A Systematic Review and Meta-Analysis of Continuous Subcutaneous Insulin Infusion vs. Multiple Daily Injections in Type-2 Diabetes.

Diabetes mellitus (DM) has a growing prevalence worldwide, even in developing countries. Many antidiabetic agents are used to improve glycemic control; however, in cases of an insufficient outcome, insulin is administered. Yet, the timing of proper insulin administration is still a subject of intense research. To date, there have been no recommendations or guidelines for the use of continuous subcutaneous insulin infusion (CSII) in Type 2 Diabetes Mellitus (T2DM). In the present study, we have performed a meta-analysis to evaluate the use of CSII in patients with T2DM. An extensive literature search was conducted through the electronic databases Pubmed, Clinicaltrials.gov, and Cochrane Central Register of Controlled Trials (CENTRAL) from October 2019-May 2022, for interventional studies related to T2DMI and CSII versus multiple daily injections (MDI). We included articles published in the English language only, yielding a total of thirteen studies. We found better outcomes in patients receiving CSII, in regard to glycated hemoglobin (HbA1c) and total insulin dose. In contrast, fasting plasma glucose and body weight did not show statistically significant differences between the two groups. Our analyses showed that CSII could be beneficial in patients with T2DM in order to achieve their glucose targets.

The Impact of GLP1 Agonists on Bone Metabolism: A Systematic Review.

Background and Objectives: The association between diabetes mellitus and increased risk of bone fractures has led to the investigation of the impact of antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP1RAs) are a relatively novel and promising class of anti-hyperglycemic drugs. In addition to their blood glucose lowering action, GLP1RAs seem to have additional pleiotropic properties such as a beneficial skeletal effect; although the underlying mechanisms are not completely understood. The present systematic review summarizes current evidence about GLP1RAs and their effects on bone metabolism and fracture. Methods: An extensive literature search was conducted based on electronic databases namely, PubMed, Google Scholar and Cochrane Central Register of Controlled Trials (CENTRAL) through October 2019 to January 2020 for articles related to bone mineral density, diabetes mellitus and GLP1RAs. We included articles published in English. Finally, we included four randomized controlled trials, three meta-analyses, a case-control study and a population-based cohort analysis. Results: Based on the articles included, the animal studies indicated the salutary skeletal effects of GLP1RAs in opposition to what has been commonly observed in human studies, showing that these agents have no impact on bone mineral density (BMD) and the turnover markers. Moreover, it was demonstrated that GLP1 was not associated with fracture risk as compared to other anti-hyperglycemic drugs. Conclusions: Findings from this systematic review have demonstrated the neutral impact of GLP1RAs on BMD. Moreover, further double-blind randomized controlled trials are needed to draw more meaningful and significant conclusions on the efficacy of GLP1RAs on BMD.

Systems Approaches in the Common Metabolomics in Acute Lymphoblastic Leukemia and Rhabdomyosarcoma Cells: A Computational Approach.

Acute lymphoblastic leukemia is the most common childhood malignancy. Rhabdomyosarcoma, on the other hand, is a rare type of malignancy which belongs to the primitive neuroectodermal family of tumors. The aim of the present study was to use computational methods in order to examine the similarities and differences of the two different tumors using two cell lines as a model, the T-cell acute lymphoblastic leukemia CCRF-CEM and rhabdomyosarcoma TE-671, and, in particular, similarities of the metabolic pathways utilized by two different cell types in vitro. Both cell lines were studied using microarray technology. Differential expression profile has revealed genes with similar expression, suggesting that there are common mechanisms between the two cell types, where some of these mechanisms are preserved from their ancestor embryonic cells. Expression of identified species was modeled using known functions, in order to find common patterns in metabolism-related mechanisms. Species expression manifested very interesting dynamics, and we were able to model the system with elliptical/helical functions. We discuss the results of our analysis in the context of the commonly occurring genes between the two cell lines and the respective participating pathways as far as extracellular signaling and cell cycle regulation/proliferation are concerned. In the present study, we have developed a methodology, which was able to unravel some of the underlying dynamics of the metabolism-related species of two different cell types. Such approaches could prove useful in understanding the mechanisms of tumor ontogenesis, progression, and proliferation.

