bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical manifestation and genetic findings in three boys with low molecular Weight Proteinuria - three case reports for exploring Dent Disease and Fanconi syndrome
Authors: Duan Nan , Huang Chenwei , Pang Lu , Jiang Shiju , Yang Wenshuang , Li Haixia
Published: January 2021

Background

Dent disease is an X-linked form of progressive renal disease. This rare disorder was characterized by hypercalciuria, low molecular weight (LMW) proteinuria and proximal tubular dysfunction, caused by pathogenic variants in CLCN5 (Dent disease 1) or OCRL (Dent disease 2) genes. Fanconi syndrome is a consequence of decreased water and solute resorption in the proximal tubule of the kidney. Fanconi syndrome caused by proximal tubular dysfunction such as Dent disease might occur in early stage of the disease.

Case presentation

Three cases reported in this study were 3-, 10- and 14-year-old boys, and proteinuria was the first impression in all the cases. All the boys presented with LMW proteinuria and elevated urine albumin-to-creatinine ratio (ACR). Case 1 revealed a pathogenic variant in exon 11 of CLCN5 gene [NM_001127899; c.1444delG] and a nonsense mutation at nucleotide 1509 [p.L503*], and he was diagnosed as Dent disease 1. Case 2 carried a deletion of exon 3 and 4 of OCRL1 gene [NM_000276.4; c.120-238delG…A] and a nonsense mutation at nucleotide 171 in exon 5 [p.E57*], and this boy was diagnosed as Dent disease 2. Genetic analysis of Case 3 showed a missense mutation located in exon 2 of HNF4A gene [EF591040.1; c.253C > T; p.R85W] which is responsible for Fanconi syndrome. All of three pathogenic variants were not registered in GenBank.

Conclusions

Urine protein electrophoresis should be performed for patients with proteinuria. When patients have LMW proteinuria and/or hypercalciuria, definite diagnosis and identification of Dent disease and Fanconi syndrome requires further genetic analyses.
Systemic oxidative stress and cognitive function in Parkinson’s disease with different PWMH or DWMH lesions
Authors: Chang Ta-Chih , Chen Yi-Cun , Huang Yu-Chi , Lin Wei-Che , Lu Cheng-Hsien
Published: January 2021

Background

Parkinson’s disease (PD), frequently accompanied by cognitive impairments, is associated with systemic oxidative stress and abnormal structural changes on brain images. We aimed to identify the correlation between systemic oxidative stress and cognitive function in PD patients with different periventricular white matter hyperintensities (PWMH) and deep white matter hyperintensities (DWMH).

Methods

A total of 146 participants with idiopathic PD underwent brain MRI, which revealed PWMH and DWMH. The number of lesions were evaluated using the Fazekas criteria. Systemic oxidative stress was determined as early or late phase changes in leukocyte apoptosis and its subsets by flow cytometry. Cognitive functions, including attention, executive function, memory, language, and visual space, were assessed.

Results

For different DWMH, the leukocyte apoptosis and its subsets were significantly different.. However, there were no significant differences in oxidative stress biomarkers in PD patients with different PWMH. Attention and memory were significantly decreased in patients with more advanced DWMH injuries. Attention, memory, and language were significantly impaired in patients with worse PWMH lesions.

Conclusion

Significant oxidative stress biomarker alternations in PD patients with DWMH, but not PWMH, might be associated with white matter injury. Systemic inflammatory responses may contribute to deep white matter damage in PD. Further, more cognitive deficits were seen in PD patients with worse deep white matter lesions, especially in moderate to severe periventricular white matter injury.

Trial registration

Retrospective study.
Systemic thromboembolism including multiple cerebral infarctions with middle cerebral artery occlusion caused by the progression of adenomyosis with benign gynecological tumor: a case report
Authors: Aiura Ryo , Nakayama Sadayoshi , Yamaga Hroo , Kato Yu , Fujishima Hirotake
Published: January 2021

Background

Adenomyosis, a benign gynecological disease, causes cerebral infarction. Similar to Trousseau’s syndrome, it elevates cancer antigen 125 (CA125) and D-dimer levels; causes hypercoagulability; and results in cerebral infarction. However, no case of adenomyosis causing major cerebral artery occlusion and requiring endovascular thrombectomy has yet been reported. We report on a woman with middle cerebral artery occlusion caused by adenomyosis progression with a benign gynecological tumor and recurrent cerebral infarction. She was successfully treated by endovascular thrombectomy and hysterectomy.

