bluuebunny/crossref_metadata_2025 huggingface dataset:
How I treat and prevent venous thrombotic complications in patients with lymphoma
Authors: Schmidt Robert A. , Lee Agnes Y. Y.
Published: September 2021

Venous thromboembolism (VTE) is a common complication occurring in 5% to 10% of patients with lymphoma. As the complexity of lymphoma management has increased with novel therapies, so too has the treatment of VTE. Therapeutic options for the treatment of cancer-associated VTE have expanded from only warfarin and low-molecular-weight heparins (LMWHs) to include the direct oral anticoagulants (DOACs) apixaban, edoxaban and rivaroxaban. There have been no head-to-head trials comparing different DOACs in this setting, and randomized trials comparing a DOAC with LMWH dalteparin differ in trial design and results. Drug–drug interactions, drug-specific side effects, and patient selection are important considerations when prescribing anticoagulant therapy. In all patients, the relative risks of thrombosis and bleeding, the availability of the anticoagulant, and the life expectancy of the patient are vital elements in selecting the most appropriate anticoagulant (which can vary over time) for the individual patient. We describe the intricacies and challenges of treating thrombotic complications in patients with lymphoma with an emphasis on evidence and guideline-based care.
KSHV/HHV8-mediated hematologic diseases
Authors: Cesarman Ethel , Chadburn Amy , Rubinstein Paul G.
Published: September 2021

Kaposi sarcoma (KS) herpesvirus (KSHV), also known as human herpesvirus 8, is the causal agent of KS but is also pathogenetically related to several lymphoproliferative disorders, including primary effusion lymphoma (PEL)/extracavitary (EC) PEL, KSHV-associated multicentric Castleman disease (MCD), KSHV+ diffuse large B-cell lymphoma, and germinotropic lymphoproliferative disorder. These different KSHV-associated diseases may co-occur and may have overlapping features. KSHV, similar to Epstein-Barr virus (EBV), is a lymphotropic gammaherpesvirus that is preferentially present in abnormal lymphoid proliferations occurring in immunecompromised individuals. Notably, both KSHV and EBV can infect and transform the same B cell, which is frequently seen in KSHV+ EBV+ PEL/EC-PEL. The mechanisms by which KSHV leads to lymphoproliferative disorders is thought to be related to the expression of a few transforming viral genes that can affect cellular proliferation and survival. There are critical differences between KSHV-MCD and PEL/EC-PEL, the 2 most common KSHV-associated lymphoid proliferations, including viral associations, patterns of viral gene expression, and cellular differentiation stage reflected by the phenotype and genotype of the infected abnormal B cells. Advances in treatment have improved outcomes, but mortality rates remain high. Our deepening understanding of KSHV biology, clinical features of KSHV-associated diseases, and newer clinical interventions should lead to improved and increasingly targeted therapeutic interventions.
An update on pediatric ITP: differentiating primary ITP, IPD, and PID
Authors: Grace Rachael F. , Lambert Michele P.
Published: September 2021

Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by immune-mediated decreased platelet production and increased platelet destruction. In the absence of a diagnostic test, ITP must be differentiated from other thrombocytopenic disorders, including inherited platelet disorders. In addition, a diagnosis of secondary ITP due to a primary immune deficiency with immune dysregulation may not be apparent at diagnosis but can alter management and should be considered in an expanding number of clinical scenarios. The diagnostic evaluation of children with thrombocytopenia will vary based on the clinical history and laboratory features. Access to genotyping has broadened the ability to specify the etiology of thrombocytopenia, whereas increasing access to immunophenotyping, functional immunologic and platelet assays, and biochemical markers has allowed for more in-depth evaluation of patients. With this greater availability of testing, diagnostic algorithms in patients with thrombocytopenia have become complex. In this article, we highlight the diagnostic evaluation of thrombocytopenia in children with a focus on ITP, including consideration of underlying genetic and immune disorders, and use hypothetical patient cases to describe disease manifestations and strategies for treatment of pediatric ITP.
Epidemiological landscape of young patients with multiple myeloma diagnosed before 40 years of age: the French experience
Authors: Caulier Alexis , Roussel Murielle , Morel Pierre , Lombion Naelle , Branco Benoît , Galtier Jean , Hulin Cyrille , Perrot Aurore , Richez Valentine , Michaud Anne-Victoire , Touzeau Cyrille , Doyen Chantal , Mariette Clara , Caillot Denis , Harel Stéphanie , Lenain Pascal , Ivanoff Sarah , Fontan Jean , Stoppa Anne-Marie , Manier Salomon , Garderet Laurent , Leleu Xavier , Marolleau Jean-Pierre , Arnulf Bertrand , Avet-Loiseau Hervé , Royer Bruno
Published: September 2021

