bluuebunny/crossref_metadata_2025 huggingface dataset:
Age differences in the association of comorbid burden with adverse outcomes in SARS-CoV-2
Authors: O’Hare A. M. , Berry K. , Fan V. S. , Crothers K. , Eastment M. C. , Dominitz J. A. , Shah J. A. , Green P. , Locke E. , Ioannou G. N.
Published: July 2021

Background

Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults.

Objective

To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18–64, 65–79 and ≥ 80 years).

Design, setting, and participants

Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021.

Measurements

Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test.

Results

The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65–79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions).

Limitations

The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden.

Conclusions

Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.
Influenza in Malaysian adult patients hospitalized with community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease or asthma: a multicenter, active surveillance study
Authors: Pang Yong Kek , Ismail Ahmad Izuanuddin , Chan Yoke Fun , Cheong Adelina , Chong Yoong Min , Doshi Paras , Lau Joanne Zhi Han , Khor Jean , Wang Lilian Phei Lian , Leong Chee Loon , Musa Aisya Natasya , Ng Kee Sing , Poh Mau Ern , Sam I-Ching , Tan Jiunn Liang , Zim Mohd Arif Mohd , Taurel Anne-Frieda
Published: July 2021

Background

Available data on influenza burden across Southeast Asia are largely limited to pediatric populations, with inconsistent findings.

Methods

We conducted a multicenter, hospital-based active surveillance study of adults in Malaysia with community-acquired pneumonia (CAP), acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and acute exacerbation of asthma (AEBA), who had influenza-like illness ≤10 days before hospitalization. We estimated the rate of laboratory-confirmed influenza and associated complications over 13 months (July 2018–August 2019) and described the distribution of causative influenza strains. We evaluated predictors of laboratory-confirmed influenza and severe clinical outcomes using multivariate analysis.

Results

Of 1106 included patients, 114 (10.3%) were influenza-positive; most were influenza A (85.1%), with A/H1N1pdm09 being the predominant circulating strain during the study following a shift from A/H3N2 from January–February 2019 onwards. In multivariate analyses, an absence of comorbidities (none versus any comorbidity [OR (95%CI), 0.565 (0.329–0.970)], p = 0.038) and of dyspnea (0.544 (0.341–0.868)], p = 0.011) were associated with increased risk of influenza positivity. Overall, 184/1106 (16.6%) patients were admitted to intensive care or high-dependency units (ICU/HDU) (13.2% were influenza positive) and 26/1106 (2.4%) died (2.6% were influenza positive). Males were more likely to have a severe outcome (ICU/HDU admission or death).

Conclusions

Influenza was a significant contributor to hospitalizations associated with CAP, AECOPD and AEBA. However, it was not associated with ICU/HDU admission in this population.

Study registration, NMRR ID: NMRR-17-889-35,174.
The LIFT trial: study protocol for a double-blind, randomised, placebo-controlled trial of K+-binder Lokelma for maximisation of RAAS inhibition in CKD patients with heart failure
Authors: Murphy Daniel , Ster Irina Chis , Kaski Juan-Carlos , Anderson Lisa , Banerjee Debasish
Published: July 2021

Background

CKD is common in heart failure (HF) and associated with morbidity and mortality, yet life-prolonging medications such as renin-angiotensin-aldosterone inhibitors (RAASi) are underused due to risk of hyperkalaemia. Sodium zirconium cyclosilicate (SZC) is a potassium-binding medication that has been shown to reduce incidence of hyperkalaemia in CKD, non-CKD, and HF populations, which we propose will support maximisation of RAASi therapy.

Methods

We propose a 1:1 randomised, double-blind, placebo-controlled trial in which participants will receive either SZC or placebo. We will up-titrate participants’ RAASi therapy while monitoring their serum potassium levels and adjusting their SZC dose if necessary. Participants with CKD and HF will be recruited from CKD and HF clinics at St George’s Hospital. The total study period will be 18 months; 130 participants will be enrolled for approximately two months each following screening. Our primary outcome will be the proportion of participants who achieve maximum RAASi dose while maintaining normokalaemia. Secondary outcomes include participants reaching maximum RAASi dose without severe hyperkalaemia; time from randomisation to hyperkalaemia; time from randomisation to severe hyperkalaemia; number of RAASi dose escalations per participant; final doses of RAASi therapy; changes in quality of life score, eGFR, ACR, serum sodium, troponin T; number and duration of hospital admissions; and within-participant change in serum potassium compared to baseline.

Discussion

This trial will be the first to examine the use of SZC for the maximisation of RAASi dosing in patients with advanced CKD and HF. We will assess the impact of achieving target RAASi dosing on hospital admission rates and duration of stay, with the hope that optimum RAASi treatment will translate into reduced morbidity and improved QoL. If clinical benefit is demonstrated, we hope that the joint multidisciplinary CKD-HF approach will be expanded.