Case presentation

A 48-year-old woman with heavy uterine bleeding was transported by ambulance to our hospital. Upon arrival, she presented with impaired consciousness. Laboratory test results revealed decreased hemoglobin (8.2 g/dL) and elevated D-dimer (79.3 µg/mL) levels. Radiological imaging revealed adenomyosis, a left ovarian tumor, multiple uterine myomas, and old and new bilateral renal infarctions. She experienced repeated episodes of excessive menstruation caused by adenomyosis and was scheduled for hysterectomy in 2 months at another hospital. After hospital admission, uterine bleeding stopped. However, 5 days after initial bleeding, she had another episode of heavy uterine bleeding and developed left hemiparesis and dysarthria 20 min later. Brain magnetic resonance imaging revealed bilateral multiple cerebral infarctions indicating right middle cerebral artery occlusion. Thus, endovascular thrombectomy was performed, and anticoagulant therapy was administered. Laboratory test results after thrombectomy revealed elevated CA125 (3536 U/mL) and CA19-9 (892 U/mL) levels. She was at a risk of recurrent heavy uterine bleeding leading to repeated cerebral infarction because of anticoagulant treatment. Therefore, we performed hysterectomy and ovariectomy 11 days after initial bleeding. Histopathological assessment revealed no malignancy. Although she developed asymptomatic pulmonary thromboembolism 14 days after initial bleeding, D-dimer and tumor marker levels returned to normal soon after gynecological surgery. At 15 months post-surgery, she had not experienced further ischemic events.

Conclusions

Adenomyosis with benign gynecological tumors may be associated with elevated D-dimer and tumor marker levels; excessive menstruation; and anemia. It may cause systemic thromboembolism, including cerebral infarction. To our knowledge, no other study has reported that adenomyosis causes major cerebral artery occlusion requiring endovascular thrombectomy. Hysterectomy may be an effective radical treatment of this condition.
Addition of carboplatin-gemcitabine as second-line neoadjuvant chemotherapy in non-responsive locally advanced breast cancer patients to standard neoadjuvant chemotherapy and evaluation of factors affecting response: a randomized controlled trial
Authors: Firouzabadi Dena , Dehghanian Amirreza , Rezvani Alireza , Mahmoudi Laleh , Talei Abdolrasoul
Published: January 2021

Background

Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response.

Methods

In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. “Control” group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). “Intervention” group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery.

Results

In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the “intervention” group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident.

Conclusion

Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the “intervention” group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity.

Trial registration

This trial was prospectively registered in IRCT.ir (IRCT2017100136491N1). Date of registration: 19 November 2017.
Adhesion G protein-coupled receptor, ELTD1, is a potential therapeutic target for retinoblastoma migration and invasion
Authors: Guihurt Santiago Jonathan , Burgos-Tirado Neikelyn , Lafontaine Daniella Dorta , Mendoza Sierra José C. , Camacho Roberto Herrera , Vecchini Rodríguez Clara M. , Morales-Tirado Vanessa , Flores-Otero Jacqueline
Published: January 2021

Background

Prognosis for pediatric metastatic Retinoblastoma (Rb) is poor and current therapies are limited by high systemic toxicity rates and insufficient therapeutic efficacy for metastatic Rb. Tumor dissemination to the brain is promoted by the heterogeneous adhesive and invasive properties of Rb cells within the tumor. In this study we evaluate, for the first time, the expression, and roles of the ELTD1 and GPR125 adhesion G protein-coupled receptors (GPCRs) in Rb cell migration, viability and invasion.

Methods

We characterized the RNA expression of adhesion-GPCRs in 64 Rb tumors compared to 11 fetal retinas using the database from the Childhood Solid Tumor Network from St Jude Children’s Research Hospital. The role of ELTD1 and GPR125 in Rb were investigated ex vivo by microarray analysis, in vitro by cell viability, Western blot and migration assays, in addition to imaging of the subcellular localization of the GPCRs. To elucidate their role in vivo we utilized siRNA technology in an established Rb orthotopic xenograft murine model.

Results

Our investigation demonstrates, for the first time, that ELTD1 but not GPR125, is significantly increased in Rb tumors compared to fetal retinas. We utilized established the Rb cell lines Y79 and Weri-Rb-1, which represent an aggressive, metastatic, and non-metastatic phenotype, respectively, for the in vitro analyses. The studies demonstrated that ELTD1 is enriched in Weri-Rb-1 cells, while GPR125 is enriched in Y79 cells. The measured differences extended to their subcellular localization as ELTD1 labeling displayed punctate clusters in cell-to-cell adhesion sites of Weri-Rb-1 cells, while GPR125 displayed a polarized distribution in Y79 cells. Lastly, we demonstrated the lack of both adhesion receptors does not affect Rb cell viability, yet inhibition of ELTD1 decreases Y79 cell migration in vitro and invasion in vivo.