Multiple myeloma (MM) is rare in young patients, especially before age 40 years at diagnosis, representing <2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study, we examined 214 patients diagnosed with MM at age ≤40 years over 15 years, in the era of modern treatments. Among them, 189 patients had symptomatic MM. Disease characteristics were similar to older patients: 35% had anemia, 17% had renal impairment, and 13% had hypercalcemia. The staging was ISS-1 in 52.4%, ISS-2 in 27.5%, and ISS-3 in 20.1%. Overall, 18% of patients had high-risk cytogenetics [del 17p and/or t(4;14)]. Ninety percent of patients received intensive chemotherapy followed by autologous stem cell transplant, and 25% of patients had allogeneic stem cell transplant predominantly at time of relapse. The median follow-up was 76 months, the estimated median overall survival was 14.5 years, and the median progression free-survival was 41 months. In multivariate analysis, bone lesions (hazard ratio [HR], 3.95; P = .01), high ISS score (HR, 2.14; P = .03), and high-risk cytogenetics (HR, 4.54; P < .0001) were significant risk factors for poor outcomes. Among predefined time-dependent covariables, onset of progression (HR, 13.2; P < .0001) significantly shortened overall survival. At 5 years, relative survival compared with same age- and sex-matched individuals was 83.5%, and estimated standardized mortality ratio was 69.9 (95% confidence interval, 52.7-91.1), confirming that MM dramatically shortens the survival of young patients despite an extended survival after diagnosis.
The antioxidant N-acetylcysteine promotes immune response and inhibits epithelial-mesenchymal transition to alleviate pulmonary fibrosis in chronic obstructive pulmonary disease by suppressing the VWF/p38 MAPK axis
Authors: Zhu Lanlan , Xu Fei , Kang Xiuhua , Zhou Jing , Yao Qinqin , Lin Yang , Zhang Wei
Published: September 2021

Background/aim

N-Acetylcysteine (NAC) demonstrates applications in the prevention of exacerbation of chronic obstructive pulmonary disease (COPD). COPD is often characterized by fibrosis of the small airways. This study aims at investigating the physiological mechanisms by which NAC might mediate the pulmonary fibrosis in COPD.

Methods

A total of 10 non-smokers without COPD and 10 smokers with COPD were recruited in this study, and COPD rat models were established. Cigarette smoke extract (CSE) cell models were constructed. The gain- or loss-of-function experiments were adopted to determine the expression of VWF and the extent of p38 MAPK phosphorylation, levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and immunoglobulins (IgG, IgM and IgA) in the serum of COPD rats and supernatant of alveolar epithelial cells and to detect cell invasion and migration and the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes.

Results

Expression of VWF and the extent of p38 MAPK phosphorylation were increased in COPD. NAC inhibited p38 MAPK phosphorylation by reducing the VWF expression. NAC could inhibit cell migration and invasion, elevate E-cadherin expression, the ratio of CD3+, CD4+, CD8+ and CD4+/CD8+T lymphocytes, and levels of IgG, IgA, and IgM, and reduce N-cadherin expression and levels of IL-6 and TNF-α in CSE cells and serum of COPD rats. NAC promoted immune response and suppressed epithelial-mesenchymal transformation (EMT) to relieve COPD-induced pulmonary fibrosis in vitro and in vivo by inhibiting the VWF/p38 MAPK axis.

Conclusions

Collectively, NAC could ameliorate COPD-induced pulmonary fibrosis by promoting immune response and inhibiting EMT process via the VWF/p38 MAPK axis, therefore providing us with a potential therapeutic target for treating COPD.
Environment Responsive Metal–Organic Frameworks as Drug Delivery System for Tumor Therapy
Authors: Yan Chao , Jin Yue , Zhao Chuanxiang
Published: September 2021

Nanoparticles as drug delivery systems can alter the drugs' hydrophilicity to affect drug uptake and efflux in tissues. They prevent drugs from non-specifically binding with bio-macromolecules and enhance drug accumulation at the lesion sites, improving therapy effects and reducing unnecessary side effects. Metal–organic frameworks (MOFs), the typical nanoparticles, a class of crystalline porous materials via self-assembled organic linkers and metal ions, exhibit excellent biodegradability, pore shape and sizes, and finely tunable chemical composition. MOFs have a rigid molecular structure, and tunable pore size can improve the encapsulation drug's stability under harsh conditions. Besides, the surface of MOFs can be modified with small-molecule ligands and biomolecule, and binding with the biomarkers which is overexpressed on the surface of cancer cells. MOFs formulations for therapeutic have been developed to effectively respond to the unique tumor microenvironment (TEM), such as high H2O2 levels, hypoxia, and high concentration glutathione (GSH). Thus, MOFs as a drug delivery system should avoid drugs leaking during blood circulation and releasing at the lesion sites via a controlling manner. In this article, we will summary environment responsive MOFs as drug delivery systems for tumor therapy under different stimuli.
DTI-HeNE: a novel method for drug-target interaction prediction based on heterogeneous network embedding
Authors: Yue Yang , He Shan
Published: September 2021

Background

Prediction of the drug-target interaction (DTI) is a critical step in the drug repurposing process, which can effectively reduce the following workload for experimental verification of potential drugs’ properties. In recent studies, many machine-learning-based methods have been proposed to discover unknown interactions between drugs and protein targets. A recent trend is to use graph-based machine learning, e.g., graph embedding to extract features from drug-target networks and then predict new drug-target interactions. However, most of the graph embedding methods are not specifically designed for DTI predictions; thus, it is difficult for these methods to fully utilize the heterogeneous information of drugs and targets (e.g., the respective vertex features of drugs and targets and path-based interactive features between drugs and targets).

