bluuebunny/crossref_metadata_2025 huggingface dataset:
Recurrent secondary genomic alterations in desmoplastic small round cell tumors
Authors: Chow Warren A. , Yee Jiing-Kuan , Tsark Walter , Wu Xiwei , Qin Hanjun , Guan Min , Ross Jeffrey S. , Ali Siraj M. , Millis Sherri Z.
Published: May 2020

Background

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive, translocation-associated soft-tissue sarcoma that primarily affects children, adolescents, and young adults, with a striking male predominance. It is characterized by t(11;22) generating a novel EWSR1-WT1 fusion gene. Secondary genomic alterations are rarely described.

Methods

Tumor tissue from 83 DSRCT patients was assayed by hybrid-capture based comprehensive genomic profiling, FoundationOne® Heme next generation sequencing analysis of 406 genes and RNA sequencing of 265 genes. Tumor mutation burden was calculated from a minimum of 1.4 Mb sequenced DNA. Microsatellite instability status was determined by a novel algorithm analyzing 114 specific loci.

Results

Comprehensive genomic profiling identified several genomically-defined DSRCT subgroups. Recurrent genomic alterations were most frequently detected in FGFR4, ARID1A, TP53, MSH3, and MLL3 genes. With the exception of FGFR4, where the genomic alterations predicted activation, most of the alterations in the remaining genes predicted gene inactivation. No DSRCT were TMB or MSI high.

Conclusions

In summary, recurrent secondary somatic alterations in FGFR4, ARID1A, TP53, MSH3, and MLL3 were detected in 82% of DSRCT, which is significantly greater than previously reported. These alterations may have both prognostic and therapeutic implications.
Three intellectual disability-associated de novo mutations in MECP2 identified by trio-WES analysis
Authors: Gu Yi , Xiang Bingwu , Zhu Lina , Ma Xiuwei , Chen Xiang , Cai Tao
Published: May 2020

Background

To date, at least 746 genes have been identified to cause intellectual disability (ID). Among them, mutations in the Methyl CpG binding protein 2 (MECP2) gene are the leading cause of Rett syndrome and associated ID.

Methods

Considering the large number of ID-associated genes, we applied trio-based whole-exome sequencing (trio-WES) and in silico analysis for genetic diagnosis of 294 children with ID.

Results

Three de novo heterozygous mutations [NM_004992.3: c.502C > T, p.(Arg168*), c.916C > T, p.(Arg306Cys), and c.879C > G, p.(Ile293Met)] in MECP2 were identified in three unrelated girls. The first two mutations were detected in two patients who were diagnosed as typical Rett syndrome, X-linked ID and psychomotor retardation. The third mutation (c.879C > G), a previously unreported, was found in a 6-year-old girl with ID, microcephaly, severe underweight and psychomotor retardation. Particularly, this extremely rare de novo mutation (DNM) is located in the transcriptional repression domain (TRD) of MECP2, where at least 62 different causal mutations are identified.

Conclusions

We identified three DNMs in MECP2 in a cohort of 294 individuals with ID. The novel c.879C > G mutation, as a likely pathogenic allele, may become a risk factor associated with X-linked ID, microcephaly and psychomotor retardation.
Detrimental role of sphingosine kinase 1 in kidney damage in DOCA-salt hypertensive model: evidence from knockout mice
Authors: Lyu Bingqing , Wang Weili , Ji Xin-Ying , Ritter Joseph K. , Li Ningjun
Published: May 2020

Background

Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingolipids and produced by sphingosine kinases (SphK1 and SphK2). SphK1/S1P pathway is implicated in the progression of chronic kidney disease. However, the role of SphK1/S1P pathway in renal injury in hypertension has not been reported. This study tested the hypothesis that SphK1/S1P pathway mediates the kidney damage in DOCA-salt hypertensive mice.

Methods

Male wild type (WT) C57BL6 and SphK1 knockout (KO) mice were subjected to unilateral nephrectomy, subcutaneous implant containing 50 mg of deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water for 7 weeks. At the end of experiments, blood pressure data, 24 h urine and kidney samples were collected. Renal mRNA levels of SphK1 were measured by real-time RT-PCR. Markers for fibrogenesis and immune cell infiltration in kidneys were detected using Western blot and immunohistochemistray analysis, respectively. The glomerular morphological changes were examined in kidney tissue slides stained with Periodic-Acid Schiff. Four groups were studied: wild type control (WT-C), WT-DOCA, KO-C and KO-DOCA.