Conclusion

Taken together, our data suggest that ELTD1, is a potential target to prevent extraocular Rb. The results within establish ELTD1 as a potential therapeutic target for metastatic Rb.
First observation of secondary childhood glaucoma in Coffin-Siris syndrome: a case report and literature review
Authors: Diel Heidi , Ding Can , Grehn Franz , Chronopoulos Panagiotis , Bartsch Oliver , Hoffmann Esther M.
Published: January 2021

Background

Severe congenital ophthalmological malformations and glaucoma might be an important occasional feature in patients with Coffin-Siris syndrome (CSS), especially Coffin-Siris syndrome 9 (CSS9, OMIM #615866) caused bySOX11mutation. Recently, primary (open-angle) glaucoma was described in two children with the most common form of Coffin-Siris syndrome, CSS1 (OMIM #135900) byARID1B(AT-rich interaction domain-containing protein 1B) gene mutation. In this article, we present the first report of glaucoma with Coffin-Siris syndrome 9 as well as the first report of secondary glaucoma with any form of Coffin-Siris syndrome. These findings indicate that secondary glaucoma is an occasional finding in patients with Coffin-Siris syndrome.

Case presentation

A child with secondary childhood glaucoma and additional ocular manifestations was evaluated and treated at the childhood glaucoma centre in Mainz, Germany. Examination under general anaesthesia revealed ocular anterior segment dysgenesis (ASD) (Peters type iridocorneal dysgenesis) in combination with congenital limbal stem cell deficiency (LSCD), aniridia, and cataract. The patient also had multiple other congenital anomalies and severe developmental delay. To explain his combination of anomalies, molecular genetic analysis from peripheral blood was performed in late 2018 and early 2019. Following normal findings with a panel diagnostic of 18 genes associated with congenital glaucoma, whole exome sequencing was performed and revealed a novel likely pathogenic heterozygous variant c.251G>T, p.(Gly84Val) in theSOX11gene (SRY-related HMG-box gene 11). The variant had occurred de novo. Thus, the multiple congenital anomalies and developmental delay of the patient represented Coffin-Siris syndrome 9 (CSS9, OMIM #615866).

Conclusions

When eye diseases occur in combination with other systemic features, genetic analysis can be seminal. Results indicate that glaucoma is an occasional feature of patients with Coffin-Siris syndrome. As early treatment may improve the visual outcome of patients with glaucoma, we suggest that patients with Coffin-Siris syndrome should receive specific ophthalmological screening.
Adolescent physical activity, sedentary behavior and sleep in relation to body composition at age 18 years in urban South Africa, Birth-to-Twenty+ Cohort
Authors: Micklesfield Lisa K. , Hanson Sara K. , Lobelo Felipe , Cunningham Solveig A. , Hartman Terryl J. , Norris Shane A. , Stein Aryeh D.
Published: January 2021

Background

Adolescence is marked by a decline in physical activity, rapid physical growth and changes in body composition, which have been linked to body composition. Prospective data on these associations are rare, particularly in Africa.

Aim

The aim of this study was to examine the association of longitudinal patterns across adolescent in physical activity, sedentary behavior and sleep, with anthropometry and body composition at age 18 years in urban South Africa.

Methods

We analyzed data from the Birth-to-Twenty Plus Cohort (Bt20+), a longitudinal study of children born in 1990 in Soweto-Johannesburg, South Africa. We used general linear models to investigate the association of adolescent (ages 12 to 18 years) longitudinal trends in physical activity, sedentary behavior and schoolnight sleep and overall physical activity patterns, with body mass index (BMI), waist circumference, fat mass index (FMI), lean mass index (LMI) and percent body fat at age 18 years.

Results

The final study sample included 1337 participants with anthropometric measurements (52% female) and 958 participants with body composition measurements (53% female). Males who were consistently more active and consistently walked to school over adolescence had lower waist circumference (B = − 2.0, 95% CI: − 3.9 to − 0.2), FMI (B = − 0.8, 95%: CI: − 1.2 to − 0.1) and percent body fat (B = -2.9, 95% CI: − 4.9 to − 0.9) at age 18 years than those who decreased activity and did not walk to school. Consistently-sedentary females had higher waist circumference than those whose sedentary behavior increased over adolescence (B = 5.4, 95% CI: 0.2 to 10.6). Males who reported sleeping 9 h or more per night on schoolnights had significantly lower BMI (B = -1.0, 95% CI: − 1.4 to- 0.5), and percent body fat (B = -1.5, 95%CI − 2.8 to − 0.1) than those who reported sleeping 8 h or less per night.

Conclusion

Patterns of adolescent physical activity, sedentary behavior and sleep are related to young-adult body composition in urban South Africa. These modifiable behaviors may be paths for public health interventions to curb overweight and obesity in many low- or middle-income countries.
Effectiveness of FIBEROPTIC phototherapy compared to conventional phototherapy in treating HYPERBILIRUBINEMIA amongst term neonates: a randomized controlled trial
Authors: Joel Helvi N. , Mchaile Deborah N. , Philemon Rune N. , Mbwasi Ronald M. , Msuya Levina
Published: January 2021

Background

Neonatal jaundice is one of the most common problems in neonates. Effective treatment of jaundice requires therapeutic intervention with high quality phototherapy. Over recent years, several studies reported fiberoptic phototherapy to be less effective than conventional phototherapy in term neonates. Our study aimed to compare the effectiveness of fiberoptic phototherapy with a larger illuminated area and higher irradiance to conventional phototherapy methods.