Results

We propose a DTI prediction method DTI-HeNE (DTI based on Heterogeneous Network Embedding), which is specifically designed to cope with the bipartite DTI relations for generating high-quality embeddings of drug-target pairs. This method splits a heterogeneous DTI network into a bipartite DTI network, multiple drug homogeneous networks and target homogeneous networks, and extracts features from these sub-networks separately to better utilize the characteristics of bipartite DTI relations as well as the auxiliary similarity information related to drugs and targets. The features extracted from each sub-network are integrated using pathway information between these sub-networks to acquire new features, i.e., embedding vectors of drug-target pairs. Finally, these features are fed into a random forest (RF) model to predict novel DTIs.

Conclusions

Our experimental results show that, the proposed DTI network embedding method can learn higher-quality features of heterogeneous drug-target interaction networks for novel DTIs discovery.
Investigating the effect of an identified mutation within a critical site of PAS domain of WalK protein in a vancomycin-intermediate resistant Staphylococcus aureus by computational approaches
Authors: Baseri Neda , Najar-Peerayeh Shahin , Bakhshi Bita
Published: September 2021

Background

Vancomycin-intermediate resistant Staphylococcus aureus (VISA) is becoming a common cause of nosocomial infections worldwide. VISA isolates are developed by unclear molecular mechanisms via mutations in several genes, including walKR. Although studies have verified some of these mutations, there are a few studies that pay attention to the importance of molecular modelling of mutations.

Method

For genomic and transcriptomic comparisons in a laboratory-derived VISA strain and its parental strain, Sanger sequencing and reverse transcriptase quantitative PCR (RT-qPCR) methods were used, respectively. After structural protein mapping of the detected mutation, mutation effects were analyzed using molecular computational approaches and crystal structures of related proteins.

Results

A mutation WalK-H364R was occurred in a functional zinc ion coordinating residue within the PAS domain in the VISA strain. WalK-H364R was predicted to destabilize protein and decrease WalK interactions with proteins and nucleic acids. The RT-qPCR method showed downregulation of walKR, WalKR-regulated autolysins, and agr locus.

Conclusion

Overall, WalK-H364R mutation within a critical metal-coordinating site was presumably related to the VISA development. We assume that the WalK-H364R mutation resulted in deleterious effects on protein, which was verified by walKR gene expression changes.. Therefore, molecular modelling provides detailed insight into the molecular mechanism of VISA development, in particular, where allelic replacement experiments are not readily available.
Perioperative risk factors for new-onset postoperative atrial fibrillation after coronary artery bypass grafting: a systematic review
Authors: Seo Eun Ji , Hong Joonhwa , Lee Hyeon-Ju , Son Youn-Jung
Published: September 2021

Background

Postoperative atrial fibrillation (POAF) is the most common cardiac dysrhythmia to occur after coronary artery bypass grafting (CABG). However, the risk factors for new-onset POAF after CABG during the perioperative period have yet to be clearly defined. Accordingly, the aim of our systematic review was to evaluate the perioperative predictors of new-onset POAF after isolated CABG.

Method

Our review methods adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. We searched seven electronic databases (PubMed, Embase, CINAHL, PsycArticles, Cochrane, Web of Science, and SCOPUS) to identify all relevant English articles published up to January 2020. Identified studies were screened independently by two researchers for selection, according to predefined criteria. The Newcastle–Ottawa Scale was used to evaluate the quality of studies retained.

Results

After screening, nine studies were retained for analysis, including 4798 patients, of whom 1555 (32.4%) experienced new-onset POAF after CABG. The incidence rate of new-onset POAF ranged between 17.3% and 47.4%. The following risk factors were identified: old age (p < 0.001), a high preoperative serum creatinine level (p = 0.001), a low preoperative hemoglobin level (p = 0.007), a low left ventricle ejection fraction in Asian patients (p = 0.001), essential hypertension (p < 0.001), chronic obstructive pulmonary disease (p = 0.010), renal failure (p = 0.009), cardiopulmonary bypass use (p = 0.002), perfusion time (p = 0.017), postoperative use of inotropes (p < 0.001), postoperative renal failure (p = 0.001), and re-operation (p = 0.005). All studies included in the analysis were of good quality.

Conclusions

The risk factors identified in our review could be used to improve monitoring of at-risk patients for early detection and treatment of new-onset POAF after CABG, reducing the risk of other complications and negative clinical outcomes.
Tri-modal management of primary small cell carcinoma of the pancreas (SCCP): a rare neuroendocrine carcinoma (NEC)
Authors: Elzein Safa , Bao Fei , Lin Ray , Schnickel Gabriel , Lowy Andrew M. , Botta Gregory P.
Published: September 2021

Background

Primary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor.