Results

The renal SphK1 mRNA expression was significantly upregulated in WT-DOCA mice, whereas this upregulation of renal SphK1 mRNA was blocked in KO-DOCA mice. There was no difference in DOCA-salt-induced hypertension between WT and KO mice. The urinary albumin was increased in both DOCA-salt groups. However, the albuminuria was significantly lower in KO-DOCA than in WT-DOCA group. There were increases in glomerulosclerosis indices in both DOCA-salt groups, whereas the increases were also significantly lower in KO-DOCA than in WT-DOCA mice. Renal protein levels of α-smooth muscle actin were upregulated in both DOCA-salt groups, but the increase was significant lower in KO-DOCA than in WT-DOCA group. The increased staining areas of collagen detected by Sirius Red-staining in kidney tissue sections were also attenuated in KO-DOCA compared with WT-DOCA mice. In contrast, the increased infiltration of CD43+ (a T cell marker) or CD68+ (a macrophage marker) cells in DOCA-salt kidneys showed no significant difference between WT-DOCA and KO-DOCA mice.

Conclusions

SphK1/S1P signaling pathway mediates kidney damage in DOCA-salt hypertensive mice independent of blood pressure and immune modulation.
Protocols of a diagnostic study and a randomized controlled non-inferiority trial comparing televisits vs standard in-person outpatient visits for narcolepsy diagnosis and care: TElemedicine for NARcolepsy (TENAR)
Authors: Ingravallo Francesca , Vignatelli Luca , Pagotto Uberto , Vandi Stefano , Moresco Monica , Mangiaruga Anastasia , Oriolo Claudia , Zenesini Corrado , Pizza Fabio , Plazzi Giuseppe
Published: May 2020

Background

Narcolepsy is a rare chronic sleep disorder that typically begins in youth. Excessive daytime sleepiness is the main disabling symptom, but the disease is often associated with severe endocrine-metabolic and psychosocial issues, worsened by a long diagnostic delay, requiring a multidisciplinary approach. The scarcity of reference Sleep Centres forces the patient and family to travel for seeking medical consultations, increasing the economic and psychosocial burden of the disease. Growing evidence suggests that Telemedicine may facilitate patient access to sleep consultations and its non-inferiority in terms of patient satisfaction, adherence to treatment, and symptom improvement for sleep disorders. However, Telemedicine clinical and economic benefits for patients with narcolepsy are still unknown.

Methods

TENAR is a two-part project, including: 1. a cross-sectional study (involving 250 children and adults with suspected narcolepsy) evaluating the accuracy of Teletriage (i.e., a synchronous live interactive sleep assessment through a Televisit) for narcolepsy diagnosis compared to the reference standard; and 2. a two-arm, parallel, open randomized controlled trial (RCT) to demonstrate the non-inferiority of the multidisciplinary care of narcolepsy through Televisits versus standard care. In this RCT, 202 adolescents (> 14 y.o.) and adults with narcolepsy will be randomly allocated (1:1 ratio) either to Televisits via videoconference or to standard in-person outpatient follow-up visits (control arm). The primary outcome is sleepiness control (according to the Epworth Sleepiness Scale). Secondary outcomes are other symptoms control, compliance with treatment, metabolic control, quality of life, feasibility, patient and family satisfaction with care, safety, and disease-related costs. At baseline and at 12 months, patients will undergo neurologic, metabolic, and psychosocial assessments and we will measure primary and secondary outcomes. Primary outcomes will be also measured at 6 months (remotely or in person, according to the arm).

Discussion

TENAR project will assess, for the first time, the feasibility, accuracy, efficacy and safety of Telemedicine procedures applied to the diagnosis and the multidisciplinary care of children and adults with narcolepsy. The study may be a model for the remote management of other rare disorders, offering care access for patients living in areas lacking medical centres with specific expertise.

Trial registration

Number of the Tele-multidisciplinary care studyNCT04316286. Registered 20 March 2020.
Spinal metastasis of glioblastoma multiforme before gliosarcomatous transformation: a case report
Authors: Hsu Bing-Hung , Lee Wei-Hwa , Yang Shun-Tai , Han Cheng-Ta , Tseng Yuan-Yun
Published: May 2020

Background

Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors. Intracranial GBM metastases to the spine are rarely detected clinically. Secondary gliosarcomas after treatment of primary GBM are rarely described.

Case presentation

Herein, we report the case of a 53-year-old woman who presented to our emergency room with progressive headache and weakness on the left side. Plain computed tomography and contrast magnetic resonance imaging of the brain revealed an approximately 6.8 cm × 4.5 cm right temporoparietooccipital intraaxial cystic tumor with surrounding diffuse perifocal edema that caused midline shift toward the left. Emergency craniotomy was performed to remove the tumor, and pathological examination revealed GBM. The patient received proton beam therapy, Gliadel implantation, and oral temozolomide chemotherapy as well as targeted therapy with bevacizumab. Approximately 15 months after diagnosis, she underwent surgical resection of the right temporal recurrent tumor and was newly diagnosed as having a metastatic spinal tumor. Pathologically, the right temporal and metastatic spinal tumors were gliosarcoma and GBM, respectively.