Adiponectin and Its Effects on Acute Leukemia Cells: An Experimental and Bioinformatics Approach.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. It is known that deregulation of adipokine pathways is probably implicated in the ontogenesis of ALL. The present work aims at investigating the role of adiponectin and its effects on an ALL cell line. The CCRF-CEM cells were used as a model. Cells have been treated with adiponectin, with different concentrations up to 72 h. Cytotoxicity and cell cycle distribution were investigated for all concentrations using flow cytometry. Selected concentrations were also used for additional microarray analysis, using a small gene set of cancer-related genes. Lower and higher adiponectin concentrations did not produce an inhibition of proliferation, as well as an increase in cell death. It was found that adiponectin regulated differentially genes, such as CD22, CDH1, IFNG, LCK, MSH2, SPINT2, and others. At the same time, it appeared that adiponectin-related gene expression was more active on chromosomes 18 and 1. Machine learning classification algorithms showed that several genes were grouped together indicating common regulatory mechanisms. The present study showed that adiponectin is able to induce gene differential expression in leukemic cells in vitro, suggesting a possible role in the progression of leukemia. It is also an indication that more studies are required in order to further understand the role of adiponectin and adipokines in general in the role of human neoplasms.

Early and Very Early GRIM19 and MCL1 Expression Are Correlated to Late Acquired Prednisolone Effects in a T-Cell Acute Leukemia Cell Line.

Glucocorticoids (GCs) are still first-line drugs for the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone is a corticosteroid and one of the most important agents in the treatment of ALL. We report here a study of Prednisolone treatment using as a model a leukemia cell line with subsequent investigation of resistance-related gene expression. Gene silencing has been used in order to identify significant targets of resistance to GC-induced apoptosis in ALL cells. We analyzed effects of increasing doses of Prednisolone on ALL cell survival and growth, and we monitored immediate effects on gene expression through gene expression assays. We determined Prednisolone cytotoxicity and cell cycle distribution as well as DNA content. Upon treatment with escalating Prednisolone concentration, we observed a gradual decline in cell survival. MCL1 and GRIM19 were investigated as possible genes for the intrinsic capacity of this cell line to respond to corticosteroid and a snapshot of early changes was examined. Early MCL1 and GRIM19 expression correlated significantly to late GC-induced apoptosis. Prednisolone competitively induces MCL1 expression. Consistently with previous studies on primary leukemia blasts, cells are sensitive to proteasome inhibitor MG132; no interference of Prednisolone with MG132 effects on this cell line was noted. The inherent plasticity of clinically evolving cancer justifies approaches to characterize and prevent undesirable activation of early oncogenic pathways. Study of the pattern of intracellular signal pathway activation by anticancer drugs can lead to development of efficient treatment strategies by reducing detrimental secondary effects.

Bone Metabolism Markers in Thalassemia Major-Induced Osteoporosis: Results from a Cross-Sectional Observational Study.

BACKGROUND: Thalassemia major (TM) patients eventually face many new health conditions, including endocrinopathies and low bone mineral density, usually observed in the aging general population. OBJECTIVE: The aim of the current study was to evaluate the biomarkers of bone remodeling in TM patients and to compare them with both osteoporotic and healthy population, in order to investigate the new therapeutic paths. METHODS: Sixty-four patients with TM (32 men and 32 women) participated in the study. The patients were evaluated with dual-energy X-ray absorptiometry (DXA) of the lumbar spine and femoral neck and with markers of bone remodeling including receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide (CTX), and sclerostin. Results were compared with those from 12 postmenopausal women with osteoporosis and 12 women with normal bone mineral density. RESULTS: The statistical analysis of the biochemical markers of bone metabolism revealed overall significant differences between the three groups only for RANKL and OPG/RANKL (p=0.049 and p=0.009). RANKL was higher and OPG/RANKL was lower in TM patients compared to osteoporosis group. CONCLUSION: Patients with TM do not have a higher probability of suffering from osteoporosis from the general population. However, some markers of osteoclast activity differ between patients with TM and osteoporosis, indicating the possible differences in terms of anti-osteoporotic treatment. The lack of significant differences among the three groups in regards to the levels of CTX and sclerostin may indicate the potential efficacy of the current osteoporotic treatment also for TM patients.

Prevalence, Wellbeing, and Symptoms of Dysmenorrhea among University Nursing Students in Greece.

Dysmenorrhea (pain during menstruation) is one of the most common medical conditions among women of reproductive age. Dysmenorrhea has been studied around the world but not yet in Greece. The aim of the present study was to investigate the prevalence, characteristics, and impact of dysmenorrhea on the wellbeing (exercising, and social and academic functioning) among nursing students in Greece. A cross-sectional study of 637 nursing students was conducted by administering a questionnaire at a university in Athens. The prevalence of dysmenorrhea was 89.2% and the rate of severe intensity was 52.5%. Factors that were associated with severe dysmenorrhea were family history (p = 0.02), early menarche (p = 0.05) and menstruation duration (p = 0.05). Women with moderate and severe pain reported using pain relievers (non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol etc., p < 0.0005). Finally, activities affected by severe pain were class attendance (p = 0.01), personal studying (p < 0.0005), exercising (p < 0.0005), and socializing (p < 0.0005). Exam attendance (p = 0.27) and clinical placement attendance (p = 0.48) were not affected by severe dysmenorrhea. Dysmenorrhea has a high prevalence among nursing students and seems to affect important aspects of wellbeing and academic performance when the pain intensity is severe. The present findings lay the foundation for further investigation of dysmenorrhea both in the Greek population and cross-culturally.