Case presentation

Here we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery

Conclusions

Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.
Study protocol of the PIMPI-project, a cohort study on acceptance, tolerability and immunogenicity of second trimester maternal pertussis immunization in relation to term and preterm infants
Authors: Immink Maarten M. , Bekker Mireille N. , de Melker Hester E. , Rots Nynke Y. , Sanders Elisabeth A. M. , van der Maas Nicoline A. T.
Published: September 2021

Background

Maternal immunization confers passive immunity to the fetus by transplacental antibody transfer. Infants may be better protected against pertussis if the mother received a diphtheriae, tetanus and acellular pertussis (Tdap) vaccination in the second trimester of pregnancy compared to the third trimester. This study evaluates IgG antibody concentrations in term and preterm infants at birth and 2 months after birth after maternal Tdap-vaccination between 200 and 240 w of gestation vs third trimester Tdap-vaccination. Further aims are assessing the determinants that underlie acceptance of second trimester maternal Tdap-vaccination as well as the tolerability of vaccination.

Methods

This prospective cohort study consists of two parts. In the acceptance part, pregnant women complete a questionnaire on determinants that underlie acceptance of a second trimester Tdap-vaccination, which is offered subsequently between 200 and 240 w of gestation. Vaccinated women complete an additional questionnaire on vaccination tolerability. Vaccinated women may also participate in the immunogenicity part, in which blood is drawn from mother at delivery and from infant at birth and 2 months after birth. Women are also eligible for the immunogenicity part if they received a Tdap-vaccination between 200 and 240 w of gestation via the national immunization program and get hospitalized for an imminent preterm delivery. Blood sampling continues until 60 term and 60 preterm mother-infant-pairs have been included. Pertussis-specific IgG antibody concentrations are determined in serum using a fluorescent bead-based multiplex immunoassay. For term infants, non-inferiority in IgG antibody concentrations against pertussis toxin (anti-PT) will be assessed referred to a historical control group in which mothers were Tdap-vaccinated between 300 and 320 w of gestation. For preterm infants, non-inferiority of anti-PT IgG concentrations is referred to as 85% of infants having ≥ 20 international units/mL at 2 months after birth.

Discussion

This study investigates acceptance, tolerability and immunogenicity regarding maternal Tdap-immunization between 200 and 240 w of gestation. Its results provide insight into the effects of second trimester Tdap-vaccination on IgG antibody concentrations in term and preterm infants before primary infant vaccinations. Results on acceptance and tolerability guide antenatal care providers in communication with pregnant women and maintain the safety of second trimester Tdap-vaccination.

Trial registration: EU Clinical Trials Register, 2018-002976-41, retrospectively registered 24 July 2019, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-002976-41.
COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis
Authors: Ihlow Jana , Seelhoff Alexander , Corman Victor M. , Gruber Achim D. , Dökel Simon , Meinhardt Jenny , Radbruch Helena , Späth-Schwalbe Ernst , Elezkurtaj Sefer , Horst David , Herbst Hermann
Published: September 2021

Background

The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism.

Case presentation

Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2).

Conclusion

Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.
Outcome evaluation of COVID-19 infected patients by disease symptoms: a cross-sectional study in Ilam Province, Iran
Authors: Sadeghifar Jamil , Jalilian Habib , Momeni Khalil , Delam Hamed , Sheleme Tadesse , Rashidi Ayoub , Hemmati Fariba , Falahi Shahab , Arab-Zozani Morteza
Published: September 2021

Background

Novel coronavirus disease-19 (COVID-19) was declared as a global pandemic in 2020. With the spread of the disease, a better understanding of patient outcomes associated with their symptoms in diverse geographic levels is vital. This study aimed to evaluate clinical outcomes of COVID-19 patients by disease symptoms in Ilam province, Iran.

Methods

This was a cross-sectional study. Data were collected from integrated health system records for all hospitals affiliated with the Ilam University of Medical Sciences between 26-Jan-2020 and 02-May-2020. All patients with a confirmed positive test were included in this study. Descriptive analyses, chi-square test, and binary logistic regression model were performed by using SPSS version 22.

Results

The mean age of participants was 46.47 ± 18.24 years. Of the 3608 patients, 3477 (96.1%) were discharged, and 129 (3.9%) died. 54.2% of the patients were male and were in the age group of 30–40 years. Cough, sore throat, shortness of breath or difficulty breathing, and fever or chills were the most common symptoms. Patients with symptoms of shortness of breath, abnormal radiographic findings of the chest, and chest pain and pressure were relatively more likely to die. According to binary logistic regression results, the probability of death in patients with shortness of breath, abnormal chest radiographic findings, and chest pain was 1.34, 1.24, and 1.32 times higher, respectively, than for those without.

Conclusion

Our study provides evidence that the presentation of some symptoms significantly impacts outcomes of patients infected with SARS-CoV-2. Early detection of symptoms and proper management of outcomes can reduce mortality in patients with COVID-19.
The correlation between serum selenium, zinc, and COVID-19 severity: an observational study
Authors: Razeghi Jahromi Soodeh , Moradi Tabriz Hedieh , Togha Mansoureh , Ariyanfar Shadi , Ghorbani Zeinab , Naeeni Sima , Haghighi Samaneh , Jazayeri Aboozar , Montazeri Mahnaz , Talebpour Mohammad , Ashraf Haleh , Ebrahimi Mehdi , Hekmatdoost Azita , Jafari Elham
Published: September 2021

Background

Without an adequate immune response, SARS-CoV2 virus can simply spread throughout the body of the host. Two of the well-known immunonutrients are selenium (Se) and zinc (Zn). Se and Zn deficiency might lead to inflammation, oxidative stress, and viral entry into the cells by decreasing ACE-2 expression; three factors that are proposed to be involved in COVID-19 pathogenesis. Thus, in the current study we aimed at evaluating the correlation between serum Se and Zn status and COVID-19 severity.