Trial registration

EudraCT number 2020–002946-18. Registered on 08 June 2020. Online record pending.
National registry for amyotrophic lateral sclerosis: a systematic review for structuring population registries of motor neuron diseases
Authors: Barbalho Ingridy , Valentim Ricardo , Júnior Mário Dourado , Barros Daniele , Júnior Hércules Pedrosa , Fernandes Felipe , Teixeira César , Lima Thaísa , Paiva Jailton , Nagem Danilo
Published: July 2021

Background

This article comprises a systematic review of the literature that aims at researching and analyzing the frequently applied guidelines for structuring national databases of epidemiological surveillance for motor neuron diseases, especially Amyotrophic Lateral Sclerosis (ALS).

Methods

We searched for articles published from January 2015 to September 2019 on online databases as PubMed - U.S. National Institutes of Health’s National Library of Medicine, Scopus, Science Direct, and Springer. Subsequently, we analyzed studies that considered risk factors, demographic data, and other strategic data for directing techno-scientific research, calibrating public health policies, and supporting decision-making by managers through a systemic panorama of ALS.

Results

2850 studies were identified. 2400 were discarded for not satisfying the inclusion criteria, and 435 being duplicated or published in books or conferences. Hence, 15 articles were elected. By applying quality criteria, we then selected six studies to compose this review. Such researches featured registries from the American (3), European (2), and Oceania (1) continent. All the studies specified the methods for data capture and the patients’ recruitment process for the registers.

Discussions

From the analysis of the selected papers and reported models, it is noticeable that most studies focused on the prospect of obtaining data to characterize research on epidemiological studies. Demographic data (ID01) are present in all the registries, representing the main collected data category. Furthermore, the general health history (ID02) is present in 50% of the registries analyzed. Characteristics such as access control, confidentiality and data curation. We observed that 50% of the registries comprise a patient-focused web-based self-report system.

Conclusion

The development of robust, interoperable, and secure electronic registries that generate value for research and patients presents itself as a solution and a challenge. This systematic review demonstrated the success of a population register requires actions with well-defined development methods, as well as the involvement of various actors of civil society.
Evidence for HPV DNA in the placenta of women who resorted to elective abortion
Authors: Bruno Maria Teresa , Caruso Salvatore , Bica Francesca , Arcidiacono Giulia , Boemi Sara
Published: July 2021

Background

It is believed that HPV infection can result in the death of placental trophoblasts and cause miscarriages or preterm birth. In clinical cases of placental villi positive for HPV DNA reported by other authors, contamination is suspected in the act of crossing the cervical canal. We analyzed placental samples of women who resorted to elective abortion obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina.

Methods

We studied the chorionic villi of the placenta of 64 women who resorted to voluntary termination of pregnancy, in the first trimester. To avoid contamination of the villi by the cervical canal, we analyzed placental samples obtained by hysterosuction of ovular material, bypassing any contact with the cervical canal and vagina. All samples of chorionic villi were manually selected from the aborted material and subjected to research for HPV DNA.

Results

HPV DNA was detected in 10 out of 60 women (16.6%). The HPV DNA identified in the placenta belonged to genotypes 6, 16, 35, 53, and 90.

Conclusion

The study shows that papillomavirus DNA can infect the placenta and that placenta HPV infection can occur as early as the first trimester of pregnancy.
A new nomogram and risk classification system for predicting survival in small cell lung cancer patients diagnosed with brain metastasis: a large population-based study
Authors: Shan Qinge , Shi Jianxiang , Wang Xiaohui , Guo Jun , Han Xiao , Wang Zhehai , Wang Haiyong
Published: July 2021

Background

The prognosis of patients with small cell lung cancer (SCLC) is poor, most of them are in the extensive stage at the time of diagnosis, and are prone to brain metastasis. In this study, we established a nomogram combined with some clinical parameters to predict the survival of SCLC patients with brain metastasis.

Methods

The 3522 eligible patients selected from the SEER database between 2010 and 2015 were randomly divided into training cohort and validation cohort. Univariate and multivariate Cox regression analysis were used to evaluate the ability of each parameter to predict OS. The regression coefficients obtained in multivariate analysis were visualized in the form of nomogram, thus a new nomogram and risk classification system were established. The calibration curves were used to verify the model. And ROC curves were used to evaluate the discrimination ability of the newly constructed nomogram. Survival curves were made by Kaplan-Meier method and compared by Log rank test.

Results

Univariate and multivariate analysis showed that age, race, sex, T stage, N stage and marital status were independent prognostic factors and were included in the predictive model. The calibration curves showed that the predicted value of the 1- and 3-year survival rate by the nomogram was in good agreement with the actual observed value of the 1- and 3-year survival rate. And, the ROC curves implied the good discrimination ability of the predictive model. In addition, the results showed that in the total cohort, training cohort, and validation cohort, the prognosis of the low-risk group was better than that of the high-risk group.

