bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexion Dislocation After Limb Lengthening: Correction With Distal Femoral Osteotomy, Quadriceps Release, and Physeal-Sparing Medial Patellofemoral Ligament (MPFL) Reconstruction
Authors: Dandu Navya , Fice Michael P. , Hur Edward , Kogan Monica , Yanke Adam B.
Published: May 2022

Background:

Patellar instability is a common clinical condition in skeletally immature individuals. Surgical treatment is considered when risk of recurrence is high.

Indications:

Distal femoral osteotomy is indicated in the setting of obligate flexion dislocation where femoral valgus contributes to a shortened lateral column, with concurrent quadriceps procedures considered for chronic contracture and medial patellofemoral ligament (MPFL) reconstruction for added stabilization.

Technique Description:

This procedure is performed in a stepwise manner as some components may not be necessary based on the patient’s specific anatomy. The procedure begins with a lateral iliotibial (IT) band soft tissue release or lengthening if possible. The distal femoral osteotomy is then performed utilizing a lateral opening wedge technique. Bone graft is placed in a structural fashion to maintain the correction while a locking plate is inserted. In patients with chronic lateral patellar dislocation, correction of bony alignment may not completely restore tracking. If lateral maltracking persists after further distal soft tissue release, a VY-lengthening quadricepsplasty can be considered. To perform this, the vastus lateralis (VL) is first released. In this patient, the patella was able to be stabilized centrally after VL release, and therefore, the VY-plasty was not performed. The soft tissue attachments for the final MPFL reconstruction are then prepared, including two at the superomedial and midbody of the patella and one at the adductor tendon. The whip-stitched graft is then passed through the adductor sling followed by the patellar periosteal tunnels with the knee in slight flexion to ensure centralization within the trochlear groove. Examination under anesthesia before final fixation of the reconstruction should demonstrate 1A lateral translation.

Results:

Correction of distal femoral valgus with osteotomy, in isolation or in combination with other patellar stabilizing procedures, has demonstrated significant improvement in patient-reported outcomes and reduced redislocation rates. However, large cohort studies are limited.

Discussion/Conclusion:

Both osseous and soft tissue abnormalities are important to consider in since they can contribute in varying degrees to patellar maltracking. Therefore, assessment of patellar tracking should be performed frequently to guide extent of surgical correction necessary.
SAKK 35/15: a phase 1 trial of obinutuzumab in combination with venetoclax in patients with previously untreated follicular lymphoma
Authors: Stathis Anastasios , Mey Ulrich , Schär Sämi , Hitz Felicitas , Pott Christiane , Mach Nicolas , Krasniqi Fatime , Novak Urban , Schmidt Christian , Hohloch Karin , Kienle Dirk Lars , Hess Dagmar , Moccia Alden A. , Unterhalt Michael , Eckhardt Katrin , Hayoz Stefanie , Forestieri Gabriela , Rossi Davide , Dirnhofer Stefan , Ceriani Luca , Sartori Giulio , Bertoni Francesco , Buske Christian , Zucca Emanuele , Hiddemann Wolfgang
Published: May 2022

This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.
Transferrin predicts trimethylamine-N-oxide levels and is a potential biomarker of cardiovascular disease
Authors: Bean Lamuel D. , Wing Jeffrey J. , Harris Randall E. , Smart Suzanne M. , Raman Subha V. , Milks M. Wesley
Published: May 2022

Introduction

Trimethylamine-N-oxide (TMAO) is a circulating biomarker associated with cardiovascular disease (CVD). Production of TMAO is facilitated by gut microbiota and dependent on micronutrients such as choline, betaine, and L-carnitine, present in foods such as red meat and eggs.

Hypothesis

We sought to predict serum TMAO quartile levels among healthy individuals at increased risk of CVD using clinical data via an ordinal logistic model.

Methods

Data from participants (n = 127) enrolled in a longitudinal observational study on CVD were used to build a predictive model for TMAO using ordinal logistic regression with demographic variables and 40 other variables considered related to CVD risk. First, univariate models for each covariate were tested (with serum TMAO quartiles as the dependent variable), and only variables with P < 0.30 were evaluated further. Second, demographic variables (age, gender, white vs. non-white race) were included in a multivariable model with each previously identified independent variable controlling for potential confounding. Last, the final model included fixed demographics and candidates from the confounder-adjusted model with P < 0.10.

Results

Eight candidate variables were included in the final model, with only transferrin, high-density lipoprotein cholesterol (HDL-C) and race (white vs. non-white) showing significant associations with TMAO. Participants had 0.16 (Q2), 0.31 (Q3), and 0.20 (Q4) odds of being in a higher TMAO quartile compared with participants in the lowest transferrin quartile. Non-white participants had 2.92 times higher odds of being in the highest TMAO quartile compared to white individuals. Participants in the second quartile of HDL-C had 2.68 times higher odds of being in a higher TMAO quartile compared with participants in the lowest HDL-C quartile.