Conclusions

Concurrent spinal metastasis and gliosarcomatous transformation, which are two types of GBM complications, are rare. To our knowledge, this is the first report of a case of recurrent GBM with gliosarcoma after proton bean therapy.
Gut microbiota in early pregnancy among women with Hyperglycaemia vs. Normal blood glucose
Authors: Gao Beibei , Zhong Mengdan , Shen Qiong , Wu Ying , Cao Mengdie , Ju Songwen , Chen Lei
Published: May 2020

Background

Recent studies suggest that there is a link between the gut microbiota and glucose metabolism. This study aimed to compare the gut microbiota during early pregnancy of women with hyperglycymia to those with normal blood glucose.

Methods

Gut microbial composition was analysed in 22 women with hyperglycaemia and 28 age-matched healthy controls during their first prenatal visits (< 20 weeks) using high throughput sequencing of the V3-V4 region of the 16S ribosomal RNA gene. Hyperglycemia was diagnosed based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups in 2010.

Results

Women with hyperglycemia in pregnancy (HIP) had significantly lower microbial richness and diversity compared with healthy pregnant women. The proportions of theFirmicutesandBacteroidetesphyla and the ratio ofFirmicutes:Bacteroideteswere not different between the two groups. We observed that individuals with HIP had an increased abundance ofNocardiaceae,Fusobacteriaceae, etc., whereas healthy controls had significantly higher levels ofChristensenellaceae,Clostridiales_vadinBB60_group,Coriobacteriaceae, etc. Similarly, levels of the members of theRuminococcaceaefamily,includingRuminococcaceae_UCG-014,Ruminococcaceae_UCG-003, andRuminococcaceae_UCG-002,were significantly reduced in the HIP group and were negatively correlated with HbA1c. HbA1c levels were positively correlated withBacteroidaceaeandEnterobacteriaceaeand negatively correlated withChristensenellaceae, etc. CRP was positively correlated with theBacteroidaceaeandFusobacteriaceaefamilies and theFusobacteriumgenus.

Conclusions

Our study revealed that individuals with HIP have gut microbial dysbiosis and that certain bacterial groups are associated with glucose metabolism during pregnancy. Further study is needed to provide new ideas to control glucose by modifying the gut microbiota.
Prevalence and factors associated with early initiation of breastfeeding among women in Moshi municipal, northern Tanzania
Authors: Lyellu Hadija Y. , Hussein Tamara H. , Wandel Margareta , Stray-Pedersen Babill , Mgongo Melina , Msuya Sia E.
Published: May 2020

Background

Early initiation of breastfeeding (EIBF) is a predetermining factor for exclusive breastfeeding, and thus a foundation for optimal breastfeeding practices. Rates of EIBF are low globally (42%) and in Tanzania (51%), yet few studies have been done on this issue in Tanzania. This study aimed to determine the prevalence and factors associated with early initiation of breastfeeding among women in northern Tanzania.

Methodology

This study extracted information from a cohort of 536 women who were followed from 3rd trimester period October 2013 to December 2015 in Moshi municipal, northern Tanzania. The data for this paper was collected by the use of questionnaires at enrolment, delivery and 7 days after delivery. The analysis is based on data from 413 women for whom complete information was obtained. Log binomial regression analysis was used to determine factors associated with early initiation of breastfeeding.

Results

The prevalence of EIBF was 83%. Overall, women had high knowledge on colostrum (94%), knowledge on exclusive breastfeeding (81%) and time of breastfeeding initiation (71%), but only 54% were counseled on breastfeeding during antenatal care. Knowledge on timely initiation of breastfeeding during pregnancy and vaginal delivery were associated with EIBF.

Conclusion

Early initiation of breastfeeding is high (83%) in Moshi Municipal but still below the universal coverage recommended by WHO and UNICEF. There is missed opportunity by health facilities to counsel and support early initiation of breastfeeding given high antenatal and facility delivery in this setting. There is a need to evaluate health facility bottle necks to optimal support of early initiation of breastfeeding in Tanzania.
Intentions to use maternity waiting homes and associated factors in Northwest Ethiopia
Authors: Endayehu Mekonen , Yitayal Mezgebu , Debie Ayal
Published: May 2020

Background

Maternity Waiting Homes (MWHs) are residential facilities located within hospitals or health centers to accommodate women in their final weeks of pregnancy to bridge the geographical gap in obstetric care. Little is known, however, about women’s intentions to use MWHs. Thus, this study aimed to assess pregnant women’s intentions to use MWHs and associated factors in East Bellesa district, northwest Ethiopia.

Methods

A community-based cross-sectional study was conducted among 525 pregnant women in East Bellesa district from March to May 2018. Study participants were selected using systematic random sampling. Binary logistic regression was used for analysis. Adjusted Odds Ratio (aOR) with 95% Confidence Interval (CI), and p-value < 0.05 were used to identify factors associated with intentions to use MWHs.