Conclusions

We established a nomogram and a corresponding risk classification system to predict OS in SCLC patients with brain metastasis. This model could help clinicians make clinical decisions and stratify treatment for patients.
Investigating defensive functioning and alexithymia in substance use disorder patients
Authors: Taurino Alessandro , Antonucci Linda A. , Taurisano Paolo , Laera Domenico
Published: July 2021

Background

Substance Use Disorder (SUD) causes a great deal of personal suffering for patients. Recent evidence highlights how defenses and emotion regulation may play a crucial part in the onset and development of this disorder.

The aim of this study was to investigate potential differences in the defensive functioning between SUD patients and non-clinical controls. Secondly, we aimed at investigating the relationships between alexithymia and maladaptive/assimilation defenses.

Methods

The authors assessed defensive functioning (Response Evaluation Measure-71, REM-71), personality (MMPI-II), and alexithymia (TAS-20) of 171 SUD patients (17% female; mean age = 36.5), compared to 155 controls. Authors performed a series of ANOVAs to investigate the defensive array in SUD patients compared to that of non-clinical controls. Student t test for indipendent samples was used to compare clinical characteristics between the SUD group and the controls. To investigate the role of single defenses in explaining alexithimia’s subscores, stepwise multiple regression analysis were carried out on socio-demographic characteristics of participants (gender, age, and years of education), with REM-71 defenses as predictors.

Results

SUD patients presented a more maladaptive/assimilation (Factor 1) defensive array (p < .001). Among SUD sub-groups, Alcohol Use Disorder patients showed more disfuncional defenses. Factor 1 defenses were related to a worse psychological functioning. In addition, alexyhimia (particularly DIF) was strongly related to Factor 1 defenses, expecially Projection (38% of variance explained, β = .270, p < .001).

Conclusion

The REM-71 and the TAS-20 might be useful screening instruments among SUD patients.
Feeling about living arrangements and associated health outcomes among older adults in India: a cross-sectional study
Authors: Srivastava Shobhit , Shaw Subhojit , Chaurasia Himanshu , Purkayastha Naina , Muhammad T.
Published: July 2021

Introduction

Advancement in the field of gerontology has been concerned with the well-being of older adults in a family setup that is associated with caregiving and support. While family life and well-being are defined by emotion, caregiving, and support activities, dissatisfaction/discontent with living arrangements is a public health concern, which is increasing with a rise in the proportion of the older population in the country. The study examines the association of dissatisfaction with living arrangements with health outcomes among older men and women in India.

Methods

The present research used data from the 'Building a Knowledge Base on Population Aging in India'. The effective sample size for the analysis was 9181 older adults. Descriptive statistics and bivariate analysis were performed to present the preliminary estimates. For finding the association between various health outcomes over explanatory variables, binary logistic regression model was used separately for men and women.

Results

About 22.8% of men and 30.8% of women who were living alone were dissatisfied with their present living arrangement. It was revealed that both men and women who were dissatisfied with their present living arrangements had significantly higher odds of experiencing poor self-rated health [OR:4.45, 3.25 ~ 6.09 and OR:3.32, 2.54 ~ 4.34], low psychological health [OR: 2.15, 1.61 ~ 2.86 and OR: 1.99, 1.57 ~ 2.53], low subjective well-being [OR: 3.37, 2.54 ~ 4.45 and OR: 3.03, 2.36 ~ 3.38], low ADL [OR: 1.77, 1.2 ~ 2.62 and OR: 1.59, 1.17 ~ 2.18, low IADL] [OR: 1.32, 1.03 ~ 1.69 and OR: 1.57, 1.24 ~ 1.98] and low cognitive ability [OR: 1.26, 0.98 ~ 1.61 and OR:1.44, 1.13 ~ 1.82] in comparison to their counterpart from men and women respectively.

Conclusion

It is found that dissatisfaction with the living arrangement of older men and women is negatively associated with major health outcomes. Hence, appropriate policies and programs must be developed to promote increased family care and support and an improved residential environment that would create a feeling of comfort and happiness among older individuals.
Effects of behavioural exercise therapy on the effectiveness of multidisciplinary rehabilitation for chronic non-specific low back pain: a randomised controlled trial
Authors: Semrau Jana , Hentschke Christian , Peters Stefan , Pfeifer Klaus
Published: July 2021

Background

The long-term effects of behavioural medical rehabilitation (BMR), as a type of multidisciplinary rehabilitation, in the treatment of chronic non-specific low back pain (CLBP) have been shown. However, the specific effects of behavioural exercise therapy (BET) compared to standard exercise therapy (SET) within BMR are not well understood. The aim of the study was to assess the effectiveness of BMR + BET compared to BMR + SET in individuals with CLBP in a two-armed, pre-registered, multicentre, parallel, randomised controlled trial (RCT).