Conclusions

Transferrin demonstrated a significant predictive association with TMAO and may represent a novel potential biomarker of increased CVD risk worthy of further study. These results warrant further examination of iron, metabolism, homeostasis, and gut microbiome to better understand and mitigate known increased CVD risk.
The association between glycosylated haemoglobin and newly diagnosed hypertension in a non-diabetic Sudanese population: a cross-sectional study
Authors: Omar Saeed M. , Musa Imad R. , Abdelbagi Omer , Sharif Manal E. , Adam Ishag
Published: May 2022

Background

Glycosylated haemoglobin (HbA1c) is considered reliable for diagnosing and monitoring diabetes mellitus (DM). It also indicates cardiovascular complications related to DM. However, only a few studies have been conducted on this topic.

Methods

We conducted a cross-sectional study to investigate the association between newly diagnosed hypertension and HbA1c among non-diabetic Sudanese adults. The sociodemographic characteristics of the participants in the sample were gathered using a questionnaire, and HbA1c was measured using an Ichroma machine.

Results

Three hundred and eighty-four healthy participants were enrolled in this study. The median (interquartile range [IQR]) age was 56.0 (14.0) years, and 72.1% of the participants were female. The median (IQR) body mass index (BMI) was 31.2 (8.7) kg/m2. One hundred and fifteen (29.9%) participants presented newly diagnosed hypertension. The results of the multivariate analysis showed that age (adjusted odd ratio [AOR] = 1.03; 95% confidence interval [CI] = 1.01‒1.05); BMI (AOR = 1.09; 95% CI = 1.05‒1.14); HbA1c levels (AOR = 2.18; 95% CI = 1.29‒3.67) was positively associated with newly diagnosed hypertension. For an HbA1c level of 5.0% or more, the sensitivity and specificity of newly diagnosed hypertension were 91.3% and 28.2%, respectively (area under the curve = 0.61; 95% CI = 0.55–0.67; P ˂ 0.001). Participants who presented HbA1c levels of 5.0% or more were found to be at higher risk for newly diagnosed hypertension (AOR = 2.53; 95% CI = 1.14‒5.61).

Conclusion

The results of this study indicated a high prevalence of newly diagnosed hypertension, and HbA1c levels were positively associated with newly diagnosed hypertension.
Application of coagulation parameters at the time of necrotizing enterocolitis diagnosis in surgical intervention and prognosis
Authors: Feng Wei , Hou Jinping , Die Xiaohong , Sun Jing , Guo Zhenhua , Liu Wei , Wang Yi
Published: May 2022

Purpose

It has been shown that abnormalities of coagulation and fibrinolysis system are involved in the pathogenesis of necrotizing enterocolitis (NEC), but not well studied challenge in the context of early detection of disease progression. The present study mainly explores the predictive significance of coagulation parameters at the time of NEC diagnosis in identifying the patients who eventually received surgery and/or NEC-related deaths.

Methods

The retrospective study of 114 neonates with NEC was conducted with assessments of demographic data, laboratory results at the time of NEC diagnosis, treatment methods and prognosis. According to treatment methods, patients were divided into surgical intervention group and medical treatment group. Predictive factors were put forward and determined by receiver operating characteristic (ROC) curve analysis. An analysis of the surgical intervention and prognosis was performed.

Results

Of 114 patients, 46 (40.4%) cases received surgical intervention and 14 (12.3%) deaths. prothrombin time (PT), PT international normalized ratio, activated partial thromboplastin time (APTT), fibrinogen and platelet count at the time of NEC diagnosis were independently associated with surgical NEC. The APTT could identify patients at high risk for surgical NEC, with 67.39% sensitivity, 86.76% specificity, better than that of other serological parameters. Coagulopathy was found in 38.6% of all patients. For surgical intervention, the area under the ROC curve (AUC) of coagulopathy was 0.869 (95% confidence interval [CI]: 0.794 ~ 0.944,P < 0.001), with 82.61% sensitivity and 91.18% specificity, outperformed APTT (95% CI: 0.236 ~ 0.173,P = 0.001). Furthermore, the AUC for coagulopathy to predict mortality was 0.809 (95% CI: 0.725 ~ 0.877,P < 0.001), with 92.86% sensitivity and 69.0% specificity.

Conclusion

Coagulation parameters at the time of NEC diagnosis were conducive to early prediction of surgical NEC and -related deaths, which should be closely monitored in neonates at high risk of NEC and validated as a clinical decision-making tool.
Serum β-catenin changes vary among different stages of osteonecrosis of the femoral head: an exploratory biomarker study
Authors: Huang Junyuan , Zhou Yingchun , Xiao Wei , Deng Peng , Wei Qiushi , Lu Weiguo
Published: May 2022

Background

Wnt/β-catenin signaling pathway is closely related to the pathogenesis Osteonecrosis of the femoral head (ONFH). β-catenin, as a major component of Wnt signaling pathway, plays a vital role in the proliferation of osteoblasts. But the effect of altering β-catenin level on the early diagnosis and staging of ONFH has not been studied. Our purpose is to investigate the role of β-catenin level in the progress of ONFH.

Method

One hundred and one patients with three stages of ONFH and fifty healthy controls were recruited between May 2016 and November 2016. We divided the patients into 32 cases of stage II, 41 cases of stage III and 28 cases of stage IV according to the Association Research Circulation Osseous (ARCO) classification. We evaluated the clinical bone histomorphology, expression position and level of β-catenin as well as the plasma β-catenin level. We investigated the level of β-catenin from the serum and tissue samples using ELISA and Western Blot assay. We also evaluated the expression of β-catenin in bone tissue by immunohistochemistry. Data were analyzed by independent t-test and ANOVA.