Methods

This was a randomized controlled trial conducted at the Kilimanjaro Christian Medical Centre (KCMC). A total of 41 term neonates, less than 7 days of age with unconjugated hyperbilirubinemia were randomized. Thirteen (13) neonates were allocated to receive fiberoptic phototherapy, 13 to blue light conventional phototherapy and 15 to white light conventional phototherapy. Effectiveness was assessed by comparing the duration of phototherapy, bilirubin reduction rate and side effects of treatment. The data was analyzed with the independent t-test.

Results

The mean overall bilirubin reduction rate was comparable in the fiberoptic phototherapy group (0.74%/h) and the blue light conventional phototherapy group (0.84%/h), with no statistically significant difference (p-value 0.124). However, white light conventional phototherapy had a significantly lower mean overall bilirubin reduction rate (0.29%/h) as compared to fiberoptic phototherapy (p-value < 0.001). The mean treatment duration of phototherapy was 69 h, 68 h and 90 h in the fiberoptic, blue light conventional and white light conventional phototherapy groups respectively. Side effects such as loose stool and skin rash were noted in some participants who received conventional phototherapy. No side effects of treatment were noted in the fiberoptic phototherapy group.

Conclusion

The effectiveness of fiberoptic PT and blue light conventional PT were comparable in terms of bilirubin reduction rate and treatment duration, whereas fiberoptic phototherapy was more effective than white light conventional PT, with a significantly higher bilirubin reduction rate and shorter treatment duration. Fiberoptic phototherapy may mitigate side effects caused by conventional phototherapy.

Trial registration

The Pan African Clinical Trial Registry, PACTR202004723570110. Registered 22nd April 2020- Retrospectively registered.
Efficacy and acceptability of parent-only group cognitive behavioral intervention for treatment of anxiety disorder in children and adolescents: a meta-analysis of randomized controlled trials
Authors: Yin Bangmin , Teng Teng , Tong Lyu , Li Xuemei , Fan Li , Zhou Xinyu , Xie Peng
Published: January 2021

Background

Anxiety disorder is the most prevalent mental disorder among children and adolescents, causing significant psychosocial problems and physical health conditions. Cognitive behavioral therapy (CBT) is an effective treatment for anxiety disorder in children and adolescents. And parent-only CBT is an alternative treatment for childhood anxiety disorder, which includes psychologists and parents rather than children in the treatment. As a new type of CBT, parent-only CBT has some advantages. However, it remains unclear whether parent-only CBT interventions are effective for treating children and adolescents with anxiety disorder.

Methods

In this study, we evaluated the efficacy (the mean change scores of the anxiety rating scale from baseline to post-treatment, standardized mean difference SMD) and acceptability (the proportion of patients in the treatment group who withdrew from treatment early for any reason, risk ratios RRs) of parent-only cognitive behavioral therapy (CBT) for children and adolescents with anxiety disorder. We searched electronic databases, including PubMed, Cochrane Library, Embase, Web of Science, ProQuest, and PsycINFO from inception to June 2019. We included randomized controlled trials (RCTs) comparing parent-only CBT either with waitlist (WL), or CBT with parents in children and adolescents with anxiety disorder.

Results

Finally, six RCTs with 407 participants were included in the meta-analyses. In terms of efficacy, pooled analyses indicated that parent-only CBT was significantly more effective than WL for reducing anxiety symptoms with SMD of − 0.72 (95% CI − 1.41 to − 0.03, p = 0.04), and more remission rate with RR of 4.33 (37.96% vs. 6.85, 95% CI 1.82 to 10.27, p = 0.0009) at post-treatment. And our analyses showed no evidence that parent-only CBT had significantly greater efficacy than CBT with parents with SMD of 0.21 (95% CI − 0.09 to 0.50, p = 0.17). Acceptability in the parent-only CBT group was not significantly different to the WL group with RR of 0.92 (95% CI 0.52 to 1.62, p = 0.77), and was significantly worse than in the CBT with parents group with RR of 1.93 (95% CI 1.05 to 3.57, p = 0.03).

Conclusions

Current evidence indicates that parent-only CBT can be an alternative and acceptable intervention for treating children and adolescents with anxiety disorder.
Regional brain volume predicts response to methylphenidate treatment in individuals with ADHD
Authors: Chang Jung-Chi , Lin Hsiang-Yuan , Lv Jinglei , Tseng Wen-Yih Issac , Gau Susan Shur-Fen
Published: January 2021

Background

Despite the effectiveness of methylphenidate for treating ADHD, up to 30% of individuals with ADHD show poor responses to methylphenidate. Neuroimaging biomarkers to predict medication responses remain elusive. This study characterized neuroanatomical features that differentiated between clinically good and poor methylphenidate responders with ADHD.