Methods

Eighty-four COVID-19 patients were enrolled in this observational study. Patients were diagnosed based on an infectious disease specialist diagnosis, using WHO interim guidance and the recommendations of the Iranian National Committee of Covid-19. The patients with acute respiratory tract infection symptoms were checked for compatibility of chest computed tomography (CT) scan results with that of Covid-19 and Real-time polymerase chain reaction (RT-PCR) for corona virus infection. The severity of Covid-19 was categorized into three groups (mild, moderate, and severe) using CDC criteria. Serum Zn and Se level of all subjects was measured. The severity of the disease was determined only once at the onset of disease.

Results

According to the results of linear regression test, there was a significant association between Zn and Se level and COVID-19 severity (β = − 0.28, P-value = 0.01 for Se; β = − 0.26, P-value = 0.02). However the significance disappeared after adjusting for confounding factors. Spearman correlation analysis showed a significant negative association between serum Zn, Se and CRP level (r = − 0.35, P-value = 0.001 for Se; r = − 0.41, P-value < 0.001 for Zn).

Conclusion

Results suggest that increasing levels of Se and Zn were accompanied by a decrease in serum CRP level. However, the significant association between Se, Zn, and disease severity was lost after adjusting for confounding factors.
Case report: Osteomalacia due to bisphosphonate treatment in a patient on hemodialysis
Authors: Hatano Masaki , Kitajima Izuru , Yamamoto Seizo , Nakamura Masaki , Isawa Kazuya , Hirota Yutaka , Hoshino Junichi , Sawa Naoki , Ubara Yoshifumi
Published: September 2021

Background

No publications have reported on osteomalacia in patients receiving intermittent cyclical therapy with etidronate (a bisphosphonate) and undergoing long-term hemodialysis (HD).

Case presentation

We report on a 46-year-old Japanese man admitted to our hospital for further examination of left forearm pain. Maintenance HD was started at age 24 years, and the man had been on HD since then. At age 38 years, surgical parathyroidectomy was performed for secondary hyperparathyroidism; iliac crest bone biopsy performed at the same time showed osteitis fibrosa. The active vitamin D3 preparation calcitriol was started, and intermittent cyclical etidronate therapy was introduced 2 years later for osteoporosis. At age 45 years, the patient stopped taking calcitriol because of hypercalcemia but continued with etidronate. At age 46 years, a pseudofracture with a Looser zone occurred in the left ulna, and left femur bone biopsy revealed osteomalacia. Etidronate was discontinued, and calcitriol was restarted; open reduction and internal fixation with an angular stability plate were performed. Union of the bone was achieved 10 months after the operation. At age 49 years, a lumber bone biopsy confirmed improved bone morphometry.

Conclusions

We believe that intermittent cyclical etidronate therapy without administration of active vitamin D3 during long-term HD might have induced osteomalacia, resulting in the ulna insufficiency fracture. Therefore, we propose that administration of active vitamin D3 is essential to prevent osteomalacia in patients on long-term HD who are receiving bisphosphonates and have potential vitamin D3 deficiency.
Impairment of the visuospatial working memory in the patients with Parkinson’s Disease: an fMRI study
Authors: Kawashima Shoji , Shimizu Yoko , Ueki Yoshino , Matsukawa Noriyuki
Published: September 2021

Background

Mild cognitive impairment (MCI) is a common symptom in the patients with Parkinson’s disease (PD). The characteristics of cognitive impairment in PD are executive function (including working memory) and visuo-perceptual processing. The visuospatial n-back test has the merit of minimizing the influence of educational biases involved in the verbal n-back test. Furthermore, it can assess both visuospatial recognition and working memory in a single test.

Methods

We aimed to clarify the advantage of the visuospatial n-back test as a tool for detecting impairments of working memory in PD. We enrolled 28 right-handed patients with PD (18 males, 10 females) and 12 age-matched healthy controls (HC; 7 males, 5 females). Thirteen patients were classified as MCI (PD-MCI), and 15 as cognitively normal PD (PD-CN). Using functional MRI (fMRI), we explored the specific brain regions associated with the performance of the n-back test in the PD-MCI, PD-CN, and HC groups. The 0-back test assesses visuospatial recognition, while the 1-back and 2-back tests assess visuospatial working memory. Group comparisons were performed for three loads of this test.

Results

Patients with PD performed significantly worse in terms of the correct answer rates of all n-back tests compared with HC. fMRI analyses performed during the 2-back test revealed reduced activation in the bilateral dorsolateral prefrontal cortex, middle frontal gyrus (MFG), and parietal lobule in the PD group compared with the HC group. In contrast, the fMRI result during the 0-back test showed only a marginal difference in the frontal lobe. On comparisons of task performance between the PD-MCI and PD-CN groups, we found that the correct answer rate in the 2-back test was lower in the PD-MCI group than in the PD-CN group. However, scores of the 0-back and 1-back tests were not significantly different between the two groups. The fMRI findings revealed that activations within the middle frontal gyrus (MFG) and inferior parietal lobule (IPL) during the 2-back test were reduced in the patients with PD-MCI when compared to those with PD-CN.