Methods

A total of 351 adults with CLBP in two rehabilitation centres were online randomised based on an ‘urn randomisation’ algorithm to either BMR + SET (n = 175) or BMR + BET (n = 176). Participants in both study groups were non-blinded and received BMR, consisting of an multidisciplinary admission, a psychosocial assessment, multidisciplinary case management, psychological treatment, health education and social counselling. The intervention group (BMR + BET) received a manualised, biopsychosocial BET within BMR. The aim of BET was to develop self-management strategies in coping with CLBP. The control group (BMR + SET) received biomedical SET within BMR with the aim to improve mainly physical fitness. Therapists in both study groups were not blinded. The BMR lasted on average 27 days, and both exercise programmes had a mean duration of 26 h. The primary outcome was functional ability at 12 months. Secondary outcomes were e.g. pain, avoidance-endurance, pain management and physical activity. The analysis was by intention-to-treat, blinded to the study group, and used a linear mixed model.

Results

There were no between-group differences observed in function at the end of the BMR (mean difference, 0.08; 95% CI − 2.82 to 2.99; p = 0.955), at 6 months (mean difference, − 1.80; 95% CI; − 5.57 to 1.97; p = 0.349) and at 12 months (mean difference, − 1.33; 95% CI − 5.57 to 2.92; p = 0.540). Both study groups improved in the primary outcome and most secondary outcomes at 12 months with small to medium effect sizes.

Conclusion

BMR + BET was not more effective in improving function and other secondary outcomes in individuals with CLBP compared to BMR + SET.

Trial registration

Current controlled trials NCT01666639, 16/08/2012.
Extra-articular migration of PEEK interference screw after anterior cruciate ligament reconstruction: a report of two cases
Authors: Fang Chao-Hua , Li Ming , Zhang Yun-Feng , Liu Hua
Published: July 2021

Background

The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, “bioresorbable,” or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction.

Case report

An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well.

Conclusions

The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.
Responsiveness of five shoulder outcome measures at follow-ups from 3 to 24 months
Authors: Skare Øystein , Brox Jostein Skranes , Schrøder Cecilie Piene , Brox Jens Ivar
Published: July 2021

Background

To assess responsiveness of five outcome measures at four different follow-ups in patients with SLAP II lesions of the shoulder.

Methods

119 patients with symptoms and signs, MRI arthrography and arthroscopic findings were included. The Western Ontario Shoulder Instability Index (WOSI), Oxford Instability Shoulder Score (OISS), EuroQol (EQ-5D3L), Rowe Score and Constant-Murley Score (CMS) were assessed at baseline, 3, 6, 12 and 24 months. The analysis contains both anchor-based and distribution-based methods, and hypothesis testing.

Results

Confidence intervals for ROC cut-off values, representing MID, for OISS, CMS and EQ-5D3L crossed zero at 3 months. Cut-off values were stable between 6- and 24-months follow-up. At 24-months ROC cut-off values (95% CI) were: Rowe 18 (13 to 24); WOSI 331 (289 to 442); OISS 9 (5 to 14); CMS 11 (9 to 15) and EQ-5D3L 0.123 (0.035 to 0.222). MID95%limitestimates were substantially higher than ROC cut-off values and MIDMEANat all follow-ups for all instruments. The reliable change proportion (RCP) values in the improved group were highest for WOSI and the Rowe Score (ranging from 68 to 87%) and significantly lower for CMS. EQ-5D3L had the lowest values (13 to 16%). We found a moderate correlation between mean change scores of the outcome measures and the anchor, except for the EQ-5D3L.

Conclusions

In patients with SLAP II-lesions the patient reported OISS and WOSI and the clinical Rowe score had best responsiveness. Our results suggest that 3 months follow-up is too early for outcome evaluation.
Longitudinal assessment of salivary vitamin D binding protein during orthodontic tooth movement
Authors: Tashkandi Nada , Zhao Yihong , Mitchell-Lee Gabrielle , Stephens Danielle , Patel Michele , Motro Melih , Will Leslie A. , Kantarci Alpdogan
Published: July 2021

Background

Vitamin D is critical for bone physiology. In this study, we quantified Vitamin D Binding Protein (VitDBP) levels in saliva as a measure of Vitamin D during orthodontic tooth movement.

Methods

In this longitudinal study, saliva samples were collected from 73 orthodontic patients for 4 timepoints for the first six months of orthodontic treatment, along with dental casts at the beginning and the end of the study period. The saliva was measured for VitDBP as a biological marker for bone apposition and clinical tooth movement. We used the absolute change in Little's Irregularity Index as a quantitative measure for alignment. In addition, we measured the levels of alkaline phosphatase (ALP) in saliva as a marker of bone turnover.