Results

In the study area, 326/499 (65.3%) pregnant women had the intention to use MWHs. Pregnant women who had good knowledge about maternal healthcare and obstetric complications (aOR 6.40; 95% CI 3.6–11.5), positive subjective norms related to women’s perceptions of social pressure (aOR 5.14; 95% CI 2.9–9.2), positive perceived behavioral control of women on the extent to which women feel confident (aOR 4.74; 95% CI 2.7–8.4), rich wealth status (aOR 4.21; 95% CI 2.1–8.4), women who decided by themselves to use maternal services (aOR 2.74; 95% CI 1.2–6.2), attended antenatal care (aOR 2.24; 95% CI 1.2–4.1) and favorable attitudes towards women’s overall evaluation of MWHs (aOR 1.86; 95% CI 1.0–3.4) had higher odds of intentions to use MWHs.

Conclusion

Two thirds (65.3%) of pregnant women had intentions to use MWHs. Factors such as women’s knowledge, subjective norms related to women’s perceptions of social pressure, perceived behavioral control of women on the extent to which women feel confident to utilize, and wealth status, decision-making power, attending antenatal care and attitude towards women’s overall evaluation of MWHs were significantly associated with the intention to use MWHs. Therefore, improving women’s awareness by providing continuous health education during antenatal care visits, devising strategies to improve women’s wealth status, and strengthening decision-making power may enhance their intention to use MWHs.
Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status
Authors: Kuriyama Naohisa , Usui Masanobu , Gyoten Kazuaki , Hayasaki Aoi , Fujii Takehiro , Iizawa Yusuke , Kato Hiroyuki , Murata Yasuhiro , Tanemura Akihiro , Kishiwada Masashi , Sakurai Hiroyuki , Mizuno Shugo , Isaji Shuji
Published: May 2020

Background

The prognosis of patients with perihilar cholangiocarcinoma have been unsatisfactory. We established new anatomical resectability classification for patients with localized perihilar cholangiocarcinoma and performed neoadjuvant chemotherapy followed by curative-intent surgery based on its resectability classification and lymph node status to improve prognosis. This study aimed to clarify the long-term outcomes and validation of our strategy.

Methods

Between September 2010 and August 2018, 72 consecutive patients with perihilar cholangiocarcinoma were classified into three groups: Resectable (R = 29), Borderline resectable (BR = 23), and Locally advanced (LA = 20), based on the two factors of tumor vascular and biliary extension. R with clinically lymph node metastasis, BR, and LA patients received neoadjuvant chemotherapy using gemcitabine plus S-1.

Results

Forty-seven patients (65.3%) received neoadjuvant chemotherapy: R in 8, BR in 21, and 18 in LA, respectively. Fifty-nine patients (68.1%) underwent curative-intent surgery: R in 26, BR in 17, and LA in 6. Five-year disease-specific survival was 31.5% (median survival time: 33.0 months): 50.3% (not reached) in R, 30.0% (31.4 months) in BR, and 16.5% (22.5 months) in LA, which were relatively stratified. Among 49 patients with resection, disease-specific survival was 43.8% (57.0 months): 57.6% (not reached) in R, 41.0% (52.4 months) in BR, and 0% (49.4 months) in LA, which were significantly good prognosis compared to 23 patients without resection (17.2 months). Multivariate analysis identified preoperative high carcinoembryonic antigen levels (more than 8.5 ng/ml) and pT4 as independent poor prognostic factor of patients with resection.

Conclusion

Neoadjuvant chemotherapy based on resectability classification and lymph node status was feasible, and was considered efficacious in selected patients.
Prognostic nutrition index as a predictor of coronary artery aneurysm in Kawasaki Disease
Authors: Tai I-Hsin , Wu Pei-Lin , Guo Mindy Ming-Huey , Lee Jessica , Chu Chi-Hsiang , Hsieh Kai-Sheng , Kuo Ho-Chang
Published: May 2020

Background

Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet.

Method

This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients.

Result

Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%.

Conclusion

PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness.
Low cyclosporine concentrations in children and time to acute graft versus host disease
Authors: Chung Eun Kyung , Yee Jeong , Kim Jae Youn , Gwak Hye Sun
Published: May 2020

Background

Achievement of target blood concentrations of cyclosporine (CsA) early after transplantation is known to be highly effective for reducing the incidence of acute graft versus host disease (aGVHD). However, no research has been conducted for predicting aGVHD occurrence with low CsA concentrations at different time periods. The objective of this study was to investigate the risk of aGVHD according to low CsA concentrations at lag days in children with allogenic hematopoietic stem cell transplantation (HSCT).

