovery
Authors: Kusumaningsih Widjajalaksmi , Triangto Kevin , Salim Harris
Published: October 2019

Introduction:

Impaired turning patterns have been considered as 1 factor which potentially leads to disability in chronic stroke patients. Mobility comprises 80% of the chief disability, and would eventually lead to falls. Expanded Timed Up and Go (ETUG) is an effective mobility assessment method. It utilizes video recording to analyze the conventional Time Up and Go (TUG) Test components, which includes turning pattern analysis.

Methods:

Six healthy males without stroke history and 21 chronic ischemic stroke males (divided into subjects with or without the presence of flexor synergy pattern subgroups) capable of independent ambulation were recruited from Neurology and Medical Rehabilitation Department outpatient clinic. ETUG tests were recorded for each subject and were analyzed thoroughly using a computer program.

Results:

Timed Up and Go time was significantly different between the 3 groups (P = .001). As compared to control, and synergy absent group, median turning time was highest in chronic stroke patients with presence of flexor synergy by 2786 ms (P = .002), but was not significantly different in percentage ETUG (14%, P = .939). Further analysis revealed that Brunnstrom stage and number of steps taken for turning significantly affect TUG duration. Other factors such as hemiparetic side, or body height were not significantly associated.

Discussion:

The presence of flexor synergy would significantly affect turning time, this would then correlate to the disability of shifting body's center of gravity, as a part of the Stroke core set of International Classification of Functioning, Disability, and Health (ICF).Therefore, stroke patients need to have early ambulatory training regarding pivoting motion rather than solely focusing on straight walking. Instead of hemiparetic side, it is possible that overall turning time is affected by coordination and orientation capability, signifying the importance of cortical plasticity.
Spontaneous cerebellar hemorrhage with severe brainstem dysfunction through minimally invasive puncture treatment by locating the simple bedside
Authors: Wang Jing , Wu Qing-Yuan , Du Cui-Ping , Liu Jin , Zhang Hua , Wang Jun-Yan , Xue Wei , Chen Sheng-Li
Published: October 2019

This study aims to evaluate the feasibility and effectiveness of minimally invasive puncture treatment by positioning the simple bedside for spontaneous cerebellar hemorrhage.

From January 2017 to March 2018, the investigators applied simple bedside positioning to perform the intracranial hematoma minimally invasive surgery for 21 patients with cerebellar hemorrhage.

For these 21 patients, the bleeding amount and Glasgow Coma Scale (GCS) score before the operation were 18.5 ± 5.0 cc and 9.5 ± 3.3, respectively; 24 hours after the operation, the GCS score was 11.0 ± 4.6. Five patients died within 7 days of the operation and the head computed tomography (CT) was re-examined. It was found that the average bleeding amount was 3.4 ± 0.9 cc, the operation success rate was 76.2%, and the accurate puncture rate was 100%. Six months later, the Modified Rankin Scale (MRS) score was 2.5 ± 2.0. The postoperative recovery was good. The situation shows that patients with favorable outcomes (MRS score 0–2) accounted for 38.1% (8/21), and the fatality rate was 33.3% (7/21).

The efficacy of the intracranial hematoma minimally invasive surgery by positioning the simple bedside for spontaneous cerebellar hemorrhage with severe brainstem dysfunction is good.
The 100 most-cited articles on prenatal diagnosis
Authors: Zhang Meilian , Zhou Yu , Lu Yanfang , He Suhui , Liu Min
Published: October 2019

Background:

The number of citations a published article receives can be used to demonstrate its impact on a field of study. The objective of this study was to identify and characterize the 100 most-cited research articles (T100) published on prenatal diagnosis.

Methods:

The Web of Science (WOS) database was searched for papers on prenatal diagnosis published between 1900 and 2018. The 100 most-cited original articles and reviews were recorded. Each eligible paper was reviewed for authors, journal name, year of publication, country, institution, total citations, citation density, H-index, research field, article type, and keywords.

Results:

The T100 were published between 1972 and 2015 with a mean of 332.7 citations per paper (range: 196–1254). Most of the T100 were published between 1990 and 2005, in 35 journals led by New England Journal of Medicine (n = 14) followed by Lancet (n = 10), and Proceedings of The National Academy of Sciences of the United States of America (n = 8). Studies on method application, which promotes field development, were the majority article type. The team of Lo YM featured prominently in the field, and the United States of America, United Kingdom, and Hong Kong, China were the leading countries/regions. Frequency of cooperation was also highest among these 3 regions. Hierarchical cluster analysis produced 4 groups of keywords.