Results

Both low (< 2.75 ng/ml) and high (> 6.48 ng/ml) VitDBP levels were associated with reduced tooth movement. Significant (p < 0.05) seasonal changes in VitDBP using a two-season year model were found with lower levels observed in the summer (Apr–Sept) than in the winter (Oct–Mar).

Conclusions

Clinically significant orthodontic tooth movement is associated with an optimal range of VitDBP in saliva. Normal levels of VitDBP correlated with more orthodontic tooth movement, suggesting a "normal" range of salivary content of VitDBP. Given the strong trend that is independent of the confounding factors (ex. age, race or gender), the predictive value or salivary VitDBP for tooth movement should be studied in larger cohorts in future studies.
Attitude and knowledge of medical students about organ donation – training needs identified from a Canadian survey
Authors: Robert Philippe , Bégin Félix , Ménard-Castonguay Sasha , Frenette Anne-Julie , Quiroz-Martinez Hector , Lamontagne François , Belley-Côté Emilie-Prudence , D’Aragon Frédérick
Published: July 2021

Background

Appropriate training of health professionals has been recommended to increase organ donation rates. Some studies have shown insufficient knowledge among medical students. This survey aims to describe their knowledge and attitude toward organ donation (OD).

Method

We designed, pre-tested and conducted an online survey of all undergraduate medical students from Montreal, Laval and Sherbrooke universities in 2016–2017. Multivariate linear regression identified factors associated with a better knowledge score.

Results

Twenty-two percent (750/3344) of students completed the survey. Ninety-one percent of students adequately knew that neurological death is irreversible; 76% acknowledged that someone could be neurologically deceased while his heart is still beating; 69% were not aware of circulatory determination of death. For only one knowledge item, senior students had a better answer than junior students. Total knowledge score was associated with exposure to OD during medical studies and comfort in answering patients’ questions about OD (p < 0,001). Regarding attitude, 96% of respondents wished to become organ donors after death and 92% supported OD training during their medical training.

Conclusion

Despite a favourable attitude, medical students have limited knowledge of OD. Findings suggest the need for a formal curriculum about OD, as students expressed.
Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics
Authors: Janiaud Perrine , Agarwal Arnav , Tzoulaki Ioanna , Theodoratou Evropi , Tsilidis Konstantinos K. , Evangelou Evangelos , Ioannidis John P. A.
Published: July 2021

Background

The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies.

Methods

We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10−6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance.

Results

3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10−6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in observational studies, 37.1% had effect estimates in opposite directions and 43.5% had effect estimates differing beyond chance in the two designs. Across 94 comparisons assessed in both MR and observational studies, such discrepancies occurred in 30.8% and 54.7%, respectively.

Conclusions

Acknowledging that no gold-standard exists to judge whether an observational association is genuine, statistically significant results are common in observational studies, but they are rarely convincing or corroborated by randomized evidence.
Importance of hematological parameters for micro- and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro type 2 diabetes cohort study
Authors: Cardoso Claudia R. L. , Leite Nathalie C. , Salles Gil F.
Published: July 2021

Background

The prognostic importance of several hematological parameters has been scarcely investigated in type 2 diabetes. So, we aimed to evaluate their prognostic importance for development of complications in a cohort of type 2 diabetes.

Methods

In a prospective study, 689 individuals with type 2 diabetes had blood red cell, platelet and leukocyte parameters obtained at baseline. Multivariate Cox analyses examined the associations between several hematological parameters (including neutrophyl-to-lymphocyte, lymphocyte-to-monocyte, platelet-to-lymphocyte, and monocyte-to-HDL ratios) and the occurrence of microvascular (retina, renal and peripheral neuropathy) and cardiovascular complications (total cardiovascular events [CVEs], and major adverse CVEs [MACEs]), and all-cause and cardiovascular mortality. Improvements in risk discrimination were assessed by C-statistics and Integrated Discrimination Improvement (IDI) index.

Results

During a median follow-up of 10.5 years, 212 patients had a CVE (174 MACEs), 264 patients died (131 cardiovascular deaths); 206 had a renal, 161 a retinopathy and 179 patients had a neuropathy outcome. In multivariate-adjusted analyses, the lymphocytes count and lymphocyte-to-monocyte ratio were protective (hazard ratios [HRs]: 0.77 and 0.72, respectively), whereas the neutrophyl-to-lymphocyte and platelet-to-lymphocyte ratios were associated with increased risks (HRs: 1.19 and 1.17) for all-cause mortality. For cardiovascular mortality, the monocytes count, the neutrophyl-to-lymphocyte and monocyte-to-HDL ratios were associated with increased risks and the lymphocyte-to-monocyte ratio was protective. Higher lymphocyte-to-monocyte ratio was protective for renal failure outcome. However, none of them improved risk discrimination.