Methods

The records of 61 consecutive children who underwent allogeneic HSCT and received CsA as prophylaxis against aGVHD between May 2012 and March 2015 were retrospectively evaluated. The main outcome was any association between low CsA concentrations at lag days and aGVHD occurrence, which was examined for the first month after transplantation. Mean CsA concentrations at three lag periods were calculated: lag days 0–6, 7–13, and 14–20 before aGVHD occurrence.

Results

Patients whose mean CsA concentrations at lag days 0–6 did not reach the initial target concentration had 11.0-fold (95% confidence interval [CI]: 2.3–51.9) greater incidence of aGVHD. In addition, the AORs of low CsA concentrations at lag days 7–13 and 14–20 for developing aGVHD were 108.2 (95% CI: 7.7–1515.5) and 12.1 (95% CI: 1.1–138.1), respectively.

Conclusions

After low CsA concentrations are detected, careful attention needs to be paid to prevent aGVHD.
How did the use of psychotropic drugs change during the Great Recession in Portugal? A follow-up to the National Mental Health Survey
Authors: Silva Manuela , Antunes Ana , Azeredo-Lopes Sofia , Cardoso Graça , Xavier Miguel , Saraceno Benedetto , Caldas-de-Almeida José Miguel
Published: May 2020

Background

Research suggests that economic recessions might be associated with a higher use of psychotropic drugs, but literature is scarce and contradictory in identifying the most vulnerable groups. This study aims to assess possible changes in the use of psychotropic drugs due to the economic recession in Portugal, by comparing self-reported consumption in 2008/09 and 2015/16.

Methods

Data from the World Mental Health Survey Initiative Portugal (2008/09) and the National Mental Health Survey Follow-Up (2015/16) were used (n = 911). McNemar’s tests were performed to estimate changes in consumption of any psychotropic drug and of antidepressants, anxiolytics, and hypnotics/sedatives. Multiple Generalised Estimating Equations models with interaction effects were used to estimate the population odds of consuming psychotropic drugs according to year, gender and age.

Results

An increase of 6.74% was estimated in the consumption of psychotropic drugs from 2008/09 to 2015/16. Population odds of consuming any psychotropic drugs in 2015/16 were estimated to be 1.5 times higher than in 2008/09 (OR = 1.50;95%CI:1.13–2.01), particularly for hypnotics/sedatives (OR = 1.60;95%CI:1.14–2.25). Women and older individuals presented higher odds of consuming any psychotropic drugs (OR = 2.79;95%CI:2.03–3.84, and OR = 1.80;95%CI:1.28–2.54), after adjusting for year of assessment and education. However, when evaluating the interaction effect of the year with gender and age, men and younger individuals reported higher odds of consuming any psychotropic drugs in 2015/16, when compared to 2008/09 (OR = 1.85;95%CI:1.08–3.17, and OR = 1.95;95%CI:1.32–2.90, respectively).

Conclusions

The findings indicate that the period of economic recession was associated with an increased risk of psychotropic drugs use in Portugal. Consumption of psychotropic drugs remained higher among women and older individuals, but the results suggest that the economic crisis had a disproportionate impact on men and younger individuals. This identification of the most vulnerable population groups is useful to design effective and targeted public health interventions aimed at alleviating the effects of economic recessions.
Protocol Across study: longitudinal transdiagnostic cognitive functioning, psychiatric symptoms, and biological parameters in patients with a psychiatric disorder
Authors: Nieman Dorien H. , Chavez-Baldini UnYoung , Vulink Nienke C. , Smit Dirk J. A. , van Wingen Guido , de Koning Pelle , Sutterland Arjen L. , Mocking Roel J. T. , Bockting Claudi , Verweij Karin J. H. , Lok Anja , Denys Damiaan
Published: May 2020

Background

Patients with psychiatric disorders, such as major depressive disorder, schizophrenia or obsessive-compulsive disorder, often suffer from cognitive dysfunction. The nature of these dysfunctions and their relation with clinical symptoms and biological parameters is not yet clear. Traditionally, cognitive dysfunction is studied in patients with specific psychiatric disorders, disregarding the fact that cognitive deficits are shared across disorders. The Across study aims to investigate cognitive functioning and its relation with psychiatric symptoms and biological parameters transdiagnostically and longitudinally.

Methods

The study recruits patients diagnosed with a variety of psychiatric disorders and has a longitudinal cohort design with an assessment at baseline and at one-year follow-up. The primary outcome measure is cognitive functioning. The secondary outcome measures include clinical symptoms, electroencephalographic, genetic and blood markers (e.g., fatty acids), and hair cortisol concentration levels.

Discussion

The Across study provides an opportunity for a transdiagnostic, bottom-up, data-driven approach of investigating cognition in relation to symptoms and biological parameters longitudinally in patients with psychiatric disorders. The study may help to find new clusters of symptoms, biological markers, and cognitive dysfunctions that have better prognostic value than the current diagnostic categories. Furthermore, increased insight into the relationship among cognitive deficits, biological parameters, and psychiatric symptoms can lead to new treatment possibilities.