Conclusion:

Our analysis provides a historical perspective on scientific progress in prenatal diagnosis and may assist clinicians and researchers in assessing the quality of research over the past 50 years. It also provides concise information to guide future research.
Immunohistochemistry of immune checkpoint markers PD-1 and PD-L1 in prostate cancer
Authors: Sharma Meenal , Yang Zhiming , Miyamoto Hiroshi
Published: October 2019

Recent availability of immune checkpoint inhibitors has facilitated research involving programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1). However, the incidence and clinical implication of PD-1 and PD-L1 expression in prostate cancer remain poorly understood. The current study aimed to determine the status of PD-1/PD-L1 expression in prostate cancer specimens and its prognostic significance.

We immunohistochemically stained for PD-1 and PD-L1 in our tissue microarray (TMA) consisting of radical prostatectomy specimens. The expression of PD-1/PD-L1 was designated as positive when moderate to strong staining or weak staining was seen in at least 1% or 10%, respectively, of tumor cells and/or associated immune cells. We then evaluated the relationship between the expression of each protein and clinicopathological features available for our patient cohort.

PD-1 and PD-L1 were positive in 3 (1.5%) and 1 (0.5%) of 201 non-neoplastic prostate tissues, and also in 17 (7.7%) and 29 (13.2%) of 220 prostate cancers, respectively. PD-1 and PD-L1 were also expressed in tumor-infiltrating lymphocytes/macrophages in 172 (78.2%) and 33 (15.0%) cases, respectively. PD-L1 expression in tumor cells was more often seen in high pT stage (pT2: 10.8% vs pT3/4: 20.4%; P = .072; pT2/3a: 11.4% vs pT3b/4: 31.6%; P = .013) or lymph node-positive (pN0: 10.1% vs pN1: 27.3%; P = .086) cases, whereas PD-1 expression in tumor cells was not significantly associated with pT/pN stage. In addition, there were no statistically significant associations between PD-1/PD-L1 expression in tumor cells or tumor-infiltrating lymphocytes/macrophages versus patient age, preoperative prostate-specific antigen level, or Gleason score. Kaplan–Meier analysis coupled with log-rank test further revealed no significant associations between PD-1/PD-L1 expression in tumor cells (P = .619/P = .315), tumor-infiltrating lymphocytes/macrophages (P = .954/P = .155), or either or both of them (P = .964/P = .767) versus disease recurrence after radical prostatectomy.

PD-1/PD-L1 expression was detected in a subset of prostate cancers. In particular, PD-L1 expression was considerably up-regulated in nonorgan-confined tumors. However, PD-1/PD-L1 expression in our TMA was found to be not very helpful in predicting tumor recurrence in prostate cancer patients who underwent radical prostatectomy.
Religious values of physicians affect their clinical practice
Authors: Kørup Alex Kappel , Søndergaard Jens , Lucchetti Giancarlo , Ramakrishnan Parameshwaran , Baumann Klaus , Lee Eunmi , Frick Eckhard , Büssing Arndt , Alyousefi Nada A. , Karimah Azimatul , Schouten Esther , Wermuth Inga , Hvidt Niels Christian
Published: October 2019

Background:

Observational studies indicate that religious values of physicians influence clinical practice. The aim of this study was to test prior hypotheses of prevalence of this influence using a meta-analysis design.

Methods:

Based on a systematic literature search we performed individual participant data meta-analysis (IPDMA) on data based on 2 preselected questionnaires. Ten samples from 7 countries remained after exclusion (n = 3342). IPDMA was performed using a random-effects model with 2 summary measures: the mean value of the scale “Religiosity of Health Professionals”; and a dichotomized value of the question “My religious beliefs influence my practice of medicine.” Also, a sensitivity analysis was performed using a mixed-models design controlling for confounders.