Results

We found that the mean (± SD) serum level of β-catenin was 66.99 ± 3.032 ng/ml in the ONFH patients, which was higher than 20.14 ± 1.715 ng/ml observed in the control group (P < 0.001). Moreover, the β-catenin levels were 49.30 ± 4.649 ng/ml, 72.54 ± 4.864 ng/ml and 79.10 ± 4.773 ng/ml in the ONFH patients with ARCO stage II, stage III and stage IV respectively, showing significant difference among them (P < 0.001). We also found that the area under the curve (AUC) calculated by ROC curve analysis to determine the values for β-catenin levels in ONFH compared with those in the control group was 0.9358 (P < 0.001), where the sensitivity was 77.23% and specificity was 98.00%.

Conclusion

Our results indicate that the increased β-catenin may play a vital role in the progress of ONFH and the level of β-catenin is correlated with ARCO stages. The cut-off concentration may be used as one of the sensitive marks to assess the disease process of ONFH.
The changes of the calf-vein deformation and femoral vein peak velocity during ankle pump exercise with or without graduated compression stockings
Authors: Zhuang Zaikai , Ai Dongmei , Yao Yao , Zheng Liming , Qin Jianghui , Chen Dongyang , Chai Senlin , Lu Jun , Jiang Qing , Li Xinhua
Published: May 2022

Objectives

To analyze the changes of lower limb hemodynamics parameters before and after wearing graduated compression stockings (GCS) during ankle pump exercise in patients preparing for arthroplastic surgery.

Method

The leg veins of 16 patients awaiting arthroplasty were analyzed using a Sonosite M-Turbo ultrasound system during ankle pump exercise with or without GCS. The age of them was 70 ± 7 years (mean ± SD) (range 56—82 years) and body mass index was 25.8 ± 3.0 kg/m2 (range 18.0—30.5 kg/m2). Measured data including the cross-sectional area (CSA), anteroposterior (AP) diameter and lateromedial (LM) diameter of the soleus vein (SV), posterior tibial vein (PTV) and great saphenous vein (GSV). Additionally, the peak velocities of femoral vein (FV) were also measured.

Results

GCS could significantly decrease the cross-sectional area of SV, PTV and GSV in supine position at rest and maximum ankle plantar flexion. But the compression effect of GCS to SV and GSV was not observed during maximum ankle dorsiflexion. It was found that GCS application reduced the peak flow velocity of the femoral vein from 61.85 cm/s (95% CI = 50.94–72.75 cm/s) to 38.01 cm/s (95% CI = 28.42–47.59 cm/s) (P < 0.001) during ankle plantar flexion and decreased the femoral vein in these patients from 80.65 cm/s (95% CI = 70.37–90.92 cm/s) to 51.15 cm/s (95% CI = 42.58–59.73 cm/s) (P < 0.001) during ankle dorsiflexion. But this effect was not significant in supine position at rest.

Conclusions

GCS could significantly reduce the peak flow velocity of the femoral vein during ankle pump exercise in the patients preparing for arthroplastic surgery.
Vascular variations encountered during laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer: a retrospective cohort study
Authors: Nakao Toshihiro , Shimada Mitsuo , Yoshikawa Kozo , Tokunaga Takuya , Nishi Masaaki , Kashihara Hideya , Takasu Chie , Wada Yuma , Yoshimoto Toshiaki , Yamashita Syoko , Iwakawa Yosuke
Published: May 2022

Background

Laparoscopic surgery for cancer located in the transverse colon or splenic flexure is difficult because of vascular variability in this region and adjacent vital organs such as the pancreas, spleen, and duodenum.

Methods

This retrospective cohort study involved 51 patients who underwent laparoscopic surgery for colon cancer at Tokushima University Hospital from July 2015 to December 2020. Variations of the middle colic artery (MCA), left colic artery (LCA), middle colic vein (MCV), and first jejunal vein (FJV) and short-term outcomes of laparoscopic surgery in patients with each vascular variation were evaluated.

Results

Variations of the MCA, LCA, MCV, and FJV were classified into four, three, five, and three patterns, respectively. The short-term outcomes of laparoscopic surgery for transverse colon cancer in patients with MCA variations and those with FJV variations were evaluated, and no significant difference was found in the operation time, blood loss, postoperative complication rate, time from surgery to start of dietary intake, or time from surgery to discharge among the different variations. Additionally, no significant differences were found in the short-term outcomes of laparoscopic surgery for descending colon cancer in patients with LCA variations.

Conclusion

Preoperative assessment of vascular variations may contribute to the stability of short-term outcomes of laparoscopic surgery for transverse colon, splenic flexure, and descending colon cancer.
Developing a culturally tailored short message service (SMS) intervention for improving the uptake of cervical cancer screening among Ghanaian women in urban communities
Authors: Bonful Harriet Affran , Addo-Lartey Adolphina Addoley , Sefenu Ransford Selasi , Nwameme Adanna , Abagre Timothy Agandah , Awua Adolf Kofi , Adu-Aryee Nii Armah , Dedey Florence , Adanu Richard Mawuena Kofi , Okuyemi Kolawole Stephen
Published: May 2022

Background

There has been extensive research across the globe to understand the barriers and facilitators of cervical cancer (CC) screening. However, few studies have focused on how such information has been used to develop text messages for mHealth screening programs, especially in resource-poor countries. This study elicited information on barriers and facilitators, the preferences of women regarding the modalities for delivery of health SMS messages on screening for cervical cancer, and demonstrates how this information was used to create a health screening program among women in the Greater Accra Region of Ghana.