Conclusions

Low lymphocytes count and leukocyte ratios that mainly included lymphocytes were predictors of macrovascular complications and mortality in individuals with type 2 diabetes. However, they did not improve risk prediction over traditional risk factors.
Up and down waves of glycemic control and lower-extremity amputation in diabetes
Authors: Caruso Paola , Scappaticcio Lorenzo , Maiorino Maria Ida , Esposito Katherine , Giugliano Dario
Published: July 2021

Lower extremity amputations (LEA) are associated with a high mortality and medical expenditure. Diabetes accounts for 45% to 70% of LEA and is one of the most potent risk factors for peripheral artery diseases (PAD). The existence of a link between the recent relaxation of glycemic targets and the resurgence of LEA is suggested from the analysis of adult participants in the National Health and Nutrition Examination Survey (NHANES) between 2010 and 2015, when diabetes-related LEA increased by more than 25% associated with a decline in glycemic control. Indeed, in “the perfect wave” of NHANES, including the years 2007–2010, there was the highest number of diabetic people with hemoglobin A1c (HbA1c), non-high-density lipoprotein (HDL) cholesterol and blood pressure levels at their respective targets, associated with the lowest number of LEA. Until now, the ACCORD study, testing the role of aggressive vs conventional glucose control, and the LEADER trial, evaluating the effects of liraglutide versus placebo, have shown a reduced incidence of LEA in people with type 2 diabetes. The results of ongoing clinical trials involving glucagon-like peptide-1 receptor agonists (GLP-1RA, liraglutide or semaglutide) hopefully will tell us whether the wider use of these drugs may provide additional vascular benefits for diabetic people affected by PAD to decrease their risk of LEA.
Designing highly stable ferrous selenide-black phosphorus nanosheets heteronanostructure via P-Se bond for MRI-guided photothermal therapy
Authors: Deng Xuanru , Liu Hongxing , Xu Yuan , Chan Leung , Xie Jun , Xiong Zushuang , Tang Zheng , Yang Fang , Chen Tianfeng
Published: July 2021

Background

The design of stable and biocompatible black phosphorus-based theranostic agents with high photothermal conversion efficiency and clear mechanism to realize MRI-guided precision photothermal therapy (PTT) is imminent.

Results

Herein, black phosphorus nanosheets (BPs) covalently with mono-dispersed and superparamagnetic ferrous selenide (FeSe2) to construct heteronanostructure nanoparticles modified with methoxy poly (Ethylene Glycol) (mPEG-NH2) to obtain good water solubility for MRI-guided photothermal tumor therapy is successfully designed. The mechanism reveals that the enhanced photothermal conversion achieved by BPs-FeSe2-PEG heteronanostructure is attributed to the effective separation of photoinduced carriers. Besides, through the formation of the P-Se bond, the oxidation degree of FeSe2 is weakened. The lone pair electrons on the surface of BPs are occupied, which reduces the exposure of lone pair electrons in air, leading to excellent stability of BPs-FeSe2-PEG. Furthermore, the BPs-FeSe2-PEG heteronanostructure could realize enhanced T2-weighted imaging due to the aggregation of FeSe2 on BPs and the formation of hydrogen bonds, thus providing accurate PTT guidance and generating hyperthermia to inhabit tumor growth under NIR laser with negligible toxicity in vivo.

Conclusions

Collectively, this work offers an opportunity for fabricating BPs-based heteronanostructure nanomaterials that could simultaneously enhance photothermal conversion efficiency and photostability to realize MRI-guided cancer therapy.

Graphic abstract
HIV-1 capsid exploitation of the host microtubule cytoskeleton during early infection
Authors: Naghavi Mojgan H.
Published: July 2021

Microtubules (MTs) form a filamentous array that provide both structural support and a coordinated system for the movement and organization of macromolecular cargos within the cell. As such, they play a critical role in regulating a wide range of cellular processes, from cell shape and motility to cell polarization and division. The array is radial with filament minus-ends anchored at perinuclear MT-organizing centers and filament plus-ends continuously growing and shrinking to explore and adapt to the intracellular environment. In response to environmental cues, a small subset of these highly dynamic MTs can become stabilized, acquire post-translational modifications and act as specialized tracks for cargo trafficking. MT dynamics and stability are regulated by a subset of highly specialized MT plus-end tracking proteins, known as +TIPs. Central to this is the end-binding (EB) family of proteins which specifically recognize and track growing MT plus-ends to both regulate MT polymerization directly and to mediate the accumulation of a diverse array of other +TIPs at MT ends. Moreover, interaction of EB1 and +TIPs with actin-MT cross-linking factors coordinate changes in actin and MT dynamics at the cell periphery, as well as during the transition of cargos from one network to the other. The inherent structural polarity of MTs is sensed by specialized motor proteins. In general, dynein directs trafficking of cargos towards the minus-end while most kinesins direct movement toward the plus-end. As a pathogenic cargo, HIV-1 uses the actin cytoskeleton for short-range transport most frequently at the cell periphery during entry before transiting to MTs for long-range transport to reach the nucleus. While the fundamental importance of MT networks to HIV-1 replication has long been known, recent work has begun to reveal the underlying mechanistic details by which HIV-1 engages MTs after entry into the cell. This includes mimicry of EB1 by capsid (CA) and adaptor-mediated engagement of dynein and kinesin motors to elegantly coordinate early steps in infection that include MT stabilization, uncoating (conical CA disassembly) and virus transport toward the nucleus. This review discusses recent advances in our understanding of how MT regulators and their associated motors are exploited by incoming HIV-1 capsid during early stages of infection.
Radiological and clinical outcomes of balloon kyphoplasty for osteoporotic vertebral compression fracture in patients with rheumatoid arthritis
Authors: Guo Ji , Zhai Weifeng , Wei Licheng , Zhang Jianpo , Jin Lang , Yan Hao , Huang Zheng , Jia Yongwei
Published: July 2021