Results:

Mean score of religiosity (95% confidence interval [CI]) was significantly lower in the European subgroup (8.46 [6.96–9.96]) compared with the Asian samples India (10.46 [9.82–10.21]) and Indonesia (12.52 [12.19–12.84]), whereas Brazil (9.76 [9.54–9.99]) and USA (10.02 [9.82–10.21]) were placed in between. The proportion of the European physicians who agreed to the statement “My religious beliefs influence my practice of medicine” (95% CI) was 42% (26%–59%) compared with Brazil (36% [29%–43%]), USA (57% [54%–60%]), India (58% [52%–63%]), and Indonesia (91% [84%–95%]).

Conclusions:

Although large cross-cultural variations existed in the samples, 50% of physicians reported to be influenced by their religious beliefs. Religiosity and influence of religious beliefs were most pronounced in India, Indonesia, and a European faith-based hospital. Education regimes of current and future physicians should encompass this influence, and help physicians learn how their personal values influence their clinical practice.
Can people self-select an exercise intensity sufficient to enhance muscular strength during weight training?
Authors: de Oliveira Segundo Victor Hugo , Piuvezam Grasiela , de Azevedo Kesley Pablo Morais , de Medeiros Humberto Jefferson , Leitão José Carlos , Knackfuss Maria Irany
Published: October 2019

Background:

Previous studies have reported that self-selection of the training intensity can be an interesting strategy to improve adherence in aerobic exercise programs. However, its effectiveness with weight training has not been systematically reviewed and remains unclear. In this study, we will describe a systematic review protocol that aims to investigate if people are able to self-select an intensity during weight training sufficient to enhance muscular strength.

Methods:

This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. In this study, we will search the following electronic databases: PubMed, Science Direct, Scopus, Web of Science and SPORTDiscus. Intervention studies with at least one weight training session performed at self-selected intensity, with people from both genders and all age ranges will be included. The Downs & Black checklist will be used for methodological quality assessment. Two experienced reviewers will independently perform the selection of studies, data extraction, and evaluation of the methodological quality.

Conclusion:

This will be the first systematic review describing the results of weight training intervention studies with self-selected intensity. This study will provide high-quality and reliable evidence for health professionals and may direct methodological recommendations for further studies.

PROSPERO registration number:

CRD42019120323
Frozen embryo transfer at the cleavage stage can be performed within the first menstrual cycle following the freeze-all strategy without adversely affecting the live birth rate
Authors: Song Jingyan , Xiang Shan , Sun Zhengao
Published: October 2019

Thus far, all clinical trials evaluating the efficacy of embryo transfer strategies have selectively delayed the first frozen embryo transfer (FET) by at least 1 menstrual cycle. Nevertheless, this approach, which is based solely on clinical experience, may create unnecessary psychological stress on infertile patients who are anxious to conceive as soon as possible. This study aimed to investigate whether the time interval between oocyte retrieval and subsequent FET affects reproductive outcomes.

We implemented a large retrospective cohort study in a single assisted reproductive technology (ART) unit at a university-based hospital, including 1540 autologous FET cycles performed in freeze-all cycles. The beginning of the FET was classified as either ‘cycle 1’ (performing FET within the first menstrual cycle) or ‘cycle ≥2’ (performing FET after one or more menstrual cycles). Live birth rate (LBR) was the primary outcome of our study.

The mean interval for ‘cycle 1’ and ‘cycle ≥2’ FETs was 25.72 ± 5.10 days and 75.33 ± 24.85 days, respectively (P < .001). The type of controlled ovarian hyperstimulation (COH) and endometrial preparation protocols differed significantly between groups (P = .008 and P = .004, respectively). However, FET groups were similar in many ways. Univariate analysis showed that there was no significant difference in LBR between the different cycles (33.1% after ‘cycle 1’ FET vs 34.2% after ‘cycle ≥2’ FET, P = .68). To evaluate whether LBR remained unchanged after adjustment for potential confounders, we performed multivariate logistic regression. FET timing had no significant impact on LBR in the first FET (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 0.80–1.39).

In accordance with the present study, it might not be necessary for clinicians to wait more than 1 menstrual cycle before performing FET. This allows us to reduce otiose deferment in FET, without adversely affecting reproductive outcomes.
Paget's disease of bone: updates for clinicians
Authors: Hsu Emory
Published: October 2019

Purpose of review

To provide clinicians an overview to the diagnosis, treatment, and management of Paget's disease, including recent guideline recommendations, with comparison of the Endocrine Society Clinical Practice Guideline (JCEM 2014) with the new Clinical Guideline review endorsed by the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the European Calcified Tissues Society, and the United Kingdom Bone Research Society (JBMR 2019).