Methods

Four main activities were carried out, including (1) a total of five focus group discussions, (2) a baseline survey involving 62 female bankers and 68 women from the communities, (3) a stakeholder meeting involving experts in cervical cancer research and clinical care, and (4) pilot testing of the text messages. Focus group discussions and the baseline survey data were collected concurrently between February and May 2017 and the results were used to develop 5 specific communication objectives during the stakeholder engagements held in June 2017.

Results

In all, 32 text messages were developed and pretested in July 2017(13 addressed knowledge on CC; 6 highlighted the importance of early detection; 5 allayed fear as a barrier to CC screening; 5 encouraged women to have time for their health, and 3 messages contained information on where to go for screening and the cost involved). Although awareness about the disease was high, knowledge of CC screening was low. For two-thirds of respondents (22/33), perceived lack of time, high cost, and fear (of cc, screening procedure, and potential for negative outcome) accounted for the reasons why respondents will not go for screening, while education on CC, especially from health workers and the mass media enabled uptake of CC screening.

Conclusion

Several factors prevent women from accessing screening services for CC, however, barriers such as low levels of education on CC, lack of time, and fear can be targeted in SMS messaging programs.
Examination of influence of social media education through mobile phones on the change in physical activity and sedentary behavior in pregnant women: a randomized controlled trial
Authors: Talebi Erfaneh , Mohaddesi Hamideh , Vahabzadeh Davoud , Rasuli Javad
Published: May 2022

Background

Nowadays because of some necessities and demands for virtual and remote education, a new model of health approach through mobile-phones is widely used to deal with improving physical activity and its beneficial effect on pregnancy. There are a small number of studies for showing this importance and the efficacy of such methods, so this study was aimed to determine the influence of social networking through mobile phones on changing the physical activity behavior in pregnant women.

Methods

This randomized controlled trial was conducted with parallel groups on 90 pregnant women referring to Urmia health centers in 2018–2019. The participants from various social and economic backgrounds were included. The participants were randomly assigned to a control and a treatment group. Demographic and Pregnancy Physical Activity Questionnaire (PPAQ) questionnaires were filled. In addition to routine cares, the treatment group received educational intervention through social network within 16 training sessions related to physical activity and nutrition in 8 weeks.

Results

The mean weight in both control and treatment groups changed significantly during the study, but in different trends (P < 0.001, Mean Difference (MD) = 4.43). At the beginning of the study, control and treatment groups were not different in terms of daily physical activity level (P = 0.17, MD = 0.62), meanwhile, there was a statistically significant difference at the end of intervention in the level of daily physical activity (P < 0.001, MD = 0.69). Comparison of both groups, based on different categories of activity level at the end of the treatment, showed a non-significant difference in sedentary activities (P = 0.89, MD = 0.46), but the intervention led to a significant difference based on the other level of activities; light (P < 0.001, MD = 51.94), moderate (P < 0.001, MD = 46.87), and sever (P = 0.05, MD = 1.07).

Conclusion

Educational intervention based on social networks through mobile phones had an effective role in behavior change in physical activity during pregnancy.

Trial registration

IRCT20151004024340N15, Registration date05/06/2020.
Socioeconomic inequalities in contraceptive use among female adolescents in south Asian countries: a decomposition analysis
Authors: Sharma Himani , Singh Shri Kant
Published: May 2022

Background

Contraceptive knowledge and use has been an emerging topic of interest in adolescents in Asia. This study quantified the contribution of the socioeconomic determinants of inequality in contraceptive use among currently married female adolescents (15–24) in four south Asian countries: India, Bangladesh, Nepal and Pakistan.

Data and methods

The data of Demographic Health Survey (DHS) for four South Asian countries, i.e. India (NFHS 2015–16), Nepal (DHS 2016), Bangladesh (DHS 2014) and Pakistan (DHS 2012–2013) has been used for examining the contraceptive use and inherent socioeconomic inequality. After employing logistic regression, concentration curves based on decomposition analysis have been made to analyse the socioeconomic inequality.

Results

The results reveal that the use of contraception among female adolescents remains low and factors like education, employment, having one or more children, media exposure were positively associated with it. In terms of socioeconomic inequality, a significant amount of variation has been observed across the countries. In India, poor economic status (95.23%), illiteracy (51.29%) and rural residence (23.06%) contributed maximum in explaining the socioeconomic inequality in contraceptive use among female adolescents. For Bangladesh, the largest contributors to inequalities were rural residence (260%), illiteracy (146.67%) while birth order 3 + (− 173.33%) contributed negatively. Illiteracy (50%), poor economic status (47.83%) and rural residence (16.30%) contributed maximum to the inequalities in contraceptive use in Pakistan while birth order 3 + (− 9.78%) contributed negatively. In Nepal, the important operators of inequalities were unemployment (105.26%), birth order 3 + (52.63%) and poor economic status (47.37%), while rural residence contributed negatively (− 63.16%) to inequalities in contraceptive use.