Trial registration

Netherlands Trial Register (NTR): NL8170.
Efficacy of revefenacin, a long-acting muscarinic antagonist for nebulized therapy, in patients with markers of more severe COPD: a post hoc subgroup analysis
Authors: Donohue James F. , Kerwin Edward , Barnes Chris N. , Moran Edmund J. , Haumann Brett , Crater Glenn D.
Published: May 2020

Background

Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV1) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD.

Methods

A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV1, St. George’s Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV1 30%–< 50% and < 30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥ 12% and ≥ 200 mL increase in FEV1) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (> 65 and > 75 years), and comorbidity risk factors.

Results

Revefenacin demonstrated significant improvements in FEV1 versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio > 2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio > 2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged > 75 years.

Conclusions

Revefenacin showed significantly greater improvements in FEV1 versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.

Trial registration

Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).
Multiple intraventricular metastases from lung adenocarcinoma with EGFR G719X mutation: a case report
Authors: Kong Chen , Zhou Dan , Wu Ning , Bai Chong
Published: May 2020

Background

Brain is one of the most common target organ of lung cancer metastasis, while descriptions of intraventricular carcinomatosis could hardly be found among previous cases. To date no cases from lung adenocarcinoma have been reported in the literature.

Case presentation

We report here a case of multiple intraventricular metastases from lung adenocarcinoma with EGFR G719X mutation. This 64-year-old woman was referred to our hospital with complaints of dizziness and vomiting. Target therapy with afatinib was initiated and the lesions in both lung and brain achieved good partial responses.

Conclusions

This case report revealed a phenomenon of rare intraventricular metastasis from lung cancer, which should be carefully distinguished from primary ventricular tumors. Compared to brain parenchyma metastasis, intraventricular lesions would cause more severe symptoms which may be rapidly progressive. Target therapy could become a potential option in such patients with non-drugresistant EGFR mutations.
Baseline low ALT activity is associated with increased long-term mortality after COPD exacerbations
Authors: Lasman N. , Shalom M. , Turpashvili N. , Goldhaber G. , Lifshitz Y. , Leibowitz E. , Berger G. , Saltzman-Shenhav G. , Brom A. , Cohen D. , Avaky C. , Segal G.
Published: May 2020

Background

COPD exacerbations have negative impact on patients’ survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.

Methods

This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.

Results

Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13–41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatic tissue damage (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11 IU; 12-16 IU; 17-20 IU and > 21 IU the mortality rates were 69%; 40.9%; 36.3 and 25% respectively (p <  0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11 IU was 2.37 (95% CI; 1.6–3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08–3.1, p <  0.05).

Conclusions

Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.
Fluoroquinolone resistance and mutational profile of gyrA in pulmonary MDR tuberculosis patients
Authors: Kabir Saba , Tahir Zarfishan , Mukhtar Nadia , Sohail Muhammad , Saqalein Muhammad , Rehman Abdul
Published: May 2020

Background

Fluoroquinolones (FQs) are potential drugs that inhibit DNA synthesis and are used in the treatment of multidrug-resistant tuberculosis (TB) and short-term anti-TB regimens. In recent years, a high proportion of FQ resistance has been observed in Mycobacterium tuberculosis isolates. The development of FQ resistance in multidrug-resistant TB negatively impacts patient treatment outcome and is a serious threat to control of TB.

Methods

The study included a total of 562 samples from patients with pulmonary TB that had been on anti-tuberculosis therapy. MTBDRsl assays were performed for the molecular detection of mutations. Sequence analysis was performed for the characterization and mutational profiling of FQ-resistant isolates.

Results

FQ resistance was observed in 104 samples (18.5%), most of which were previously treated and treatment failure cases. A total of 102 isolates had mutations in DNA gyrase subunit A (gyrA), while mutations in gyrB were observed in only two isolates. Mutational analysis revealed that the mutations mostly alter codons 94 (replacing aspartic acid with glycine, D94G) and 90 (replacing alanine with valine, A90V). In MDR and treatment failure cases, resistance to FQs was most commonly associated with the D94G mutation. In contract, a high proportion of A90V mutations were observed in isolates that were newly diagnosed.

Conclusion

The findings suggest that genotypic assays for FQ resistance should be carried out at the time of initial diagnosis, before starting treatment, in order to rule out mutations that impact the potential use of FQs in treatment and to control drug resistance.
A comparison study of posterior cervical percutaneous endoscopic ventral bony decompression and simple dorsal decompression treatment in cervical spondylotic radiculopathy caused by cervical foraminal and/or lateral spinal stenosis: a clinical retrospective study
Authors: Tong Yuexin , Huang Zhangheng , Hu Chuan , Fan Zhiyi , Bian Fucheng , Yang Fengkai , Zhao Chengliang
Published: May 2020

Background

Percutaneous endoscopic cervical decompression (PECD) is an ideal minimally invasive decompression technique for the treatment of cervical spondylotic radiculopathy (CSR). However, the mainstream is the resection of dorsal bone and removal of free nucleus pulposus. The necessity of excision of ventral osteophytes and hyperplastic ligaments in the treatment of CSR caused by cervical foraminal and/or lateral spinal stenosis (CFa/oLSS) to be discussed.