Methods

Using a naturalistic observation design selected from a larger cohort, we included 79 drug-naive individuals (aged 6–42 years) with ADHD without major psychiatric comorbidity, who had acceptable baseline structural MRI data quality. Based on a retrospective chart review, we defined responders by individuals’ responses to at least one-month treatment with methylphenidate. A nonparametric mass-univariate voxel-based morphometric analysis was used to compare regional gray matter volume differences between good and poor responders. A multivariate pattern recognition based on the support vector machine was further implemented to identify neuroanatomical indicators to predict an individual’s response.

Results

63 and 16 individuals were classified in the good and poor responder group, respectively. Using the small-volume correction procedure based on the hypothesis-driven striatal and default-mode network masks, poor responders had smaller regional volumes of the left putamen as well as larger precuneus volumes compared to good responders at baseline. The machine learning approach identified that volumetric information among these two regions alongside the left frontoparietal regions, occipital lobes, and posterior/inferior cerebellum could predict clinical responses to methylphenidate in individuals with ADHD.

Conclusion

Our results suggest regional striatal and precuneus gray matter volumes play a critical role in mediating treatment responses in individuals with ADHD.
Healing, surviving, or dying? – projecting the German future disease burden using a Markov illness-death model
Authors: Milan Valeska , Fetzer Stefan , Hagist Christian
Published: January 2021

Background

In view of the upcoming demographic transition, there is still no clear evidence on how increasing life expectancy will affect future disease burden, especially regarding specific diseases. In our study, we project the future development of Germany’s ten most common non-infectious diseases (arthrosis, coronary heart disease, pulmonary, bronchial and tracheal cancer, chronic obstructive pulmonary disease, cerebrovascular diseases, dementia, depression, diabetes, dorsal pain and heart failure) in a Markov illness-death model with recovery until 2060.

Methods

The disease-specific input data stem from a consistent data set of a major sickness fund covering about four million people, the demographic components from official population statistics. Using six different scenarios concerning an expansion and a compression of morbidity as well as increasing recovery and effective prevention, we can show the possible future range of disease burden and, by disentangling the effects, reveal the significant differences between the various diseases in interaction with the demographic components.

Results

Our results indicate that, although strongly age-related diseases like dementia or heart failure show the highest relative increase rates, diseases of the musculoskeletal system, such as dorsal pain and arthrosis, still will be responsible for the majority of the German population’s future disease burden in 2060, with about 25–27 and 13–15 million patients, respectively. Most importantly, for almost all considered diseases a significant increase in burden of disease can be expected even in case of a compression of morbidity.

Conclusion

A massive case-load is emerging on the German health care system, which can only be alleviated by more effective prevention. Immediate action by policy makers and health care managers is needed, as otherwise the prevalence of widespread diseases will become unsustainable from a capacity point-of-view.
The association between ambient temperature and mortality of the coronavirus disease 2019 (COVID-19) in Wuhan, China: a time-series analysis
Authors: Zhu Gaopei , Zhu Yuhang , Wang Zhongli , Meng Weijing , Wang Xiaoxuan , Feng Jianing , Li Juan , Xiao Yufei , Shi Fuyan , Wang Suzhen
Published: January 2021

Background

The COVID-19 has caused a sizeable global outbreak and has been declared as a public health emergency of international concern. Sufficient evidence shows that temperature has an essential link with respiratory infectious diseases. The objectives of this study were to describe the exposure-response relationship between ambient temperature, including extreme temperatures, and mortality of COVID-19.

Methods

The Poisson distributed lag non-linear model (DLNM) was constructed to evaluate the non-linear delayed effects of ambient temperature on death, by using the daily new death of COVID-19 and ambient temperature data from January 10 to March 31, 2020, in Wuhan, China.

Results

During the period mentioned above, the average daily number of COVID-19 deaths was approximately 45.2. Poisson distributed lag non-linear model showed that there was a non-linear relationship (U-shape) between the effect of ambient temperature and mortality. With confounding factors controlled, the daily cumulative relative death risk decreased by 12.3% (95% CI [3.4, 20.4%]) for every 1.0 °C increase in temperature. Moreover, the delayed effects of the low temperature are acute and short-term, with the most considerable risk occurring in 5–7 days of exposure. The delayed effects of the high temperature appeared quickly, then decrease rapidly, and increased sharply 15 days of exposure, mainly manifested as acute and long-term effects. Sensitivity analysis results demonstrated that the results were robust.

Conclusions

The relationship between ambient temperature and COVID-19 mortality was non-linear. There was a negative correlation between the cumulative relative risk of death and temperature. Additionally, exposure to high and low temperatures had divergent impacts on mortality.
Exercise-therapy and education for individuals one year after anterior cruciate ligament reconstruction: a pilot randomised controlled trial
Authors: Patterson Brooke E. , Barton Christian J. , Culvenor Adam G. , Cooper Randall L. , Crossley Kay M.
Published: January 2021

Background

Guided rehabilitation beyond 6-months is rare following anterior cruciate ligament reconstruction (ACLR), despite high prevalence of unacceptable symptoms and quality of life (QoL). Our primary aim was to determine the feasibility of a randomised controlled trial (RCT) evaluating a physiotherapist-guided intervention for individuals 1-year post-ACLR with persistent symptoms. Our secondary aim was to determine if a worthwhile treatment effect could be observed for the lower-limb focussed intervention (compared to the trunk-focussed intervention), for improvement in knee-related QoL, symptoms, and function.