Conclusions

Using a cross country perspective, this study presents an socioeconomic inequality analysis in contraceptive use and the important factors involved in the same. Since the factors contributing to inequalities in contraceptive use vary across countries, there is a need to imply country-specific initiatives which will look after the special needs of this age-group.
Eating disorders and their relationship with menopausal phases among a sample of middle-aged Lebanese women
Authors: Khalil Joe , Boutros Sarah , Kheir Nelly , Kassem Maha , Salameh Pascale , Sacre Hala , Akel Marwan , Obeid Sahar , Hallit Souheil
Published: May 2022

Objectives

The objective of our study was to evaluate the association between the transition to menopause, body dissatisfaction, and abnormal eating habits (restrained eating, binge eating, and orthorexia nervosa) in a sample of middle-aged Lebanese women.

Methods

A cross-sectional study conducted between July 2019 and January 2020 enrolled 1001 women aged 40 years and above from all Lebanese governorates. Data were collected by face-to-face interviews with all participants. The Body dissatisfaction subscale of the Eating Disorder Inventory‑second version was used to assess body dissatisfaction, whereas the Binge Eating Scale, Dutch Restrained Eating Scale, ORTO-15, Dusseldorf Orthorexia Scale (DOS), and Teruel Orthorexia Scale (TOS) were used to assess eating disorders (binge eating, restrained eating and orthorexia nervosa respectively. Multivariable analysis of covariance (MANCOVA) was used to compare multiple measures among the three menopausal phases, after adjustment over potential confounding variables (age, monthly income, body mass index, marital status, education level, and body dissatisfaction).

Results

Postmenopause was significantly associated with more orthorexia nervosa tendencies (lower ORTO-15 scores) than premenopause (β = − 1.87; p = 0.022). Perimenopause was associated with more binge eating (β = 1.56; p = 0.031), and less orthorexia nervosa (as measured by the DOS) than premenopause, with this association tending to significance (β  = − 1.10; p = 0.051). Furthermore, higher body dissatisfaction was significantly associated with higher restrained eating (β = 0.02; p < 0.001), binge eating (β = 0.48; p < 0.001), and orthorexia nervosa as measured by ORTO-15 (β = − 0.17; p < 0.001) and TOS (β = 0.08; p = 0.002), but not DOS.

Conclusion

Our study showed that menopausal stages are associated with some disordered eating behaviors (binge eating and orthorexia nervosa) among middle-aged women. Those results may serve as a first step towards spreading awareness among women within this age group regarding eating attitudes. Moreover, healthcare professionals should screen for the presence of disordered eating during those women’s routine visits to the clinics.
Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients
Authors: Liu Kun , Liu Xuzhong , Sun Qing , Tang Zhiwang , Wang Gongcheng , Xu Zongyuan
Published: May 2022

Background

ccRCC is considered as the main subtype of RCC, which accounted for sixth deadliest cancer worldwide. Recently, ubiquitination has been reported to be closely involved in the progression of tumore. The purpose of this study was to identify the ubiquitination-associated genes and co-expressed lncRNAs on the prognosis of clear cell renal cell carcinoma (ccRCC) patients.

Methods and patients

We downloaded 530 cases and the corresponding transcriptome profiling from The Cancer Genome Atlas (TCGA) database. We distinguished mRNA and lncRNA expression data from the transcriptome profiling and then extracted the expression of mRNAs that regulate protein ubiquitination. We obtained lncRNAs associated with protein ubiquitination regulation from the lncRNA data by gene co-expression analysis. Cox regression analysis of survival time, survival status, and lncRNA expression level was carried out, and a prognostic index (PI) was constructed.

Results

The PI was established based on 8 prognostic lncRNAs that regulate protein ubiquitination and distinguish the high-risk group patients from all patients. Multivariate analysis indicated that this PI was an individualized clinical prognostic factor for patients with ccRCC. Regarding clinical characteristics, a ubiquitination-associated clinical-prognostic index (UCPI), containing 8 ubiquitination-related lncRNAs and age, was established and tested with AUC of 0.80.

Conclusion

We established a UCPI containing 8 lncRNAs related to protein ubiquitination. This UCPI may become an appropriate model to predict the prognosis in ccRCC patients and guide clinicians to adjust the follow-up regimen.
Clinical outcomes in central nervous system solitary-fibrous tumor/hemangiopericytoma: a STROBE-compliant single-center analysis
Authors: Yu Yang , Hu Yu , Lv Liang , Chen Cheng , Yin Senlin , Jiang Shu , Zhou Peizhi
Published: May 2022

Background

Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) are rare mesenchymal tumors in the central nervous system with a high tendency to relapse, having a significant impact on quality of life (QoL). Due to the rarity of intracranial SFT/HPC, the prognostic factors and optimal treatment remain to be elucidated. Meanwhile, quality of life in patients with intracranial SFT/HPC is seldomly concerned. Thus, we aim to survey about the quality of life and underline some aspects demanding concern in intracranial SFT/HPC treatment through summarizing our case series in recent ten years.