Conclusions

This study reports reduced activation of the MFG and IPL in patients with PD-MCI. These regions may be associated with the pathophysiology of working memory impairment in patients with PD, which involves fronto-striatal network dysfunction.
Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study
Authors: Moran-Lev Hadar , Cohen Shlomi , Webb Muriel , Yerushalmy-Feler Anat , Amir Achiya , Gal Dana L. , Lubetzky Ronit
Published: September 2021

Background

Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD.

Methods

Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months.

Results

Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001).

Conclusion

Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population.

Trial registration

TRN NCT04561804 (9/17/2020)
Factors associated with bone health status of Malaysian pre-adolescent children in the PREBONE-Kids Study
Authors: Chang Chung Yuan , Arasu Kanimolli , Wong Soon Yee , Ong Shu Hwa , Yang Wai Yew , Chong Megan Hueh Zan , Mavinkurve Meenal , Khoo Erwin Jiayuan , Chinna Karuthan , Weaver Connie Marie , Chee Winnie Siew Swee
Published: September 2021

Background

Modifiable lifestyle factors and body composition can affect the attainment of peak bone mass during childhood. This study performed a cross-sectional analysis of the determinants of bone health among pre-adolescent (N = 243) Malaysian children with habitually low calcium intakes and vitamin D status in Kuala Lumpur (PREBONE-Kids Study).

Methods

Body composition, bone mineral density (BMD), and bone mineral content (BMC) at the lumbar spine (LS) and total body (TB) were assessed using dual-energy X-ray absorptiometry (DXA). Calcium intake was assessed using 1-week diet history, MET (metabolic equivalent of task) score using cPAQ physical activity questionnaire, and serum 25(OH) vitamin D using LC-MS/MS.

Results

The mean calcium intake was 349 ± 180 mg/day and mean serum 25(OH)D level was 43.9 ± 14.5 nmol/L. In boys, lean mass (LM) was a significant predictor of LSBMC (β = 0.539, p < 0.001), LSBMD (β = 0.607, p < 0.001), TBBMC (β = 0.675, p < 0.001) and TBBMD (β = 0.481, p < 0.01). Height was a significant predictor of LSBMC (β = 0.346, p < 0.001) and TBBMC (β = 0.282, p < 0.001) while fat mass (FM) (β = 0.261, p = 0.034) and physical activity measured as MET scores (β = 0.163, p = 0.026) were significant predictors of TBBMD in boys. Among girls, LM was also a significant predictor of LSBMC (β = 0.620, p < 0.001), LSBMD (β = 0.700, p < 0.001), TBBMC (β = 0.542, p < 0.001) and TBBMD (β = 0.747, p < 0.001). Calcium intake was a significant predictor of LSBMC (β = 0.102, p = 0.034), TBBMC (β = 0.122, p < 0.001) and TBBMD (β = 0.196, p = 0.002) in girls.

Conclusions

LM was the major determinant of BMC and BMD among pre-adolescent Malaysian children alongside other modifiable lifestyle factors such as physical activity and calcium intake.
Characteristics and surgical outcomes of cleft palate in kabuki syndrome: a case series of 11 patients
Authors: Kim Jong-Ho , Kang Jiwon , Oh Joon Seok , Ahn Taeseon , Kim Baek-kyu , Baek Rong-Min
Published: September 2021

Objective

A significant number of patients with KS have cleft palate (CP) or submucous cleft palate (SMCP) and show delayed speech development. However, few reports have discussed the characteristics of CP in KS and the outcomes of postoperative speech development. The purpose of this study was to investigate the characteristics and surgical outcomes of CP in patients with KS, and to discuss the importance of the diagnosis of CP or SMCP.

Methods

We conducted a retrospective study on patients with clinically diagnosed KS who underwent palatoplasty. Clinical and surgical data were collected from patients’ medical records, and velopharyngeal function was evaluated using nasopharyngoscopy and speech analysis.

Results

In 11 cases, 5 patients had CP (45.5%) and 6 had SMCP (54.5%). Four patients who were genetically tested had a pathogenic variant of KMT2D. Seven of nine patients (77.8%) who underwent conventional palatoplasty showed velopharyngeal insufficiency and hypernasality. All patients who underwent pharyngeal flap surgery achieved velopharyngeal competency. Statistical analysis revealed a statistically significant difference in postoperative results between non-syndromic and KS patients.

Conclusion

Patients with SMCP may be more common than previously reported. The results showed that it is difficult to produce optimal results with conventional palatoplasty; therefore, pharyngeal flap surgery should be considered as a treatment to obtain favorable results. Pharyngeal flap surgery in patients with KS should be carefully designed based on speech evaluation and nasopharyngoscopic findings.
Vitamin D, pregnancy and caries in children in the INMA-Asturias birth cohort
Authors: Suárez-Calleja Claudia , Aza-Morera Jaime , Iglesias-Cabo Tania , Tardón Adonina
Published: September 2021

Background

Vitamin D is traditionally associated with the metabolism of calcium and phosphorus, a process essential for the mineralization of hard tissue such as bone or tooth. Deficiency of this vitamin is a problem worldwide, however. Given the possibly significant role of Vitamin D in odontogenesis in children, the objective of our study was to determine the influence of vitamin D levels in the blood on dental anomalies in children between 6 and 10 years of age, by means of 25-hydroxy vitamin D tests performed during pregnancy and the first years of life.