Design

Participant- and assessor-blinded, pilot feasibility RCT.

Methods

Participant eligibility criteria: i) 12–15 months post-ACLR; ii) < 87.5/100 on the Knee injury and Osteoarthritis Outcome Score (KOOS) QoL subscale; and either a one-leg rise test < 22 repetitions, single-hop < 90% limb symmetry; or Anterior Knee Pain Scale < 87/100. Participants were randomised to lower-limb or trunk-focussed focussed exercise and education. Both interventions involved 8 face-to-face physiotherapy sessions over 16-weeks. Feasibility was assessed by eligibility rate (> 1 in 3 screened), recruitment rate (> 4 participants/month), retention (< 20% drop-out), physiotherapy attendance and unsupervised exercise adherence (> 80%). Between-group differences for knee-related QoL (KOOS-QoL, ACL-QoL), symptoms (KOOS-Pain, KOOS-Symptoms), and function (KOOS-Sport, functional performance tests) were used to verify that the worthwhile effect (greater than the minimal detectable change for each measure) was contained within the 95% confidence interval.

Results

47% of those screened were eligible, and 27 participants (3 participants/month; 48% men, 34±12 years) were randomised. Two did not commence treatment, and two were lost to follow-up (16% drop-out). Physiotherapy attendance was > 80% for both groups but reported adherence to unsupervised exercise was low (< 55%). Both interventions had potentially worthwhile effects for KOOS-QoL and ACL-QoL, while the lower-limb focussed intervention had potentially greater effects for KOOS-Sport, KOOS-Pain, and functional performance.

Conclusions

A larger-scale RCT is warranted. All feasibility criteria were met, or reasonable recommendations could be made to achieve the criteria in future trials. Strategies to increase recruitment rate and exercise adherence are required. The potential worthwhile effects for knee-related QoL, symptoms, and function indicates a fully-powered RCT may detect a clinically meaningful effect.

Trial registration

Prospectively registered (ACTRN12616000564459).
Association of cardiotrophin-like cytokine factor 1 levels in peripheral blood mononuclear cells with bone mineral density and osteoporosis in postmenopausal women
Authors: Chen Xuan , Li Jianyang , Ye Yunjin , Huang Jingwen , Xie Lihua , Chen Juan , Li Shengqiang , Chen Sainan , Ge Jirong
Published: January 2021

Background

Recent research has suggested that cardiotrophin-like cytokine factor 1 (CLCF1) may be an important regulator of bone homeostasis. Furthermore, a whole gene chip analysis suggested that the expression levels of CLCF1 in the peripheral blood mononuclear cells (PBMCs) were downregulated in postmenopausal women with osteoporosis. This study aimed to assess whether the expression levels of CLCF1 in PBMCs can reflect the severity of bone mass loss and the related fracture risk.

Methods

In all, 360 postmenopausal women, aged 50 to 80 years, were included in the study. A survey to evaluate the participants’ health status, measurement of bone mineral density (BMD), routine blood test, and CLCF1 expression level test were performed.

Results

Based on the participants’ bone health, 27 (7.5%), 165 (45.83%), and 168 (46.67%) participants were divided into the normal, osteopenia, and osteoporosis groups, respectively. CLCF1 protein levels in the normal and osteopenia groups were higher than those in the osteoporosis group. While theCLCF1mRNA level was positively associated with the BMD of total femur (r= 0.169,p= 0.011) and lumbar spine (r= 0.176,p= 0.001), the protein level was positively associated with the BMD of the lumbar spine (r= 0.261,p< 0.001), femoral neck (r= 0.236,p= 0.001), greater trochanter (r= 0.228,p= 0.001), and Ward’s triangle (r= 0.149,p= 0.036). Both the mRNA and protein levels were negatively associated with osteoporosis development (r= − 0.085,p= 0.011 andr= − 0.173,p= 0.014, respectively). The association between CLCF1 protein level and fracture risk was not significant after adjusting for BMD.

Conclusions

To our knowledge, this is the first clinical study to show that CLCF1 expression levels in the PBMCs of postmenopausal women can reflect the amount of bone mass or the severity of bone mass loss.
Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report
Authors: Takao Ken , Tani Ayaka , Suwa Tetsuya , Kuwabara-Ohmura Yayoi , Nonomura Kenta , Liu Yanyan , Kato Takehiro , Mizuno Masami , Hirota Takuo , Enya Mayumi , Iizuka Katsumi , Horikawa Yukio , Saigo Chiemi , Kito Yusuke , Miyazaki Tatsuhiko , Ohe Naoyuki , Iwama Toru , Yabe Daisuke
Published: January 2021

Background

Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions.