Methods

Patients with intracranial SFT/HPC who underwent surgical resection from January 2009 to June 2019 were included in the study. Clinical features, such as age, gender, and resection extent, were collected. The EuroQol Five Dimensions Questionnaire (EQ-5D) was used to assess the patients’ quality of life (QoL). Prognosis factors related to progression-free survival (PFS) and overall survival (OS) were also evaluated.

Results

Thirty-six patients with a mean follow-up period of 61.6 months (range 13–123 months) were included in this study. Sixteen (44.4%) patients achieved gross total resection (GTR). Fourteen patients (38.9%) with tumor progression experienced adjuvant radiotherapy (11.1%) or Gamma Knife surgery (GKS, 27.8%). According to the 2016 WHO classification, there were 6 (16.7%) grade I SFT/HPC, 11 (30.5%) grade II SFT/HPC, and 19 (52.8%) grade III SFT/HPC. The PFS and OS were 29 months (range 4–96 months) and 38 months (range 4–125 months). The median EQ5D-3 L tariff with or without progression was 0.617 (95% CI 0.470–0.756) and 0.939 (95% CI 0.772–0.977) respectively. Gross total resection (GTR, p = 0.024) and grade I SFT/HPC (p = 0.017) were significantly associated with longer PFS. In multivariate analysis, GTR (HR 0.378, 95% CI 0.154–0.927) and adjuvant therapy (HR 0.336, 95% CI 0.118–0.956) result in significantly longer PFS in patients with SFT/HPC.

Conclusions

Patients underwent GTR and adjuvant therapy had longer PFS. Similarly, patients with lower WHO grade had relatively longer PFS. Therefore, GTR is advocated for the treatment of SFT/HPC. And adjuvant therapy such as GKS could be an alternative treatment for patients who underwent STR or with tumor progression. Further, the QoL decreased in patients with tumor progression and metastasis, and more attention is demanded to the QoL of intracranial SFT/HPC patients.
Comparison of deep vein thrombosis risks in acute respiratory distress syndrome caused by COVID-19 and bacterial pneumonia: a retrospective cohort study
Authors: Cui Na , Jiang Chunguo , Yang Chenlu , Zhang Liming , Feng Xiaokai
Published: May 2022

Background

High incidence of deep vein thrombosis (DVT) has been observed in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 and those by bacterial pneumonia. However, the differences of incidence and risk factors of DVT in these two groups of ARDS had not been reported before.

Study design and methods

We performed a retrospective cohort study to investigate the difference of DVT in incidence and risk factors between the two independent cohorts of ARDS and eventually enrolled 240 patients, 105 of whom with ARDS caused by COVID-19 and 135 caused by bacterial pneumonia. Lower extremity venous compression ultrasound scanning was performed whenever possible regardless of clinical symptoms in the lower limbs. Clinical characteristics, including demographic information, clinical history, vital signs, laboratory findings, treatments, complications, and outcomes, were analyzed for patients with and without DVT in these two cohorts.

Results

The 28-days incidence of DVT was higher in patients with COVID-19 than in those with bacterial pneumonia (57.1% vs 41.5%, P = 0.016). Taking death as a competitive risk, the Fine-Gray test showed no significant difference in the 28-day cumulative incidence of DVT between these two groups (P = 0.220). Fine-Gray competing risk analysis also showed an association between increased CK (creatine kinase isoenzyme)-MB levels (P = 0.003), decreased PaO2 (partial pressure of arterial oxygen)/FiO2 (fraction of inspired oxygen) ratios (P = 0.081), increased D-dimer levels (P = 0.064) and increased incidence of DVT in COVID-19 cohort, and an association between invasive mechanical ventilation (IMV; P = 0.001) and higher incidence of DVT and an association between VTE prophylaxis (P = 0.007) and lower incidence of DVT in bacterial pneumonia cohort. The sensitivity and specificity of the corresponding receiver operating characteristic curve originating from the combination of CK-MB levels, PaO2/FiO2 ratios, and D-dimer levels ≥0.5 μg/mL were higher than that of the DVT Wells score (P = 0.020) and were not inferior to that of the Padua prediction score (P = 0.363) for assessing the risk of DVT in COVID-19 cohort.

Conclusions

The incidence of DVT in patients with ARDS caused by COVID-19 is higher than those caused by bacterial pneumonia. Furthermore, the risk factors for DVT are completely different between these two ARDS cohorts. It is suggested that COVID-19 is probably an additional risk factor for DVT in ARDS patients.
Identification of ISG15 and ZFP36 as novel hypoxia- and immune-related gene signatures contributing to a new perspective for the treatment of prostate cancer by bioinformatics and experimental verification
Authors: Lyu Fang , Li Yunxue , Yan Zhecheng , He Qingliu , Cheng Lulin , Zhang Pu , Liu Bing , Liu Chunyu , Song Yarong , Xing Yifei
Published: May 2022

Background

Prostatic cancer (PCa) is one of the most common malignant tumors in men worldwide. Emerging evidence indicates significance of hypoxia and immunity in PCa invasion and metastasis. This study aimed to develop a hypoxia- and immune-related gene risk signature and explore the molecular mechanisms to formulate a better prognostic tool for PCa patients.