The role of biphosphonates in the management of thalassemia-induced osteoporosis: a systematic review and meta-analysis.

Thalassemia Major (TM) is a clinical entity with a high prevalence of low bone mass. The aim of the present study was to perform a meta-analysis of all available data on the role of bisphosphonates (BPs) in the therapy of thalassemia major-induced osteoporosis. The PRISMA recommendations for reporting systematic reviews and meta-analyses were used to guide the present study. We searched PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 31, 2017 for articles related to thalassemia and BPs. To meta-analytically synthesize the primary endpoint, we used the standardized mean difference (SMD) after Hedges's g transformation under the scenario of a random effects model. Heterogeneity across studies was examined using the I2 statistic. Nine randomized controlled trials (RCTs) containing original data were included in this review. Three studies were performed in Italy, one in Australia, three in Greece, one in Cyprus, and one in China. The BPs investigated included zoledronate, alendronate, pamidronate, clodronate, and neridronate. Zoledronate and alendronate showed a tendency to perform best as compared to neridronate and the placebo effect with respect to femoral neck, lumbar spine, total hip, and total body in terms of bone mass density (g/cm2). BPs and in particular, zolendronate, were quite effective in the treatment of osteoporosis. These findings suggested that bisphosphonates are still a front-line treatment of osteoporosis in TM. However, to draw more meaningful and significant conclusions for the use and efficacy of BP in TM, larger and more complete RCTs should be conducted.

Statins, bone formation and osteoporosis: hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

Coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. A retrospective study.

OBJECTIVE: The association between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains controversial in medical bibliography. The main objective of our study was to determine the prevalence of PTC and HT coexistence in histopathologic material of thyroidectomized patients. DESIGN: In a retrospective study, the clinicohistopathologic data of 140 patients (19 males/121 females), who underwent a total or near total thyroidectomy for any thyroid pathology from January 2005 to December 2009 at the Naval Hospital of Crete, were analysed. The mean age of the patients was 52 years (range 16-74). RESULTS: HT was detected in 42 (30%) and PTC in 32 (22.9%) specimens. Coexistence of HT with PTC was present in 12 (8.6%) specimens. Among 32 specimens with PTC, the prevalence of HT was 37.5%. Among 42 specimens with HT, the prevalence of PTC was 28.6%. There was no statistically significant difference between the presence of PTC and HT in histopathologic material. CONCLUSIONS: The prevalence of PTC and HT coexistence in histopathologic material of 140 thyroidectomized patients was 8.6%, whereas the difference between PTC and HT was not statistically significant.

Exemestane-induced subclinical hypothyroidism : a case report.

Several conditions and drugs induce subclinical hypothyroidism. We report the first case of subclinical hypothyroidism in a 65-year-old woman with breast cancer receiving therapy with the third-generation aromatase inhibitor exemestane 25 mg/day for 2 months. The patient presented with complaints of increasing fatigue and weakness since being commenced on exemestane and was taking no other drugs. There was no past history or family history of thyroid disease. Thyroid function tests prior to breast cancer surgery were normal. Detailed clinical examination and laboratory tests to determine the cause of the patient's increasing fatigue and weakness revealed only subclinical hypothyroidism, that is, an elevated level of thyroid-stimulating hormone (thyrotropin, TSH) only. Ultrasonography revealed a normal thyroid gland. Based on a diagnosis of symptomatic subclinical hypothyroidism, the patient was commenced on levothyroxine sodium 50 microg/day and exemestane was withdrawn. Thyroid dysfunction was restored 4 months after her admission with a significant improvement in symptoms. Levothyroxine sodium was withdrawn 6 months later and no recurrence of thyroid dysfunction occurred during a 1-year follow-up. We believe that the increasing fatigue and weakness in our patient might have been associated either with subclinical hypothyroidism or with administration of exemestane (a known adverse effect of the drug) or both. Further studies are required to investigate how exemestane influences thyroid function.

Acute rhabdomyolysis caused by Spirulina (Arthrospira platensis).

Rhabdomyolysis is a potentially life-threatening disorder that occurs as a primary disease or as a complication of a broad spectrum of other diseases. We report the first case of acute rhabdomyolysis after ingestion of Spirulina (Arthrospira platensis), a plantonic blue-green alga, as a dietary supplement.