Recent findings

Radionuclide bone scans are recommended for assessing the extent of Paget's disease. Bisphosphonates remain the mainstay for therapy with evidence of reducing symptomatic bone pain. One 5 mg intravenous dose of zoledronic acid is the current standard therapy for Paget's disease.

Paget's disease of the bone is characterized by focal increased bone remodeling activity, resulting in sclerotic or lytic lesions and poor bone quality at one or more sites. Patients may be symptomatic with bone pain, or may be asymptomatic, and identified through unexplained elevations in serum alkaline phosphatase. Diagnosis is through plain film imaging, with radionuclide bone scan to determine the extent. A single dose of IV zoledronic acid typically results in extended suppression of bone turnover and amelioration of bone pain. There remains a lack of evidence regarding efficacy of this treatment with regards to other complications of Paget's, but in general, bisphosphonate treatment is recommended.
Nonalcoholic Fatty Liver Disease
Authors: Sivell Christopher
Published: October 2019

Nonalcoholic fatty liver disease is a growing condition among adolescent and adult populations, present in around 20%–30% of people in the United Kingdom. Nonalcoholic fatty liver disease is known as a silent disease and over many years may go on to cause nonalcoholic steatohepatitis. In the future it may become a leading contributor to cirrhosis, liver transplantation, and mortality. In recent years, programs have been set up to raise awareness of this condition with the first International NASH (nonalcoholic steatohepatitis) Day taking place in 2018; nevertheless, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis is still not clearly understood by many. An extensive review has shown a lack of nursing literature on this topic, and effective specialist nurse input for this patient group should be a key component in tackling this growing epidemic in the years to come.
Older Adults With Subjective Cognitive Decline Worry About the Emotional Impact of Cognitive Test Results
Authors: Wong Sara , Smith Samantha , Jacova Claudia
Published: October 2019

Introduction:

Older adults with subjective cognitive decline (SCD) would benefit from routine cognitive testing as they are twice as likely to develop dementia. Worries about concerning test results may diminish participation. The current study aimed to characterize the pattern of worries among older adults with and without SCD.

Methods:

Adults 50 years or above completed the Attitudes Around Cognitive Testing questionnaire on Mechanical Turk.com or in a primary care setting. Mechanical Turk.com is an online crowdsourcing site where requesters (eg, researchers) post jobs (eg, surveys or tasks) and workers (eg, respondents) choose which jobs to do for pay. Respondents were asked about perceived cognitive decline and about different types of worries they anticipated having if they received concerning test results.

Results:

We report data for 393 respondents (online: n=296, primary care: n=97), mean age of 63 years, age range of 50 to 91 years, and 60% endorsing SCD. Compared with No SCD, those with SCD anticipated a higher number of worries centered disproportionately on worries of becoming depressed, ashamed or embarrassed, feeling “stupid” and unable to do things, and being put in a nursing home. We observed this SCD pattern of worries in both samples.

Discussion:

Individuals with SCD worry about the emotional consequences of cognitive testing. This at-risk group would benefit from interventions focused on these concerns to increase patient engagement with cognitive tests.
Engineering a synthetic gut model to explore Clostridioidesdifficile infections
Authors: Hassall Jack , Unnikrishnan Meera
Published: October 2019

Our intestines play home to over one thousand bacterial species, often referred to as the gut microbiota. This microbiota profoundly affects our bodies, providing an array of benefits. Disturbances to this community are associated with pathogenic infection and diseases such as obesity, diabetes and inflammatory bowel disease.Our aim is to engineer a synthetic microbiota, with an emphasis on tracking individual species. Introducing this community into our in vitro gut epithelial culture system will provide insights into pathogen infection strategies, and mechanisms by which the microbiota generates resistance. This tool can be used for the screening of drug/probiotic candidates, potentially reducing the need for animals. Using PMA-qPCR we are able to track up to ten single species in a mixed biofilm. Clostridium difficile an opportunistic pathogen targets the gut during times of depleted microbiota. We have begun using our tracking technology to see how a representative microbiota reacts to a C. difficile invasion. Alongside this, we investigated the effect of the gut commensal - Bacteroides dorei on C. difficile utilizing classical quantification. In both a standard biofilm and in our in vitro model, we see a reduced number of C. difficile when in mixed culture.
Poo and Puns: The representation of Faecal Microbiota Transplants in English-language print media (2003 – 2017)
Authors: McLeod Carmen , Nerlich Brigitte
Published: October 2019