Methods

The hypoxia and immune scores of all PCa patients in The Cancer Genome Atlas (TCGA) dataset were calculated via the maximally selected rank statistics method and the ESTIMATE algorithm. From common genes identified overlapping hypoxia- and immune-related differentially expressed genes (DE-HRGs and DE-IRGs), a hypoxia- and immune-related gene risk signature was developed utilizing univariate and multivariate Cox regression analyses, and validated in the Memorial Sloan Kettering Cancer Centre (MSKCC) database. The immune cell infiltration level of PCa samples were evaluated with ssGSEA algorithm. Differential expression of prognostic genes was evidenced by immunohistochemistry and western blot (WB) in paired PCa samples. Expression levels of these genes and their variations under regular and hypoxic conditions were examined in cell lines. The functional effects of the prognostic gene on PCa cells were examined by wound healing and transwell assays.

Results

A hypoxia- and immune-related gene risk signature constructed by ISG15 and ZFP36 displays significant predictive potency, with higher risk score representing worse survival. A nomogram based on independent prognostic factors including the risk score and Gleason score exhibited excellent clinical value in the survival prediction of PCa. Infiltration levels of eosinophils, neutrophils, Tcm, Tem, TFH, Th1 cells, and Th17 cells were significantly lower in the high-risk group. Conversely, aDC, pDC, T helper cells, and Tregs were significantly higher. Additionally, the two prognostic genes were closely correlated with the tumor-infiltrating immune cell subset in PCa progression. RT-qPCR and WB presented higher and lower expression of ISG15 and ZFP36 in PCa cells, respectively. They were correspondingly increased and decreased in PCa cells under hypoxic conditions. Wound healing and transwell assays showed that over-expression of ISG15 promoted the migration and invasion of PCa cells.

Conclusion

Our study identified a novel hypoxia- and immune-related gene signature, contributing a new perspective to the treatment of PCa
The PDE4 inhibitor tanimilast shows distinct immunomodulatory properties associated with a type 2 endotype and CD141 upregulation
Authors: Nguyen Hoang Oanh , Salvi Valentina , Tiberio Laura , Facchinetti Fabrizio , Govoni Mirco , Villetti Gino , Civelli Maurizio , Barbazza Ilaria , Gaudenzi Carolina , Passari Mauro , Schioppa Tiziana , Sozio Francesca , Del Prete Annalisa , Sozzani Silvano , Bosisio Daniela
Published: May 2022

Background

Tanimilast is a novel and selective inhaled inhibitor of phosphodiesterase-4 in advanced clinical development for chronic obstructive pulmonary disease (COPD). Tanimilast is known to exert prominent anti-inflammatory activity when tested in preclinical experimental models as well as in human clinical studies. Recently, we have demonstrated that it also finely tunes, rather than suppressing, the cytokine network secreted by activated dendritic cells (DCs). This study was designed to characterize the effects of tanimilast on T-cell polarizing properties of DCs and to investigate additional functional and phenotypical features induced by tanimilast.

Methods

DCs at day 6 of culture were stimulated with LPS in the presence or absence of tanimilast or the control drug budesonide. After 24 h, DCs were analyzed for the expression of surface markers of maturation and activation by flow cytometry and cocultured with T cells to investigate cell proliferation and activation/polarization. The regulation of type 2-skewing mediators was investigated by real-time PCR in DCs and compared to results obtained in vivo in a randomized placebo-controlled trial on COPD patients treated with tanimilast.

Results

Our results show that both tanimilast and budesonide reduced the production of the immunostimulatory cytokine IFN-γ by CD4+T cells. However, the two drugs acted at different levels since budesonide mainly blocked T cell proliferation, while tanimilast skewed T cells towards a Th2 phenotype without affecting cell proliferation. In addition, only DCs matured in the presence of tanimilast displayed increased CD86/CD80 ratio and CD141 expression, which correlated with Th2 T cell induction and dead cell uptake respectively. These cells also upregulated cAMP-dependent immunosuppressive molecules such as IDO1, TSP1, VEGF-A and Amphiregulin. Notably, the translational value of these data was confirmed by the finding that these same genes were upregulated also in sputum cells of COPD patients treated with tanimilast as add-on to inhaled glucocorticoids and bronchodilators.

Conclusion

Taken together, these findings demonstrate distinct immunomodulatory properties of tanimilast associated with a type 2 endotype and CD141 upregulation in DCs and provide a mechanistic rationale for the administration of tanimilast on top of inhaled corticosteroids.
Gastric antral vascular ectasia in systemic sclerosis: a study of its epidemiology, disease characteristics and impact on survival
Authors: Morrisroe Kathleen , Hansen Dylan , Stevens Wendy , Sahhar Joanne , Ngian Gene-Siew , Hill Catherine , Roddy Janet , Walker Jennifer , Proudman Susanna , Nikpour Mandana
Published: May 2022

Background

To describe the epidemiology, determinants and survival impact of gastric antral vascular ectasia (GAVE) in systemic sclerosis (SSc).

Methods

Consecutive SSc patients prospectively enrolled in the Australian Scleroderma Cohort Study (ASCS) were included. Univariable and multivariable logistic regression were used to determine the associations of GAVE with clinical manifestations and serological parameters. Kaplan-Meier (K-M) survival curves were used to estimate survival.