Background

This study was conducted to investigate the outcomes and complications of balloon kyphoplasty (KP) for the treatment of osteoporotic vertebral compression fracture (OVCF) in patients with rheumatoid arthritis (RA) and compare its radiological and clinical effects with OVCF patients without RA.

Methods

Ninety-eight patients in the RA group with 158 fractured vertebrae and 114 patients in the control group with 150 vertebrae were involved in this study. Changes in compression rate, local kyphotic angle, visual analog scale (VAS) and Oswestry disability index (ODI) scores, conditions of bone cement leakage, refracture of the operated vertebrae, and new adjacent vertebral fractures were examined after KP. In addition, patients in the RA group were divided into different groups according to the value of erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and whether they were glucocorticoid users or not to evaluate their influence on the outcomes of KP.

Results

KP procedure significantly improved the compression rate, local kyphotic angle, and VAS and ODI scores in both RA and control groups (p<0.05). Changes in compression rate and local kyphotic angle in the RA group were significantly larger than that in the control group (p<0.05), and patients with RA suffered more new adjacent vertebral fractures after KP. The outcomes and complications of KP from different ESR or CRP groups did not show significant differences. The incidence of cement leakage in RA patients with glucocorticoid use was significantly higher than those who did not take glucocorticoids. In addition, RA patients with glucocorticoid use suffered more intradiscal leakage and new adjacent vertebral fractures.

Conclusions

OVCF patients with RA obtained more improvement in compression rate and local kyphotic angle after KP when compared to those without RA, but they suffered more new adjacent vertebral fractures. Intradiscal leakage and new adjacent vertebral fractures occurred more in RA patients with glucocorticoid use.

Trial registration

Retrospectively registered.
Minimally invasive plate osteosynthesis with dual plating for periprosthetic distal femoral fractures following total knee arthroplasty
Authors: Park Yong-Geun , Kang Hyunseong , Song Jung-Kook , Lee Jaehwang , Rho Joseph Y. , Choi Sungwook
Published: July 2021

Introduction

Adequate treatment for periprosthetic distal femur fractures is challenging because of various reasons, including severe osteoporosis and distal fragments that are too small or too distal. We have introduced a new surgical technique for dual plating of periprosthetic distal femur fractures following total knee arthroplasty (TKA) and determined the clinical and radiological outcomes of minimally invasive plate osteosynthesis (MIPO) with a dual locking compression plate (LCP).

Materials and methods

Between January 2010 and July 2019, 18 patients [mean age, 74.8 (68–89) years; average follow-up period, 14.8 (12–43) months] underwent MIPO with distal femoral LCP laterally and proximal humeral internal locking system (PHILOS) medially for periprosthetic distal femoral fractures following TKA. The minimum follow-up was 1 year. The clinical and radiological outcomes were assessed using the modified WOMAC scores, knee range of motion, time to callus formation, time to union, and complications of malunion, nonunion, and shortening.

Results

The average time to union was 18.4 weeks (range, 10–51 weeks) and to callus formation was 7.8 weeks (range, 2–14 weeks). At the 1-year follow-up, the average JLETS was 37.6 (range, 24–53), average knee ROM was 110.3° (range, 80–135°), and average varus-valgus angles of the distal femur were 3.2° (range, −2.9–10.5°). No nonunion, broken plates, or implant failure occurred. Malunion occurred in three patients.

Conclusion

MIPO with dual LCP is a reliable method for stabilizing periprosthetic distal femoral fractures following TKA, with satisfactory bone union rates and low complication rates.
Anthropometric measurements of patellar ridge using computed tomography-based three-dimensional computer models
Authors: Mei Xiaoliang , Ding Hao , Meng Jia , Zhao Jianning
Published: July 2021

Background

The objectives of this study were to investigate the anatomic morphology of patellar ridge using computed tomography-based three-dimensional (3D) computer models and to assess the center of the patellar ridge after virtual resections.