This study investigates how English-language news sources represented faecal microbiota transplants (FMT) between 2003 and 2017. In the context of this study, FMT is understood to be the process of transferring stool from a healthy donor to a recipient with a dysfunctional intestinal flora in order to repopulate their gut microbiome. A corpus of news articles on FMT, was produced by searching for ‘fa(e)cal microbial’, ‘microbiota transplant‘ and ‘stool transplant’ on the Nexis® UK news database, generating a corpus suitable for qualitative analysis (n = 504 articles). In order to uncover emerging social representations, we investigated press coverage of stool transplants, as well as broader themes associated with health and the gut microbiome. Our findings show that print media focused particularly on creating novel, mainly hopeful, social representations of faeces through wordplay and punning, side-lining issues of risk and fear. We also identify changing metaphorical framings of microbes and bacteria from ‘enemies’ to ‘friends’. Additionally, we found readers are familiarised with FMT through the depiction of the process as being both mundane and highly medicalised. We argue emerging media representations have the potential to shape more positive social representations of FMT in the general population, paving the way for FMT to become a more socially acceptable and effective medical procedure. Future research can build on this baseline in order to study how social representations circulate in the wider media and public sphere, and how they may change over time and differ between countries as research into FMT progresses.

https://www.tandfonline.com/doi/full/10.1080/14636778.2019.1637721
The Sensitivity of PCR combined with the Specificity of Toxin Enzyme Immunoassay: Could an Ultra-sensitive Single Molecule Counting Technology Offer a Standalone Solution for Diagnosis of Clostridioides difficile Infection?
Authors: Perry Michael , Graham Lee , Perry Lauren , Parida Sweta , Katzenbach Phoebe , Baptista Jose , Sandlund Johanna , Anderson Bethan , Copsey Sarah , Scotford Selina , Morris Tefor
Published: October 2019

Background

Clostridioides difficile infection (CDI) continues to cause significant morbidity and avoidable mortality worldwide. Results from an ultra-sensitive toxin immunoassay (Singlulex Clarity C. diff toxins A/B assay) were compared with those of various other diagnostic and reference methods/algorithms for the detection of C. difficile.

Methods

293 residual clinical stool samples were tested using the Singulex assay. In total, 188 samples were tested by GDH and 239 were tested by PCR. All toxin B PCR (Serosep EntericBio C. difficile assay) positive samples (n=168) and prospectively tested GDH samples (n=97) were also tested using membrane-type toxin EIA (MT-EIA; Techlab Tox A/B Quik Chekò). Culture (alcohol shock and Brazier’s media; Oxoid) and ribotyping (capillary electrophoresis using Bidet et al. primers) information was available for 205 samples.

Results

The positive percent agreement (PPA) and negative percent agreement (NPA) of the Singulex Clarity C. diff toxins A/B assay compared with: GDH; toxin EIA; PCR; GDH/toxin EIA; GDH/toxin EIA/PCR; PCR/toxin EIA and culture were – 61% & 92%; 97% & 50%; 69% & 90%; 100% & 51%; 81% & 77%; 96% & 65%; and 69% AND 52% respectively.

Conclusions

The Singulex Clarity C. diff toxins A/B assay had high PPA compared to toxin EIA and multistep algorithms ending with toxin EIA, and high NPA compared to PCR and a multistep algorithm ending with PCR. The Singulex Clarity assay has the potential to be used as a standalone test for CDI diagnosis; additional clinical studies are required and will soon be underway.
The use of MALDI-TOF MS as a rapid test to detect carbapenem resistance in Bacteroides fragilis
Authors: Copsey-Mawer Sarah , Scotford Selina , Copsey-Mawer Bethan , Davis Carol , Perry Michael , Morris Trefor , Hughes Harriet
Published: October 2019

Background

The frequency of resistance to carbapenems in Bacteroides fragilis isolates is rising and is conferred by a metallo-β-lactamase encoded by the cfiA gene. The utilisation of existing technologies such as MALDI-TOF MS (MTMS) may allow for the early detection of this important resistance phenotype.