Results

The prevalence of GAVE in this SSc cohort of 2039 SSc patients was 10.6% (n = 216) over a median follow-up period of 4.3(1.7–8.4) years. SSc patients with a history of GAVE compared with those without a history of GAVE were older at SSc onset [49.5 (40.0–58.2) vs 46.7 (36.0–56.7) years, p = 0.05]; more likely to have diffuse disease subtype (dcSSc) (35.3% vs 24.1%, p < 0.001); be negative for Scl-70, U1RNP and Scl/PM antibody (4.0% vs 16.1%, p < 0.001, 3.5% vs 7.4%, p = 0.041, 0.0% vs 2.0%, p = 0.042; and respectively) and positive for RNAP III antibody (24.9% vs 8.3%, p < 0.001). Those with GAVE had a worse HRQoL (p = 0.002). Independent determinants of GAVE included the presence of RNAP III antibody (OR 3.46, p < 0.001), absence of Scl-70 antibody (OR 0.23, p = 0.001), presence of GIT dysmotility (OR 1.64, p = 0.004), and digital ulcers; pits; or digital amputation (OR 1.59, p = 0.014).

Conclusions

GAVE is an underestimated and underappreciated SSc manifestation of SSc, which occurs with a relatively high frequency. Identifying an at-risk GAVE phenotype, as presented herein, is of practical importance as screening may prove advantageous given GAVE can be easily diagnosed and treated.
The course of primary progressive aphasia diagnosis: a cross-sectional study
Authors: Mouton A. , Plonka A. , Fabre R. , Tran T. M. , Robert P. , Macoir J. , Manera V. , Gros A.
Published: May 2022

Background

The primary progressive aphasia (PPA) diagnosis trajectory is debated, as several changes in diagnosis occur during PPA course, due to phenotype evolution from isolated language alterations to global cognitive impairment.

The goal of the present study, based on a French cohort, was to describe the demographics and the evolution of subjects with (PPA) in comparison with Alzheimer’s disease (AD) on a period of 7 years.

Methods

We conducted a repeated cross-sectional study. The study population comprised individuals with PPA and AD diagnosis (N=167,191) from 2010 to 2016 in the French National data Bank (BNA). Demographic variables, MMSE scores, diagnosis status at each visit and prescribed treatments were considered.

Results

From 2010 to 2016, 5186 patients were initially diagnosed with PPA, 162,005 with AD. Compared to AD subjects, significant differences were found concerning age (younger at first diagnosis for PPA), gender (more balanced in PPA), education level (higher in PPA) and MMSE score (higher of 1 point in PPA).

Percentage of pending diagnosis, delay between first consultation and first diagnosis and the number of different diagnoses before the diagnosis of interest were significantly higher in PPA group compared to AD group. Pharmacological and non-pharmacological treatments were significatively more recommended following PPA than AD diagnosis.

Conclusion

This study improves the knowledge of PPA epidemiology and has the potential to help adopting appropriate public health service policies. It supports the hypothesis that PPA is diagnosed later than AD. The PPA diagnosis increases the prescription of non-pharmacological treatments, especially speech and language therapy (SLT) that is the main treatment available and most effective when at the initial stage.

Trial registration

ClinicalTrials.gov identifierNCT03687112
Intraocular pressure improvement in patients receiving teprotumumab for the treatment of thyroid eye disease: a case series
Authors: Chu Matthew , Sung Jonathan , Song Michael , Song Alice , Song Julia
Published: May 2022

Background

Teprotumumab is a novel treatment that reduces inflammation and symptoms caused by thyroid eye disease. There are limited data on teprotumumab’s effect on intraocular pressure.

Case presentation

We report nine patients diagnosed with thyroid eye disease whose intraocular pressure decreased during teprotumumab treatment for 8 weeks: patient 1, a 67-year-old Hispanic woman; patient 2, an 86-year-old African-American man; patient 3, a 71-year-old Caucasian woman; patient 4, a 72-year-old Hispanic woman; patient 5, a 65-year-old Caucasian woman; patient 6, a 54-year-old Caucasian man; patient 7, a 54-year-old Asian man; patient 8, a 31-year-old Asian woman; patient 9, a 60-year-old Caucasian woman. The diagnosis of thyroid eye disease was based on increased redness, swelling, and excessive tearing; abnormal proptosis, lid retraction, and diplopia measurements were also taken during physical examination. Intraocular pressure in primary, lateral gaze, and upgaze was documented. There was significant (p = 0.0397) improvement of primary gaze eye pressure from pre-teprotumumab infusions (baseline) to completion of the treatment course.

Conclusions

Teprotumumab significantly decreased the intraocular pressure for patients during the duration of the study. Teprotumumab is a novel medication that is approved for the primary treatment of thyroid eye disease in both acute and chronic thyroid eye disease. Previous treatments used to treat thyroid eye disease include glucocorticoids, radiotherapy, or orbital decompression surgery; however, these treatments all have significant limitations. Teprotumumab is an effective noninvasive alternative for decreasing symptoms of thyroid eye disease and, as shown, also lowers intraocular pressure. However, teprotumumab should not be used as a substitute for glaucoma medications; its ability to lower intraocular pressure may be in addition to lowering periorbital pressure and retro-orbital pressure.