Methods

We performed a retrospective study of 46 patients with CSR caused by CFa/oLSS from January 2017 to November 2018. These patients received posterior percutaneous endoscopic cervical decompression-ventral bony decompression (PPECD-VBD)(23 cases, classified as VBD group) or posterior percutaneous endoscopic cervical decompression-simple dorsal decompression (PPECD-SDD)(23 cases, classified as SDD group). Following surgery, we recorded Visual Analogue Scale (VAS), Neck Disable Index (NDI), Japanese Orthopaedic Association (JOA) Scores and myodynamia. We further evaluated the changes of cervical curvature and cervical spine motion in the VBD group and recorded the operation time and complications during the follow-up of each patient.

Results

All patients underwent successful operations, with an average follow-up time of 16.53 ± 9.90 months. The excellent and good rates in the VBD and SDD groups were 91.29 and 60.87%, respectively. In the SDD group, neck-VAS, arm-VAS, and NDI scores were significantly higher than those of the VBD group at 1 day, 6 months, and 12 months after surgery (P < 0.05), while the JOA scores and improvement rate of JOA were significantly lower than those of the VBD group (P < 0.05). There were no significant differences in terms of angular displacement (AD), horizontal displacement (HD), segmental angle (SA) and cervical curvature (CA) before and after the operation in the VBD group (P > 0.05).

Conclusion

PPECD-VBD was significantly better than PPECD-SDD as well as PPECD-VBD had no significant effects on cervical spine stability or cervical curvature.
The OPTIMIZE study: protocol of a pragmatic sequential multiple assessment randomized trial of nonpharmacologic treatment for chronic, nonspecific low back pain
Authors: Skolasky Richard L. , Wegener Stephen T. , Aaron Rachel V. , Ephraim Patti , Brennan Gerard , Greene Tom , Lane Elizabeth , Minick Kate , Hanley Adam W. , Garland Eric L. , Fritz Julie M.
Published: May 2020

Background

Low back pain is a prevalent condition that causes a substantial health burden. Despite intensive and expensive clinical efforts, its prevalence is growing. Nonpharmacologic treatments are effective at improving pain-related outcomes; however, treatment effect sizes are often modest. Physical therapy (PT) and cognitive behavioral therapy (CBT) have the most consistent evidence of effectiveness. Growing evidence also supports mindfulness-based approaches. Discussions with providers and patients highlight the importance of discussing and trying options to find the treatment that works for them and determining what to do when initial treatment is not successful. Herein, we present the protocol for a study that will evaluate evidence-based, protocol-driven treatments using PT, CBT, or mindfulness to examine comparative effectiveness and optimal sequencing for patients with chronic low back pain.

Methods

The Optimized Multidisciplinary Treatment Programs for Nonspecific Chronic Low Back Pain (OPTIMIZE) Study will be a multisite, comparative effectiveness trial using a sequential multiple assessment randomized trial design enrolling 945 individuals with chronic low back pain. The co-primary outcomes will be disability (measured using the Oswestry Disability Index) and pain intensity (measured using the Numerical Pain Rating Scale). After baseline assessment, participants will be randomly assigned to PT or CBT. At week 10, participants who have not experienced at least 50% improvement in disability will be randomized to cross-over phase-1 treatments (e.g., PT to CBT) or to Mindfulness-Oriented Recovery Enhancement (MORE). Treatment will consist of 8 weekly sessions. Long-term outcome assessments will be performed at weeks 26 and 52.

Discussion

Results of this study may inform referring providers and patients about the most effective nonoperative treatment and/or sequence of nonoperative treatments to treat chronic low back pain.

Trial registration

This study was prospectively registered on March 1, 2019, withClinicaltrials.govunder the registration number NCT03859713 (https://clinicaltrials.gov/ct2/show/NCT03859713).
Initial assessment of femoral proximal fracture and acute hip arthritis using pocket-sized ultrasound: a prospective observational study in a primary care setting in Japan
Authors: Akimoto Takashi , Kobayashi Tadashi , Maita Hiroki , Osawa Hiroshi , Kato Hiroyuki
Published: May 2020

Background

Acute hip pain caused by femoral proximal fractures or acute hip arthritis requires imaging for accurate diagnosis. Although pocket-sized ultrasound (PsUS) offers several advantages over other imaging modalities, there is limited information regarding its use in diagnosing femoral proximal fractures or acute hip arthritis. Thus, we aimed to validate the diagnostic accuracy of PsUS for both disorders.