Methods

168 B. fragilis isolates were tested. Meropenem MICs were performed by agar dilution and the results interpreted using EUCAST guidelines. All isolates were identified to species level by MTMS and the presence of CfiA detected using the Bruker MBT subtyping module. The presence of thecfiA gene was confirmed by PCR. Next generation sequencing (NGS) was utilised for discrepant results.

Results

108 isolates (64%) were phenotypically susceptible, with 98% of these testing negative for cfiA by both MTMS and PCR. 40 isolates (25%) were phenotypically resistant, of which 65% were positive by PCR and MTMS with 35% negative by both methods.

35% of positive isolates were found to have an IS element upstream of cfiA, and all had an MIC ≥ 64 mg/L.

Discordant results included two isolates which were susceptible, cfiApositive and IS negative, and three cfiA negative resistant isolates.

Conclusion

Overall, a good correlation was observed between methods. Discrepancies highlight an important distinction between the presence of the cfiAgene and its expression.

Although a negative MTMS result does not rule out resistance, it is a rapid and valuable tool to guide early therapeutic decisions for this important pathogen.
Authenticating Anaerobes – Use of MALDI-TOF MS to identify anaerobes in the NCTC Collection
Authors: McGregor Hannah , Pindoria Dipali , Rai Rupa , Alexander Sarah
Published: October 2019

The National Collection of Type Cultures (NCTC) is the world’s oldest repository of medically-relevant bacteria. NCTC contains 5,500 bacterial strains, 500 of which are anaerobes, with the collection regularly receiving new Type strains and recent clinical isolates.

Fastidious anaerobes pose a unique challenge during the authentication process. NCTC must ensure that the strains are free from contamination and that the organism survives the lyophilisation process. Species-level identification of anaerobic bacterial strains is achieved using a combination of the both MALDI-TOF MS and VITEK2 instruments.

This study evaluates the use of MALDI-TOF MS (Bruker) and VITEK2 (BioMerieux) to identify the anaerobic strains in the NCTC collection. 176 NCTC strains were tested on the MALDI-TOF platform and 60 strains were identified using VITEK2.

MALDI-TOF was able to identify 79% anaerobes to genus-level and 64% to species-level. In comparison the VITEK2 identified 68% to genus and 46% to species-level. The main limiting factor for both these platforms is the database. This may be due to novel anaerobe species NCTC receives not being present on the databases. In the event of no identification, 16S ribosomal RNA sequencing is employed. Furthermore, detection of specific characteristics is carried out by specialist reference laboratories in Cardiff and Colindale, ensuring a robust collection of anaerobic bacteria for use in research and as control strains.
Hexokinase 2 is dispensable for photoreceptor development but is required for survival during aging and outer retinal stress
Authors: Weh Eric , Lutrzykowska Zuzanna , Smith Andrew , Hager Heather , Pawar Mercy , Wubben Thomas , Besirli Cagri G.
Published: October 2019

Photoreceptor death is the ultimate cause of vision loss in many retinal degenerative conditions. Identifying novel therapeutic avenues for prolonging photoreceptor health and function has the potential to improve vision and quality of life for patients suffering from degenerative retinal disorders. Photoreceptors are metabolically unique among other neurons in that they process the majority of their glucose via aerobic glycolysis. One of the main regulators of aerobic glycolysis is hexokinase 2 (HK2). Beyond its enzymatic function of phosphorylating glucose to glucose-6-phosphate, HK2 has additional non-enzymatic roles, including the regulation of apoptotic signaling via AKT signaling. Determining the role of HK2 in photoreceptor homeostasis may identify novel signaling pathways that can be targeted with neuroprotective agents to boost photoreceptor survival during metabolic stress. Here we show that following experimental retinal detachment, p-AKT is upregulated and HK2 translocates to mitochondria. Inhibition of AKT phosphorylation in 661W photoreceptor-like cells results in translocation of mitochondrial HK2 to the cytoplasm, increased caspase activity, and decreased cell viability. Rod-photoreceptors lacking HK2 upregulate HK1 and appear to develop normally. Interestingly, we found that HK2-deficient photoreceptors are more susceptible to acute nutrient deprivation in the experimental retinal detachment model. Additionally, HK2 appears to be important for preserving photoreceptors during aging. We show that retinal glucose metabolism is largely unchanged after HK2 deletion, suggesting that the non-enzymatic role of HK2 is important for maintaining photoreceptor health. These results suggest that HK2 expression is critical for preserving photoreceptors during acute nutrient stress and aging. More specifically, p-AKT mediated translocation of HK2 to the mitochondrial surface may be critical for protecting photoreceptors from acute and chronic stress.
The Popgen Pipeline Platform: A Software Platform for Facilitating Population Genomic Analyses
Authors: Webb Andrew , Knoblauch Jared , Sabankar Nitesh , Kallur Apeksha Sukesh , Hey Jody , Sethuraman Arun
Published: October 2019