Case presentation

We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized.

Conclusions

While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.
Advanced care planning during the COVID-19 pandemic: ceiling of care decisions and their implications for observational data
Authors: Straw Sam , McGinlay Melanie , Drozd Michael , Slater Thomas A. , Cowley Alice , Kamalathasan Stephe , Maxwell Nicholas , Bird Rory A. , Koshy Aaron O. , Prica Milos , Patel Peysh A. , Relton Samuel D. , Gierula John , Cubbon Richard M. , Kearney Mark T. , Witte Klaus K.
Published: January 2021

Background

Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic.

Methods

Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation.

Results

A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were ‘not for resuscitation’. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86–0·93 p < 0·001), frailty (odds 0·48, 0·38–0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52–1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care.

Conclusion

Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.
Making it stick: use of active learning strategies in continuing medical education
Authors: Bucklin Brenda A. , Asdigian Nancy L. , Hawkins Joy L. , Klein Ulrich
Published: January 2021

Background

Despite the known benefits of active learning (AL), the predominate educational format in higher education is the lecture. The reasons for slow adaptation of AL in medical education are not well understood. The purpose of this survey was to determine knowledge, usage, attitudes, and barriers to AL use in academic Continuing Medical Education (CME).

Method

A 20-item questionnaire was developed and sent with a link to an online questionnaire to the Society of Academic Continuing Medical Education (SACME) listserv of ~ 350 professionals representing academic medical centers, teaching hospitals, and medical specialty societies in the United States (U.S.) and Canada. Responses were collected with SurveyMonkey® from October–November, 2019. Data were analyzed using SPSS®.

Results

Responses from 146 SACME members in 91 CME units yielded a ~ 42% survey response rate. Many respondents reported their self-perceived knowledge of AL as high. Advanced training (e.g., certificate, Master of Education degree) was positively correlated with AL knowledge. AL methods were reportedly used in half of the CME activities in the majority (80%) of institutions. Higher levels of self-perceived knowledge were correlated with an increased percentage of AL-related CME activities. Commonly perceived barriers to use of AL were presenters’ lack of familiarity and a need for more time-consuming preparation.

Conclusions

More efforts are needed to increase innovation and incorporate evidence-based AL strategies in medical education, especially to foster learner engagement, critical thinking, and problem-solving ability.
Maternal death surveillance and response in Tanzania: comprehensiveness of narrative summaries and action points from maternal death reviews
Authors: Said Ali , Pembe Andrea B. , Massawe Siriel , Hanson Claudia , Malqvist Mats
Published: January 2021

Background

Maternal deaths reviews are proposed as one strategy to address high maternal mortality in low and middle-income countries, including Tanzania. Review of maternal deaths relies on comprehensive documentation of medical records that can reveal the sequence of events leading to death. The World Health Organization’s and the Tanzanian Maternal Death and Surveillance (MDSR) system propose the use of narrative summaries during maternal death reviews for discussing the case to categorize causes of death, identify gaps in care and recommend action plans to prevent deaths. Suggested action plans are recommended to be Specific, Measurable, Attainable, Relevant and Time bound (SMART). To identify gaps in documenting information and developing recommendations, comprehensiveness of written narrative summaries and action plans were assessed.

Methods

A total of 76 facility maternal deaths that occurred in two regions in Southern Tanzania in 2018 were included for analysis. Using a prepared checklist from Tanzania 2015 MDSR guideline, we assessed comprehensiveness by presence or absence of items in four domains, each with several attributes. These were socio-demographic characteristics, antenatal care, referral information and events that occurred after admission. Less than 75% completeness of attributes in all domains was considered poor while 95% and above were good/comprehensive. Action plans were assessed by application of SMART criteria and according to the place of planned implementation (community, facility or higher level of health system).

Results

Almost half of narrative summaries (49%) scored poor, and only1% scored good/comprehensive. Summaries missed key information such as demographic characteristics, time between diagnosis of complication and commencing treatment (65%), investigation results (47%), summary of case evolution (51%) and referral information (47%). A total of 285 action points were analysed. Most action points, 242(85%), recommended strategies to be implemented at health facilities and were mostly about service delivery, 120(42%). Only 42% (32/76) of the action points were deemed to be SMART.

Conclusions

Abstraction of information to prepare narrative summaries used in the MDSR system is inadequately done. Most recommendations were unspecific with a focus on improving quality of care in health facilities.
Prioritization of interventions in pursuit of maternal health policy objectives to mitigate stillbirth risks. An exploratory qualitative study at subnational level in Uganda
Authors: Ssegujja Eric , Ddumba Isaac , Andipartin Michelle
Published: January 2021

Background

Global calls for renewed efforts to address stillbirth burden highlighted areas for policy and implementation resulting in national level translations. Information regarding adapted strategies to effect policy objectives into service delivery by frontline health workers remains scanty especially at subnational level. The study explored strategies prioritized to mitigate stillbirth risk in the context of operationalizing recommendations from the global campaigns at a subnational level in Uganda.