Methods

The data analyzed were sourced from data belonging to the INMA-Asturias birth cohort, a prospective cohort study initiated in 2004 as part of the INMA Project. The 25-hydroxy vitamin D (25(OH)D) test was performed with samples from 188 children in the INMA-Asturias birth cohort with a dental examination performed between 6 and 10 years of age. The samples were taken at three stages: in the mother at 12 weeks of gestation, and subsequently in the child at 4 and 8 years of age. Diet, nutritional and oro-dental hygiene habits were also analyzed by means of questionnaires.

Results

The results indicate a significant association between caries and correct or incorrect brushing technique. With incorrect brushing technique, the prevalence of caries was 48.89%, but this dropped to 22.38% with correct brushing technique. An association was also found between tooth decay and frequency of sugar intake. The prevalence of caries was 24.54% with occasional sugar intake, but this rose to 56% with regular sugar intake. On the other hand, levels < 20 ng/ml in both mother and child at 8 years of age would also be risk factors (ORgest = 2.51(1.01–6.36) and OR8years = 3.45(1.14–11.01)) for the presence of caries in children. The risk of caries practically tripled where 25(OH) D values were < 20 ng/ml.

Conclusions

Although incorrect brushing technique and regular sugar consumption was found to be the main cause of caries in the children, the low concentrations of vitamin D in the blood of the pregnant mothers may have magnified this correlation, indicating that the monitoring of vitamin D levels during pregnancy should be included in antenatal programmes. It is particularly striking that 50% of the children were deficient in vitamin D at the age of 4, and that dental floss was practically absent from regular cleaning routines.
Reliability of visual assessment of neonatal jaundice among neonates of black descent: a cross-sectional study from Tanzania
Authors: Dionis Ikunda , Chillo Omary , Bwire George M. , Ulomi Calvin , Kilonzi Manase , Balandya Emmanuel
Published: September 2021

Background

Jaundice is common among neonates and if untreated can lead to kernicterus. Diagnosing neonatal jaundice (NJ) using Kramer’s method (visual assessment) is considered user-friendly in resource-limited areas. However, there are conflicting findings on reliability of the Kramer’s method in the diagnosis of NJ, particularly of black descent. Therefore, study aimed to determine the accuracy of Kramer’s method in comparison to the total serum bilirubin (TSB) test in the diagnosis of NJ among neonates of black descent in Tanzania.

Methods

A cross-sectional study was conducted between June and July 2020 at Muhimbili National Hospital (MNH) in Dar es Salaam Tanzania. A total of 315 neonates were recruited consecutively. In each neonate, jaundice was assessed using Kramer’s method and TSB test. NJ A total of 315 neonates were recruited i. A 2 X 2 table was created for the determination of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (+LR/−LR), and diagnostic accuracy (effectiveness) of Kramer’s method. Cohen kappa (κ) was used to analyze the agreement between Kramer’s method and TSB. Association between independent variables and presence of jaundice were assessed using the chi-square test and the p < 0.05 was considered to be statistically significant.

Results

The prevalence of NJ was 49.8% by Kramer’s method and 63.5% by TSB. The Sensitivity, Specificity, PPV, and NPV of Kramer’s method were 70.5, 86.1, 89.8, and 62.6%, respectively. The +LR and –LR were 5.07 and 0.34, respectively. The diagnostic accuracy of Kramer’s method was 76.1%. There was a moderate agreement between Kramer’s method and TSB results (κ = 0.524, P<0.001). No significant relationship was observed between the independent variables and the presence of NJ.

Conclusion

Kramer has a good positive predictive value. However, due to low sensitivity and NPV one cannot say that overall predictive ability is good. Also, clinical assessment by Kramer’s method should not be used for screening of NJ. Further studies are needed to investigate the utility of other non-invasive techniques in detecting NJ among neonates of black descent.
Association between intimate partner violence during pregnancy and risk of preterm birth
Authors: Yaya Sanni , Odusina Emmanuel Kolawole , Adjei Nicholas Kofi , Uthman Olalekan A.
Published: September 2021

Background

Preterm birth is a risk factor for child survival in both the short and long term. In Zimbabwe, the prevalence of preterm birth is rising, and there are growing concerns about the adverse consequences. This study explored the association between intimate partner violence (IPV) during pregnancy and preterm birth in Zimbabwe.

Methods

Using data from the 2015 Zimbabwe Demographic and Health Survey, we applied propensity score matching to estimate the effect of IPV during pregnancy on preterm birth among women of reproductive age (15–49 years). A total of 4833 pregnant women who gave birth during the five years preceding the survey were analysed.