Methods

We selected 80 patients, 40 males (age, 33.2±6.8 years) and 40 females (age, 30.6±7.2 years), who were slightly symptomatic with soft tissue injury of the knee joint. The right or left knees were scanned by computed tomography (CT). The CT data of 160 knees was used to construct 3D computer models by image analysis software (Mimics). Variables such as the angle between the patellar ridge and patellar long axis, the distance between the center of the patellar ridge and the center of patellar cut after virtual resections were measured. We detect differences between the sides and genders with the 3D computer models by Student’s t test. Simple linear regression and correlation test was used to correlate the patellar ridge center to the center of the patellar cut.

Results

According to the available data, there were significant gender differences in the length and width of patellar cut after virtual resections even with strict control for the height and weight of the patients. The angle between the patellar ridge and the patellar long axis was 11.24° ± 3.62°. The angle in male patients was 10.17° ± 4.82°, and it was 12.28°± 3.78° in female patients. The morphological difference was statistically significant (P < 0.05). After using the subchondral method to virtually resect the patellae, with reference to the center of the patellar cut, the center of the patellar ridge lies superiorly and medially in 88.75%, inferiorly and medially in 8.75%, laterally and superiorly in 2.5%, and in no case laterally and inferiorly. The intra-observer reliability regarding the dimensional measurements was excellent in this study.

Conclusions

Advances in 3D computer models had resulted in the availability of preoperative measurement and virtual planning. The anthropometric dimensions of this study could provide general information for guiding surgical management of the patella in total knee arthroplasty (TKA) and were useful in designing patellar implants.

Clinical relevance

The placement of the patellar component during TKA differs from one patella to another. The anatomic morphology information of the patellar ridge is helpful for surgeons to perform patellar resurfacing in TKA.
Right apical-posterior segmentectomy with abnormal anterior segmental bronchus and artery: a case report
Authors: Zhang Xining , Lin Gang , Li Jian
Published: July 2021

Background

Displaced anterior segmental bronchus and pulmonary artery is extremely rare. A keen knowledge of such variations is required in the field of pulmonary segmentectomy, for unawareness of the structural variation could lead to intra- and postoperative complications.

Case presentation

A 50-year-old female presented to our department with suspected lung adenocarcinoma. Preoperative 3-dimensional computed tomographic bronchography and angiography revealed anterior segmental bronchus and anterior segmental pulmonary artery variation: the anterior segmental bronchus derived from the middle lobe bronchus, accompanied by a distally distributed anterior segmental pulmonary artery branch. A right apical-posterior segmentectomy using inflation-deflation technique was performed successfully.

Conclusions

The keen observation and proper application of modern imaging technology and operative technique could greatly aid segmentectomy, preventing intra- and postoperative complications from happening.
Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins
Authors: Montero-Bullón Javier-Fernando , González-Velasco Óscar , Isidoro-García María , Lacal Jesus
Published: July 2021

Background

RASopathies are a group of syndromes showing clinical overlap caused by mutations in genes affecting the RAS-MAPK pathway. Consequent disruption on cellular signaling leads and is driven by phosphoproteome remodeling. However, we still lack a comprehensive picture of the different key players and altered downstream effectors.

Methods

An in silico interactome of RASopathy proteins was generated using pathway enrichment analysis/STRING tool, including identification of main hub proteins. We also integrated phosphoproteomic and immunoblotting studies using previous published information on RASopathy proteins and their neighbors in the context of RASopathy syndromes. Data from Phosphosite database (www.phosphosite.org) was collected in order to obtain the potential phosphosites subjected to regulation in the 27 causative RASopathy proteins. We compiled a dataset of dysregulated phosphosites in RASopathies, searched for commonalities between syndromes in harmonized data, and analyzed the role of phosphorylation in the syndromes by the identification of key players between the causative RASopathy proteins and the associated interactome.

Results

In this study, we provide a curated data set of 27 causative RASopathy genes, identify up to 511 protein–protein associations using pathway enrichment analysis/STRING tool, and identify 12 nodes as main hub proteins. We found that a large group of proteins contain tyrosine residues and their biological processes include but are not limited to the nervous system. Harmonizing published RASopathy phosphoproteomic and immunoblotting studies we identified a total of 147 phosphosites with increased phosphorylation, whereas 47 have reduced phosphorylation. The PKB signaling pathway is the most represented among the dysregulated phosphoproteins within the RASopathy proteins and their neighbors, followed by phosphoproteins implicated in the regulation of cell proliferation and the MAPK pathway.

Conclusions

This work illustrates the complex network underlying the RASopathies and the potential of phosphoproteomics for dissecting the molecular mechanisms in these syndromes. A combined study of associated genes, their interactome and phosphorylation events in RASopathies, elucidates key players and mechanisms to direct future research, diagnosis and therapeutic windows.