Methods

A cross-sectional qualitative exploratory study was conducted among a purposively selected sample of sixteen key informants involved in delivery of maternal and child health services in Mukono district. Analysis followed thematic content analysis deductively focusing on those policy priorities highlighted in the global stillbirth campaigns and reflected at the national level in the different guidelines. Results.

Interventions to address stillbirth followed prioritization of service delivery aspects to respond to identified gaps. Efforts to increase uptake of family planning services for example included offering it at all entry points into care with counseling forming part of the package following stillbirth. Referrals were streamlined by focusing on addressing delays from the referring entity while antenatal care attendance was boosted through provision of incentives to encourage mothers to comply. Other prioritized aspects included perinatal death audits and improvements in data systems while differentiated care focused on aligning resources to support high risk mothers. This was in part influenced by the limited resources and skills which made health workers to adapt routine to fit implementation context.

Conclusions

The resource availability determined aspects of policy to prioritize while responding to stillbirth risk at subnational level by frontline health workers. Their understanding of risk, feasibility of implementation and the desire for optimal health systems performance worked to define the nature of services delivered calling for purposeful consideration of resource availability and implementation context while prioritizing stillbirth reduction at subnational level.
Beyond weight: examining the association of obesity with cardiometabolic related inpatient costs among Canadian adults using linked population based survey and hospital administrative data
Authors: Gupta Neeru , Sheng Zihao
Published: January 2021

Background

The global population has transitioned to one where more adults are living with obesity than are underweight. Obesity is associated with the development of cardiometabolic diseases and widely attributed to increased hospital resource use; however, empirical evidence is limited regarding obesity prevention to support hospital cost containment. This study aims to test for obesity in predicting hospitalization costs for cardiometabolic conditions among the Canadian population aged 45 and over.

Methods

Data from the 2007−2011 Canadian Community Health Survey were linked to eight years of hospital discharge records. A cohort was identified of inpatients admitted for diabetes, hypertension, and other cardiometabolic diseases. Multiple linear regressions were used to investigate the association between obesity status and inpatient costs, controlling for sociodemographic and behavioural factors.

Results

The target cohort included 23,295 admissions for cardiometabolic diseases. Although inflation-adjusted inpatient costs generally increased over time, compared with the non-obese group, living with obesity was not a significant predictor of differences in cardiometabolic-related resource use (0.972 [95% CI: 0.926–1.021]). Being female and rural residence were found to be protective factors.

Conclusions

Obesity was not found in this study to be independently linked to higher cardiometabolic hospitalization costs, suggesting that actions to mitigate disease progression in the population may be more beneficial than simply promoting weight loss. Results amplified the need to consider gender and urbanization when formulating which levers are most amenable to adoption of healthy lifestyles to reduce impacts of obesogenic environments to the healthcare system.
Apolipoprotein C1 stimulates the malignant process of renal cell carcinoma via the Wnt3a signaling
Authors: Jiang Hao , Tang Jing-Yuan , Xue Dong , Chen Yi-Meng , Wu Ting-Chun , Zhuang Qian-Feng , He Xiao-Zhou
Published: January 2021

Background

Renal cell carcinoma (RCC) is a clinically common tumor in the urinary system, showing an upward trend of both incidence and mortality. Apolipoprotein C1 (APOC1) has been identified as a vital regulator in tumor progression. This study aims to uncover the biological function of APOC1 in RCC process and the underlying mechanism.

Methods

Differential levels of APOC1 in RCC samples and normal tissues in a downloaded TCGA profile and clinical samples collected in our center were detected by quantitative reverse transcription PCR (qRT-PCR). The prognostic value of APOC1 in RCC was assessed by depicting Kaplan–Meier survival curves. After intervening APOC1 level by transfection of sh-APOC1 or oe-APOC1, changes in phenotypes of RCC cells were examined through CCK-8, colony formation, Transwell assay and flow cytometry. Subsequently, protein levels of EMT-related genes influenced by APOC1 were determined by Western blot. The involvement of the Wnt3a signaling in APOC1-regulated malignant process of RCC was then examined through a series of rescue experiments. Finally, a RCC xenograft model was generated in nude mice, aiming to further clarify the in vivo function of APOC1 in RCC process.

Results

APOC1 was upregulated in RCC samples. Notably, its level was correlated to overall survival of RCC patients, displaying a certain prognostic value. APOC1 was able to stimulate proliferative, migratory and invasive abilities in RCC cells. The Wnt3a signaling was identified to be involved in APOC1-mediated RCC process. Notably, Wnt3a was able to reverse the regulatory effects of APOC1 on RCC cell phenotypes. In vivo knockdown of APOC1 in xenografted nude mice slowed down the growth of RCC.

Conclusions

APOC1 stimulates the malignant process of RCC via targeting the Wnt3a signaling.