Methods

In this prospective observational study, outpatients with acute hip pain were diagnosed according to a fixed procedure of the PsUS probe handling. We verified the diagnostic accuracy of PsUS findings (cortical discontinuity and joint fluid retention) and compared it with that of radiography, computed tomography, and magnetic resonance imaging.

Results

Our study included 52 outpatients (mean age, 78.0 years; female, 88.5%). Of 26 patients diagnosed with femoral proximal fractures, 14 had femoral neck fractures and 12 had femoral trochanteric fractures. The sensitivity and specificity for identifying cortical discontinuity in femoral proximal fractures were 0.96 and 0.92, respectively. The sensitivity for identifying either cortical discontinuity or joint fluid retention in femoral proximal fractures or acute hip arthritis was 0.97.

Conclusions

Negative PsUS findings of cortical discontinuity and joint fluid retention in the hip are useful for ruling out femoral proximal fractures and acute hip arthritis. PsUS and radiography have comparable diagnostic accuracies, and PsUS could aid in the initial assessment of acute hip pain among the elderly in primary care settings.
Antibiotic prophylaxis in primary and revision shoulder replacement: a systematic review
Authors: Longo Umile Giuseppe , Candela Vincenzo , Facchinetti Gabriella , Marchetti Anna , Dsoke Silvia , Mazzella Claudia , Risi Ambrogioni Laura , De Marinis Maria Grazia , Denaro Vincenzo
Published: May 2020

Background

One of the most common bacteria responsible for most Periprosthetic joint infection (PJI) is Propionibacterium acnes. Even though the rate of infections in patients undergoing total shoulder arthroplasty is increasing, effective diagnostic tests and the precautions taken during the surgery are not yet adequate. This systematic review aims to evaluate the effectiveness of antimicrobial prophylaxis in PJI in shoulder replacement and to provide health workers with the best approach to the use of antimicrobial agents based on currently available clinical evidence.

Methods

a systematic review of the literature was carried out in accordance with the PRISMA Statement. Studies concerning the effectiveness of antimicrobial prophylaxis in the prevention of PJI in patients undergoing shoulder replacement were included.

Results

Seven studies were included in the final analysis because they were considered valid. A total of 3272 patients underwent a surgical procedure, most of which were males. The male population has a greater presence of hair, therefore a greater risk of P. acnes. in surface cultures. Patients were assessed at an average follow-up period of 20 months ranging from 9 weeks to 53 months.

Conclusion

The optimal perioperative antimicrobial regimen is controversial. The clinical guidelines recommend the use of only one antibiotic as prophylaxis but considering the increase in the rates of antibiotic-resistant infections, the question arises whether antibiotic prophylaxis should be extended for adequate coverage. Shoulder arthroplasty performed on the male population must be carefully checked after surgery for the possible presence of P. Acnes.
An exploration of the experiences of professionals supporting patients approaching the end of life in medicines management at home. A qualitative study
Authors: Wilson Eleanor , Caswell Glenys , Latif Asam , Anderson Claire , Faull Christina , Pollock Kristian
Published: May 2020

Background

The management of medicines towards the end of life can place increasing burdens and responsibilities on patients and families. This has received little attention yet it can be a source of great difficulty and distress patients and families. Dose administration aids can be useful for some patients but there is no evidence for their wide spread use or the implications for their use as patients become increasing unwell. The study aimed to explore how healthcare professionals describe the support they provide for patients to manage medications at home at end of life.

Methods

Qualitative interview study with thematic analysis. Participants were a purposive sample of 40 community healthcare professionals (including GPs, pharmacists, and specialist palliative care and community nurses) from across two English counties.

Results

Healthcare professionals reported a variety of ways in which they tried to support patients to take medications as prescribed. While the paper presents some solutions and strategies reported by professional respondents it was clear from both professional and patient/family caregiver accounts in the wider study that rather few professionals provided this kind of support. Standard solutions offered included: rationalising the number of medications; providing different formulations; explaining what medications were for and how best to take them. Dose administration aids were also regularly provided, and while useful for some, they posed a number of practical difficulties for palliative care. More challenging circumstances such as substance misuse and memory loss required more innovative strategies such as supporting ways to record medication taking; balancing restricted access to controlled drugs and appropriate pain management and supporting patient choice in medication use.

Conclusions

The burdens and responsibilities of managing medicines at home for patients approaching the end of life has not been widely recognised or understood. This paper considers some of the strategies reported by professionals in the study, and points to the great potential for a more widely proactive stance in supporting patients and family carers to understand and take their medicines effectively. By adopting tailored, and sometimes, ‘outside the box’ thinking professionals can identify immediate, simple solutions to the problems patients and families experience with managing medicines.