Results

We successfully matched 79 women who were exposed to IPV during pregnancy to 372 unexposed during pregnancy. Using the matched sample, the probability of preterm delivery was significantly higher among women who were exposed to IPV during pregnancy than those who were not exposed. The findings showed that 7 out of 79 (8.9%) of women exposed to IPV during pregnancy experienced preterm delivery, and 11 out of 372 (3.0%) of those who were not exposed to IPV during pregnancy experienced preterm delivery. In the urban areas, those exposed to IPV during pregnancy were almost five times more likely to experience preterm delivery (OR = 4.8, 95% CI 2.0–11.6), but the association was not significantly different among women in rural areas.

Conclusion

The findings showed that women exposed to IPV during pregnancy were at increased risk of preterm birth. Some of the risk factors associated with IPV were urban residence, low economic status and unemployment. Effective policies and programmes are required to address the issue of IPV in Zimbabwe.
Association between neighborhood social cohesion, awareness of chronic diseases, and participation in healthy behaviors in a community cohort
Authors: Rosenblatt Andrew M. , Crews Deidra C. , Powe Neil R. , Zonderman Alan B. , Evans Michele K. , Tuot Delphine S.
Published: September 2021

Background

Neighborhood social cohesion (NSC) is the network of relationships as well as the shared values and norms of residents in a neighborhood. Higher NSC has been associated with improved cardiovascular health, largely among Whites but not African Americans. In a bi-racial cohort, we aimed to study the association between NSC and chronic disease awareness and engagement in healthy self-management behaviors, two potential mechanisms by which NSC could impact cardiovascular health outcomes.

Methods

Using the Healthy Aging in Neighborhoods of Diversity Across the Lifespan Study (HANDLS), we cross-sectionally examined the association between NSC and awareness of three chronic conditions (diabetes, chronic kidney disease (CKD), and hypertension) and engagement in healthy self-management behaviors including physical activity, healthy eating, and cigarette avoidance.

Results

Study participants (n = 2082) had a mean age of 56.5 years; 38.7% were White and 61.4% African American. Of the participants, 26% had diabetes, 70% had hypertension and 20.2% had CKD. Mean NSC was 3.3 (SD = 0.80) on a scale of 1 (lowest score) to 5 (highest score). There was no significant association between NSC and any chronic disease awareness, overall or by race. However, each higher point in mean NSC score was associated with less cigarette use and healthier eating scores, among Whites (adjusted odds ratio [aOR], 95% confidence interval [CI]: =0.76, 0.61–0.94; beta coefficient [βc]:, 95% CI: 1.75; 0.55–2.97, respectively) but not African Americans (aOR = 0.95, 0.79–1.13; βc: 0.46, − 0.48–1.39, respectively; Pinteraction = 0.08 and 0.06). Among both Whites and African Americans, higher NSC scores were associated with increases in self-reported physical activity (βc: 0.12; 0.08–0.16; Pinteraction = 0.40).

Conclusions

Community engagement and neighborhood social cohesion may be important targets for promotion of healthy behaviors and cardiovascular disease prevention. More research is needed to understand the different associations of NSC and healthy behaviors by race.
Is adolescent multiple risk behaviour associated with reduced socioeconomic status in young adulthood and do those with low socioeconomic backgrounds experience greater negative impact? Findings from two UK birth cohort studies
Authors: Tinner Laura , Wright Caroline , Heron Jon , Caldwell Deborah , Campbell Rona , Hickman Matthew
Published: September 2021

Background

Adolescent multiple risk behaviour (MRB) is associated with negative outcomes such as police arrests, unemployment and premature mortality and morbidity. What is unknown is whether MRB is associated with socioeconomic status (SES) in adulthood. We test whether adolescent MRB is associated with socioeconomic status (SES) in young adulthood and whether it is moderated by early life SES variables.

Methods

Prospective cohort studies; British Cohort Study 1970 (BCS70) and Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991–1992, were used and two comparable MRB variables were derived. Logistic regression was used to determine the association between MRB and young adult SES. The moderating effect of three early life SES variables was assessed using logistic regression models with and without interaction parameters. Evidence to support the presence of moderation was determined by likelihood ratio tests ≤p = 0.05. Multiple imputation was used to account for missing data.

Results

Adolescents had a median of two risk behaviours in BCS70 and three in ALSPAC. Adolescent MRB was negatively associated with young adult SES (university degree attainment) in BCS70 (OR 0.81, 95% CI: 0.76, 0.86) and ALSPAC (OR 0.85, 95% CI: 0.82, 0.88). There was a dose response relationship, with each additional risk behaviour resulting in reduced odds of university degree attainment. MRB was associated occupational status at age 34 in BCS70 (OR 0.86 95% CI: 0.82, 0.90). In BCS70, there was evidence that maternal education (p = 0.03), parental occupational status (p = 0.009) and household income (p = 0.03) moderated the effect of adolescent MRB on young adult SES in that the negative effect of MRB is stronger for those with low socioeconomic backgrounds. No evidence of moderation was found in the ALSPAC cohort.

Conclusions

Adolescence appears to be a critical time in the life course to address risk behaviours, due to the likelihood that behaviours established here may have effects in adulthood. Intervening on adolescent MRB could improve later SES outcomes and thus affect health outcomes later in life. Evidence for a moderation effect in the BCS70 but not ALSPAC suggests that more detailed measures should be investigated to capture the nuance of contemporary young adult SES.