Here we present the Pop-Gen Pipeline Platform (PPP), a software platform with the goal of reducing the computational expertise required for conducting population genomic analyses. The PPP was designed as a collection of scripts that facilitate common population genomic workflows in a consistent and standardized Python environment. Functions were developed to encompass entire workflows, including: input preparation, file format conversion, various population genomic analyses, output generation, and visualization. By facilitating entire workflows, the PPP offers several benefits to prospective end users - it reduces the need of redundant in-house software and scripts that would require development time and may be error-prone, or incorrect. The platform has also been developed with reproducibility and extensibility of analyses in mind. The PPP is an open-source package that is available for download and use athttps://ppp.readthedocs.io/en/latest/PPP_pages/install.html
Enhancing droplet-based single-nucleus RNA-seq resolution using the semi-supervised machine learning classifier DIEM
Authors: Alvarez Marcus , Rahmani Elior , Jew Brandon , Garske Kristina M. , Miao Zong , Benhammou Jihane N. , Ye Chun Jimmie , Pisegna Joseph R. , Pietiläinen Kirsi H. , Halperin Eran , Pajukanta Päivi
Published: October 2019

Single-nucleus RNA sequencing (snRNA-seq) measures gene expression in individual nuclei instead of cells, allowing for unbiased cell type characterization in solid tissues. Contrary to single-cell RNA seq (scRNA-seq), we observe that snRNA-seq is commonly subject to contamination by high amounts of extranuclear background RNA, which can lead to identification of spurious cell types in downstream clustering analyses if overlooked. We present a novel approach to remove debris-contaminated droplets in snRNA-seq experiments, called Debris Identification using Expectation Maximization (DIEM). Our likelihood-based approach models the gene expression distribution of debris and cell types, which are estimated using EM. We evaluated DIEM using three snRNA-seq data sets: 1) human differentiating preadipocytes in vitro, 2) fresh mouse brain tissue, and 3) human frozen adipose tissue (AT) from six individuals. All three data sets showed various degrees of extranuclear RNA contamination. We observed that existing methods fail to account for contaminated droplets and led to spurious cell types. When compared to filtering using these state of the art methods, DIEM better removed droplets containing high levels of extranuclear RNA and led to higher quality clusters. Although DIEM was designed for snRNA-seq data, we also successfully applied DIEM to single-cell data. To conclude, our novel method DIEM removes debris-contaminated droplets from single-cell-based data fast and effectively, leading to cleaner downstream analysis. Our code is freely available for use at https://github.com/marcalva/diem.
Putting the brain in a box: a toolbox for creating Cartesian Geometric Representations with Isometric Dimensions (Cgrids)
Authors: Raemaekers Mathijs , Bruurmijn Mark , Ramsey Nick
Published: October 2019

The folding of the human cortex complicates extraction of position information and recognition of patterns across the cortical surface. As straight lines correspond better to our intuitions in spatial orientation, we developed an approach for imposing Cartesian grids on portions of the cortical surface, which can then be represented in a rectangular matrix. These functions have been implemented in the Cgrid (Cartesian Geometric Representation with Isometric Dimensions) toolbox. Cgrids can be generated based on regions of interest, or combinations thereof, according to any one of the Freesurfer’s annotation schemes.

The toolbox was evaluated using the surface reconstructions of T1-weighted images of 30 subjects, and 17 different Cgrids that in combination covered nearly the entire surface area of the brain. The vast majority of Cgrids (94.6%) could be generated without issues.

In addition to facilitating spatial orientation and pattern recognition, the toolbox also allows detailed comparison between the left and right hemisphere, and performing surface based analysis using a volumetric data format. The output of the toolbox is fully compatible with most existing fMRI/MRI analyses packages, and is immediately suitable as input for second level analysis. The toolbox can be downloaded from:https://github.com/mathijsraemaekers/Cgrid-toolbox